ERMA New Zealand
Evaluation and Review Report
Application for Approval to Import or
Manufacture Frontier-P for Release
Application Number: HSR08124
Prepared for the Environmental Risk Management
Authority
EXECUTIVE SUMMARY
Background information

BASF New Zealand Limited is seeking approval to import Frontier-P for release.

Frontier-P is a herbicide containing 720 g/litre dimethenamid-P in the form of an
emulsifiable concentrate.

Frontier-P is proposed to be used as a pre-emergence selective herbicide for the
control of annual grasses and broadleaf weeds in a number of field crops.

Frontier-P will be applied as a herbicide at a maximum application rate of 1.3 L/ha
(0.936 kg dimethenamid-P/ha) with a maximum of 1 application per year.

The applicant advises that application will be by either aerial or ground based
methods.

Dimethenamid-P is a new active ingredient to New Zealand.
Classification


The Agency and the applicant have independently classified Frontier-P based on the
available information on Frontier-P and its components. The classifications are
summarised in the table below:
Hazardous Property
Applicant’s Assessment
Agency’s Assessment
Acute Toxicity (Oral)
6.1D
6.1D
Acute Toxicity (Inhalation)
6.1D
(aspiration hazard)
─
Skin Irritancy
6.3B
6.3B
Eye Irritancy
6.4A
6.4A
Skin Sensitisation
6.5B
6.5B
Carcinogenicity
6.7B
6.7B
Target Organ Toxicity
6.9B
─
Aquatic Ecotoxicity
9.1A
9.1A
Soil Ecotoxicity
9.2A
9.2A
Ecotoxicity to Terrestrial
Vertebrates
9.3C
9.3C
Biocide
9.1D
─
Differences between Agency’s and the applicant’s classifications are:
o The applicant’s incorrect inclusion of the biocide classification. This has been
removed as the substance has triggered ecotoxicity classifications.
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o The applicant assigned a 6.9B classification based on the 2-year feeding study
in rats. However, results from this study do not support classification of
Frontier-P as a target organ toxicant.
o The applicant assigned a 6.1D (aspiration hazard) classification to Frontier-P
because component A2 is classified as presenting an aspiration hazard.
However, an aspiration hazard only triggers 6.1E classification and
furthermore, component A2 is present at below the threshold for triggering
aspiration hazard classification. Formulation test data indicates Frontier-P
does not trigger classification as an inhalation toxicant.
Risk Assessment

The Agency notes that dimethenamid-P has been recently reviewed by APVMA
(2007) and by PMRA-ARLA (Canada) (2009). The outcomes of these reviews have
been considered within the Agency’s assessment of Frontier-P.

The Agency’s assessment of the risks posed by Frontier-P to the environment and to
human health, during the substance’s lifecycle, is based on qualitative assessment and
quantitative modelling using the GENEEC2 and German BBA models.

The Agency considers that the risk assessments indicate that the risks associated with
Frontier-P are negligible with the proposed controls in place.

The Agency has evaluated information supplied by the applicant about the benefits of
Frontier-P and considers that benefits are likely to be realised through the release of
this substance.
Controls

The Agency has proposed that the default controls for Frontier-P be modified, such
that:
- no Tolerable Exposure Limits (T1), Workplace Exposure Standards (T2) or
Environmental Exposure Limits (E1) are set at the present time and any
default values are deleted;
- the maximum application rate for Frontier-P shall be 1.3 L/ha (0.936 kg
dimethenamid-P/ha) with a maximum application frequency of 1 application
per year.
- the maximum quantity for passenger service vehicles (T7) is increased from
0.1 L to 1 L;
- the approved handler (E7, AH1) controls are retained, but modified to apply
to use only;
- the tracking control (TR1) is deleted;
- further controls regarding stationary containment systems and pipework are
added; and
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- a control which prohibits application of Frontier-P onto or into water is
added.
Agency Conclusion

In conclusion, the Agency considers that there are negligible risks to human health
and to the environment and potential benefits associated with the release of FrontierP. Therefore, the Agency considers that it is evident that the benefits of releasing
Frontier-P outweigh the costs and the application may be approved in accordance
with clause 26.
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TABLE OF CONTENTS
1
2
3
4
5
6
7
8
9
10
11
12
Application Details ............................................................................................................. 6
Legislative Criteria for the Application .............................................................................. 6
Application Process ............................................................................................................ 6
Notification and Consultation ............................................................................................. 7
Application Synopsis and Information Review .................................................................. 8
Hazardous Properties, Thresholds and Classification ....................................................... 10
Default Controls ................................................................................................................ 12
Risk Assessment ............................................................................................................... 12
Assessment of Beneficial Effects...................................................................................... 18
Controls ............................................................................................................................. 19
Overall Evaluation of Risks, Costs and Benefits .............................................................. 22
Conclusion ........................................................................................................................ 23
Appendix 1: Decision Path ...................................................................................................... 24
Appendix 2: Hazard Classification .......................................................................................... 25
Appendix 3: Risk Assessment ............................................................................................... 101
Appendix 4: Discussion on Controls ..................................................................................... 111
Appendix 5: List of Proposed Controls for Frontier-P .......................................................... 137
Appendix 6: Scales for Qualitative Risk Assessment ............................................................ 144
Appendix 7: Government Departments, Crown Entities and Interested Parties Notified ..... 147
Appendix 8: Confidential Material ........................................................................................ 149
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1 APPLICATION DETAILS
Application Code
HSR08124
Application Type
To import or manufacture for release any hazardous
substance under Section 28 of the Hazardous Substances
and New Organisms Act 1996 (“the Act”)
Applicant
BASF New Zealand Limited
Date Application Received
10 December 2008
Submission Period
20 January 2009 – 4 March 2009
To be considered by
A Committee of the Authority (‘the Committee”)
Purpose of the Application
To import Frontier-P as a pre-emergence selective
herbicide for the control of annual grasses and broadleaf
weeds in a number of field crops (Category C).
2 LEGISLATIVE CRITERIA FOR THE APPLICATION
2.1
The application was lodged pursuant to section 28.
2.2
This report takes into account matters to be considered in section 29; matters
specified under Part II of the Act; and the relevant provisions of the Hazardous
Substances and New Organisms (Methodology) Order 1998 (“the
Methodology”). Unless otherwise stated, references to section numbers in this
report refer to sections of the Act and clauses to clauses of the Methodology.
3 APPLICATION PROCESS
3.1
3.2
Evaluation of the application was undertaken by the ERMA New Zealand
project team (“the Agency”) which comprised the following staff members:
Haydn Murdoch
Advisor (Hazardous Substances)
Eugene Georgiades
Advisor (Hazardous Substances)
Tonderai Kaitano
Advisor (Hazardous Substances)
Patrick Gemmell
Senior Advisor (Kaupapa Kura Taiao).
The report was reviewed and signed out by:
Noel McCardle
Senior Advisor (Hazardous Substances).
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3.3
3.4
Timeline
Application formally received
10 December 2008
Application notified
20 January 2009
Submission closing date
4 March 2009.
Due to delays in completing this E&R Report, the Authority postponed the
consideration under section 58(3) until 31 July 2009.
4 NOTIFICATION AND CONSULTATION
4.1
The Minister for the Environment was advised of the application1 and given the
opportunity to “call-in” the application2. This action was not initiated.
4.2
The Department of Labour (Workplace Group), the New Zealand Food Safety
Authority (Agricultural Compounds and Veterinary Medicines (ACVM) Group)
and the Department of Conservation were identified as having a specific interest
in the application and were provided with a copy of the application (excluding
the confidential information but with the opportunity to access this if necessary).
4.2.1
4.3
Other Government departments, Crown agencies and other interested parties, as
listed in Appendix 7, were provided with a copy of the application summary and
given the opportunity to comment or to make a submission.
4.3.1
4.4
No comments or submissions were received.
No comments or submissions were received.
The application was publicly notified on the ERMA New Zealand website on 20
January 2009 and subsequently advertised in The Dominion Post, the New
Zealand Herald, the Christchurch Press and the Otago Daily Times3.
4.4.1
No submissions were received.
1
section 53(4)(a)
section 68
3
section 53
2
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5 APPLICATION SYNOPSIS AND INFORMATION
REVIEW
Information supplied by the applicant
5.1
The applicant supplied the following documents:

the application;

a confidential appendix (including full formulation data and a draft
label).
Information review
5.2
The confidential information on the composition of Frontier-P has been
withheld at the request of the applicant for reasons of commercial sensitivity.
The information is provided for the Committee in Confidential Appendix 8.
5.3
The Agency notes that dimethenamid-P (Frontier-P) has been recently reviewed
by APVMA (2007). This product was assessed at similar use quantities
(maximum rate 1.4 L/ha) as are proposed for New Zealand (maximum rate 1.3
L/ha). This report highlighted the following environmental concerns:
5.4

Aerial application is prohibited on the label (this route was not considered
in the Australian assessment);

The chemical is very toxic to aquatic plants, algae and terrestrial plants.
To protect these plants spray-drift buffers of 20 metres for aquatic plants,
or 15 metres for terrestrial plants are required assuming medium spray
quality;

If a fine spray is used (or as a default where spray quality is not defined on
the label), then the risk is higher and buffers of 50 metres for aquatic
plants and 40 metres for terrestrial plants are required;

Risks to algae and terrestrial and aquatic plants have also been identified
from run-off events. A clear relationship was established for the time
between application and storm events and run-off. It is recommended that
restrictions on application be restricted when there is the expectation of
heavy rain. This would provide a better chance for dimethenamid to
bind/degrade prior to a run-off event and therefore limit the risk from
runoff.
The Agency notes that dimethenamid-P (Frontier-Max) has been recently
reviewed by PMRA-ARLA (Canada) (2009). This report highlighted the
following environmental concerns:

Dimethenamid-P has a potential for leaching in soils.
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
A buffer zone of 3 m is calculated for the use of Frontier Max Herbicide
for protection of terrestrial plants.

A buffer zone of 1 m is calculated for the use of Frontier Max Herbicide
for protection of aquatic habitats.
5.5
The outcomes of these reviews have been considered within the Agency’s
assessment of the substance.
5.6
The Agency considers that there are no significant uncertainties sufficient to
influence decision making in the scientific and technical information relating to
the potential adverse effects of Frontier-P4. Therefore, the Agency considers that
the information constitutes an adequate and appropriate basis for considering the
application5.
Description and use of the substance
5.7
Frontier-P is a herbicide containing 720 g/litre dimethenamid-P in the form of
an emulsifiable concentrate. Frontier-P is proposed to be used as a preemergence selective herbicide for the control of annual grasses and broadleaf
weeds in a number of field crops.
Lifecycle
Manufacture/Importation
5.8
The applicant has indicated that Frontier-P will be manufactured overseas and
imported into New Zealand fully formulated and packaged in the sale packs.
5.9
While Frontier-P will be manufactured overseas, it is possible that the substance
could be manufactured in New Zealand in the future. Consequently, the risks
associated with the manufacture of Frontier-P have been evaluated, so that
approval of this substance will be applicable to both the import and manufacture
of Frontier-P.
Transport, storage and packaging
4
5
5.10
Packaging for Frontier-P will conform to Packaging Group II. FRONTIER-P
will be marketed in mould blown high-density polyethylene (HDPE) containers
with inner barrier (e.g. polyamide) and with foil seals. These are protected by
screw caps of polypropylene.
5.11
The substance will be transported within New Zealand in accordance with the
relevant New Zealand Transport Legislation.
5.12
The substance will be stored in accordance with the requirements of
NZS8409:2004 Management of Agrichemicals, the Act and the Resource
Management Act 1991.
clauses 29 and 30
clause 8
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Use
5.13
Frontier-P is a post-plant, pre-emergence selective herbicide applied to prepared
ground for the control of annual grasses and broadleaf weeds in maize, squash,
sweetcorn, dwarf beans, onions and forage brassica.
5.14
The proposed use rate of Frontier-P for New Zealand conditions is 0.5 to 1.3
litres formulation/ha or 360-936 g a.i./ha. Frontier-P is intended for use only
once a year. Frontier-P is not intended for direct use over water.
5.15
The applicant advises that application will be by either aerial or ground based
methods.
Disposal
5.16
The applicant advises that the normal method of disposal of the substance will
be via use.
5.17
Frontier-P as well as its damaged packaging, contaminated adsorbents, and
other materials shall be disposed of in a suitable landfill. Additional methods are
described in the GIFAP monograph “Disposal of unwanted pesticide stocks”
1991. Unclean empty containers are to be treated in that context like full ones.
5.18
Empty primary packages of Frontier-P shall be triple rinsed as described in the
ECPA “Guidelines for rinsing agrochemical containers”, 1993. That reduces the
amount of product to below 0.01% of the original amount. Pressure rinsing or
integrated pressure rinsing of the packaging material achieves a similar or better
result. The rinsate is to be added to the spray liquid.
5.19
Triple rinsed primary packages shall be rendered unusable, and then they may
be disposed off according to local regulations and best available practice. The
rinsed container may be offered for recycling under the Agrecovery Rural
Recycling Programme.
5.20
In all cases, the substance and its packaging will be disposed of in accordance
with the Hazardous Substances (Disposal) Regulations 2001 and the Resource
Management Act 1991.
6 HAZARDOUS PROPERTIES, THRESHOLDS AND
CLASSIFICATION
6.1
The Agency has evaluated the information supplied by the applicant and also
referred to other data sources in assessing the hazardous properties of
Frontier-P. This assessment is attached as Appendix 2.
6.2
The applicant’s and the Agency’s classification of the hazard profiles of
Frontier-P are listed in Table 6.1.
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Table 6.1: Summary of applicant’s and Agency’s HSNO classification of
Frontier-P
6.3
6.4
Hazardous Property
Applicant’s
Assessment
Agency’s Assessment
Acute Toxicity (Oral)
6.1D
6.1D
Acute Toxicity (Inhalation)
6.1D
(aspiration
hazard)
─
Skin Irritancy
6.3B
6.3B
Eye Irritancy
6.4A
6.4A
Skin Sensitisation
6.5B
6.5B
Carcinogenicity
6.7B
6.7B
Target Organ Toxicity
6.9B
─
Aquatic Ecotoxicity
9.1A
9.1A
Soil Ecotoxicity
9.2A
9.2A
Ecotoxicity to Terrestrial
Vertebrates
9.3C
9.3C
Biocide
9.1D
─
The differences between Agency’s and the applicant’s classifications of
Frontier-P are:
6.3.1.
The applicant’s incorrect inclusion of the biocide classification. This
has been removed, as the substance has triggered ecotoxicity
classifications and therefore the biocide rider does not apply.
6.3.2.
The applicant assigned 6.9B classification based on the 2-year feeding
study in rats. However, results from this study do not support
classification of Frontier-P as a target organ toxicant.
6.3.3.
The applicant assigned 6.1D (aspiration hazard) classification to
Frontier-P because component A2 is classified in as presenting an
aspiration hazard. However, aspiration hazard only triggers 6.1E
classification and furthermore, component A2 is present at below the
threshold for triggering aspiration hazard classification. Formulation
test data indicates Frontier-P does not trigger classification as an
inhalation toxicant.
The risk assessment in section 8 of this report is based on the Agency’s
classifications of Frontier-P
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7 DEFAULT CONTROLS
7.1
Based on the hazard classification shown in Table 6.1, the set of associated
controls has been identified. These default controls are listed in Appendix 4.
7.2
The Authority is able to vary the default controls and impose controls under
sections 77 and 77A to produce a set of controls relevant to Frontier-P.
Variations and additional controls for Frontier-P are considered in Section 10 of
this report.
8 RISK ASSESSMENT
Identification of potentially non-negligible risks and costs
8.1
Potentially non-negligible risks were identified for evaluation following clauses
9 and 11, which incorporate sections 5, 6 and 8.
8.2
A “cost” is defined in Regulation 2 of the Methodology as “the value of a
particular adverse effect expressed in monetary or non-monetary terms”. Thus,
these have been assessed in an integrated fashion together with the risks of the
adverse effects in the following assessment.
8.3
The applicant has identified potential sources of risk to the environment and to
human health and safety through release, spillage or exposure throughout the
lifecycle of the substance. The Agency has also identified potential sources of
risk and these, along with those identified by the applicant, are tabulated in
Table 8.1.
Table 8.1: Potential sources of risks associated with Frontier-P
Lifecycle Activity
Associated Source of Risk
Manufacture / Import
An incident during the manufacture or importation of Frontier-P
resulting in spillage and subsequent exposure of people or the
environment to the substance.
Packing
An incident during the packing of Frontier-P resulting in spillage and
subsequent exposure of people or the environment to the substance.
Transport or storage
An incident during the transport or storage of Frontier-P resulting in
spillage and subsequent exposure of people or the environment to the
substance.
Use
Application of Frontier-P resulting in exposure of users or bystanders
or the environment; or an incident during use resulting in spillage and
subsequent exposure of users or the environment to the substance.
Disposal
Disposal of Frontier-P or packaging resulting in exposure of people or
the environment to the substance.
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Assessment of potentially significant risks
8.4
In accordance with sections 5 and 6 and clauses 9 and 12, the Agency has
assessed the potentially non-negligible risks of this substance in terms of risks to
the environment, to human health and safety, to the relationship of Māori to the
environment, to society and the community, to the market economy, and to New
Zealand’s international obligations.
8.5
The Agency notes that the evidence provided by the applicant and additional
evidence found by the Agency, relating to the hazardous properties of FrontierP, is largely scientific in nature6. However, as some of the evaluation of risks,
costs and benefits has been carried out on a qualitative basis, it is recognised
that there is a degree of uncertainty in the risk analysis.
8.6
The analysis of risk takes into account the controls that derive from the HSNO
Regulations (in particular the default controls identified in Appendix 4) and
from other legislation such as the Resource Management Act 1991 and the
Health and Safety in Employment Act 1992. That is, the analysis assumes
controls are in place.
8.7
A quantitative risk assessment has been carried out to evaluate the level of risk
to operators, bystanders and the environment arising from the use of Frontier-P
(see Appendix 3).
8.8
A qualitative assessment has been undertaken for all other stages of the
lifecycle. In these cases, the level of risk has been evaluated on the basis of the
magnitude and likelihood of adverse effects occurring to people or the
environment (see Appendix 3).
Assessment of the risks to the environment
6
8.9
The Agency has classified Frontier-P as being very toxic in the aquatic
environment (9.1A), very toxic to soil organisms (9.2A) and harmful to
terrestrial vertebrates (9.3C). Dimethenamid-P is considered persistent in the
environment. Thus, a range of organisms in the environment may be adversely
affected if exposed to Frontier-P.
8.10
The Agency considers that the likelihood of exposure to the environment is
greatest during use of the substance.
8.11
This quantitative assessment of the environmental risks associated with the use
of Frontier-P show that it presents a high acute risk to the aquatic environment
and a high risk to non-target plants (see Appendix 3).
8.12
The Agency notes the results of the quantitative modelling and considers that
application of the following controls will reduce the level of risk to the
environment to negligible:
clause 25(1)
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8.13

The approved handler controls (triggered by the 9.1A and 9.2A
classification). The Agency considers that requiring people using the
substance to be approved handlers, will minimise the risks associated with
exposure to the aquatic and terrestrial environments; and

Prohibiting the application of Frontier-P into or onto water; and

Setting a maximum application rate and application frequency.
The risks of Frontier-P to the environment (with controls in place) at various
stages of its lifecycle are summarised below in Table 8.2 and discussed more
fully in Appendix 3.
Table 8.2: Level of risk of Frontier-P to the environment.
Lifecycle Stage
Potential Adverse
Effect
Likelihood of
Adverse Effect
Occurring
Magnitude of
Adverse
Effect
Level of
Risk
Manufacture,
importation,
transport and
storage
Spillage resulting in
death or adverse effects
to aquatic or terrestrial
organisms in the
environment.
Highly
improbable
Moderate
Negligible
Use
Use resulting in death
or adverse effects to
aquatic organisms in the
environment.
Quantitative assessment indicated that there was a
high risk to the aquatic environment from the use
of Frontier-P. The Agency considers that the
application of controls will reduce this risk to
negligible.
Use resulting in death
or adverse effects to
non-target plants.
Quantitative assessment indicated that there was a
high risk to non-target plants during the use of
Frontier-P. The Agency considers that the
application of controls will reduce this risk to
negligible.
Use resulting in death
or adverse effects to
terrestrial vertebrates.
Quantitative assessment indicated that there was a
low risk to birds during the use of Frontier-P. The
Agency considers that the application of controls
will reduce this risk to negligible.
Use resulting in death
or adverse effects to
terrestrial invertebrates
Quantitative assessment indicated that there was a
negligible risk to bees and other beneficial insects
during the use of Frontier-P.
Disposal resulting in
death or adverse effects
to aquatic or terrestrial
organisms in the
environment
Highly
improbable
Disposal
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Minor
Negligible
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Assessment of the risks to human health and safety
8.14
The Agency has classified Frontier-P as an acute oral toxicant (6.1D), a skin
irritant (6.3B), an eye irritant (6.4A), a skin sensitiser (6.5B) and a suspected
carcinogen (6.7B).
8.15
In the Agency’s opinion, chronic hazards normally require repeated exposure to
the substance for the adverse effects to occur and are therefore most relevant to
the end-users.
8.16
The Agency assessed the health risk to operators on the basis of the German
BBA model predictions for exposure estimates. The quantitative modelling
indicates that at the highest application rates the exposure to Frontier-P, when
used as recommended on the label, is not likely to present a high health risk to
the mixers or applicators, as long as “full” Personal Protective Equipment (PPE)
is worn during mixing, loading and applying the substance. The use of
respirators is not required.
8.17
The Agency notes that the requirement for PPE is triggered as a default control
for Frontier-P as a result of its 6.1D, 6.3B, 6.4A, 6.5B and 6.7B classifications.
The Agency, therefore, concludes that the health risk to operators, with controls
in place, is negligible. Further details on this quantitative assessment are given
in Appendix 3.
8.18
The Agency notes that the main potential source of exposure to the general
public from Frontier-P (other than via food residues) is via spray drift. The
Agency has undertaken an assessment of the risks to public/bystander health
using the United Kingdom Chemicals Regulation Directorate’s (CRD) current
formula to assess public/bystander exposure for pesticides. The results of this
modelling indicate that the risks posed to bystanders from the use of Frontier-P
are considered to be at acceptable levels and the default controls triggered by the
toxicity hazards associated with the substance are sufficient to mitigate risks.
The Agency, therefore, concludes that the health risk to bystanders is negligible.
Further details on this quantitative assessment are given in Appendix 3.
8.19
The risks of Frontier-P to human health and safety (with controls in place) at
various stages of the lifecycle are summarised below in Table 8.3 and discussed
more fully in Appendix 3.
Table 8.3: Level of risk of Frontier-P to human health and safety.
Lifecycle stage
Potential Adverse
Effect
Likelihood
of Adverse
Effect
Occurring
Magnitude of
Adverse
Effect
Level of Risk
Manufacture/packing
Acute toxicity
Highly
improbable
Moderate
Negligible
Skin irritancy
Eye irritancy
Highly
improbable
Minimal
Negligible
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Lifecycle stage
Importation, transport
or storage
Use
Potential Adverse
Effect
Likelihood
of Adverse
Effect
Occurring
Magnitude of
Adverse
Effect
Level of Risk
Skin sensitisation
Highly
improbable
Minor to
moderate
Negligible
Carcinogenicity
Quantitative assessment indicates that the chronic
risks to human health and safety are acceptable when
PPE is worn. This reduces the level of risk to
negligible.
Acute toxicity
Highly
improbable
Moderate
Negligible
Skin irritancy
Eye irritancy
Highly
improbable
Minimal
Negligible
Skin sensitisation
Highly
improbable
Minor to
moderate
Negligible
Acute effects: operators & bystanders (qualitative assessment)
Acute toxicity
Highly
improbable
Moderate
Negligible
Skin irritancy
Eye irritancy
Highly
improbable
Minimal
Negligible
Skin sensitisation
Highly
improbable
Minor to
moderate
Negligible
Chronic effects: operators (quantitative assessment)
Carcinogenicity
Quantitative assessment indicated that the chronic
risks to human health and safety are acceptable if
PPE is worn during mixing, loading and application.
The use of PPE reduces the level of risk to negligible.
Chronic effects: bystanders (quantitative assessment)
Disposal
Carcinogenicity
Quantitative assessment indicated that the chronic
risks to bystander human health and safety are
acceptable and the level of risk is considered to be
negligible.
Acute toxicity
Highly
improbable
Moderate
Negligible
Skin irritancy
Eye irritancy
Highly
improbable
Minimal
Negligible
Skin sensitisation
Highly
improbable
Minor to
moderate
Negligible
Carcinogenicity
Quantitative assessment indicates that the chronic
risks to human health and safety during disposal are
acceptable and the level of risk is considered to be
negligible.
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Relationship of Māori to the Environment
8.20
ERMA New Zealand has considered this application in accordance with the
clauses 9(b)(i) and 9(c)(iv) and sections 6(d) and 8. In addition, the framework
contained in the ERMA New Zealand user guide “Working with Māori under
the HSNO Act 1996” has been used to assess the effects of this application on
the relationship of Māori to the environment.
8.21
The Agency notes that Frontier-P triggers a number of hazardous properties
giving rise to the potential for cultural risk including the deterioration of the
mauri of taonga flora and fauna species, the environment and the general health
and well-being of individuals and the community.
8.22
In addition, the introduction and use of this substance has the potential to inhibit
the ability of iwi/Māori to fulfil their role as kaitiaki, particularly in relation to
the guardianship of waterways given the highly ecotoxic nature of the substance
to aquatic species, and potential risks to the mauri ora of human health under
prolonged exposure to this substance.
8.23
On considering the information outlined here and elsewhere in this report, the
Agency considers a minimal impact from Frontier-P on the relationship of
Māori and their culture and traditions with their ancestral lands, water, sites,
wāhi tapu, valued flora and fauna and other taonga to be highly improbable. In
addition there is no evidence to suggest that the controlled use of Frontier-P will
breach the principles of the Treaty of Waitangi.
8.24
The overall level of risk is therefore considered to be negligible assuming that
the substance will be handled, stored, transported, used, and disposed of, in
accordance with the explicitly stated default and additional controls proposed in
this report, and any other controls required by other legislation.
8.25
However, the Agency notes that should inappropriate use, or accident, result in
the contamination of waterways or the environment generally, that users notify
the appropriate authorities including the relevant iwi authorities in that region.
This action should include advising them of the contamination and the measures
taken to contain and remediate.
Assessment of the risks to society and the community
8.26
There are not expected to be any significant adverse impacts on the social
environment with the controlled use of Frontier-P, apart from the health effects
and environmental effects already discussed. Consequently, the Agency
considers that this aspect of potential risk need not be considered further.
Assessment of the risks to the market economy
8.27
Taking into account the level of risk to the environment and to human welfare,
no sources of additional risk have been identified that could result in an adverse
economic impact on a community.
ERMA New Zealand Evaluation and Review Report: Application HSR08124
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8.28
The Agency notes that direct economic costs will be borne by the applicant and
users of the substance. The HSNO default controls intentionally do not manage
direct economic effects. These are for suppliers and users of the substance to
address.
New Zealand’s international obligations
8.29
The Agency does not anticipate that Frontier-P will pose any risks to New
Zealand’s international obligations.
9 ASSESSMENT OF BENEFICIAL EFFECTS
Potentially non-negligible benefits
9.1
A “benefit” is defined in Regulation 2 of the Methodology as “the value of a
particular positive effect expressed in monetary or non-monetary terms”.
Benefits that may arise from any of the matters set out in clauses 9 and 11 were
considered in terms of clause 13.
9.2
The applicant claims that the approval of Frontier-P will provide the following
benefits:
9.3
9.2.1
The active ingredient in Frontier-P belongs to a chemical class of
herbicides which has been extensively used on a worldwide scale in
different crops and cropping systems for more than 30 years and has
experienced very little resistance development. The main reason for
the lack of wide spread resistance is to be seen in the complex mode of
action of this chemical class.
9.2.2
The change from the racemic active ingredient in the current product
Frontier to the resolved active isomer in Frontier-P will result in:
a 47% reduction in the amount of herbicidal active ingredient
applied per hectare;

the total amount of chemistry (litres of substance) applied per
hectare being reduced by 35%;

significant savings relative to packaging, storage, transport and
disposal (an estimated 36%);

and, linked to this, a significant reduction in the environmental
impact of these activities.
The Agency considers that economic and related benefits are likely to be
derived from the use of Frontier-P.
ERMA New Zealand Evaluation and Review Report: Application HSR08124
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Likely effects of the substance being unavailable
9.4
In accordance with section 29, consideration has been given to the likely effects
of Frontier-P being unavailable.
9.5
The Agency notes that there are similar herbicide products already available in
New Zealand with a comparable range of hazards, but none that contain the
resolved active isomer of dimethenamid-P.
9.6
The likely effects of Frontier-P being unavailable would thus be a reduction in
consumer choice for end-users, the use of less effective forms of the active
ingredient, resulting in higher quantities of herbicide being applied into the
environment.
Risk reduction implications
9.7
The applicant has provided information about some potential risk reduction
implications as outlined in section 9.2.2. The Agency also notes that there are
herbicides available in New Zealand which contain the racemic active
ingredient dimethenamid.
10 CONTROLS
Setting of exposure limits and application rates
10.1
Control T1 relates to the requirement to limit public exposure to toxic
substances by the setting of Tolerable Exposure Limits (TELs), which are
derived from Acceptable Daily Exposure (ADE) values. The Agency is not
proposing that any TEL values be set for Frontier-P until implementation of a
pending review of setting such values under section 77B. However, the Agency
notes that Frontier-P is intended for use on food crops and contains a new active
ingredient to New Zealand and, therefore, ADE and PDE values are proposed
for dimethenamid-P (see Appendix 4).
10.2
Control T2 relates to the requirement to limit worker exposure to toxic
substances by the setting of Workplace Exposure Standards (WESs). No WES
values are proposed for any component Frontier-P (See Appendix 4).
10.3
Control E1 relates to the requirements to limit exposure of non-target organisms
in the environment through the setting of Environmental Exposure Limits
(EELs). It is proposed that no EELs are set at this time for Frontier-P and the
default values are deleted (see Appendix 4).
10.4
Control E2 relates to the requirement to set an application rate for a class 9
substance that is to be sprayed on an area of land (or air or water) and for which
an EEL has been set. As no EEL has been proposed for Frontier-P, the Agency
is not able to propose the setting of a maximum application rate under this
regulation. However, the Agency notes that risk quotients derived from the
environmental exposure modelling are above the level of concern (refer
Appendix 3). This indicates that Frontier-P may cause adverse environmental
ERMA New Zealand Evaluation and Review Report: Application HSR08124
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effects when used according to the specific parameters of the risk assessment.
The Agency, therefore, considers it appropriate to set a maximum application
rate under section 77A (see paragraph 10.5).
Proposed additions and modifications to controls
10.5
The Agency notes that the risk quotients derived from the quantitative
modelling indicate that restrictions on use are necessary to mitigate the risks to
the environment (refer Appendix 3). Accordingly, the Agency considers that
the application of controls addressing these risks will be more effective than the
specified (default) controls in terms of their effect on the management, use and
risks of the substance (section 77A(4)(a)). Consequently, the following
additional control is proposed for Frontier-P to restrict the level of risk to the
environment:
10.5.1
The maximum application rate for Frontier-P shall be 1.3 L/ha
(0.936 kg dimethenamid-P/ha) with a maximum application frequency
of 1 application per year; and
10.5.2
Frontier-P shall not be applied onto or into water.
10.6
The Agency notes that the specified controls do not address the risks associated
with stationary container systems, nor do they allow for dispensation where it is
unnecessary for any associated pipework to have secondary containment.
Accordingly, the Agency considers that the application of controls addressing
these risks will be more effective than the specified (default) controls in terms of
their effect on the management, use and risks of the substance7. The proposed
controls are shown in Table 5.1 of Appendix 5.
10.7
Control EM12 relates to the requirements for secondary containment of pooling
substances8. The EM12 secondary containment requirements have been
triggered for Frontier-P as a result of its 9.1A classification. The Agency
considers that the risks associated with the containment of substances which are
not class 1 to 5 substances (i.e. do not ignite or explode) are different to those
associated with class 1 to 5 substances. Consequently the Agency considers that
the secondary containment requirements can be reduced. The Agency considers
that these reduced secondary containment measures are adequate to manage the
risks of a spillage of Frontier-P. Therefore, the proposed additional control,
which varies the EM12 control, is more cost-effective in terms of managing the
risks of the substance. The proposed controls are shown in Table 5.1 of
Appendix 5.
10.8
Control I169 includes a requirement to identify certain toxic components on
product labels. The Agency, consistent with the guidance provided by the
Global Harmonised System (GHS), considers that regulation 25(e) should be
varied such that the concentration cut-offs that apply to a component with a
7
section 77A(4)(a)
Regulations 35 – 41 of the Hazardous Substances (Emergency Management) Regulations 2001
9
Regulation 25 of the Hazardous Substances (Identification) Regulations 2001
8
ERMA New Zealand Evaluation and Review Report: Application HSR08124
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hazard classification of 6.5, 6.6, 6.7, 6.8 or 6.9, for the purpose of triggering this
requirement, should be as follows:
10.9
HSNO Classification of Component
Concentration Cut-off for Label (%)
6.5A, 6.5B
0.110
6.6A, 6.7A
0.1
6.6B, 6.7B
1
6.8A, 6.8C
0.3
6.8B
3
6.9A, 6.9B
10
The Agency considers that the following controls should be varied under section
77(4)(b) for Frontier-P, as the variations will not significantly increase the
adverse effects of the substance:
10.9.1
Control T7 relates to restrictions on the carriage of hazardous
substances on passenger service vehicles. The Agency notes that the
trigger quantity for this control was varied for the sensitisation hazard
for pesticides transferred to the Act under the Hazardous Substances
(Pesticides) Transfer Notice 2004. Consequently, the Agency considers
that the quantity of Frontier-P triggering these requirements should
likewise be varied from 0.1 L to 1 L.
10.9.2
Control E7 relates to requirements for ecotoxic substances to be under
the control of an approved handler. The Agency considers that this
control should be modified for Frontier-P so as to apply only during
use. Accordingly, the Agency is proposing that the following control be
substituted for Regulation 9(1) of the Hazardous Substances (Classes
6, 8, and 9 Controls) Regulations 2001:
“(1). Frontier-P must be under the personal control of an approved
handler when the substance is –
(a) applied in a wide dispersive manner; or
(b) used by a commercial contractor.”
10.9.3
Control TR1 relates to the requirements for a substance to be tracked
and is triggered for Frontier-P only by virtue of its ecotoxicity.
Consequently, the Agency considers that tracking the substance would
be unduly onerous, as the key risks can be managed through other
controls such as approved handler, packaging, labelling and emergency
management requirements. Thus, this control may be deleted.
10
Identification of sensitising components may be required below the 0.1% level if a lower value has been
used for classification.
ERMA New Zealand Evaluation and Review Report: Application HSR08124
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10.10
The Agency considers that the following controls may be combined11 for
Frontier-P as they relate to the same requirements:
10.10.1 Controls T4 and E6 which relate to requirements for equipment used to
handle hazardous substances.
10.10.2 Controls P13 and P15 which relate to requirements for packaging
hazardous substances.
10.10.3 Controls D4 and D5 which relate to requirements for disposal of
Frontier-P.
Control precedents
10.11
The Agency considered the Authority’s approvals given to pesticides under
Part 5 of the Act as well as those transferred to the Act under the Hazardous
Substances (Pesticides) Transfer Notice 2004 (as amended).
Summary of controls
10.12
The Agency considers that the customised controls listed in Appendix 5 should
apply to Frontier-P.
Environmental user charges
10.13
Section 96 provides that the Authority may identify and report to the Minister
where it considers that a reduction in the likely occurrence of adverse effects
similar to that achieved by the controls attached to any substance could be
achieved by any environmental user charge, or a combination of an
environmental user charge and controls.
10.14
The Agency considers that use of controls is the most effective means of
managing the risks throughout the lifecycle of Frontier-P. The imposition of an
environmental user charge instead of, or in combination with controls, is
therefore not required at this time.
11 OVERALL EVALUATION OF RISKS, COSTS AND
BENEFITS
11.1
The Agency considers the risks of Frontier-P to human health to be negligible.
11.2
The Agency’s quantitative and qualitative assessments identified a high risk to
the aquatic environment and non-target plants during the use of Frontier-P.
However, the Agency considers that approved handler requirements and the
setting of a maximum application rate will reduce the level of this risk to
negligible.
11
section 77(5)
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11.3
The Agency does not consider there to be significant risks to Māori cultural
wellbeing, society and the community, the market economy, or to New
Zealand’s international obligations.
11.4
The Agency has taken the type and severity of the risks, and the characteristics
of such risks into account, and considers that the overall level of risk posed by
the substance is negligible.
11.5
The Agency considers that there are benefits associated with the release of
Frontier-P as are specified in Section 9 of this report.
11.6
Thus, the Agency considers that it is evident that the benefits of releasing
Frontier-P outweigh the costs.
12 CONCLUSION
12.1
BASF New Zealand Limited has applied for approval to import for release in
New Zealand the substance identified as Frontier-P.
12.2
The Agency considers Frontier-P triggers the following hazard classifications:

6.1D Acute oral toxicity

6.3B Skin irritancy

6.4A Eye irritancy

6.5B Skin sensitisation

6.7B Carcinogenicity

9.1A Aquatic ecotoxicity

9.2A Soil ecotoxicity

9.3C Terrestrial vertebrate ecotoxicity.
12.3
The Agency considers that there are negligible risks to the environment and
human health and benefits associated with the release of Frontier-P. Therefore,
the Agency considers that it is evident that the benefits of releasing Frontier-P
outweigh the costs and the application may be approved in accordance with
clause 26.
12.4
The Agency considers the controls listed in Appendix 5 should apply to
Frontier-P.
ERMA New Zealand Evaluation and Review Report: Application HSR08124
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APPENDIX 1: DECISION PATH
1
Review the content of the
application and all relevant
information
2
Is this information sufficient
to proceed?
No
3
Seek additional
information
4
Sufficient?
Yes
No
5
Identify the composition of the substance,
classify the hazardous properties of the
substance, and determine default controls
Yes
6
Identify all risks, costs and benefits that are
potentially non-negligible
Decline
(section 29(1)(c))
7
Assess each risk assuming controls in place.
Add, substitute or delete controls in
accordance with clause 35 and sections77,
77A, 77B
8
Undertake combined consideration of all risks
and costs, cognisant of proposed controls
9
Are all risks with controls in place
negligible?
Clause 27
No
12
Establish position on risk averseness
and appropriate level of caution
Clause 26 Yes
10
Review controls for cost-effectiveness in
accordance with clause 35 and sections 77,
77A, 77B
11
Is it evident that benefits outweigh
costs?
Yes
Yes
16
Confirm and set controls
13
Review controls for cost-effectiveness
in accordance with clause 35 and
sections 77, 77A, 77B
No
14
Assess benefits
15
Taking into account controls,
do positive effects outweigh adverse
effects?
No
Approve
Decline
(section 29(1)(a))
(section 29(1)(b))
ERMA New Zealand Evaluation and Review Report: Application HSR08124
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APPENDIX 2: HAZARD CLASSIFICATION
Classification of Frontier–P
Formulation data were not provided for all endpoints of Frontier–P. Where no data
were available classification was estimated using mixture rules based on information
on the components. Details of the methods used to derive the classifications are
presented in Table A2.1. The relevant sections of the User Guide to Thresholds and
Classifications under the HSNO Act (ERMA 2008a) that describe the mixture rules
are listed in Table A2.2.
The active ingredient, dimethenamid-P, is a new pesticide active ingredient to New
Zealand. The Agency has provided a summary of the physical/chemical properties,
the toxicity, ecotoxicity and environmental fate data in Tables A2.4 to A2.15A.
Data quality – overall evaluation
The applicant has proposed the bridging of data between the racemic mixture
dimethenamid and the resolved enantiomer dimethenamid-P by providing the original
test reports for the former for comparison with the latter. The toxicology,
ecotoxicology and environmental fate data appear comparable; therefore this
proposition is accepted where there are gaps in the dimethenamid-P data.
The Agency has adopted the Klimisch et al (2001) data reliability scoring system for
evaluating data used in the hazard classification and risk assessment of
dimethenamid-P and Frontier–P (section 1.2.4 in ERMA 2008a). Scores for individual
studies, as evaluated by the Agency, are included in the data assessment tables A2.5
to A2.12. Overall, data provided for dimethenamid-P and Frontier–P were of high
quality [Klimisch scores 1 or 2]. Data on components of Frontier–P were generally of
lower quality [Klimisch scores 3 or 4]. However, the effect of the lower quality data
on the overall evaluation of the effects of Frontier–P was not significant because of
the volume of high quality data provided.
The Agency acknowledges that there are frequently data gaps in the hazard
classification for chemicals which have been in use internationally for a long time.
International programmes such as the OECD High Production Volume programme
(OECD 1990) and REACH (EU 2006) are progressively working towards filling these
data gaps. As new information becomes available, and resources permit, the Agency
will endeavour to update the HSNO classifications for those substances.
Note:
Following submission of the EU dossier for Frontier-P the formulation BAS 656 07 H
was immediately modified to BAS 656 08 H for commercialisation. Subsequently
BAS 656 08H has also been modified. The changes made are not expected to
significantly affect/alter the physic-chemical properties or the
toxicological/ecotoxicological properties of the formulated product. For full details
see Confidential Appendix 8.
ERMA New Zealand Evaluation and Review Report: Application HSR08124
Page 25 of 149
References
ERMA New Zealand 2008a. User Guide to HSNO Thresholds and Classifications.
ERMA New Zealand, Wellington.
European Union 2006. Regulation (EC) No 1907/2006 of the European Parliament
and of the Council of 18 December 2006 concerning the Registration, Evaluation,
Authorisation and Restriction of Chemicals (REACH), establishing a European
Chemicals Agency, amending Directive 1999/45/EC and repealing Council
Regulation (EEC) No 793/93 and Commission Regulation (EC) No 1488/94 as well as
Council Directive 76/769/EEC and Commission Directives 91/155/EEC, 93/67/EEC,
93/105/EC and 2000/21/EC. http://reach.jrc.it/
Klimisch, HJ, Andreae, E, Tillman, U 1997. A systematic approach for evaluating the
quality of experimental and ecotoxicological data. Regulatory Toxicology and
Pharmacology 25: 1–5.
OECD 1990. Manual for Investigation of HPV Chemicals.
http://www.oecd.org/document/21/0,3343,en_2649_34379_1939669_1_1_1_1,00.htm
l Retrieved 23 January 2008.
ERMA New Zealand Evaluation and Review Report: Application HSR08124
Page 26 of 149
Table A2.0: Physical and chemical properties of Frontier–P (BAS 656 08H).*
Test
Condition
Frontier–P
Clear liquid
Colour
Red brown
Physical state
Liquid
Odour
Strong aromatic
Flash point
105°C
pH (1%)
3.3 (CIPAC water D)
3.2 (pure water)
27.9
Dynamic viscosity
20°C
Surface tension
(mN/m)
Auto ignition
29.5 (0.25%)
29.9 (1.5%)
410°C
Method
Visual inspection
Internal method no.
CF/P 062.4
Visual inspection
Internal method no.
CF/P 038.5
Visual inspection
Internal method no.
CF/P 039.5
Organoleptic
Internal method no.
CF/P 040.5
Pensky-Martens
method
EC A9.1.6.3.2
CIPAC MT 75
OECD guideline
114
Internal method no.
CF/P 014.12
EEC A5 1.6.1
92/69/EC A15
Reference
Kästel, 1999
Report No. 01951
GLP
Klimisch score: 1
BAS 656 07H
Löffler, 1998
Report No. SIKNr.98/1682
GLP
Klimisch score: 1
Test substance
BAS 656 07H
*The Agency notes that although the formulation of Frontier is BAS 656 08H, the test
substance used was a previous formulation BAS 656 07 H. The Agency has read
across the data from the test substance to the new formulation based on similarities
between the two substances.
As a result, the Agency has taken the density for Frontier-P® as 1.1271g/cm3 based on
the composition of the formulation given in Appendix 8.
Conclusions:
Frontier–P (656 08 H) is classified as non flammable as a result of it’s flashpoint of
105°C.
ERMA New Zealand Evaluation and Review Report: Application HSR08124
Page 27 of 149
Table A2.1: Summary of the tox and ecotox hazard classifications of Frontier–P.
Hazardous Property
Agency Classification
Classification Method
6.1 oral
6.1 dermal
6.1 inhalation
6.3/8.2 Skin
irritation/corrosion
6.4/8.2 Eye
irritation/corrosion
6.5 contact
sensitisation
6.6 Mutagenicity
6.7 Carcinogenicity
6.8 Reproductive
developmental toxicity
6.9 Target organ
systemic toxicity
9.1 Aquatic ecotoxicity
Aquatic Persistence
Bioaccumulative
9.2 Soil ecotoxicity
Soil Persistence
9.3 Terrestrial
vertebrate ecotoxicity
9.4 Terrestrial
invertebrate ecotoxicity
6.1D
Not triggered
Not triggered
6.3B
Formulation data
Formulation data
Formulation data
Formulation data
Component(s) driving
classification
N/A
N/A
N/A
N/A
6.4A
Formulation data
N/A
6.5B
Formulation data
N/A
Not triggered
6.7B
Not triggered
Mixture rules
Mixture rules
Mixture rules
N/A
A6 and C2
N/A
Not triggered
Mixture rules
N/A
9.1A
Not readily degradable
Not bioaccumulative
9.2A
Not persistent
9.3C
Formulation data
Mixture rules
Mixture rules
Formulation data
Mixture rules
Formulation data
N/A
Active ingredient
Active ingredient
N/A
Active ingredient
N/A
Not triggered
Formulation data
N/A
Table A2.2: Location of mixture rules within the HSNO Thresholds and
Classifications User Guide (V2.0. March 2008).
Hazard
Subclass 6.1 Acute Toxicity
Subclass 6.3/8.2 Skin Irritancy/Corrosivity
Subclass 6.4/8.3 Eye Irritancy/Corrosivity
Subclass 6.5 Contact and Respiratory Sensitisation
Subclass 6.6 Mutagenicity
Subclass 6.7 Carcinogenicity
Subclass 6.8 Reproductive Developmental Toxicity
Subclass 6.9 Target Organ Systemic Toxicity
Subclass 9.1 Aquatic Ecotoxicity
Subclass 9.2 Soil Ecotoxicity
Subclass 9.3 Terrestrial Vertebrate Ecotoxicity
Subclass 9.4 Terrestrial Invertebrate Ecotoxicity
User Guide to HSNO
Thresholds and
Classifications Reference
Part V, Chapter 10, Page 12
Part V, Chapter 11, Page 7
Part V, Chapter 12, Page 9
Part V, Chapter 13, Page 8
Part V, Chapter 14, Page 5
Part V, Chapter 15, Page 8
Part V, Chapter 16, Page 11
Part V, Chapter 17, Page 10
Part VI, Chapter 19, Page 18
Part VI, Chapter 20, Page 8
Part VI, Chapter 21, Page 7
Part VI, Chapter 22, Page 5
ERMA New Zealand Evaluation and Review Report: Application HSR08124
Page 28 of 149
Identity of the Active Ingredient
As this is the first full Part 5 application considered for this active ingredient, general
and physico-chemical data about dimethenamid-P are provided in the Tables A2.3 and
A2.4.
Table A2.3: Identification of dimethenamid-P (SAN 1289 H).
CAS number:
163515-14-8
S-2-Chloro-N-(2,4-dimethyl-3-thienyl)-N-(2IUPAC name
methoxy-1-methylethyl)acetamide
Dimethenamid-P
Common name
C12-H18-Cl-N-O2-S
Molecular formula
275.8
Molecular weight
See Figure 1
Structural formula
94%
Purity
Significant impurities/additives
(% concentration)
Herbicide
Known uses
6.1D (overall), 6.1D (oral and inhalation), 6.5B,
HSNO classification
9.1A, 9.2A, 9.3B
Other classification & labelling
Figure 1: Structural formula of dimethenamid-P (SAN 1289 H).
http://chem.sis.nlm.nih.gov/chemidplus/
Physical and chemical properties of dimethenamid-P relevant to the interpretation of
ecotoxicity test, environmental fate and exposure assessment are summarized in Table
A2.4A. For endpoints for which data are lacking on dimethenamid-P, data are given
on dimethenamid in Table 2.4B.
Table A2.4A: Physical and chemical properties of dimethenamid-P (SAN 1289
H).
Property
Condition
Dimethenamid-P
clear liquid
Colour
Yellow brown
Test method
Visual inspection
Internal method no.
CF/P 062.4
Visual inspection
Internal method no.
CF/P 038.5
ERMA New Zealand Evaluation and Review Report: Application HSR08124
Reference
Krohl, 1999
Report No.
01985
GLP
Klimisch score: 1
Page 29 of 149
Physical state
Liquid
Odour
Faint aromatic
Surface Tension
0.1%: 52.0 mN/m
0.5% : 50.7 mN/m
Density (20°C)
1.195 - 1.196 g/cm3
Visual inspection
Internal method no.
CF/P 039.5
Organoleptic
determination
Internal method no.
CF/P 040.5
Internal method no.
CF/P 014.12
EC A5 1.6.1
Internal method no.
CF/P 082.1
EC A3 1.4.2
AM-7070
ASTMD891
AM-7075
ASTM D792
Internal method no.
CF/P 58.3
EC A1
ASTM D1120
ASTM D850
ASTM D86
Melting point/
Solidification point
-50°C
Boiling Point
122.6°C
at 0.07 mmHg
Vapour pressure
3.47 x 10-3 Pa (20°C)
2.51 x 10-3 Pa (25°C)
T-0338-0296-0
Gas saturation
method
Henry’s Law constant
4.72 x 10-9 atm-m3/mole
4.80 x 10-4 Pa-m3/mole
Calculation
Physical state
(Appearance)
Dark brown liquid
Visual Observation
Odour
Strong unpleasant musty
odour
Method T-0319
Water Solubility
(25°C)
1149 ± 17 mg/L
USEPA 40CFR
Subdivision D
Series 63-8
Solvent Solubility
(20°C)
Soluble in all proportions in:
Tetrahydrofuran
isopropyl alcohol
acetone
acetonitrile
dimethyl sulfoxide
dichloromethane
USEPA 40CFR
Subdivision D
Series 63-8
ERMA New Zealand Evaluation and Review Report: Application HSR08124
Widlak, 1997
Report No.
97/5193
GLP
Klimisch score: 1
SAN 1289 H
Chen, 1999
Report No.
97/5194
GLP
Klimisch score: 1
SAN 1289 H
Chen & Laster,
1996
Report No.
96/5418
GLP
Klimisch score: 1
SAN 1289 H
Hsieh, 1999
Report No.
1999/5002
SAN 1289 H
Chen, 1997
Report No.
97/5198
GLP
Klimisch score: 1
SAN 1289 H
Jones, 1997
Report No.
97/5186
SAN 1289 H
Laster, 1996
Report No.
96/5411
GLP
Klimisch score:1
SAN 1289 H
Liu, 1997
Report No.
97/5196
GLP
Klimisch score: 1
SAN 1289 H
Page 30 of 149
toluene
n-octanol
hexane: 24.8/100 mL solvent
77.6 ± 17
1.89 ± 0.10
OPPTS 830.7550
Shake flask method
Hydrolysis (25°C)
pH 5 Stable
pH 7 Stable
pH 9 Stable
USEPA
Subdivision N
Section 161-1
Photolysis
DT50: 13.7 + 1.9 days
(pH 7, 25°C at 100 ppm)
25.7 noon sunlight at 40°N
latitude
USEPA
Subdivision N
Section 161-2
Flash point
174°C
USEPA
Subdivision N
Section 63-15
AM-7068
ASTM D93-73
Oxidizing properties
Moderate reducing agent
should not be mixed or stored
in close proximity to strong
oxidizing agents such as
KMnO4
Does not react with iron.
Special precautions against
reducing agents are
unnecessary.
Does not react with MAP.
In case of fire, extinguishing
agents containing MAP can be
used with this product.
OPPTS 830.6314
Pow
Log Pow
Lam, 1998
Report No.
98/5071
GLP
Klimisch score: 1
SAN 1289 H
Guirguis, 1997
Report No.
97/5184
GLP
Klimisch score: 1
SAN 1289 H
Guirguis, 1997
Report No.
97/5195
GLP
Klimisch score: 1
SAN 1289 H
Widlak, 1997
Report No.
94/5177
GLP
Klimisch score: 1
SAN 1289H
Jones, 1998
Report No.
98/5161
GLP
Klimisch score: 1
BAS 656 PH
SAN 1289H
Table A2.4B: Physical and chemical properties of dimethenamid (SAN 582 H).
Property
Auto ignition point
dimethenamid
395°C
Test method
EC A15
DIN 51794
IEC 79-4
Explosive properties
No explosion or ignition
observed
USEPA
Subdivision N
Section 63-15
Stresau Laboratory
test FD305
Quantum yield
0.007402
Lifetime (5.98 days)
Spring sunlight at 40°N
USEPA
Subdivision N
Section 161-2
ERMA New Zealand Evaluation and Review Report: Application HSR08124
Reference
van Helvoirt, 1994
Report No.
94/11877
GLP
Klimisch score: 1
SAN 582H
Srnak, 1991
Report No.
91/11850
Non-GLP
Klimisch score: 2
SAN 582H
Sen & Yu, 1994
Report No.
94/10636
Page 31 of 149
latitude.
Dissociation constant
No indication of dissociation
of SAN 582H taking place
between pH of 1 and 11 at
25°C.
USEPA
Subdivision N
Section 63-10
Photochemical
oxidative degradation
t1/2 = 2.45 h (12 h day)
Rate constant:
52.336 x 10-12 cm3/molecules
QSAR estimate
GLP
Klimisch score: 1
SAN 582H
Rozek, 1988
Report No.
88/11352
GLP
Klimisch score: 1
SAN 582H
Scarf, 1999
Report No.
99/10075
SAN 582H
The rate constant for reactions
of dimethenamid with OH
radicals in the atmosphere was
calculated using the AOPWIN
program based on
ATKINSON’S increment
method.
Biological Hazards: Class 6 Toxicity
The active ingredient dimethenamid-P is a new active ingredient to New Zealand.
Dimethenamid-P [also known by the name S-dimethenamid and by the code
SAN1289] is the purified, active, R-enantiomer of dimethenamid. The substance
dimethenamid [also known by the code name SAN 582 H] was transferred under the
HSNO Act in 2004 (Approval number: HSR000673).
Dimethenamid is a racemate containing 50% M- and P-isomers. Frontier-P has been
developed because the P-isomer only has herbicidal activity and thus if the M-isomer
is removed the amount of dimethenamid applied can be cut by 50%. However the
same amount of the active dimethenamid-P is still applied.
Rather than repeat all the mammalian toxicity studies bridging principles were applied
along with some limited testing on the P-isomer to demonstrate that the P-isomer was
no more toxic than the racemic mixture.
Based on the fact the P-isomer is 50% of the racemic mixture, then 100 mg of the
racemate contains 50 mg P-isomer. So if the toxicity of the racemic mixture was
purely associated with the P-isomer and the LOAEL for the racemic mixture was 100
mg/kg/day the LOAEL for the P-isomer would be expected to be 50 mg/kg/day.
If the P-isomer alone was more toxic than the racemic mixture then the LOAEL
would be expected to be lower. The P-isomer could be more toxic on its own if the
M-isomer somehow blocked the expression of toxicity of the P-isomer.
In order to determine whether it was appropriate to read across the toxicity of the
racemic mixture to the P-isomer either using mixture rules or formulation test data,
the following studies performed on both the racemic and P-isomer were considered:
 Acute Toxicity – rat oral; rabbit dermal; inhalation; skin and eye irritation;
dermal sensitisation
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


Repeat dose – 90 day rat
Prenatal teratogenicity – rat
Mutagenicity – Ames; CHO/HGPRT in vitro; in vitro chromosomal aberration
CHO;
Similar toxicity with respect to these endpoints justifies use of data on the racemic
mixture to estimate the effects of dimethenamid-P for carcinogenicity,
developmental/reproductive toxicity and target organ effects, including setting AOEL
and ADE.
Table A2.5.1: Summary of Acute Oral Toxicity Data on Dimethenamid-P versus
Racemic Dimethenamid.
Racemic Dimethenamid
Materials and methods:
Five fasted Sprague-Dawley rats per sex and dose;
test substance administered undiluted; dose levels of
150, 300 and 600 mg/kg bw; observation period of
14 days
Dimethenamid-P
Materials and methods:
Five fasted Sprague-Dawley rats per sex and dose;
test substance administered undiluted; dose levels of
350, 400 and 500 mg/kg bw; observation period of
15 days
LD50 :
371 (186) mg/kg bw (m);
427 (214) mg/kg bw (f);
397(200) mg/kg bw (combined)
LD50 :
429 mg/kg bw (m);
531 mg/kg bw (f);
466 mg/kg bw (combined)
Comment:
Comparison of racemate and P-isomer study results LD50 values similar between two substances i.e.
similar ballpark figures which would not result in an
alteration of classification class.
The LD50 of the P-isomer alone is higher than that of
the racemic mixture, suggesting that the M-isomer is
contributing to the toxicity of the racemate.
The results here indicate that by using read across
from racemate to P-isomer would represent a
precautionary approach.
() – represents amount of P-isomer
Clinical symptoms:
Day of dosing - Ocular and oral discharges, and
hypoactivity all groups; nasal discharge, wet rales,
fecal staining, soft stool and abdominal griping in
mid and high dose groups.
Days after dosing –hypoctivity, decreased food
consumption and red ocular discharge.
Clinical symptoms:
Day of dosing – Lacrimation and salivation all dose
groups, decreased activity at high dose;
Days after dosing – lethargy, decreased food
consumption, yellow ano-genital staining, black
and/or brown staining on the snout, oral area, buccal
area and/or extremities, and decreased fecal volume
or stool.
All symptoms reversible by day 4
All symptoms reversible by day 5.
Comment:
Comparison of racemate and P-isomer study results
– there is some concordance. As the studies were
run a number of years apart and considering the
subjective nature of clinical signs it is inappropriate
to do a detailed analysis.
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Racemic Dimethenamid
Macroscopic findings:
Animals that died:
Stomach/intestine: discoloured and thickened walls,
red coloured fluids, test material.
Dimethenamid-P
Macroscopic findings:
Animals that died:
Stomach: black mucosa, brown fluid.
Lungs: discoloured and red foci.
Lungs: discoloured.
Thymus: discoloured region (red/black)
Thoracic cavity: fluid
Testes: discoloured (red).
Surviving animals:
No macroscopic findings related to treatment.
Surviving animals:
No macroscopic findings related to treatment.
Comment:
Comparison of racemate and P-isomer study results
– there is some concordance. As the studies were
run a number of years apart and considering the
subjective nature of clinical signs it is inappropriate
to do a detailed analysis.
Conclusion:
The acute oral toxicity studies with racemic dimethenamid and dimethenamid-P resulted in similar
outcomes, which supports read-across.
Table A2.5.2: Summary of Acute Dermal Toxicity Data on Dimethenamid-P
versus Racemic Dimethenamid.
Racemic Dimethenamid
Dimethenamid-P
Materials and methods:
Five New Zealand white rabbits per sex and dose;
test substance administered undiluted; single dose
level - 2000 mg/kg bw; observation period of 14
days
Materials and methods:
Five New Zealand white rabbits per sex and dose;
test substance administered undiluted; single dose
level - 2000 mg/kg bw; observation period of 15
days
LD50 :
> 2000 mg/kg bw
LD50 :
> 2000 mg/kg bw
Clinical symptoms:
None related to treatment.
Clinical symptoms:
None related to treatment.
No dermal effects.
3/10 treated animals had red subcutaneous
discoloration foci at treatment site.
Macroscopic findings:
None related to treatment.
Macroscopic findings:
None related to treatment.
Conclusion:
The acute dermal toxicity studies of racemic dimethenamid and dimethenamid-P did not only result in
similar LD50 values but also in a similar lack of clinical symptoms and macroscopic findings. This again
supports a read-across approach.
Table A2.5.3: Summary of Acute Inhalation Toxicity Data on Dimethenamid-P
versus Racemic Dimethenamid.
Racemic Dimethenamid
Dimethenamid-P
Materials and methods:
Materials and methods:
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Racemic Dimethenamid
Dimethenamid-P
Five Wistar rats per sex; head-nose inhalation
system; exposure period four hours; liquid aerosol;
concentration of 4.99 mg/l; observation period of 14
days
Five Sprague-Dawley rats per sex and dose; headnose inhalation system, exposure period four hours;
liquid aerosol; concentration of 2.2 mg/l;
observation period of 15 days
LC 50 :
> 4.99 mg/l (2.5 mg/l P-isomer)
LC 50 :
>2.2 mg/l air
(highest concentration tested)
(highest concentration tested)
Cumulated mortality:
No mortalities.
Cumulated mortality:
No mortalities.
Clinical symptoms:
During exposure: Sedation, dyspnea, curved body
position and ruffled fur.
Hours after exposure: sedation, dyspnea, curved
body position and ruffled fur.
Clinical symptoms:
During exposure: Labored breathing during last two
hours.
Hours after exposure: Secretory effects (lacrimation,
chromodacryorrhea, red and clear nasal discharge,
dried red facial material) and respiratory responses
(labored breathing and moist rales).
Days after exposure: dried red material on skin/fur;
yellow anogenital stains.
Days after exposure: Sedation, dyspnea, curved
body posture, ruffled fur.
No symptoms after day 3.
No symptoms after day 3.
Body weight gain was normal.
Body weight gain was normal.
Macroscopic findings:
Macroscopic findings:
At sacrifice no findings related to the test substance At sacrifice no findings related to the test substance.
Conclusion:
The acute inhalation exposure of rats to racemic dimethenamid and dimethenamid-P resulted in no deaths
at the highest concentrations tested. Minor clinical observations observed in both studies cleared by day 3
after exposure. It can be concluded that both forms have a low acute inhalation hazard and are
comparable in toxicity. Supporting appropriateness of read-across.
Table A2.5.4: Summary of Dermal Irritation Data on Dimethenamid-P versus
Racemic Dimethenamid.
Racemic Dimethenamid
Dimethenamid-P
Materials and methods:
Six New Zealand white rabbits; 0.5 ml test
substance administered undiluted dermally for four
hours; observation period of 72 hours.
Materials and methods:
Six New Zealand white rabbits; 0.5 ml test
substance administered undiluted dermally for four
hours; observation period of 72 hours.
Irritation Results:
Irritation Results :
Very slight erythema in 5/6 animals and edema in 1 Slight erythema in 3/6 animals, very slight
erythema in 2/6 animals; no edema
animal.
Irritation cleared:
Irritation cleared:
24 hr
72 hr
Conclusion:
Slight dermal irritation that cleared within 72 hr was noted both with racemic dimethenamid and
dimethenamid-P. These results demonstrate that both forms present a potential for only slight dermal
irritation. The later clearing of the irritation in the P-isomer study may be due to a difference in calling
levels or twice as much P-isomer being present. However the later clearing is considered not to represent
a toxicologically important event which indicates that read across is not appropriate.
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Table A2.5.5: Summary of Eye Irritation Data on Dimethenamid-P versus
Racemic Dimethenamid.
Racemic Dimethenamid
Dimethenamid-P
Materials and methods:
Six New Zealand white rabbits; 0.1 ml test
substance administered undiluted to conjunctival sac
of one eye; no wash; observation period of 72 hours.
Materials and methods:
Six New Zealand white rabbits; 0.1 ml test
substance administered undiluted to conjunctival sac
of one eye; no wash; observation period of 72 hours.
Irritation Results :
Irritation Results :
Conjunctiva: redness and mild discharge in all
animals; chemosis in 4 animals.
Cornea: none
Iris: none
Conjunctiva: Slight redness and/or chemosis and
moderate to severe discharge.
Cornea: none
Iris: none
Irritation cleared:
Irritation cleared:
72 hr
48 hr
Conclusion:
Both racemic dimethenamid and dimethenamid-P produce mild transient ocular irritation in rabbits which
cleared within 72 hr. No significant differences in eye irritation potential were observed between the two
forms. Read-across is again supported.
Table A2.5.6: Summary of Dermal Sensitisation Data on Dimethenamid-P versus
Racemic Dimethenamid.
Racemic Dimethenamid
Dimethenamid-P
Materials and methods:
Maximization method; 10 guinea pigs in control, 20
in treatment group. Phase 1 induction with 5% test
material given intracutaneous, phase 2 one week
later with 100% applied dermally for 48 hr.
Challenge two weeks later with 100% applied
dermally. Skin reactions scored at 24 and 48 hr.
Materials and methods:
Buehler method; 20 (10/sex) Dunkin Hartley guinea
pigs for treatment group and 10 (5/sex) for control.
Induction and challenge with undiluted test material.
Induction – dermally, six hours, once a week for
three weeks. Challenge - dermally for six hours, 14
days after induction. Dermal scoring at 24 and 48 hr
after challenge.
Positive dermal responses:
Positive dermal responses:
24 hr: 9/19 vs. 0/10 control
24 hr: 16/20 vs. 0/10 control
48 hr: 15/19 vs. 0/10 control
48 hr: 13/20 vs. 0/10 control
Conclusion:
An increased incidence of positive dermal responses was seen with both racemic dimethenamid and
dimethenamid-P indicating both compounds are dermal sensitizers. Read across is supported
Table A2.5.7: Summary of Short-term Toxicity Data on Dimethenamid-P versus
Racemic Dimethenamid.
Racemic Dimethenamid
Dimethenamid-P
Materials and methods:
Test substance administration to 10 Sprague-Dawley
rats per sex in the diet for 3-months;
Concentrations: 0; 50, 150, 500; 1500 and 3,000 ppm
Materials and methods:
Test substance administration to 10 Sprague-Dawley
rats per sex in the diet for 3-months;
Concentrations: 0; 500; 1500; and 3,000 ppm
Mortality and clinical symptoms:
no substance-related deaths and no adverse clinical
symptoms,
Mortality and clinical symptoms:
no substance-related deaths and no adverse clinical
symptoms,
Body Weight Gain:
Retarded body weight gain at 1500 and 3,000 ppm
Body Weight Gain:
retarded body weight gain at 1,500 and 3,000 ppm
ERMA New Zealand Evaluation and Review Report: Application HSR08124
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Racemic Dimethenamid
and slight decrease in 500 ppm males
Food consumption:
No effect.
Hematology:
No effect.
Dimethenamid-P
Food consumption:
No effect.
Hematology:
Increased activated partial pro-thromin time (APTT)
at high dose. No other effects.
Clinical chemistry:
Decreased APT and ALT at all levels.
Alk Phos. decreased at 1500 and 3000 ppm.
GGT increased at 3000.
Cholesterol increased at 3000 and in females at 1500
ppm.
Clinical chemistry:
Decreased APT and alkaline phosphatase at all
levels.
Urinalysis:
no substance-related effect
Urinalysis:
no substance-related effect
Relative Liver weight:
Increased at 3000 ppm both sexes and in females at
1500 ppm.
Pathology:
Hepatocellular hypertrophy:
Centrilobular in females at 1500 and 3000 ppm.
Relative Liver weight:
Increased at 1500 and 3000 ppm both sexes and in
males at 500 ppm.
Pathology:
Hepatocellular hypertrophy:
Centrilobular in females at all dose levels.
Periportal in males at 1500 and 3000 ppm.
NOAEL:
500 ppm
NOAEL:
500 ppm (250 ppm P-isomer)
GGT increased at 3000 and in males at 1500 ppm.
Cholesterol increased in at 3000 ppm.
Conclusion:
The 3-month feeding studies led to no biologically relevant differences between racemic dimethenamid and
dimethenamid-P. The NOAEL is considered to be 500 ppm for both forms. The NOAEL is based on the
consideration that minor effects observed with both compounds at 500 ppm were due to a physiological
response to the chemical and not due to frank toxicity. Read across is again supported. When considering Pisomer content between the two studies, the M-isomer does appear to contribute to toxicity when the
substance is tested as a racemate.
Table A2.5.8: Summary of Prenatal Toxicity Data on Dimethenamid-P versus
Racemic Dimethenamid.
Racemic Dimethenamid
Materials and methods:
Groups of 25 pregnant Sprague-Dawley rats;
Test substance administration in 0.5% CMC
suspension with HiSil 233.
Dose levels: 0; 50 (25), 215 (108) and 425 (213)
mg/kg bw once daily by gavage from day 6 through
day 15 of gestation.
() represents P-isomer content.
Maternal toxicity:
425 (213) mg/kg/day: Clinical signs. Body weight
loss days 6-9, decreased weight gain days 6-16 (35%). Decrease in food consumption. Increase in
relative liver weight.
Dimethenamid-P
Materials and methods:
Groups of 25 pregnant Sprague-Dawley rats;
Test substance administration in 0.5% aqueous
CMC suspension with HiSil 233.
Dose levels: 0; 25, 150 and 300 mg/kg bw once
daily by gavage from day 6 through day 15 of
gestation
Maternal toxicity:
300 mg/kg/day: Clinical signs. Body weight loss
during treatment days 6-9, decreased weight gain
days 6-16 (-25%). Decreased food consumption.
Increase in relative liver weight. 150 mg/kg/day:
Decreased body weight gain days 6-16 (-18%).
215 (108) mg/kg/day: Decreased body weight gain Decreased food consumption.
days 6-16 (-16%). Decreased food consumption.
Increased liver weight.
25 mg/kg/day: Slightly decreased body weight gain
and food consumption (days 6-9 only). Considering
50 (25) mg/kg/day: Slightly decreased body weight range-find data these changes were spurious and not
gain and food consumption (days 6-9 only) – not an adverse effects.
adverse effect.
Comment: no indication that the P-isomer alone
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Racemic Dimethenamid
Dimethenamid-P
is more toxic than when in the racemate form.
Supporting read across
Embryo-/fetotoxicity:
425 (213) mg/kg/day: Slight decrease in fetal body
weight (-2%). Increased incidence of early
resorptions.
Embryo-/fetotoxicity:
300 mg/kg/day: Slight decrease in fetal body weight
(-3%). Retarded ossifications of 2nd sternal centra
and pelvis pubis
215 (108) mg/kg/day: Slight decrease in fetal body
weight (-1%). Increased incidence of early
resorptions.
150 mg/kg/day: Slight decrease in fetal body weight
(-2%). Retarded ossifications of pelvis pubis and 2nd
sterna
25 mg/kg/day: No effect.
50 (25) mg/kg/day: No effect.
Comment: no indication that the P-isomer alone
is more toxic then when in the racemate form.
Supporting read across
Teratogenic effect: no
Teratogenic effect: no
NOAEL:
NOAEL:
Maternal toxicity: 50 (25) mg/ kg bw
maternal toxicity: 25 mg/kg/day
Embryo-/fetotoxicity: 50 (25) mg/kg bw
embryo-/fetotoxicity: 25 mg/kg bw
Conclusion: These studies demonstrate the similarity of the prenatal toxicity of racemic dimethenamid
and dimethenamid-P. No teratogenic effects were noted at any dose level with either compound. Only the
highest doses that were clearly maternally toxic caused signs of fetotoxicity. The slight and transient
decreases in maternal body weight gain seen at the low doses in both studies were not considered to be
toxicologically meaningful. The mid doses for both compounds showed some evidence of fetotoxicity.
For the racemic mixture, the slight increase in resorptions was not considered to be toxicologically
relevant and the mid dose was considered a NOAEL. For the P-isomer, the only fetotoxic effect at the mid
dose was an increase in delayed ossifications, but this dose could not be excluded as an effect level
resulting in the lowest dose being determined the fetotoxic NOAEL. In terms of P-isomer content the
NOAEL’s are comparable between the two studies supporting read-across.
Table A2.5.9: Summary of Mutagenicity Data on Dimethenamid-P versus
Racemic Dimethenamid.
Racemic Dimethenamid
Dimethenamid-P
Ames Assay.
Ames Assay:
Test 1 -
Strains tested: TA 98, TA 100, TA 1535, TA 1537
and TA 1538; with and without activation.
Levels: 100 (50) to 10000 (5000) µg/plate.
Results: Negative
91.1% technical material.
Strains tested: TA 98, TA 100, TA 1535, TA 1537
and E. coli WP2 uvrA with and without activation.
Levels: 50 to 6500 µg/plate (non-act.),
100 to 10000 µg/plate (with activation)
Results: Weakly positive only for TA 100 without
activation. Negative for TA 100 with activation
and all other strains with and without activation.
Tests 2 -and 3
91.1% technical material and 99.4% analytical grade
material
Strains tested: TA 98, TA 100, TA 1535, TA 1537
and E. coli WP2 uvrA with and without activation.
Levels: 4 to 5000 µg/plate
Results: Negative for both technical and analytical
grade materials.
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Racemic Dimethenamid
Dimethenamid-P
Test 4
91.1% technical material
Strain tested: TA 100 without activation
Levels: 100 to 5000 µg/plate
Results: Negative
CHO/HGPRT mammalian cell mutation assay:
Dose levels: 33(16) to 333 (166) µg/ml (with and
without activation)
CHO/HGRT mammalian cell mutation assay:
Dose levels: 100 -400 µg/ml (without activation);
100 -450 µg/ml (with activation).
Cytotoxicity at highest dose levels.
Cytotoxicity at highest dose levels.
Results: Negative
Results: Negative
In vitro chromosome aberration:
Chinese hamster ovary cells.
Dose levels: 10 (5) to 150 (75) µg/ml for 17 hr
without activation; 150 (75) to 500 (250) µg/ml for 2
hours with activation.
Toxicity evident at high doses.
Results: Negative
In vitro Unscheduled DNA synthesis (UDS) with
rat primary hepatocytes:
Test 1.
Dose levels 0, 1, 3, 10, 30 and 100 nl/ml.
Results: Negative
Test 2.
Dose levels trial 1: 0, 0.025, 0.050, 0.10, 0.50, 1.00,
2.50, 5.0 and 10.0 µg/ml.
Dose levels trial 2: 0, 0.10, 0.25, 1.00, 2.50, 5.00,
and 10.0 µg/ml.
Results: Equivocal positive.
Test 3.
Dose levels trial 1: 0, 0.32, 1.6, 8, 40, 200 µg/ml.
Dose levels trial 2: 0, 7.8, 15.6, 31.3, 62.5 and 125
µg/ml.
Results: Negative
In vitro chromosome aberration:
Chinese hamster ovary cells.
Dose levels: 0, 15, 30, 60 and 120 µg/ml for 20 hr
without activation; 0, 63, 125, 250 and 500 µg/ml for
4 hours with activation.
Toxicity was evident at highest doses tested.
Results: Negative
In vitro Unscheduled DNA synthesis (UDS) with
rat primary hepatocytes:
Mouse micronucleus assay:
Test 1.
Mouse micronucleus assay:
Intraperitoneal exposure.
Single oral exposure.
Dose levels: 0 and 1000 mg/kg.
Dose levels: 0, 103, 205 or 410 mg/kg (67% of
LD50).
Results: Negative
Results: Negative
Dose levels 0, 7.8, 15.6, 31.3, 62.5, 125, 250, 500 or
1000 µg/ml.
Results: Negative
Test 2.
Two oral exposures.
Dose levels: 0 and two doses of 710 mg/kg (50% of
LD50).
Results: Negative.
Conclusion: Extensive mutagenicity testing has been conducted both with the racemic and P-isomer forms
of dimethenamid. The assays were conducted at comparable dose levels for the racemic and P-isomer
forms of dimethenamid. Racemic dimethenamid was negative in all genotoxicity studies except for an
equivocal positive in one in vitro UDS assay which could not be reproduced. All other studies were
negative. With the P-isomer, a positive effect was noted in one strain without activation in the Ames assay.
However, this could not be repeated in three separate studies. Negative results were obtained in all other
mutagenicity studies conducted with Dimethenamid-P.
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Racemic Dimethenamid
Dimethenamid-P
Although the route of exposure for the mouse micronucleus assay was different for the two forms (single
oral exposure for the racemic mixture and intraperitoneal for the P-isomer), this is not consider to have any
material effect on the comparability of the test results, which were both negative.
The overall weight of the evidence demonstrates no mutagenic potential for both the racemate and
Dimethenamid-P. Thus, read across is again supported.
Having determined that the toxicity profiles of racemic dimethenamid and
dimethenamid-P are comparable and thus read-across is acceptable, the toxicity
profile of dimethenamid-P is summarised in Table A2.6. Where a test on
dimethenamid-P was not carried out, the equivalent test on the racemate is used
instead. Specifically, carcinogenicity, reproductive and chronic toxicity studies were
not undertaken using dimethenamid-P, so tests using the racemate are used instead
(see table A2.7). A summary of the studies taken into consideration in the
determination of the Acceptable Operator Exposure Level (AOEL) and Acceptable
Daily Exposure (ADE) is provided in Table A2.9.
Table A2.6: Summary of toxicity data on dimethenamid-P and its metabolites.
ACUTE TOXICITY
Acute oral toxicity
Acute dermal toxicity
Acute inhalation toxicity
TEST SUBSTANCE: SAN 1289
(S-dimethenamid technical)
Purity 96.3% dimethenamid
(91.1% S-dimethenamid)
TEST SUBSTANCE: SAN
1289 (S-dimethenamid
technical) Purity 96.3%
dimethenamid (91.1% Sdimethenamid).
TEST SUBSTANCE: SAN
1289 - 96.3% S-Dimethenamid
technical
SPECIES: Rabbit
STRAIN: Sprague-Dawley CD
STRAIN: New Zealand White
NUMBER/SEX/GROUP: 5
NUMBER/SEX/GROUP: 5
DOSE LEVELS: 2,000 mg/kg
bw
DOSE: 2.2 mg/L for four hours.
The applicant has not indicated
whether or not this was the
maximum dose practicable.
ADMINISTRATION ROUTE:
24-Hour occluded dermal
application.
ADMINISTRATION ROUTE:
Nose-only inhalation exposure
to a mist of the substance.
VALUE: 466 mg/kg bw (both
sexes), 429 mg/kg bw males,
531 mg/kg bw females.
ENDPOINT: LD50
ENDPOINT: LC50
VALUE: >2,000 mg/kg bw
VALUE: >2.2 mg/L
RESULTS:
Deaths:
 350 mg/kg bw group: 0.
 400 mg/kg: 1 male (day 3);
 500 mg/kg: All males died
(one within 23 hours of
dosing, three on day 3 and
the fifth on day 5). Two
females died (both within
23hours of dosing).
Signs on day of dosing:
 Animals in all groups
RESULTS: No signs of
toxicity observed in-life or at
necropsy.
RESULTS: From exposure
through the first two days,
animals showed lacrimation,
chromodacryorrhea, red nasal
discharge, laboured breathing
and moist rales. No responses
were seen after day two.
Treatment with the test
substance did not produce any
adverse effect on body weight
gain. There were no abnormal
post-mortem findings.
SPECIES: Rat
SPECIES: Rat
STRAIN: Sprague-Dawley CD
NUMBER/SEX/GROUP: 5
DOSE LEVELS: 350, 400 and
500 mg/kg bw
ADMINISTRATION ROUTE:
Oral intubation.
ENDPOINT: LD50
GLP: Yes
TEST GUIDELINES:
US EPA FIFRA Series 81-2,
Acute Dermal Toxicity Study.
REFERENCE SOURCE:
Blaszcak, D.L. (1996). Acute
ERMA New Zealand Evaluation and Review Report: Application HSR08124
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showed lacrimation and
excessive salivation.
 All high-dose animals
exhibited decreased activity,
yellow ano-genital staining,
lethargy, decreased food
consumption, decreased
faecal volume or no stool.
[Note that animals were
individually housed].
 Surviving animals were free
of abnormalities by Day 5.
Body weights:
 350 mg/kg bw group - all
animals showed body weight
gains on days 8 and 15.
 400 mg/kg group – one
female showed weight loss
on day 8 and weight gain by
day 15, whilst another
showed weight loss on day 8
and no weight change by day
15. All surviving males
recorded weight gains on
both days.
 500 mg/kg group - one
female showed weight loss
by day 8 but gained weight
by day 15. All other
surviving animals showed
weight gains on both days.
Necropsy findings:
 Animals found dead during
the study revealed the
following: red thymic
region, fluid in the thoracic
cavity, red lungs, black
mucosa and brown fluid in
the stomach, and red testes.
 No abnormalities were
observed in animals
sacrificed at study
termination.
Dermal Toxicity Study with
SAN 1289 H Technical in
Rabbits. Study No.: 96-1405.
Sandoz Agro, Inc. 1300 East
Touhy Avenue, Des Plaines, IL
60018.
RELIABILITY (KLIMISCH
SCORE): 1
TEST GUIDELINES:
US EPA FIFRA Series 81-3,
Acute Inhalation Toxicity Study.
REFERENCE SOURCE:
Hoffman, G.M. (1996). An
Acute (4-hour) Inhalation
Toxicity Study of SAN 1289 H
Technical In the Rat via Noseonly Exposure. Study No.: 965279. Sandoz Agro, Inc. 1300
East Touhy Avenue, Des
Plaines, Illinois 60018-3300.
RELIABILITY (KLIMISCH
SCORE): 1
Comments:
The threshold for classifying a
substance in mist form as an
inhalation toxicant is 5 mg/L. In
this study, the substance was
only tested up to 2.2 mg/L and
the applicant did not indicate
whether or not this was the
maximum possible dose. The
effects seen at 2.2 mg/L are
sufficient to trigger 6.1D
classification. Moreover, these
effects could worsen with
increasing dose.
GLP: Yes.
TEST GUIDELINES:
US EPA FIFRA Series 81-1,
Acute Oral Toxicity
REFERENCE SOURCE:
Blaszcak, D.L. (1996). Acute
Oral Toxicity Study with SAN
1289 H Technical in Rats. Study
No.: 96-1404. Sandoz Agro, Inc.
1300 East Touhy Avenue, Des
Plaines, IL 60018.
RELIABILITY (KLIMISCH
SCORE): 1
ERMA New Zealand Evaluation and Review Report: Application HSR08124
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Classification:
6.1D (oral) classification is
assigned on the basis of the
combined LD50 466 mg/kg).
IRRITATION
Classification:
The test substance does not
trigger classification as an
acute dermal toxicant.
Classification:
The test substance triggers 6.1D
classification as an acute
inhalation toxicant.
Eye irritation
Skin irritation
TEST SUBSTANCE: 96.3% dimethenamid
(91.1% S-dimethenamid)
TEST SUBSTANCE: 96.3% dimethenamid
(91.1% S-dimethenamid)
SPECIES: Rabbit
SPECIES: Rabbit
STRAIN: New Zealand White
STRAIN: New Zealand White
NUMBER/SEX/GROUP: 2 males and 4 females
NUMBER/SEX/GROUP: 3 males and 3 females
APPLICATION: 0.1 mL of test material into the
lower conjunctival sac of one eye.
APPLICATION: 0.5 mL semi-occluded, 4-hour
exposure
RESULTS:
All six animals exhibited slight conjunctival
redness and or chemosis and moderate to severe
conjunctival discharge. Four animals were free of
all irritation by 24 hours and the remaining two
animals were free of all irritation by 48 hours.
Mean Draize Scores, 24-72 hours:
Corneal opacity: 0/6 = 0
Iritis: 0/6 = 0.
Conjunctival redness. 0/6 = 0
Conjunctival oedema: 0/6 = 0
Thus, the substance caused mild, transient ocular
irritation.
RESULTS:
Three of the six animals exhibited slight
erythema with no oedema; two animals exhibited
very slight erythema with no oedema. The sixth
animal did not show any signs of irritation.
 Mean Draize Score 24-72 hours for
erythema: 14/18 = 0.77
 Mean Draize Score 24-72 hours for
oedema: 0/18 =0
TEST GUIDELINES:
US EPA FIFRA Series 81-4, Primary Eye
Irritation Study.
REVERSIBILITY OF EFFECT: erythema
reversed within 72 hours in all animals
TEST GUIDELINES:
US EPA FIFRA Series 81-5, Primary Dermal
Irritation.
REFERENCE SOURCE:
Blaszcak, D.L. (1996). Primary Eye Irritation
Study with SAN 1289 H Technical in Rabbits.
Study Number 96-1407. Sandoz Agro, Inc. 1300
E. Touhy Avenue, Des Plaines, IL 60018-3300
REFERENCE SOURCE:
Blaszcak, D.L. (1996). Primary Dermal
Irritation Study with SAN 1289 H Technical in
Rabbits. Study Number 96-1406. Sandoz Agro,
Inc. 1300 E. Touhy Avenue, Des Plaines, IL
60018-3300
RELIABILITY (KLIMISCH SCORE): 1
RELIABILITY (KLIMISCH SCORE): 1
Conclusion on Classification:
The test substance does not trigger classification
as an eye irritant.
SENSITISATION
Conclusion on Classification:
The test substance does not trigger
classification as a skin irritant.
Respiratory sensitization
No tests undertaken.
Contact sensitization
TEST SUBSTANCE: 96.3% dimethenamid (91.1% Sdimethenamid)
SPECIES: Guinea pig
STRAIN: Dunkin Hartley (albino)
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NUMBER/SEX/GROUP: Range finding – 3/sex; Sensitization
study – 10/sex; Irritation control – 5/sex.
METHOD: Buehler method (3-Induction)
APPLICATION: Closed patch technique using undiluted test
substance.
RESULTS:
Induction dose administered once per week for three weeks. All
animals showed positive response by third induction dose.
Challenge dose administered 14 days later with all animals
showing a positive response: 17/20 scored ≥ 1 and the remaining
3/20 scored 0.5. Incidence index of 85%.
TEST GUIDELINES:
US EPA FIFRA Series 81-6, Dermal Sensitization Study.
REFERENCE SOURCE:
Blaszcak, D.L. (1996). Closed-Patch Repeated Insult Dermal
Sensitization Study with SAN 1289 H Technical in Guinea Pigs
(Buehler Method). Study No.: 96-1408. Sandoz Agro, Inc. 1300
E. Touhy Avenue, Des Plaines, IL 60018-3300
RELIABILITY (KLIMISCH SCORE): 1
Conclusion on classification:
Conclusion on classification
The substance triggers 6.5B classification (contact sensitizer).
MUTAGENICITY
In vitro studies
In vivo studies
STUDY TYPE: Bacterial Plate Incorporation
Mutagenicity Assay with and without S9
Activation
STUDY TYPE: Micronucleus cytogenic assay in
mice
SPECIES: ICR Mice
CELL TYPE: Salmonella typhimurium histidine
auxotrophs TA98, TA100, TA1535, TA1537 and
Escherichia coli tryptophan auxotroph WP2 uvr A.
TEST SUBSTANCE: 96.3% dimethenamid,
(91.1% S-dimethenamid)
DOSE RATE: 6.7, 10, 33, 67, 100, 333, 667,
1,000, 3,333 and 5,000 μg per plate.
RESULTS:
Precipitate observed at >3,333 μg/plate with no
appreciable toxicity. Positive mutagenicity
response with tester strain TA100 without S9
activation.
GUIDELINE:
US EPA FIFRA Series 84-2
REFERENCE SOURCE:
Wagner, V.O and Coffman, N. (1996).
Salmonella / Escherichia coli Plate Incorporation
Mutagenicity Assay. Reg. Doc. #BASF 96/5403.
TEST SUBSTANCE: S-Dimethenamid (96.45%)
ANIMALS/SEX/GROUP:
 15 of each sex in the vehicle only, low
and mid-dose groups;
 20 of each sex in the high dose group;
and
 5 of each sex in the positive control
group.
DOSE LEVELS: 103, 205 and 410 mg/kg bw by
intraperitoneal injection
RESULTS:
No deaths observed. Clinical signs following
dosing included lethargy (7/15 males at 205
mg/kg bw, 4/15 females at same dose; all animals
in both sexes at 410 mg/kg bw), hyperactivity
and aggressiveness in all animals at 205 and 410
mg/kg bw. No significant increase in
micronucleated polychromatic erythrocytes in the
treated groups relative to the controls at 24, 48 or
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Sandox Agro, Inc. 1300 East Touhy Avenue, Des
Plaines, IL 60018.
72 hours after administration. The substance
was thus negative in the mouse micronucleus
assay.
RELIABILITY (KLIMISCH SCORE): 1
GUIDELINE: FIFRA 84-2.
…………………………………………………...
CELL TYPE: Salmonella typhimurium histidine
auxotrophs TA98, TA100, TA1535, TA1537 and
Escherichia coli tryptophan auxotroph WP2 uvr A.
REFERENCE SOURCE:
Puman, D.L., Gudi, R., and Poris, S.K. (1996).
Micronucleaus cytogenetic Assay in Mice.
Microbiological Associates, Inc. 5221 River
Road, Bethesda, Maryland 20816 and 9900
Blackwell Road, Rockville, Maryland 20850.
Study Number G95CB09.122
TEST SUBSTANCE: S-dimethenamid (99.4%)
RELIABILITY (KLIMISCH SCORE): 1
STUDY TYPE: Bacterial reverse mutation assay
with and without S9 Activation.
DOSE RATE: 20 μg – 5,000 µg/plate standard
plate test and 4 μg – 2,500 µg/plate pre-incubation
test.
RESULTS:
No mutagenic response was observed with or
without activation. No precipitation of the test
substance was found. Toxicity was observed at
>500 μg/plate.
Comments:
The Agency notes that the signs reported
following dosing i.e. lethargy,
hyperactivity/aggressiveness contradict each
other. The authors have not commented on this.
GUIDELINE:
OECD Nos. 471 and 472.
REFERENCE SOURCE:
Engelhardt, G. and Hoffman, H. (1997).
Salmonella typhimurium/Escherichia coli Reverse
Mutation Assay (Standard Plate Test and
Preincubatuion Test) with S-Dimethenamid. Reg.
Doc. #BASF 97/10621. Department of
Toxicology, BASF Aktiengesellschaft D-67056
Ludwigshafen/Rhein, FRG.
RELIABILITY (KLIMISCH SCORE): 1
…………………………………………………...
STUDY TYPE: Bacterial reverse mutation assay
with and without S9 Activation.
CELL TYPE: Salmonella typhimurium histidine
auxotrophs TA98, TA100, TA1535, TA1537 and
Escherichia coli tryptophan auxotroph WP2 uvr A.
TEST SUBSTANCE: S-dimethenamid technical
(91.1%)
DOSE RATE: 20; 100; 500; 2,500 and 5,000
µg/plate
RESULTS:
Toxicity observed from >500 μg/plate. No test
substance precipitation found. Test substance did
not cause any increase in the number of revertant
colonies either with or without S9 mix. Hence,
ERMA New Zealand Evaluation and Review Report: Application HSR08124
Page 44 of 149
under these experimental conditions, the test
substance is not mutagenic.
GUIDELINE: OECD 471 and 472
REFERENCE SOURCE:
Engelhardt, G. and Hoffman, H. (1997).
Salmonella typhimurium/Escherichia coli Reverse
Mutation Assay (Standard Plate Test and
Preincubation Test) with S-Dimethenamid
technical. Reg. Doc. #BASF 97/10622.
Department of Toxicology, BASF
Aktiengesellschaft D-67056 Ludwigshafen/Rhein,
FRG.
RELIABILITY (KLIMISCH SCORE): 1
…………………………………………………...
STUDY TYPE: Bacterial reverse mutation assay
with and without S9 Activation.
STRAIN: Salmonella typhimurium histidine
auxotroph TA100
TEST SUBSTANCE: 91.1% S-dimethenamid
DOSE RATE: 100; 333; 1,000; 2,000; 3,333;
4,000 and 5,000 µg/plate.
RESULTS:
No positive mutagenic response observed.
Precipitate was observed at >2,000 g/plate. No
appreciable toxicity observed.
GUIDELINE: US EPA 84-2
REFERENCE SOURCE: Wagner, V.O. and
Klug, M.L. (1997). Bacterial Reverse Mutation
Assay. BASF Reg. Doc # 97/5271. MA
BioServices, Inc. 9630 Medical Center Drive,
Rockville, MD 20850.
RELIABILITY (KLIMISCH SCORE): 1
…………………………………………………...
STUDY TYPE: CHO/HGPRT mutation assay.
CELL TYPE: Chinese Hamster Ovary cells CHOK1-BH4
TEST SUBSTANCE: 91.1% S-dimethenamid
DOSE RANGE: 50 – 400 µg/ml non-activated
cultures; 25 – 450 µg/ml S9 activated cultures.
RESULTS:
No positive mutagenic response obtained. No
precipitate observed. Toxicity observed at <350
ERMA New Zealand Evaluation and Review Report: Application HSR08124
Page 45 of 149
μg/plate without activation and 400 and 450
μg/plate with activation.
GUIDELINE: FIFRA 84-2
REFERENCE SOURCE:
San, R.H.C and Clarke, J.J. (1996).
CHO/HGPRT mutation assay: SAN1289 H
technical. BASF Reg. Doc. #96/5404.
Microbiological Associates, Inc. 9900 Blackwell
Road, Rockville, MD 20850.
RELIABILITY (KLIMISCH SCORE): 1
…………………………………………………...
STUDY TYPE: Chromosome aberration test in
Chinese hamster ovary (CHO) cells
CELL TYPE: Chinese Hamster Ovary cells CHOK1
TEST SUBSTANCE: 91.1% S-dimethenamid
DOSE RANGE: 2 – 120 µg/ml non-activated
cultures; 8 - 500 µg/ml S9 activated cultures.
RESULTS:
The only positive result obtained was at the 60
μg/plate dose level in the non-activated test
system. However, this positive response was
within the historical range of the solvent control
and not considered biologically significant. Based
on this, the authors concluded that the test was
negative for the induction of structural
aberrations in CHO cells.
GUIDELINE: FIFRA 84-2
REFERENCE SOURCE:
Curry, P.T. and Schadly, E. (1996).
Chromosome Aberrations in Chinese hamster
ovary (CHO) cells. Reg. Doc. #BASF 96/5400.
Microbiological Associates, Inc. 9900 Blackwell
Road, Rockville, MD 20850.
RELIABILITY (KLIMISCH SCORE): 1
…………………………………………………...
STUDY TYPE: Unscheduled DNA synthesis.
CELL TYPE: Primary hepatocytes from a male
Sprague-Dawley rat.
TEST SUBSTANCE: 91.1% S-dimethenamid
DOSE LEVELS: 7.8, 15.6, 31.3, 62.5, 125 µg/ml
RESULTS:
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Page 46 of 149
The test article did not induce a significant
increase in the mean number of net nuclear grain
counts at any dose level compared to the solvent
control. Thus, S-dimethenamid was negative in
the UDS assay.
GUIDELINE: FIFRA 84-4
REFERENCE SOURCE:
San, R., Sly, J (1996). Unscheduled DNA
Synthesis Assay in Rat Primary Hepatocytes.
Reg. Doc. #BASF 96/5399. Microbiological
Associates, Inc. 9900 Blackwell Road, Rockville,
MD 20850.
RELIABILITY (KLIMISCH SCORE): 1
ERMA New Zealand Comments
ERMA notes that although one of the assays
returned a positive mutagenicity result with the
TA100 tester strain of Salmonella typhimurium,
three more assays were subsequently run. All of
these gave negative results with all strains used.
ERMA therefore concurs with the conclusions
drawn by the Authors.
Conclusion on classification:
Based on a weight-of-evidence approach, in-vitro and in-vivo studies indicate that the active ingredient
is not mutagenic, therefore no classification is assigned.
CARCINOGENICITY
Refer to studies with SAN 582 H (racemic mixture of r and s dimethenamid).
Conclusion on classification:
Racemic dimethenamid (and hence dimethenamid-P) does not trigger classification as a carcinogen.
REPRODUCTIVE/DEVELOPMENTAL TOXICITY
Developmental studies
STUDY TYPE: Developmental Toxicity Study
SPECIES: Rat
STRAIN: Sprague-Dawley Crl:CD® BF
TEST SUBSTANCE: SAN 1289 H Technical (S-Dimethenamid Technical).
DOSES: 0, 25, 150 and 300 mg/kg/day
ROUTE: Orally by gavage
TEST GUIDELINE: US EPA Pesticide Assessment Guidelines Subdivision F, 83-3.
RESULTS:
Maternal
1. No deaths, abortions or premature deliveries in any group;
2. Significantly higher number of rats with excess lacrimation, piloerection, salivation, decreased
motor activity, swollen ocular membrane, ptosis, dark pink skin (nose, mouth, forepaws,
ERMA New Zealand Evaluation and Review Report: Application HSR08124
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3.
4.
5.
6.
7.
hindpaws, hindlimbs or ears) and urine stains on abdominal fur in 300 mg/kg/day dose group;
Absolute feed consumption significantly reduced in the 150 and 300 mg/kg/day groups throughout
the dosing period (days 6 through 15);
Absolute and relative feed consumption values significantly reduced in the 150 and 300 mg/kg/day
groups for the entire gestation period after dosing was begun,
Reduced body weight gain in the 150 mg/kg/day groups and a significant weight loss in the 300
mg/kg/kg group on days of presumed gestation 6 to 9;
Maternal body weights for the 150 and 300 mg/kg/day groups significantly less than for the
control groups from days 9 and 8 respectively;
Percentage liver weight significantly increased in the 300 mg/kg/day group. This observation
reflected dosage-dependent but not statistically significant tendencies for increased absolute liver
weight and reduced terminal body weight in this group.
Foetal
1. Foetal body weights reduced in the 150 and 300 mg/kg/day groups;
2. Significant increases in foetal alterations in the 150 and 300 mg/kg/day groups due to retarded
ossifications of sternal centra and pelvic pubes. Occurred at doses where maternal toxicity was
evident;
3. Foetal alterations noted were as follows:
 Umbilical hernia and oedema of head, neck and thoracic regions in one 300mg/kg/day dose
group foetus. Skeletal examination of this foetus identified alterations commonly associated
with compression secondary to oedema including incomplete ossification of the tympanic
rings, irregular ossification of the left scapulae and absence of the bones in the forelimbs
(humerus, radius and ulna) and the right hindlimb (femur) and incompletely ossified pubes.;
 Two 300 mg/kg/day foetuses had a depressed eye bulge associated with microphthalmia of the
affected eye;
4. Analyses of the average numbers of foetal ossification sites per litter did not reveal biologically
important or statistically significant differences among the three dosage groups.
REFERENCE SOURCE:
York, R.G. (1996). Oral (Gavage) Developmental Toxicity Study of SAN 1289 H in Rats.
Reg.Doc.#BASF 97/5274. Argus Research Laboratories, Inc. 905 Sheehy Drive, Building A,
Horsham, Pennsylvania 19044-1297.
RELIABILITY (KLIMISCH SCORE): 1
DEVELOPMENTAL STUDIES
MATERNAL TOXICITY:
NOAEL: 25 mg/kg/day.
LOAEL: 150 mg/kg/day due to effects on body weight.
FOETAL TOXICITY
NOAEL: >300 mg/kg/day
LOAEL: >300 mg/kg/day
ERMA New Zealand Comments:
ERMA New Zealand concurs with the conclusions of the Authors – the maternal LOAEL is 150
mg/kg/day whilst maternal NOAEL is 25 mg/kg/day.
As described above, the dams showed reduced food intake and body weight gain at the mid and high
doses, which results in poor nutritional status. Therefore, the foetal effects seen at the highest dose
tested were secondary to maternal toxicity. Moreover, foetal effects seen at all the doses tested were
neither biologically important nor statistically significant compared with those seen in the control
animals. Therefore, both the foetal LOAEL and NOAEL > 300 mg/kg bw/day, the highest dose
tested.
Reproductive studies
Racemic dimethenamid (and hence dimethenamid-P) does not trigger classification as a reproductive
toxicant (Refer to studies with SAN 582 H, the racemic mixture of R- and S-dimethenamid).
ERMA New Zealand Evaluation and Review Report: Application HSR08124
Page 48 of 149
Conclusion on classification:
The test substance does not trigger classification as a developmental toxicant because the effects seen
at the highest dose were secondary to maternal toxicity.
TARGET ORGAN SYSTEMIC TOXICITY
Subchronic toxicity – oral
TYPE OF STUDY: 4-week range-finding study of SAN1289H in rat via dietary administration
SPECIES/STRAIN: Sprague-Dawley CD BR rats
NO.ANIMALS/SEX/GROUP: 5
TEST SUBSTANCE: 94.7% active ingredient (S-dimethenamid)
DOSE LEVELS:
0, 150, 500, 1500 and 3000 ppm corresponding to 0, 15, 50, 155, 306 mg/kg bw /day (males);
 0, 12, 52, 143, 290 mg/kg bw /day (females)
ROUTE: Oral, via the diet
GLP: YES
TEST GUIDELINES: None identified
RESULTS:
1. Mean body weights of male animals receiving the highest dose (306 mg/kg bw / day) were lower
than those of the control animals throughout the study (percentage difference from mean control
body weight was -7.1%);
2. Slight increase in mean gamma-glutamyl transferase values in the high-dose animals (7+2 IU/L
compared to 0 IU/L for the control animals);
3. Relative and absolute liver weights of animals in the high-dose group (both sexes) were
significantly increased compared with the control values at the termination of the study;
LOEL: 306 mg/kg bw /day (males), 290 mg/kg bw /day (females)
NOEL: 155 mg/kg bw /day (males), 143 mg/kg bw /day (females)
REFERENCE SOURCE:
Randall, M et al (1996). A 4-week Range-finding Study of SAN 1289 H in the Rat via Dietary
Administration. Study No. 95-2400. Sandoz Agro, Inc. 1300 East Touhy Avenue, Des Plaines, IL
60018.
RELIABILITY (KLIMISCH SCORE): 1
.........................................................................................................................................
TYPE OF STUDY: Subchronic (3-month) toxicity study in rats.
SPECIES/STRAIN: Crl: CD® BR Sprague-Dawley rats
NO. ANIMALS/SEX/GROUP: 10
TEST SUBSTANCE: 96.3% dimethenamid, 91.1 % S-dimethenamid
DOSE LEVELS: 0, 500, 1500, 3000 ppm corresponding to 0, 37, 110 and 222 mg/kg bw / day for
males and 0, 40, 125 and 256 mg/kg bw / day for females.
ERMA New Zealand Evaluation and Review Report: Application HSR08124
Page 49 of 149
ROUTE: oral (dietary)
GLP: yes
TEST GUIDELINES: US EPA FIFRA 82-1
RESULTS:
1. No deaths were recorded during the study;
2. Terminal mean body weights for 1500 and 3000 ppm dose males were 5% and 7% lower than
those of control animals respectively. For females, they were 4% and 5% lower than controls
respectively. Group mean body weights for treated animals were lower than those of controls
beginning week 1 after dosing through the end of the study;
3. Mean activated partial thromboplastin time of 3000 ppm dose animals was higher than that of
controls. However, the difference was only statistically significant in females [this is not reported
in any other study];
4. Gamma glutamyl transferase (GGT) increased in males in the 1500 and 3000 ppm dose groups and
in females in the 3000 dose group;
5. Dose related trend towards decreased serum aspartate aminotransferase (AST) for males in all
groups and statistically significant decreases in serum alanine aminotransferase (ALT), and serum
alkaline phosphatase (ALP) in the 1500 and 3000 ppm male animals;
6. Trend toward slightly increased cholesterol values in treated animals, statistically significant in
high dose males;
7. Increase in absolute and relative liver weights of males in all dose groups and females in the 1500
and 3000 ppm dose groups;
8. Treatment related slight periportal hepatocellular hypertrophy in males in 8/10 mid-dose animals
and all high dose animals;
9. Treatment related slight centrilobular hepatocellular hypertrophy in females at an incidence of
3/10, 8/10 and 8/10 for the low, mid and high dose animals respectively which were not seen in
controls;
10. The cytoplasm of enlarged hepatocytes had ring-like eosinophilic inclusions of variable sizes in
3/10 and 7/10 males of the mid and high dose groups respectively. These inclusions were not
observed in females.
NOAEL: 500 ppm (37 mg/kg bw/day males; 40 mg/kg bw / day females).
LOAEL: 1500 ppm (110 mg/kg bw/day males; 125 mg/kg bw / day females) based on presence of
eosinophilic cytoplasmic inclusions in hepatocytes and hepatocellular hypertrophy.
REFERENCE SOURCE:
Blanset, D (1996). A Subchronic (3-month) Toxicity study of SAN 1289 H in the Rat via Dietary
Administration. Reg. Doc. # BASF 96/5420. Sandoz Agro, inc., 1300 East Touhy Avenue, Des
Plaines, IL 60018.
RELIABILITY (KLIMISCH SCORE): 1
Comments:
The toxicological significance of decreases of the enzymes ALT, AST and ALP is questionable.
Normally, increases in activity of these enzymes indicate liver damage. The LOAEL obtained from the
4-week range-finding study in Sprague-Dawley rats described above was 306 mg/kg/day. It is also
noted that in the developmental toxicity study also carried out with Sprague-Dawley rats, the LOAEL
for maternal toxicity was 150 mg/kg/day driven by effects on body weight without any other evidence
of specific target organ toxicity. Taken together, the weight of evidence suggests that 6.9 classification
is not warranted for dimethenamid-P.
Conclusion on Classification
The test substance does not trigger classification as a 6.9 target organ toxicant.
Table A2.7: Summary of toxicity data on SAN 582 H (racemic mixture of r/sdimethenamid).
ABSORPTION, DISTRIBUTION AND METABOLISM OF SAN 582
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Page 50 of 149
TYPE OF STUDY: Absorption, Distribution And Metabolism in Rats
SPECIES/STRAIN: male and female kfm:WIST rats
TEST SUBSTANCE: SAN 582 H
DOSE LEVELS: 10 mg/kg bw for acute low oral and intravenous administration and 1000 mg/kg bw
high oral dose. 10 mg/kg bw for repeated oral doses once a day for 14 days.
RESULTS:
After single oral low dose exposure, lowest absorption obtained ~ 90%
After single oral high dose exposure, lowest absorption obtained ~ 63%
After repeated low doses, absorption was similar to that after a single oral low dose exposure.
REFERENCE SOURCE:
Vollmin, S. (1992). Absorption, Distribution Metabolism and Excretion of (14C) SAN 582 H in rat
after single and multiple doses (addendum to: SAN 582 H metabolism in rat; BASF RegDoc#
89/11026. SANDOZ Agro, Ltd., Basle, CH. BASF RegDoc.# 92/12428
GLP: Yes.
..................................................................................................................
TYPE OF STUDY: Dermal Absorption of 14C-R,S-dimethenamid and 14C-S-dimethenamid in rats
SPECIES/STRAIN: Wistar rats
TEST SUBSTANCE:
 [14C]-Racemic dimethenamid radiochemical purity 99.69%
 [14C]-Dimethenamid-P radiochemial purity 99.51%
 Unlabeled racemic dimethenamid purity 99.0%
 Unlabeled dimethenamid-P purity 93.0%
GUIDELINES: EEC Directive 87/302, part B; OECD 417
EXPERIMENTAL PROCEDURE:
The absorption, distribution and excretion of radioactivity was studied in male Wistar rats following a
single dermal administration of [14C]-labelled racemic dimethenamid or dimethenamid-P. Racemic
dimethenamid was tested dissolved in the neat solvent of a commercial formulation (Frontier 6.0
herbicide) at nominal dose levels of 0.004, 0.04 and 0.4 mg/cm². The doses were selected on the basis
of model calculations giving a range of expected field exposure. Animals were exposed for either 4 or
8 hours after which the patches with test substance were removed and the skin was washed with a mild
soap solution. Sacrifice was at 4 hours for the 4 hour exposure and at 8, 24 or 72 hours after the 8 hour
exposure.
Four animals were used per dose group and sacrifice time. In this balance/excretion study animals were
placed in metabolism cages in order to collect excreta up to 72 hours. At the end of the various
collection periods animals were sacrificed and the following specimens/tissues were checked for
remaining radioactivity:
Excreta (urine and faeces), blood cells, plasma, kidney, liver, carcass, treated skin (application
site) and non-treated skin surrounding the application site.
The cage wash, skin wash and the application material (protective cover) were also checked for
radioactivity.
To compare dermal penetration rates of racemic and dimethenamid-P, a second experiment was
performed using [14C]-labelled dimethenamid-P dissolved in the neat solvent of the formulation BAS
656 07 H. The same nominal dose levels were used of 0.004, 0.04 and 0.4 mg/cm 2. The animals were
exposed for 8 hours and sacrificed at 72 hours after the end of treatment. This exposure and sacrifice
time was chosen as it produced the greatest penetration results in the racemic dimethenamid study.
To assess the effect of the formulation on dermal penetration, a third experiment was performed using
[14C]-dimethenamid in the BAS 656 07 H formulation. The exposure time was 8 hours and the
ERMA New Zealand Evaluation and Review Report: Application HSR08124
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sacrifice time was 72 hours. This exposure and sacrifice time was chosen as it gave the highest
penetration results in the second experiment using dimethenamid-P and the same solvent.
RESULTS:
 Recoveries of radioactivities from all dose groups were acceptable.
 The maximum dermal absorption of [14C]-racemic-dimethenamid was 18 % at 72 hours after
an 8 hour exposure with the lowest dose of 0.004 mg/cm².
 The maximum dermal absorption of [14C]-dimethenamid-P in the proposed BAS 656 07 H
formulation was 27.32% and occurred the 0.04 mg/cm² dose level.
 After an 8 h-exposure of [14C]-racemic-dimethenamid in BAS 656 07 H at a dose level of 0.4
mg/cm², 24.7 % was absorbed after 72 hours. This is very similar to the 23% absorption
observed with dimethenamid-P at the same exposure and sacrifice times using the same
formulation.
CONCLUSION:
Following a single dermal administration of [14C]-racemic dimethenamid diluted in a commercial
formulation (Frontier 6.0 Herbicide) there was a partial dermal absorption which had a maximum of
18% at 72 hours after an 8 hour exposure period. The penetration was increased slightly to 25% when
the proposed formulation BAS 656 07 H was used as a carrier. A similar penetration of 27% was
observed with dimethenamid-P in the BAS 656 07 H formulation.
Overall, the in vivo dermal penetration of dimethenamid or dimethenamid-P is approximately
26%.
REFERENCE SOURCE:
Leibold E. (1999). Preliminary information: 14C-R,S-dimethenamid and 14C-S-dimethenamid-study
of the dermal absorption in rats. BASF RegDoc.# 99/10283 (unpublished) BASF Aktiengesellschaft,
Ludwigshafen, Germany
GLP:
yes
.................................................................................................................................
TYPE OF STUDY: Rates of permeation through human and rat epidermis using an in vitro assay
SPECIES/STRAIN: Wistar rats
TEST SUBSTANCE:
 [14C]-dimethenamid thiophene label; radiochemical purity: > 98%.
 Unlabeled dimethenamid purity: 97.6%.
Guidelines:
None available
EXPERIMENTAL PROCEDURE:
An in vitro study was used to compare the dermal penetration rates of racemic [ 14C]-dimethenamid
through human and rat skin. Post mortem human skin was obtained and dermatomed to a thickness of
300 m. Wistar rats were sacrificed, the abdominal region was clipped free of hair and skin samples
excised. The excised rat skin was cut free of fatty tissue and resulting samples were approximately
2000 m thick. The excised human and rat skin epidermis and upper dermis were mounted in Franztype static dermal penetration cells. Each skin sample was checked for integrity using transepithelial
electrical resistance. Three different dose solutions were prepared using the [14C]-dimethenamid, cold
dimethenamid and an ethanol water solvent. The dose levels used were 2.55, 10.2 and 40.8 mg/cm 2.
The test solutions were applied as a single dermal application at a dose volume of approximately 500
µl/cm2 for 24 hours. Three replicates were used for each dose level and skin type, and each experiment
was repeated twice giving a total of nine cells tested per dose group and skin type. Samples of the
receptor fluid (ethanol and water) were taken at 0, 2, 4, 6, 8, 20, 22 and 24 hours and analyzed for
radioactivity. At the end of exposure the skin samples were removed from the cells and washed with
ethanol and water. Both the skin samples and the skin wash were analyzed for radioactivity.
RESULTS:
Skin penetration rates of [14C]-dimethenamid through human and rat skin as reported for 24 hr are were
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as follows:
2
Dose level (mg/cm )
2.55
10.2
40.8
Rate of penetration (g/cm2/hr)
Rat
Human
3.3
3.2
13.2
11.8
30.8
67
The rat skin samples used were 6.67 times thicker than human skin. After adjusting the above results
for the differences in skin thickness, the following results were obtained:
Penetration rates of [14C]-dimethenamid through human and rat skin corrected for skin thickness.
Dose Level (mg/cm2) Rate Of Penetration (g/cm2/Hr) Relative Penetration
Rat/Human
Rat
Human
2.55
22
3.2
7
10.2
88
11.8
7
40.8
205
67
3
Correcting for the difference in skin thickness, the rate of penetration through human skin is 3 to 7
times less than that through rat skin. However, saturation has occurred at the high dose in the rat skin
as the penetration rate no longer continues to increase linearly with dose. Human exposure from the
mixing, loading and application of dimethenamid has been predicted with worker exposure modes to be
at most 0.4 mg/cm2. Therefore, the comparative values of rat/human skin from the lower doses is
considered more appropriate for use in predicting human exposure.
CONCLUSION:
Dermal penetration studies in rats demonstrated, that the in vivo dermal penetration of dimethenamid
or dimethenamid-P is approximately 26%. Based on the results of in vitro penetration comparisons
between human and rat skin, it can be concluded that the rate of dermal penetration (µg/cm 2/h) through
rat skin is 7-fold higher than through human skin. Overall the human dermal penetration of
dimethenamid is predicted to be approximately 4%.
REFERENCE SOURCE:
Sommer E., Mueller F. (1993). 14C-dimethenamid technical: Rates of permeation through human
and rat epidermis using an in vitro assay. SANDOZ Agro Ltd., Department of Toxicology, Muttenz,
Switzerland (unpublished). BASF RegDoc.# 93/11759
GLP:
yes
TARGET ORGAN TOXICITY
Subchronic toxicity – oral
TYPE OF STUDY: 13 week dose range finding study in CD-1 mice
SPECIES/STRAIN: CD1 mice
NO.ANIMALS/SEX/GROUP: 12/sex/group
TEST SUBSTANCE: 91.5 +/- 1% SAN 582 H
DOSE LEVELS: 0, 300, 700, 2000, 5000 ppm corresponding to 0, 45.9, 104.6, 301.3 and 805.4 mg/kg/
bw/day in males and 0, 59.5, 137.2, 383.4 and 972.3 mg/kg/ bw/day in females.
ROUTE: oral (dietary)
GLP: YES
RESULTS:
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1.
2.
3.
4.
5.
6.
No deaths occurred as a result of compound administration;
5000 ppm findings: in males – food consumption was decreased and body weight gains were
decreased by 50% compared with controls. Males and females showed an increase in the absolute
and relative liver weights and relative kidney weights. No treatment-related microscopic findings
in animals of either sex.
2000 ppm findings: males and females showed increased absolute and relative liver weights.
Increased relative kidney weights in both sexes, though not statistically significant. No
macroscopic changes were reported;
700 ppm findings: increase in relative liver weights observed in males;
300 ppm: no treatment-related findings;
Authors concluded dose-related response to treatment was demonstrated at 700 and 2000 ppm.
NOAEL: 700 ppm (104.6 mg/kg bw / day males, 137.2 mg/kg bw / day females).
LOAEL: 2000 ppm (301.3 mg/kg bw / day males, 383.4 mg/kg bw / day females) based on effects on
the liver and kidneys
REFERENCE SOURCE:
Warren, S., Karapally, J., Ettlin, R., Carpy, S. and Muller, F. (1988). SAN 582 H: 13-Week DoseRange Finding Study in C D-1 Mice. Reg. Doc. #BASF 88/11360. Sandoz Ltd, Agro Development.
Toxicological Department. Basle, Switzerland.
RELIABILITY (KLIMISCH SCORE): 1
.......................................................................................................................
TYPE OF STUDY: 13 week oral toxicity study in dogs
SPECIES/STRAIN: Beagle dog
NO. ANIMALS/SEX/GROUP: 4/sex/group
TEST SUBSTANCE: 91.4% SAN 582 H
DOSE LEVELS: 0, 91.5, 750, 2000 ppm corresponding to 0, 5, 37 and 96 mg/kg/day respectively.
ROUTE: oral (dietary)
GLP: YES
TEST GUIDELINES: US EPA Pesticide Assessment Guidelines Subdivision F, 82-1
RESULTS:
1. No deaths occurred at any of the doses tested.
2. Body weight gain was reduced in all animals at 2000 ppm and in females at 750 ppm. One high
dose animal lost 1kg over the dosing period whilst another had marginal losses during the first
week of dosing;
3. No haematological changes observed;
4. Clinical chemistry: increase in blood cholesterol and alkaline phosphatase levels in the high dose
group;
5. Organ changes: absolute and relative liver weights significantly increased in 2000 ppm dose group.
Relative liver weights significantly increased for 750 ppm dose group;
6. Gross pathology: one high dose male had a pale liver with a 10mm diameter irregular area on the
parietal surface of the median lobe, loosely adhered to the diaphragm. A high dose female showed
prominent liver lobulation;
7. Histopathological changes: Periportal cytoplasmic vacuolation of hepatocytes detected in all high
dose animals and 2 intermediate dose animals (one of each sex). The vacuoles were negative for
fat and glycogen;
8. Dilatation of liver sinusoids in three males and three females from the high dose group, and in one
female from the 750 ppm dose group;
9. Conclusion: hepatotoxicity occurred in all animals at 2000 ppm and in individual animals at 750
ppm.
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NOAEL: 91.5 ppm (5 mg/kg bw/day both sexes)
LOAEL: 750 ppm (37 mg/kg bw/day both sexes) based on decreased body weight gain, cytoplasmic
vacuolation and hepatic sinusoidal dilatation.
REFERENCE SOURCE:
Greenough, R.J. and Goburdhun, R. (1986). SAN 582 H: 13-Week Oral Toxicity Study in Dogs.
Reg. Doc. #BASF 86/11159. Sandoz Ltd., Agro Development, Toxicological Department, Basle,
Switzerland.
RELIABILITY (KLIMISCH SCORE): 1
Comment:
Although the results from this study suggest 6.9B classification for the test material, progression of
liver effects was not evident in the 52-week oral toxicity study in the same do species summarised
below. Therefore, the substance is not considered to trigger 6.9 classification.
Chronic toxicity/carcinogenicity
TYPE OF STUDY: 52-week oral toxicity study in dogs
SPECIES: beagles
NO. ANIMALS/SEX/GROUP: 4/sex/group
TEST SUBSTANCE: 91.3% SAN 582 H
DOSE LEVELS: 0, 50, 250, 1250 ppm equivalent to 0, 1.95, 10.1, 48.7 mg/kg bw / day in males and 0,
2.1, 9.1, and 49.3 mg/kg bw /day in females respectively.
ROUTE: dietary
GLP: Yes
TEST GUIDELINES: US EPA Pesticide Assessment Guidelines Subdivision F, 83-1.
RESULTS:
1. No unscheduled deaths were recorded throughout the duration of the study.
2. Reduced body weight gain in high dose animals (both sexes) and mid-dose males. One mid dose
male dog showed a body weight loss of 0.4 kg over the dosing period whilst a high dose male lost
0.5 kg during the treatment period.
3. There were treatment-related increase in blood cholesterol and alkaline phosphatase levels for the
high dose animals. The effect on cholesterol was present in the males up to midway through the
study whilst significant increases in alkaline phosphatase were maintained in females throughout
the treatment period.
4. Liver weights were significantly increased for the high dose males and all treated females;
5. There were no gross pathological lesions that could be related to treatment with the compound;
6. Clinical chemistry changes indicate effects on liver function in the high dose group especially.
 Dose related increases in blood cholesterol levels were observed in males during weeks 13
and 26. Changes in the high dose group were statistically significant at week 26. High dose
males also showed significant increased in alkaline phosphatase levels at week 26.
 Females showed increased blood cholesterol at week 13. AP levels increased in the high dose
female group and this effect was statistically significant at all measurement points (weeks 13,
26 and 51).
7. Statistically significant increase in liver weights in high dose males and all treated females –
authors concluded that this was spurious for 50 and 250 ppm animals as there were neither
histopathological effects in the liver nor changes in blood chemistry;
8. Periportal hepatocytes vacuolation in 2/4 males and 4/4 females in the high dose group. The
vacuoles contained neither lipid nor glycogen;
9. Minimal to mild hepatocytes enlargement, mid-zonal region, in 2 males and one female from the
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high dose group.
NOAEL: 50 ppm (1.95 mg/kg bw/day)
LOAEL: 250 ppm (10.1 mg/kg bw/day) based on body weight effects.
REFERENCE SOURCE:
Greenough, R.J., Goburdhun, R. And Macnaughtan, F. (1988). SAN 582 H: 52 Week Oral
Toxicity Study in Dogs. Reg. Doc. # BASF 88/11361. Sandoz AG. CG-4002 Basle, Switzerland.
RELIABILITY (KLIMISCH SCORE): 1
Comments
These findings do not support 6.9 classification of dimethenamid.
......................................................................................................................................................
TYPE OF STUDY: Chronic Toxicity / Carcinogenicity
SPECIES/STRAIN: Charles River Crl: CD (SD) BR rats
NO.ANIMALS/SEX/GROUP: 50/sex/group for the main group; 20/sex/group for satellite group
TEST SUBSTANCE: 91.3% SAN 582 H
DOSE LEVELS: 0, 100, 700, 1500 ppm corresponding to
 0, 5.1, 36 and 80 mg/kg bw / day for males ;
 0, 6.8, 49 and 109 mg/kg bw / day for females.
ROUTE: dietary
GLP: yes
TEST GUIDELINES:
US EPA FIFRA Guideline No. 83-5, OECD and Japanese MAFF Guidelines.
REMARKS:
1500ppm treatment group = males: 80 mg/kg/bw/day; females: 108 mg/kg/bw/day
1. 62% of the animals (both sexes) survived to study termination.
2. Authors concluded no treatment related clinical signs at this dose;
3. Reduced food utilisation efficiency (both sexes) during the first 25 weeks of treatment;
4. Decrease in bodyweight gain during weeks 0-10 in both males and females. This trend was
maintained in males and increased in females until the end of the main growth phase (week 80).
At Week 80, the decrease in absolute mean body weight compared with controls was 10 and 16%
in males and females respectively.
5. Ocular lesions were not observed at 53 weeks but at week 104. Increased incidence of posterior
capsular lenticular opacities in males and females were considered to be a treatment related
exacerbation of a normal age-related change;
6. Clinical biochemistry:
 Increased GGT for males throughout the whole study;
 Increased cholesterol in females ;
 Decreased glutamic-oxaloacetic transaminase and glutamic-pyruvic transaminase noted for
females in weeks 13, 26, 52 and males in week 78.
 Decreased calcium in males in weeks 52 and 104
7. Urinalysis showed marginal increases in detectable urinary ketone content for males in weeks 26,
52 and 78;
8. 104 week group: slight increase in the number of animals showing liver masses, liver cysts and
pale areas of the liver compared with control rats;
9. Terminal studies showed 17/50 males and 19/50 females with paleness of the liver compared with
6/50 and 10/50 controls respectively;
10. Increased liver weights in female rats in the 52 and 104 week groups;
11. Neoplastic pathology:
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

Increased incidence of liver cell tumours in males;
Increased incidence of tubular adenomata of the ovaries, considered by the study authors to be
of “equivocal” toxicological significance;
12. Non-neoplastic pathology:
 Increased incidence of circumscribed areas of altered eosinophilic hepatocytes in the liver
(males);
 Increased bile duct hyperplasia noted (females);
 Increased incidence of cystically dilated bile ducts;
 Increased incidence and severity of epithelial hyperplasia at the limiting ridge of the stomach
(males) but this was considered by the authors to be of “equivocal” toxicological significance.
700ppm treatment group = males: 36 mg/kg bw/day; females: 49 mg/kg bw/day
1. 50% of the males and 60% of the females survived to study termination.
2. Females showed lower food utilisation efficiency during the first 25 weeks of treatment;
3. Marginal increase in gamma-glutamyl transferase (GGT) activities in weeks 78 and 104, Lower
glutamic-oxaloacetic transaminase(GOT) and glutamic-pyruvic transaminase (GPT) activities
were noted for females in weeks 13, 26, and 52 and for males in week 78;
4. Organ weight analysis showed increased liver weights for females at the interim kill;
5. Terminal studies showed macroscopic difference in treated males compared with controls with
14/50 showing paleness of the liver compared with 6/50 controls;
6. Increased incidence of bile duct hyperplasia in females;
7. Increased incidence of ovarian tubular hyperplasia;
8. Increased incidence of parathyroid hyperplasia was noted for males but was considered to be of
“equivocal” toxicological significance.
100ppm treatment group = males: 5.1 mg/kg bw/day; females: 6.8 mg/kg bw/day
No treatment related findings
a.
Non-neoplastic effects
NOAEL: 100 ppm (males: 5.1 mg/kg bw/day; females: 6.8 mg/kg bw/day)
LOAEL: 700 ppm (males: 36 mg/kg bw/day; females: 49 mg/kg bw/day) based on bile duct
hyperplasia, ovarian tubular hyperplasia, and effects on the enzymes GGT, GOT and GPT.
Comment:
These findings suggest a 6.9B classification for racemic dimethenamid. However, the effects only
became apparent at the terminal kill and may represent an exacerbation of age-related pathologies.
They are therefore not considered to drive 6.9 classification.
b.
Neoplastic effects
Analysis of tubular adenomas – females
Dose Group
Original diagnosis
Granulosa cell tumour
Tubular adenoma
Tubular hyperplasia
Review with external pathologist
Granulosa cell tumour
Sertoli tubular adenoma
Sertoliform tubular hyperplasia
Sertoliform tubular hyperplasia + adenoma
Control
100 ppm
700 ppm
1500 ppm
2
12
1
1
7
1
2
14
6
22
3
18
21
3
12
12
1
4
12
14
5
23
24
Comment
Following the initial diagnosis of tubular adenoma by the study pathologist, an external consultant was
brought in to offer his own assessment. The results of both the initial and the subsequent reassessment
are detailed in the table above. The tubular adenoma was redefined as Sertoli tubular adenoma.
Although there was no statistically significant increase in adenomas, there appeared to be a trend of
increasing occurrence in higher dose groups. Nevertheless, The combined incidence of sertoliform
tubular hyperplasia and adenoma does not show a similar trend. The reviewers further argue that the
ovarian adenomas are:
 unique to Sprague-Dawleys;
 rarely found in other rat species;
ERMA New Zealand Evaluation and Review Report: Application HSR08124
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 not found in man or domestic animals;
 do not metastise and their potential for malignancy is doubtful
The reviewers conclude that these lesions have no toxicological significance and have limited
relevance to man. The Agency concurs with the conclusions reached by the reviewers. The findings
do not support classification of the test substance as a carcinogen or potential carcinogen.
Analysis of Liver Tumours – males
Dose Group
Benign liver cell tumour
Malignant liver cell tumour
Control
0
0
100 ppm
1
0
700 ppm
0
0
1500 ppm
3
2
All the above tumours were noted in sacrificed animals, not those dying before end of study. Given
that high dose animals showed superior survival (62%) compared with control males ((36%), low dose
males (40%) and mid dose males (50%). This superior survival may also result in exaggeration of the
difference in tumour incidence between control and high dose animals.
TUMOURS BACKGROUND INCIDENCE:
 Male Liver Cell Tumour Data: HRC Historical Control – Benign = 0-1.8%, Malignant = 03.6%; Charles River Historical Control (updated 1991, unpublished) – Benign = 0-15.4%;
Malignant = 0-7.7%.
 Female Tubular Adenoma Data: HRC Historical Control – 0-5.5%; Charles River Historical
Control (updated 1991, unpublished) –0-1%.
SURVIVAL:
 Males: Controls – 36 %; 100 ppm – 40%; 700 ppm – 50%; 1500 ppm – 62%;
 Females: Controls – 50%; 100 ppm – 44%; 700 ppm – 60%; 1500 ppm – 62%.
NOAEL: 1500 ppm (80 mg/kg bw / day for males and 109 mg/kg bw / day for females)
LOAEL: >1500 ppm
REFERENCE SOURCE:
Ruckman, S.A., Waterson, L.A., Crook, D., Buist, D., Gopinath, C., Read, R., Gibson, W.A.,
Anderson, A., Dawe, I.S. and Chanter, D.O. (1990). Potential tumorigenic and toxic effects in
prolonged dietary administration to rats. Reg. Doc. #BASF 90/11138. Sandoz Ltd., Agrochemical
Toxicology Dept., CH-4002 Basle, Switzerland.
RELIABILITY (KLIMISCH SCORE): 1
Comments:
The Agency notes that although there was an increased incidence of liver tumours amongst rats
receiving the 1500 ppm dose, the Authors argued that this was well within the range observed among
historical control data. They attributed the increased incidence of malignant liver cell tumours to the
incidence of benign liver cell tumours. They further argued that although there were a greater number
of ovarian tubular adenomas amongst female rats receiving 1500 ppm, there was no statistically
significant effect on pair-wise comparison and on Fisher’s exact method, and so this result is
considered to be of equivocal toxicological significance.
The explanation given by the Authors is plausible given that the rodent species used here shows a high
background tumour incidence. The view that these tumours are not treatment-related is further
corroborated by findings from the carcinogenicity study in mice detailed below.
.................................................................................................................................
TYPE OF STUDY: Carcinogenicity
SPECIES/STRAIN: Charles River (UK) Crl: CD-1 (ICR) BR mice
NO.ANIMALS/SEX/GROUP: 52/sex/group for the main group; 16/sex/group for satellite group
TEST SUBSTANCE: 91.4% SAN 582 H
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DOSE LEVELS: 0, 30, 300, 1500, 3000 ppm corresponding to
 3.8, 40.8, 205 and 431 mg/kg/bw/day for males;

4.1, 40.1, 200, 411 mg/kg/bw/day for females
ROUTE: dietary
GLP: yes
TEST GUIDELINES:
US EPA FIFRA Guideline No. 83-5, OECD and Japanese MAFF Guidelines.
REMARKS:
3000 ppm treatment group (males: 431 mg/kg/bw/day; females: 411 mg/kg/bw/day)
1. No apparent treatment-related clinical signs;
2. Survival considered unaffected by treatment;
3. Lower body weight gain during the first 52 weeks, food consumption unaffected but impaired food
utilisation efficiency apparent in males over weeks 1 to 13;
4. Higher liver weights at the interim kill (Week 66) in both sexes and in females at terminal kill
(Week 95). Higher kidney weights in the females at terminal kill but not associated with any
specific pathological changes;
5. Neoplastic pathology – no evidence of tumorigenic potential;
6. Non-neoplastic pathology:
 Interim kill – higher incidence of centrilobular hepatocytes enlargement, both sexes;
 Minimally increased incidence of hyperkeratosis of the limiting ridge of the stomach, both
sexes.
1500 ppm treatment group (males: 205 mg/kg/bw/day; females: 200 mg/kg/bw/day)
1. No treatment related clinical signs at this dose;
2. Survival considered unaffected by treatment;
3. Lower body weight gain was apparent during the first 52 weeks of treatment, food consumption
was unaffected;
4. Higher liver and kidney weights in females at the terminal kill. Specific pathological changes only
noted in the liver;
5. Neoplastic pathology – no evidence of tumorigenic potential;
6. Non-neoplastic pathology:
 No treatment related changes at interim kill;
 Higher incidence of enlarged hepatocytes at terminal kill and for dying animals.
300 ppm treatment group (males: 40.8 mg/kg bw/day; females: 40.1 mg/kg bw/day)
1. No treatment related clinical signs;
2. Survival, food consumption, body weight gain, organ weights unaffected;
3. Neoplastic pathology - no evidence of tumorigenic potential observed;
4. Non-neoplastic pathology – higher incidence of enlarged hepatocytes in the liver for those main
group animals dying or killed;
30 ppm treatment group (males: 3.8 mg/kg bw/day; females: 4.1 mg/kg bw/day)
No treatment related findings observed.
a.
Non-neoplastic effects
NOAEL: 300 ppm (males: 40.8 mg/kg bw/day; females: 40.1 mg/kg bw/day)
LOAEL: 1500 ppm (males: 205 mg/kg/bw/day; females: 200 mg/kg/bw/day) based on effects on
liver, kidney and body weight gain.
b.
Neoplastic effects
No evidence of tumorigenic potential.
SURVIVAL:
 Males: Controls – 33%; 30 ppm – 48%; 300 ppm – 48%; 1500 ppm – 37%; 3000 ppm – 46%;
 Females: Controls – 63%; 30 ppm – 79%; 300 ppm – 79%; 1500 ppm – 65%; 3000 ppm –
73%.
REFERENCE SOURCE:
Hooks, W., Chambers, P.R., Majeed, S.K., Gibson, W.A., Gopinath, C. and Dawe, I.S. (1990).
ERMA New Zealand Evaluation and Review Report: Application HSR08124
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SAN 582 H: Potential tumorigenic and toxic effects in prolonged dietary administration to mice. Reg.
Doc. #BASF 90/11139. Sandoz Ltd., Agrochemical Toxicology Dept., CH-4002 Basle, Switzerland.
RELIABILITY (KLIMISCH SCORE): 1
ERMA New Zealand Comments
ERMA concurs with the conclusions drawn by the authors regarding the tumorigenic potential of the
test compound.
Conclusion on classification:
The test substance does not trigger 6.7 classification as a carcinogen.
REPRODUCTIVE/DEVELOPMENTAL TOXICITY
Developmental studies
STUDY TYPE: Developmental toxicity (embryo/foetal toxicity and teratogenic potential).
SPECIES/STRAIN: New Zealand White Rabbit
DOSE: 0, 37.5, 75 and 150 mg/kg/day
ROUTE: Oral (stomach tube)
GUIDELINE:
U.S. EPA Pesticide Assessment Guidelines Subdivision F, 83-3.
TEST SUBSTANCE: SAN 582 H, 92.0% purity.
RESULTS:
Pilot Study:
Doses of 0, 37.5, 75, 150, 300 and 425 mg/kg/day administered orally (stomach tube) to four presumed
pregnant rabbits per group on days 6 to 18 of gestation. Deaths occurred in the 300 and 425 mg/kg/day
dosage groups. Reduced body weight gain and food consumption occurred in animals given 150
mg/kg/day.
Developmental Study
Based on the results of the pilot study, dose levels of 0, 62.5, 75, 125 and 250 mg/kg/day administered
to 20 rabbits per group on days 6 to 18 of presumed gestation for the Developmental Study. There
were 13 deaths and seven abortions in the high dosage group and so the study was terminated prior to
scheduled Caesarean-sectioning on day 29 of gestation. Only one pregnant high dose doe survived to
day 25 of gestation. Maternal body weight gain and feed consumption were reduced at 125 and 250
mg/kg/day.
Second Developmental Study – Maternal Effects
1. Dosages of 0, 37.5, 75 and 150 mg/kg/day used at a volume of 10 mL/kg on days 6 through 18 of
presumed gestation;
2. No deaths occurred during the study;
3. Two does from the 150 mg/kg/day group prematurely delivered/aborted and this was considered to
be treatment-related. Authors considered this to be evidence of maternal and developmental
toxicity;
4. Animals from the 150 mg/kg/day and 75 mg/kg/day groups infrequently had dried faeces or no
faeces at all as well as decreased food consumption. There was increased incidence of localised
alopecia in the 150 mg/kg/day animals compared with controls. However, there was no
statistically significant difference from the control animals;
5. Inhibited maternal body weight gain during the dosage period in the 150 mg/kg/day and 75
mg/kg/day groups. This was statistically significant for the high dose group during days 12 to 15
of gestation. This group experienced remarkable weight loss during days 15 to 19;
6. Reduced absolute food consumption for the high and middle dose group animals, statistically
significant for the high dose animals;
7. There were 18, 16, 16 and 17 pregnant does in the control, low, middle and high dose groups
respectively. Since two high dose does aborted/prematurely delivered, there were 18, 16, 16 and
15 litters available for evaluation in the control, low, middle and high dose animals at Caesarean;
8. There were 129, 109, 120 and 110 live foetuses in the control, low, middle and high doses
respectively;
ERMA New Zealand Evaluation and Review Report: Application HSR08124
Page 60 of 149
9. There was one dead foetus in a control litter and two low dose animals with 100% resorption;
10. There were no test substance-related effects on implantation, live litter size, foetal sex ratio or
foetal body weight.
Second Developmental Study – Foetal Effects
1. No external, soft tissue or skeletal foetal alterations considered to be related to treatment with the
test compound;
2. Alterations noted in high dose specimens did not occur in more than one foetus;
3. Litter incidences for all alterations (malformations and variations) were not significantly increased
compared with control values;
4. No ossification delays were noted.
MATERNAL TOXICITY
NOAEL: 37.5 mg/kg bw
LOAEL: 75 mg/kg bw based on effects on food consumption and body weight gain as well as
faecal abnormalities.
DEVELOPMENTAL TOXICITY
NOAEL: 75 mg/kg bw
LOAEL: 150 mg/kg bw based on premature delivery / abortions.
REFERENCE SOURCE:
Hoberman, A.M. (1988). Developmental Toxicity (Embryo/Fetal Toxicity And Teratogenic
Potential) Study of SAN 582 H Administered Orally (Stomach Tube) to New Zealand White Rabbits.
Reg. Doc. #BASF 88/11376. Argus Research Laboratories, Inc., 935 Horsham Road, Horsham, PA
19044.
RELIABILITY (KLIMISCH SCORE): 1
Comments
The abortions seen in 2/20 high dose animals are likely due to the remarkable weight loss seen in the
dams during days 15 to 19 and significantly reduced food consumption. One of these animals
consumed less than 20 g of feed per day on days 8 to 11 and less than 2 g per day from day 12 through
day 28 when it aborted. The other animal consumed less than 2 g per day from day 13 through 26.
These two animals showed the lowest food consumption compared to the rest of the group.
Furthermore, there were no other significant observations noted in the surviving high dose foetuses.
Therefore, the Agency considers that the findings of this study do not justify classification of the test
compound as a developmental toxicant.
Reproductive studies
STUDY TYPE: Two-Generation Reproductive Toxicity Study
SPECIES/STRAIN: Wistar/HAN Rat.
DOSES: 0, 100, 500, and 2000 ppm corresponding to 10, 50 and 150 mg/kg bw / day.
ROUTE: Via the diet.
TEST SUBSTANCE: SAN 582 H, 92.6% purity.
GUIDELINES:
 Reproductive and Fertility Effects, Pesticide Assessment Guidelines, Subdivision F, Hazard
Evaluation: Human and Domestic Animals, No. 83-4, U.S. Environmental Protection Agency;
 Two –Generation Reproduction Toxicity Study, OECD Guidelines for the Testing of
Chemicals, Section 4, Health Effects, No. 416.
RESULTS:
The following effect were considered treatment-related:
1. There were no deaths in any of the parent animals;
2. Reduced food consumption at 2000 ppm in males of the P generation during pre-pairing and postERMA New Zealand Evaluation and Review Report: Application HSR08124
Page 61 of 149
3.
4.
5.
6.
7.
8.
pairing, and in the males of the F1 generation during the pre-pairing period;
Reduced mean body weights in the males of the P and F1 generations at 2000 ppm;
Reduced food consumption at 2000 ppm in P generation females during pre-pairing and lactation;
Reduced mean body weight and body weight gain in both the F1 and F2 pups during the lactation
period at 2000 ppm;
Statistically significant increase in the absolute and relative liver weight of the P and F1 parent
animals both sexes) at 2000 ppm;
Marginally increased relative liver weight, both sexes of both generations at 500 ppm, statistically
significant for females of the P generation;
No treatment related effects seen at 100 ppm in any of the animals;
The following were considered to be unaffected by treatment with the test substance:
1. Viability of the parent animals at all doses tested;
2. Food consumption of the parent animals in both the P and F1 generations at 100 and 500 ppm and
of the females of the F1 generation at 2000ppm;
3. Body weight gain of the P and F1 parent animals at 100 and 500 ppm and of the females at 2000
ppm;
4. Percentage of animals mating, fertility index, conception rate, gestation index, mean pre-coital
time, duration of gestation, mean number of implantation sites per dam, post-implantation loss,
mean number of pups per dam, postnatal and breeding loss in the dose groups up to and including
2000 ppm;
5. Appearance of the pups at external examination and sex ratios of the F1 and F2 pups at all doses
tested;
6. Mean body weight and body weight gain of the F1 and F2 pups at 100 and 500 ppm;
7. Liver weight of the parent animals at 100ppm;
REPRODUCTIVE TOXICITY STUDIES
PARENTAL TOXICITY
NOAEL: 500 ppm (50 mg/kg bw)
LOAEL: 2000ppm (150 mg/kg bw) based on effects on body and liver weight.
REPRODUCTIVE EFFECTS
NOAEL: 2000 ppm (200 mg/kg bw / day).
LOAEL: None since the highest dose tested was the NOAEL.
DEVELOPMENTAL TOXICITY
NOAEL: 2000 ppm
LOAEL: None since the highest dose tested was the NOAEL.
REFERENCE SOURCE:
Suter, P, Biedermann, K., Wilson, J.Th., Terrier, Ch. (1989). SAN 582 H: Two-Generation
Reproduction Study in the Rat. Part I. Reg. Doc. #BASF 90/11140. Research and Consulting
Company AG., P.O. Box CH 4452 Itingen, Switzerland.
RELIABILITY (KLIMISCH SCORE): 1
Comments
The findings from this study do not support classification of the test compound as a reproductive /
developmental toxicant.
Conclusion on classification:
The test substance does not trigger 6.8A/B/C classification.
Table A2.8: Toxicity of BAS 656 08 H (current formulation of Frontier®-P) and
BAS 656 07 H (previous formulation).
BAS 656 08 H (current formulation)
BAS 656 07 H (previous formulation)
Acute oral toxicity
Acute oral toxicity
ERMA New Zealand Evaluation and Review Report: Application HSR08124
Page 62 of 149
SPECIES: Rat
SPECIES: Rat
STRAIN: Wistar Albino
STRAIN: Wistar Albino
NUMBER/GROUP: 3 females
NUMBER/GROUP/SEX: 5
TEST SUBSTANCE: BAS 656 08 H
TEST SUBSTANCE: BAS 656 07 H (previous
formulation of Frontier®-P).
CONTENT OF ACTIVE INGREDIENT: 70.5%
(w/v)
DOSE LEVELS: Two groups of 500 mg/kg bw
and one of 2,000 mg/kg bw
CONTENT OF ACTIVE INGREDIENT: 64.0 %
(w/w)
DOSE LEVELS: 1000 mg/kg bw, 1414 mg/kg
bw, 2000 mg/kg bw
ADMINISTRATION ROUTE: oral gavage.
ADMINISTRATION ROUTE: oral gavage.
ENDPOINT: LD50
ENDPOINT: LD50
VALUE: >500 mg/kg/bw but < 2,000 mg/kg bw
(females).
RESULTS:
All animals in the 2,000 mg/kg bw group died
within day 1 of administration, no deaths in the
other groups. Main clinical observations in the
2,000 mg/kg bw group included dyspnoea,
staggering, tremor, twitching, piloerection and
salivation. Symptoms in the 500 mg/kg groups
included impaired general state, dyspnoea,
staggering, piloerection, salivation and
lacrimation. Mean body weights in the 500
mg/kg bw groups increased throughout the
duration of the study. No significant necropsy
findings were observed in any of the groups.
GLP: Yes.
TEST GUIDELINES:
 OECD Guideline for the Testing of
Chemicals No. 423, December 17, 2001
(“Acute Oral Toxicity – Acute Toxic Class
Method”);
 EC Directive 2004/73, No. L216, B.1 tris.
June 16, 2004 (“Acute Oral Toxicity – Acute
Toxic Class Method”);
 US EPA Health Effects Test Guidelines
OPPTS 870.1100, December 2002 (“Acute
Oral Toxicity”).
REFERENCE SOURCE:
Gamer, A.O. and Landsiedel, R. (2006). BAS
656 08 H Acute Oral Toxicity Study in Rats.
BASF DocID 2006/1026825. Experimental
Toxicology and Ecology, BASF
Aktiengesellschaft, 67056 Ludwigshafen,
Germany.
RELIABILITY (KLIMISCH SCORE): 1
VALUE:
 1473 mg/kg/bw (males);
 1686 mg/kg bw (females);
 1581 mg/kg bw (combined).
RESULTS:
Preliminary assay:
Dose levels of 1200, 2000 and 5000 mg/kg were
administered. Main clinical signs observed were
hypoactivity, piloerection and dyspnoea.
Mortality occurred in the female given 1200
mg/kg (day three) and in the male and female
given 5000 mg/kg (day 2 and 1 respectively).
Main test:
1. At 2000 mg/kg dose level, the main findings
were :
 Hypoactivity, piloerection and dyspnoea
in all animals on day 1;
 Lateral recumbency in one animal on
day 1;
 Mortality occurred in 2/5 males and 4/5
females on day 1. Two other males were
found dead on day 2;
 Hypoactivity continued in surviving
animals through day 2, complete
recovery by day 3.
2. At 1414 mg/kg the main findings were:
 Hypoactivity and piloerection in all
animals on day 1;
 Death of 1/5 males on day 1 and one
male and one female on day 2;
 Hypoactivity and piloerection persisted
in surviving animals up to day 4,
complete recovery by day 5.
3. At 1000 mg/kg, no clinical signs were
observed. One male was found dead on day
2.
Summary of mortality (given as number of
animals that died/total number of animals in the
ERMA New Zealand Evaluation and Review Report: Application HSR08124
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group):
 1000 mg/kg: Males – 1/5; Females – 0/5;
 1414 mg/kg: Males – 2/5; Females – 1/5;
 2000 mg/kg: Males – 4/5; Females – 4/5
GLP: Yes.
TEST GUIDELINES:
 OECD Guideline for the Testing of
Chemicals No. 401, 24 February 1987;
 EC Directive No. 92/69/EEC, B.1, 31 July
1992;;
 US EPA FIFRA Guidelines: Subdivision F
Series 81, November 1984.
REFERENCE SOURCE:
Manciaux, X. (1998). BAS 656 07 H: Acute
Oral Toxicity in Rats. Reg. Doc. #BASF
98/10858. Centre International de Toxicologie,
Miserey – 27005 Evreux, France.
RELIABILITY (KLIMISCH SCORE): 1
Conclusion on Classification
The test substance triggers classification as a
6.1D oral toxicant.
Acute dermal toxicity (current formulation)
Conclusion on Classification
The test substance triggers classification as a
6.1D oral toxicant.
Acute inhalation toxicity (previous formulation)
SPECIES: Rat
SPECIES: Rat
STRAIN: Wistar Albino
STRAIN: Wistar Albino
TEST SUBSTANCE: BAS 656 08 H
ANIMALS/SEX/GROUP: 5
CONTENT OF ACTIVE INGREDIENT: 70.5%
(w/v)
TEST SUBSTANCE: BAS 656 07 H
ADMINISTRATION ROUTE: Percutaneous
ENDPOINT: LD50
CONTENT OF ACTIVE INGREDIENT: 64%
(w/v)
ADMINISTRATION ROUTE: Inhalation (liquid
aerosol of substance, head and nose exposure).
VALUE: >5000 mg/kg bw (both sexes).
ENDPOINT: LC50
RESULTS:
No mortalities or clinical signs of toxicity were
observed in this study. Very slight erythema
(days 1-2) and scaling (days 5-6) at the
application site were noted in one male animal.
Males gained weight during the 14-day study
period, but females only gained weight during the
second week of the observation period. No gross
pathological changes were observed at necropsy.
TEST METHOD:
1. OECD Guideline 402 (24 Feb 1987);
2. EPA OPPTS 870.1200 (Aug 1998)
GLP: Yes.
Gamer, A.O. and Landsiedel, R. (2006). BAS
VALUE: > 5.6 mg/l (4 h) (both sexes).
RESULTS:
No mortality occurred during the exposure or the
14-day post-exposure observation period. The
following symptoms were observed during or
after exposure: attempts to escape, irregular and
accelerated respiration, respiratory sounds,
squatting posture, smeared fur and piloerection.
No clinical signs were observed on day 7 and
thereafter. Body weight gain was depressed
during the first week, but recovered in the second
week.
Necropsy revealed gray-red discoloration of the
lungs in all animals. Histopathological
examination was performed on the lungs of two
ERMA New Zealand Evaluation and Review Report: Application HSR08124
Page 64 of 149
656 08 H Acute dermal toxicity study in rats.
BASF Aktiengesellschaft unpublished Report No.
2006/1026826. Experimental Toxicology and
Ecology, BASF Aktiengesellschaft, 67056
Ludwigshafen, Germany
RELIABILITY (KLIMISCH SCORE): 1
animals, which revealed acute congestion, slight
alveolar edema, slight diffuse alveolar
histiocytosis and slight multifocal perivascular
infiltration of eosinophils (one animal only).
TEST GUIDELINES:
1. OECD 403,
2. EEC Annex V, B2
GLP:
yes
Gamer A.O., et al (1998). BAS 656 07 H Acute inhalation toxicity study in Wistar rats.
BASF Aktiengesellschaft, Ludwigshafen,
Germany. Unpublished BASF
RegDoc.#98/10838.
RELIABILITY (KLIMISCH SCORE): 1
Conclusion on Classification
The test substance does not trigger classification
as an acute dermal toxicant.
Dermal Irritation/Corrosion (current
formulation)
Conclusion on Classification
The test substance does not trigger classification
as an acute inhalation toxicant.
Eye Irritation/Corrosion (current formulation)
SPECIES: Rabbit
SPECIES: Rabbit
STRAIN: New Zealand White
STRAIN: New Zealand White
TEST SUBSTANCE: BAS 656 08 H
TEST SUBSTANCE: BAS 656 08 H
CONTENT OF ACTIVE INGREDIENT: 70.5%
(w/v)
CONTENT OF ACTIVE INGREDIENT: 70.5%
(w/v)
ADMINISTRATION ROUTE: 2.5x2.5 patch
under semi-occlusive conditions.
ADMINISTRATION DOSE: 0.1 mL into
conjunctival sac.
RESULTS:
Slight or moderate erythema, partly extending
beyond the area of exposure, slight oedema and
scaling were observed in the animals during the
course of the study. The cutaneous reactions
were reversible in one animal within 7 days after
removal of the patch. In two animals moderate
erythema and scaling were still observed at study
termination on day 14. The average score (24 to
72 hours) for irritation was calculated to be 1.8
for erythema and 0.1 for oedema.
RESULTS:
The average score (24 to 72 hours) for irritation
was calculated to be 0.6 for corneal opacity, 0.3
for iris, 2.9 for conjunctival redness and 1.7 for
chemosis. The findings were reversible in 2 of 3
animals within 14 days, and within 21 days for
the third animal. One animal exhibited loss of
corneal tissue, while the third animal exhibited
discharge of blood and suppuration
TEST METHOD:
1. OECD Guideline 404
2. EPA OPPTS 870.2500 (Aug 1998);
GLP: Yes.
Remmele, M.. and Landsiedel, R. (2006). BAS
656 08 H Acute dermal irritation / corrosion in
rabbits. BASF Aktiengesellschaft unpublished
Report No. 2006/1026827. Experimental
Toxicology and Ecology, BASF
TEST METHOD:
1. OECD Guideline 405 (24 Feb 1987);
2. EPA OPPTS 870.2400 (Aug 1998).
GLP: Yes
Wiemann, C. & Hellwig, J. (2000). BAS 656 08
H Acute eye irritation in rabbits. BASF
Aktiengesellschaft unpublished Report No.
2000/1012350. Experimental Toxicology and
Ecology, BASF Aktiengesellschaft, 67056
Ludwigshafen, Germany.
ERMA New Zealand Evaluation and Review Report: Application HSR08124
Page 65 of 149
Aktiengesellschaft, 67056 Ludwigshafen,
Germany.
RELIABILITY (KLIMISCH SCORE): 1
RELIABILITY (KLIMISCH SCORE): 1
Conclusion on Classification
The test substance triggers 6.3B (skin irritation)
classification
Contact Sensitisation (current formulation)
Conclusion on Classification
The test substance triggers 6.4A (eye irritant)
classification.
Respiratory sensitization
No tests undertaken.
TEST SUBSTANCE: BAS 656 08 H
CONTENT OF ACTIVE INGREDIENT: 63.7%
(w/v)
SPECIES: Guinea pig
STRAIN: HsdPoc: DH
NUMBER/SEX/GROUP:
METHOD: Buehler method (9-Induction)
APPLICATION: Closed patch technique using
undiluted test substance.
RESULTS:
The first until third induction did not cause any
skin irritation in the test group animals. Discrete
or patchy to intense erythema and swelling,
scaling and eczematoid skin change were noticed
in the animals of the test group after the
remaining induction treatments. Due to
cumulative skin irritation, the test patch was
moved to the middle of the flank in some animals
for the eighth and ninth induction.
The challenge caused discrete or patchy or
moderate and confluent erythema in test group
animals. Positive challenges were noted in 11/20
test group animals at 24 hours, and 4/20 at 48
hours, while negative controls gave no responses
throughout.
GLP: Yes
TEST GUIDELINES:
1. OECD Guideline 406 (17 Jul 1992);
2. EPA OPPTS 870.2600 (Mar 2003).
REFERENCE SOURCE:
Gamer, A.O. and Landsiedel, R. (2006). BAS
656 08 H Modified BUEHLER Test (9
inductions) in guinea pigs. BASF
Aktiengesellschaft unpublished Report No.
2006/1026828. Experimental Toxicology and
Ecology, BASF Aktiengesellschaft, 67056
Ludwigshafen, Germany.
RELIABILITY (KLIMISCH SCORE): 1
ERMA New Zealand Evaluation and Review Report: Application HSR08124
Page 66 of 149
Conclusion on Classification:
The substance triggers 6.5B classification
(contact sensitizer).
Table A2.9 Summary of toxicity studies considered in determining the
Acceptable Operator Exposure Level (AOEL) and Acceptable Daily Exposure
(ADE) for dimethenamid-P
Study
Developmental toxicity study
in Sprague-Dawley rats with
S-Dimethenamid
Subchronic (3-month) toxicity
study in Sprague-Dawley rats
with S-dimethenamid
NOAEL
25 mg/kg bw / day
(maternal)
LOAEL
150 mg/kg bw /
day (maternal)
37 mg/kg bw/day
males; 40 mg/kg
bw / day females
110 mg/kg bw/day
males; 125 mg/kg
bw / day females
13 week dose range finding
study in CD-1 mice with r/sdimethenamid
104.6 mg/kg bw /
day males, 137.2
mg/kg bw / day
females
5 mg/kg bw/day,
average for both
sexes.
301.3 mg/kg bw /
day males, 383.4
mg/kg bw / day
females
37 mg/kg bw / day
average for both
sexes.
52-week oral toxicity study
in beagle dogs with r/sdimethenamid
1.95 mg/kg
bw/day
10.1 mg/kg
bw/day
Chronic Toxicity /
Carcinogenicity (104 weeks)
in Sprague-Dawley rats with
r/s-dimethenamid
Males: 5.1mg/kg
bw/day; Females:
6.8 mg/kg bw/day
Males: 36 mg/kg
bw/day; Females:
49 mg/kg bw/day
Carcinogenicity (104 weeks)
in CD-1 mice with r/sdimethenamid
Males: 40.8 mg/kg
bw/day; Females:
40.1 mg/kg bw/day
Developmental toxicity study
in rabbits with r/sdimethenamid
37.5 mg/kg bw
(maternal toxicity)
Males: 205
mg/kg/bw/day;
Females: 200
mg/kg/bw/day
75 mg/kg bw
(maternal toxicity)
13 week oral toxicity study in
beagle dogs with r/sdimethenamid
Critical effect
Reduced food
consumption and body
weight gain
Increase in GGT,
decreases in AST, ALT,
ALP, lower terminal
weight and
hepatocellular
hypertrophy and
eosinophilic inclusions
Increase in relative liver
and kidney weights in
both sexes.
Decreased body weight
gain, cytoplasmic
vacuolation and hepatic
sinusoidal dilatation.
Reduction in mean
body weight gain in
males and increased
liver weights in females.
Bile duct hyperplasia,
ovarian tubular
hyperplasia, increased
GGT activity; decreased
activity of GOT, GPT.
Increased liver and
kidney weights in
females, reduced body
weight gain, both sexes.
Based on effects on food
consumption and body
weight gain as well as
faecal abnormalities.
Based on increased liver
weight.
Reproductive toxicity study in 200 mg/kg bw /
50 mg/kg bw
Wistar/HAN Rats with r/sday (parental
(parental toxicity)
toxicity)
dimethenamid
Acceptable Operator Exposure Level (AOEL)
 NOAEL = 1.95 mg/kg bw/day (from the 52 week oral toxicity study in dogs above);
 Uncertainty factor = 100 (accounts for intra- and interspecies variation);
 Oral absorption factor of 90% (see ADME summary in Table A2.7).
AOEL = 1.95 mg/kg bw/day x 90% = 0.018 mg/kg bw/day.
100
Acceptable Daily Exposure (ADE)
 NOAEL = 1.95 mg/kg bw/day (from the 52 week oral toxicity study in dogs above);
 Uncertainty factor = 100 (accounts for intra- and interspecies variation);
 Oral absorption factor of 90% (see ADME summary in Table A2.7).
ERMA New Zealand Evaluation and Review Report: Application HSR08124
Page 67 of 149
ADE = 1.95 mg/kg bw/day x 90% = 0.018 mg/kg bw/day.
100
Class 9 Ecotoxicity and Environmental Fate
Sub-class 9.1 Aquatic ecotoxicity, fate and degradation
Classification under this sub-class requires consideration of the acute and chronic
aquatic toxicity of the substance and the bioaccumulative and persistence properties
of the components of the substance.
Aquatic fate and degradation of dimethenamid-P and its metabolites
Information on aquatic fate and degradation is summarised in Tables A2.10 and
A2.10B.
Table A2.10: Summary of aquatic fate and degradation of dimethenamid-P
(SAN 1289H) and the metabolites N-(2,4-dimethyl-thiopen-3-yl)-N-(2-methoxy-1methyl-ethyl)-acetamide (M3), dimethenamid oxaloamide (M23) and
dimethenamid sulfonate (M27).
Test results
Test method
Study type
[reference number]
SAN 1289 H
Metabolites
Abiotic degradation
Hydrolysis
pH 5: Stable
(25°C)
pH 7: Stable
pH 9: Stable
Photolysis
Guirguis, 1997
Report No.
97/5184
USEPA
Subdivision N
Section 161-1
GLP
Klimisch score: 1
SAN 1289 H
Guirguis, 1997
Report No.
97/5195
USEPA
Subdivision N
Section 161-2
GLP
Klimisch score: 1
SAN 1289 H
DT50: 13.7 ± 1.9 days
(pH 7, 25°C at 100 ppm)
DT50: 25.7 days
(noon sunlight at 40°N
latitude)
Biodegradation (laboratory)
See Table A2.10B (SAN 582 H)
Bioaccumulation
See Table A2.10B (SAN 582 H)
Octanol/water
partition
coefficient
Octanol/water
partition
coefficient
No data for SAN 1289 H
No data for SAN 1289 H
Metabolite M3
Log Kow: 2.58
M3 has no dissociation
constant, therefore the log
Kow is not dependent on pH
Metabolite M23
Log Kow: 2.26 (pH 2.1)
ERMA New Zealand Evaluation and Review Report: Application HSR08124
Daum, 1999
OECD 117
Report No. 99/10261
GLP
Klimisch score: 1
Daum, 1999
OECD 117
Report No. 99/10264
Page 68 of 149
Study type
Test results
SAN 1289 H
Test method
Metabolites
Log Kow: -2.16 (pH 7)
Octanol/water
partition
coefficient
Metabolite M27
Log Kow: -2.63
(deionised water, pH 5.8)
Log Kow: -1.57 (pH 7)
[reference number]
GLP
Klimisch score: 1
Daum, 1999
OECD 117
Report No. 99/10307
GLP
Klimisch score: 1
Table A2.10B: Summary of aquatic fate and degradation of dimethenamid (SAN
582 H).
Test results
Test method
Study type
[reference number]
SAN 582 H
Metabolites
Abiotic degradation
Hydrolysis
pH 5: Stable
(25°C)
pH 7: Stable
pH 9: Stable
Photolysis
DT50: 16.4 ± 1.1 days
(pH 7, 25°C at 100 ppm)
DT50: 23.9 days
(noon sunlight at 40°N
latitude)
Photolysis
Top layer of
Aqueous systems
Photochemical
oxidative
degradation
(Troposphere)
Conditions
Location:
Central Europe
Thickness of aqueous layer:
1 cm
Substance concentration:
1 μg/mL
DT50: 0.3 d (April)
DT50: 0.2 d (May)
DT50: 2.45 h (12 h day)
Biodegradation (laboratory)
Water/sediment
Application rate:
system
0.4834 mg ai/L
(Field rate: 1.44 kg ai/ha)
River system
ERMA New Zealand Evaluation and Review Report: Application HSR08124
Fostiak & Hsieh, 1988
Report No.
88/11332
USEPA
Subdivision N
Section 161-1
GLP
Klimisch score: 1
SAN 582H
Sabat & Yu, 1992
Report No.
92/12388
USEPA
Internal protocol
GLP
Klimisch score: 1
SAN 582 H
Scharf, 1999
Report No.
99/10073
Calculation based on
Frank& Klopffer, 1985
SAN 582 H
Scharf, 1999
Report No.
99/10075
QSAR estimate
AOPWIN Program
SAN 582 H
Wyss-Benz&Völkel
1994
Report No. 94/10641
BBA Part IV: 5-1
GLP
Page 69 of 149
Study type
Test results
SAN 582 H
Test method
Metabolites
pH 7.46, TOC 0.9
(before test)
loamy sand
DT50 (water): 20.3 days
DT50 (total): 23.4 days
[reference number]
Klimisch score:1
SAN 582 H
DT90 (water): 67.4 days
DT90 (total): 77.8 days
Pond system
pH 7.6, TOC 2.6
(before test)
sandy loam
DT50 (water): 27.7 days
DT50 (total): 33.4 days
DT90 (water): 92.1 days
DT90 (total): 110.9 days
Activated Sludge
Respiration
inhibition Test
< 25% deviation from control
at 100 mg/L
Not toxic to wastewater
bacteria at a concentration of
< 100 mg/L
Bioaccumulation
BCF = 58
Bluegill
Lepomis
Steady state = 21 days
macrochirus
(whole body and inedible
tissues)
Steady state = > 28 days
(edible tissues)
Desmares-Koopmans,
1996
OECD209
Report No.
95/11327
GLP
Klimisch score: 1
SAN 582 H
Sabourin, 1988
USEPA Guidelines
1982
Report No. 88/11365
GLP
Klimisch score: 1
SAN 582 H
Elimination DT50: 10.7 days
Conclusion
Dimethenamid-P is not considered bioaccumulative based on the results of the study
of dimethenamid in fish (BCF=58) and is considered not readily degradable (DT50 >
16 days). As the value used to determine ready degradability is in this instance for the
loss of parent compound only, the value for ultimate degradation of the substance will
be a much longer.
ERMA New Zealand Evaluation and Review Report: Application HSR08124
Page 70 of 149
Aquatic toxicity
The toxicity of dimethenamid-P, dimethenamid and Frontier-P® to aquatic organisms
is summarized in Tables A2.11, A2.11A, A2.11B and A2.11C.
Table A2.11: Summary of aquatic toxicity data for dimethenamid-P (SAN 1289
H) and the metabolites M3, M23 and M27.
Test type Test results a, b
Test method c
Test species
&
[reference number]
SAN 1289 H
Metabolites
duration
Fish
Rainbow trout,
Oncorhynchus
mykiss
Bluegill
Lepomis
macrochirus
96 h
Flowthrough
96 h
Flowthrough
LC50:
6.3 mg/L
95% CI:
3.7 – 11 mg/L
Graves & Swigert,
1996
FIFRA 72-1
Report No. 96/5417
GLP
Klimisch score: 1
SAN 1289 H
[measured]
> 80% < 120% of
[nominal]
LC50:
10 mg/L
95% CI:
7.5 - 12 mg/L
Graves & Swigert,
1996
FIFRA 72-1
Report No. 96/5414
GLP
Klimisch score: 1
SAN 1289 H
[measured]
> 90% < 110% of
[nominal]
Rainbow trout,
Oncorhynchus
mykiss
96 h Static
Rainbow trout,
Oncorhynchus
mykiss
96 h Static
Rainbow trout,
Oncorhynchus
mykiss
96 h Static
Invertebrates
Daphnia magna
48 h
Flowthrough
Metabolite M3
LC50:
60.8 mg/L
95% CI:
49.2 – 75.1 mg/L
[measured]
> 90% < 110% of
[nominal]
Metabolite M23
Limit Test
LC50: > 87 mg/L
[measured]
Metabolite M27
Limit Test
LC50: > 100 mg/L
[measured]
EC50:
12 mg/L
95% CI:
10 – 13 mg/L
48 h Static
Van der Kolk, 1995
FIFRA 72-1
OECD 203
Report No. 95/11318
GLP
Klimisch score: 1
Van der Kolk, 1995
FIFRA 72-1
OECD 203
Report No. 95/11330
GLP
Klimisch score: 1
Graves and Swigert,
1996
FIFRA E 72-2
Report No. 96/5415
GLP
Klimisch score: 1
SAN 1289 H
[measured]
> 80% < 120% of
[nominal]
Daphnia magna
Grützner, 1997
FIFRA 72-1
OECD 203
Report No. 97/10271
GLP
Klimisch score: 1
Metabolite M3
EC50:
ERMA New Zealand Evaluation and Review Report: Application HSR08124
Grützner, 1997
OECD 202
Page 71 of 149
Test species
Daphnia magna
Daphnia magna
Test type
&
duration
Test results a, b
SAN 1289 H
Metabolites
[reference number]
> 101.6 mg/L
FIFRA E 72-2
Report No. 97/10272
GLP
Klimisch score:1
[measured]
> 90% < 105% of
[nominal]
Metabolite M23
Limit test
EC50:
> 95 mg/L
[measured]
48 h Static
*pH of the test lower
than the control
range:
Test: 6.49- 7.41
Control: 7.66 – 7.71
Metabolite M27
Limit test
EC50:
> 100 mg/L
[measured]
48 h Static
Algae/Aquatic plants
120 h Static
Green alga
Selenastrum
capricornutum
Test method c
EC50 (density):
0.017 mg/L
95% CI:
0.0041 – 0.030 mg/L
120 h Static
* control pH range >
1.5.
EC50 (density):
0.38 mg/L
95% CI:
0.18 – 0.83 mg/L
Hoberg, 1997
FIFRA guidelines
122-2, 123-2
Report No. 97/5173
GLP
Klimisch score: 1
SAN 1289 H
[measured] > 75 and
< 110% [nominal]
Freshwater
diatom
Navicula
pelliculosa
120 h Static
EC50 (density):
0.34 mg/L
95% CI:
0.17 – 0.71 mg/L
Hoberg, 1997
FIFRA guidelines
122-2, 123-2
Report No. 97/5171
GLP
Klimisch score: 1
SAN 1289 H
[measured] > 80 and
< 89% [nominal]
Green alga
Scenedesmus
subspicatus
72 h Static
Van der Kolk, 1995
FIFRA 72-1
OECD 203
Report No. 95/11330
GLP
Klimisch score: 1
Hoberg, 1997
FIFRA guidelines
122-2, 123-2
Report No. 97/5170
GLP
Klimisch score: 1*
SAN 1289 H
[measured] > 72 and
< 88% [nominal]
Blue-green alga
Anabaena flosaquae
Van der Kolk, 1995
FIFRA 72-1
OECD 203
Report No. 95/11319
GLP
Klimisch score: 1*
Metabolite M3
ErC50:
97.4 mg/L*
*Calculated by linear
regression analysis.
50% inhibition at
ERMA New Zealand Evaluation and Review Report: Application HSR08124
Grützner, 1997
OECD 201
FIFRA J 122
Report No. 97/10274
GLP
Klimisch score: 2*
Page 72 of 149
Test species
Test type
&
duration
Test results a, b
SAN 1289 H
Test method c
Metabolites
[reference number]
concentration > than
concentrations tested.
[measured] > 90 and
< 105% [nominal]
Green alga
Scenedesmus
subspicatus
Green alga
Scenedesmus
subspicatus
72 h Static
Metabolite M23
Limit test
ErC50:
> 94 mg/L
[measured]
*pH of the test lower
than the control
range:
Test: 6.67- 7.32
Control: 7.61 – 7.76
Metabolite M27
ErC50:
> 208 mg/L
72 h Static
[measured] > 95 and
< 110% [nominal]
Duckweed
Lemna gibba
14 d Static
EC50 (Frond density):
0.016 mg/L
95% CI:
0.0055 – 0.048 mg/L
(dry weight)
EC50 (frond biomass):
0.0089 mg/L
95% CI:
0.0025 – 0.032 mg/L
(dry weight)
van der Kolk, 1995
OECD 201
FIFRA J 122
Report No. 95/11320
GLP
Klimisch score:1*
van der Kolk, 1995
OECD 201
FIFRA J 122
Report No. 95/11332
GLP
Klimisch score:1
Hoberg, 1997
FIFRA guidelines
122-2, 123-2
Report No. 97/10742
GLP
Klimisch score: 2*
SAN 1289 H
Test initiation:
[measured] > 80 and
< 120% [nominal]
*Test completion:
[measured] > 10 and
< 40% [nominal]
EC50: based on initial
[measured] – note
this calculation
should have been
based on the
geometric mean of
the measured
concentrations
leading to a lower
EC50 than given for
the calculation
performed.
ERMA New Zealand Evaluation and Review Report: Application HSR08124
Page 73 of 149
Test species
Test type
&
duration
Test results a, b
SAN 1289 H
Test method c
Metabolites
[reference number]
a
Results are reported on the basis of nominal concentrations except where otherwise stated, Standard
test guidelines provide for reporting of results on a nominal basis where measurements indicate the test
substance remains within 20% of nominal.
b
95% confidence intervals are stated where available
c
Unless otherwise stated, the tests were conducted according to the test method identified
Table A2.11A: Summary of aquatic toxicity data for dimethenamid (SAN 582 H).
Test type
Test results a, b
Test method c
Test species
&
[reference number]
duration
Fish
Rainbow Trout
Salmo gairdneri
96h static
LC50:
2.6 mg/L
95% CI:
1.7 – 5.8 mg/L
[measured] > 95% < 105% [nominal]
Bluegill
Lepomis
macrochirus
96 h static
LC50:
6.4 mg/L
95% CI:
3.3 – 10 mg/L
[measured] = [nominal]
Bowman, 1988
FIFRA 72-1
Report No.
88/11366
GLP
Klimisch score: 1
SAN 582 H
Bowman, 1988
FIFRA 72-1
Report No.
88/11368
GLP
Klimisch score: 2*
SAN 582 H
*DO range: 46 – 100%
Rainbow trout,
Oncorhynchus
mykiss
21-day
Flowthrough
NOEC:
0.63 mg/L
LOEC:
1.25 mg/L
(pigmentation, loss of co-ordination)
Rainbow trout,
Oncorhynchus
mykiss
Early Life
Stage
90-days
[measured]
> 83% < 108% of [nominal]
NOEC:
0.12 mg/L
LOEC:
0.24 mg/L
(Growth during first 31 days)
Invertebrates
Daphnia magna
48 h static
LC50:
16 mg/L
95% CI:
12 – 22 mg/L
ERMA New Zealand Evaluation and Review Report: Application HSR08124
Jenkins, 1991
OECD204
Report No. 91/11906
GLP
Klimisch score: 1
SAN 582 H
Graves & Smith,
1992
FIFRA E 72-4
ASTM E 1241-88
Report No. 92/12456
GLP
Klimisch score: 1
SAN 582 H
Frazier, 1988
FIFRA 72-2
Report No.
95/11367
GLP
Page 74 of 149
Test species
Test type
&
duration
Test results a, b
[reference number]
[measured] > 85% < 95% [nominal]
Daphnia magna
21 day
Flowthrough
Test method c
NOEC:
1.36 mg/L
LOEC:
2.51 mg/L
(survival, 1st generation)
(weight, 2nd generation)
Klimisch score: 1
SAN 582 H
Holmes& Swigert,
1992
FIFRA 72-2
Report No. 92/12455
GLP
Klimisch score: 1
SAN 582 H
[measured]
> 95% < 120% of [nominal]
Algae/Aquatic plants
120 h static
Freshwater alga
Anabaena
flos-aquae
ErC50:
1.2 mg/L
95% CI:
0.11-65.0 mg/L
EbC50:
0.45 mg/L
95% CI:
0.072-3.0 mg/L
Freshwater
diatom
Navicula
pelliculosa
120 h static
[measured] > 55% , < 95% of [nominal]
calculations based on [measured]
Limit test
ErC50:
> 1.2 mg/L
EbC50:
>1.2 mg/L
[measured]
Freshwater alga
Selenastrum
capricornutum
120 h
ErC50:
0.096 mg/L
95% CI:
0.049 – 0.112 mg/L
[measured]
Duckweed
Lemna gibba
14 d
IC50 (mean % inhibition):
0.028 mg/L
95% CI:
002 – 0.074 mg/L
Hoberg, 1992
FIFRA 122-2, 123-2
Report No.
92/12457
GLP
Klimisch score: 1
SAN 582 H
Hoberg, 1992
FIFRA 122-2, 123-2
Report No.
92/12458
GLP
Klimisch score: 1
SAN 582 H
Thompson & Peters,
1991
FIFRA 123-2
Report No. 91/11907
GLP
Klimisch score: 1
SAN 582 H
Thompson et al. 1991
FIFRA 123-2
Report No. 91/11907
GLP
Klimisch score: 1
SAN 582 H
[measured] used
Table A2.11B: Summary of aquatic toxicity data for Frontier–P (BAS 656 07 H).
Test species
Test type Test resultsa, b
Test methodc
[reference number]
&
BAS 656 07 H
duration
Fish
Rainbow trout,
96 h static
LC50:
ERMA New Zealand Evaluation and Review Report: Application HSR08124
Zok, 1999
Page 75 of 149
Test species
Test type
&
duration
Oncorhynchus
mykiss
Test resultsa, b
BAS 656 07 H
Test methodc
7.94 mg/L
FIFRA 72-1
OECD 201
Report No. 99/10317
GLP
Klimisch score: 1
BAS 656 07 H
[measured] > 100%, < 115% [nominal]
Invertebrates
Daphnia magna
48 h static
LC50:
17.1 mg/L
95% CI:
16 – 18.3 mg/L
[measured] > 100%, < 120% [nominal]
Algae/Aquatic plants
72 h static
Scenedesmus
subspicatus
ErC50:
0.1327 mg/L
[measured] > 75%, < 115% [nominal]
Duckweed
Lemna gibba
14 d
ErC50:
0.054 mg/L
95% CI:
0.038 – 0.075 mg/L
[reference number]
Jatzek, 1999
OPPTS 850.1010
OECD 202
Report No. 99/10316
GLP
Klimisch score: 1
BAS 656 07 H
Reuschenbach, 1999
OPPTS 850.1010
OECD 202
Report No. 99/10315
GLP
Klimisch score: 1
BAS 656 07 H
Dohmen, 1999
OPPTS 850.44
Report No. 99/10314
GLP
Klimisch score: 1
BAS 656 07 H
[measured] > 98%, < 120% [nominal]
a
Results are reported on the basis of nominal concentrations except where otherwise stated, Standard
test guidelines provide for reporting of results on a nominal basis where measurements indicate the test
substance remains within 20% of nominal.
b
95% confidence intervals are stated where available
c
Unless otherwise stated, the tests were conducted according to the test method identified
Table A2.11C: Summary of aquatic toxicity data for the leachates of Frontier-P.
Test type
Test results a, b
Test method c
Test species
&
[reference number]
duration
Fish
Rainbow trout,
Oncorhynchus
mykiss
96 h static
No clinical signs nor mortality were observed
in the fish exposed to the control and treated
leachate over the 96 hour exposure period.
Mixed leachates of the 2nd year of lysimeter
study number: 321726 with 14C-SAN 582 H
(Lysimeter 2).
Wüthrich, 1995
OECD 203
Report No.
95/11351
GLP
Klimisch score: 1
The leachate tested appears to be non-toxic to
fish.
Invertebrates
Daphnia magna
48 h static
No immobility was observed in the daphnia
exposed to the control and treated leachate
over the 48 hour exposure period.
ERMA New Zealand Evaluation and Review Report: Application HSR08124
Wüthrich, 1995
OECD 202
Report No.
Page 76 of 149
Test species
Test type
&
duration
Test results a, b
Test method c
[reference number]
Note: the immobility of a single animal was
noted after 48 h in one replicate of treated
leachate – not considered to have occurred as
an effect of the treated leachate mixture.
95/11326
GLP
Klimisch score: 1
Mixed leachates of the 2nd year of lysimeter
study number: 321726 with 14C-SAN 582 H
(Lysimeter 2).
The leachate tested appears to be non-toxic to
daphnia.
Algae/
Aquatic plants
Pseudokirchneriella
subcapitata
72 h static
Test
mixture
OECD
medium
Tap water
control
Control
leachate
Treated
leachate
Growth rate
% inhibition
--
Biomass
% inhibition
--
93.8
96.7
72.9
79.9
24.0
53.8
Wüthrich, 1995
OECD 201
Report No.
95/11326
GLP
Klimisch score: 1
Toxicity of the SAN 582H leachates is
inconclusive based on the failure of the
controls.
a
Results are reported on the basis of nominal concentrations except where otherwise stated, Standard
test guidelines provide for reporting of results on a nominal basis where measurements indicate the test
substance remains within 20% of nominal.
b
95% confidence intervals are stated where available
c
Unless otherwise stated, the tests were conducted according to the test method identified
Conclusion
Dimethenamid-P is classified as 9.1A due to its toxicity to aquatic plants (Hoberg,
1997, Report No. 97/10742).
Frontier-P is classified as 9.1A due to its toxicity to aquatic plants (Dohmen, 1999,
Report No. 99/10314).
The leachates of Frontier-P® tested did not trigger a 9.1 classification (Wüthrich,
1995, Report No. 95/11326 ).
Notes:
 Comparison of fish and invertebrate acute toxicity values of dimethenamid
and dimethenamid-P shows similar concentrations causing effects. On this
basis the chronic toxicity of dimethenamid has been extrapolated to
dimethenamid-P.

The algal toxicity of dimethenamid-P appears greater than that of
dimethenamid to an extent that cannot be explained by the concentration of the
S-isomer in dimethenamid.
ERMA New Zealand Evaluation and Review Report: Application HSR08124
Page 77 of 149
Sub-class 9.2 Soil ecotoxicity and terrestrial fate
Classification under this sub-class requires consideration of the persistence of the
components of the Frontier-P in soil, and the toxicity to soil-dwelling invertebrates
(e.g. earthworm), soil microbial function and terrestrial plants resulting from soil
based exposure.
Data on the adsorption, mobility and field dissipation of the active ingredient is used
in the ecological risk assessment for the substance. Refer to Appendix 3.
Terrestrial fate and degradation of dimethenamid-P, dimethenamid and
Frontier–P
Information of terrestrial fate and degradation is summarised in Table A2.12, Table
A2.12A, respectively.
Table A2.12: Terrestrial fate and degradation of dimethenamid-P (SAN 1289 H)
and its metabolites.
Test results
Test method a
Test type
[reference
Metabolites
Active
number]
Abiotic degradation
Photolysis
Bridging study
SAN 582H and SAN
1289H
Elliot clay loam soil
(pH 6.4, OM 4.1%)
SAN 1289H (P)
DT50: 44.71 days
Corrected for spring
40°N
DT50: 56.8 days
Nietschmann &
Yu, 1997
Report No.
97/5181
USEPA
Subdivision N
Section 161-2
GLP
Klimisch score: 1
Major degradation
product:
CO2 10%
SAN582H
DT50: 29.87 days
Corrected for spring
40°N
DT50: 40 days
Major degradation
product:
CO2 12%
Biodegradation - aerobic
(Laboratory)
Bridging study
SAN 1289H (P) and SAN
582H
Elliot clay loam soil
(pH 6.4, OM 4.1%,
23°C)
SAN 1289H (P)
DT50: 10 days
SAN582H
DT50: 10 days
Wendt, 1997
Report No.
97/5257
USEPA 162-1
GLP
Klimisch score: 1
Pathways of
degradation were
also identical.
ERMA New Zealand Evaluation and Review Report: Application HSR08124
Page 78 of 149
Conclusion:
No metabolic
differences will
occur regarding the
fate of
dimethenamid –P
(S) versus the
dimethenamid R,Senantiomer mixture.
Soil accumulation
Adsorption/desorption
SAN 1289H
Soil
Clay
Ad
Kd
2.09
Koc
211
Des
Kd
3.24
Koc
328
2.51
105
3.31
139
3.02
247
3.89
319
(pH 8.00, OC 0.99%)
Clay loam
(pH 6.40, OC 2.38%)
Loam sediment
(pH 7.30, OC 1.22%)
Sandy loam
1.38
395
1.40
Tong & Su, 1997
Report No.
97/5180
OECD 106
USEPA guideline
GLP
Klimisch score: 1
401
(pH 7.00, OC 0.35%)
Silt loam
1.95
129
2.09
138
(pH 6.70, OC 1.51%)
Sandy clay loam
6.61
474
8.32
596
2.51
123
2.4
118
2.14
90
2.63
110
1.23
101
2.63
215
13.49
393
20.89
609
(pH 5.6, OC 1.40%)
Clay loam
(pH 8.0, OC 2.03%)
Sandy loam
(pH 5.5, OC 2.38%)
Silt loam
(pH 6.6, OC 1.22%)
Sand
(pH 3.9, OC 3.43%)
Soil accumulation
Adsorption/desorption
Oxalamide (M23)
Sulfonate (M27)
Conclusion:
Dimethenamid-P is expected to have high to medium
mobility in soil.
Koc values 50-150 high mobility,
Koc values 150-500 medium mobility
Ads
Des
Oxalamide
Soil
Kd
Koc
Kd
Koc
Loamy sand
0.06
3.48
(pH 6.4, OC 1.6%)
Loamy sand
0.24
17.22
-
-
0.11
3.88
-
-
0.05
4.13
-
-
0.09
9.61
-
-
0.35
7.91
-
-
Kd
0.23
Koc
14.38
Kd
-
Koc
-
0.14
10.29
-
-
0.10
3.52
-
-
0.00
0.00
-
-
(pH 4.2, OC 1.4%)
Silty clay
Mamouni, 1995
Report No.
95/101821
OECD 106
GLP
Klimisch score: 1
(pH 7.8, OC 2.9%)
Loam
(pH 7.9, OC 1.1%)
Sandy loam
(pH 7.5, OC 0.9%)
Silt loam
Amendment
Tong, 1999
Report No.
99/5014
(pH 7.1 CaCl2,
OC 4.39%)
Sulfonate
Loamy sand
(pH 6.4, OC 1.6%)
Loamy sand
(pH 4.2, OC 1.4%)
Silty clay
(pH 7.8, OC 2.9%)
Loam
ERMA New Zealand Evaluation and Review Report: Application HSR08124
Page 79 of 149
(pH 7.9, OC 1.1%)
Sandy loam
0.02
2.23
-
-
0.43
9.87
-
-
(pH 7.5, OC 0.9%)
Silt loam
(pH 7.1 CaCl2,
OC 4.39%)
Conclusion: The metabolites M23 and M27 are
characterised as highly mobile compounds.
a
unless otherwise stated, the tests were conducted in accordance with the named test guideline
Table A2.12A: Terrestrial fate and degradation of dimethenamid (SAN 582 H).
Test results
Test methoda
Test type
Active
[reference
number]
Abiotic degradation
Photolysis
SAN 582 H
Biodegradation - aerobic
(Laboratory)
SAN 582
Kenyon loam soil
(pH 7.4, OM 3.2%)
DT50: 5.3 ± 0.3 days
Corrected for spring 40°N
DT50: 7.8 days
Kenyon Loam soil
(pH 6.2, OM 3.8%, 25°C)
DT50: 38 days
Major metabolite:
oxalamide (M23)
Biodegradation - aerobic
(Laboratory)
SAN 582 H
SAN 582 H
Loamy sand
(pH 5.8, OC 2.29%,
20°C)
DT50: 13 days
Major metabolites
Oxalic acid (M23)
8.86%
Sulfonic acid (M27)
10.87%
Metabolites
Loamy sand
M23
DT50: 41 d
M27
DT50: 140 d
Sabat & Yu, 1992
Report No.
92/12387
USEPA
Subdivision N
Section 161-3
GLP
Klimisch score: 1
Krueger & Bade,
1990
Report No.
90/11105
USEPA 162-1
GLP
Klimisch score: 1
König, 1995
Report No.
95/10128
BBA Part IV, 4-1
GLP
Klimisch score: 1
Sandy loam
M23
DT50: 24 d
M27
DT50: 60 d
Sandy loam
(pH 6.6, OC 1.34%,
, 20°C)
DT50: 13 days
Biodegradation - aerobic
(Laboratory)
SAN 582H
Major metabolites
Oxalic acid (M23)
10.17%
Sulfonic acid (M27)
12.69%
SAN 582 H
Sandy clay loam
(pH 7.95, OC
1.34%, , 20°C)
DT50: 7.8 days
Metabolites
M23
DT50: 25.9 days
M27
DT50: 40 days
ERMA New Zealand Evaluation and Review Report: Application HSR08124
König, 1996
Report No.
96/11006
BBA Part IV, 4-1
GLP
Page 80 of 149
Extrapolation to
different soil
temperatures
SAN 582H
SAN 582 H
10°C
DT50:
17.2
28.6
28.6
123.2
26.4
28.6 days
20°C
DT50:
7.8
13
13
56
12
13 days
Klimisch score: 1
Gottesbüren, 1999
Report No.
99/10071
Non-GLP
(calculation)
Klimisch score: 1
Metabolites
10°C
M23
DT50:
57.2
90.2
52.8days
M27
DT50:
88
308
132 days
20°C
M23
DT50:
25.9
41
24 days
M27
DT50:
40
140
60 days
Biodegradation –
anaerobic
SAN 582H
Kenyon loam soil
(pH 6.2, OM 3.8%)
DT50: 53.8 days
Bade, 1990
Report No.
90/11111
USEPA 162-2
Major metabolites
Oxalic acid (M23)
8.7%
Soil accumulation
Adsorption/desorption
SAN 582 H
Linear Isotherm model
Soil
Sand
Ad
Kd
0.3
Koc
61
Des
Kd
-
Koc
-
1.59
144
4.36
311
0.65
59
-
-
0.62
62
-
-
1.10
38
2.38
82
0.32
64
-
-
1.6
114
4.19
299
0.73
67
-
-
0.62
62
-
-
1.15
40
2.59
89
(pH, OC 0.5%)
Loamy sand
(pH, OC 1.4%)
Clay loam
Völlmin, 1995
Report No.
95/10123
OECD 106
GLP
Klimisch score: 1
(pH, OC 1.1%)
Silt loam
(pH, OC 1.0%)
Silty clay
(pH, OC 2.9%)
Freundlich model
Sand
(pH 6.9, OC 0.5%)
Loamy sand
(pH 4.2, OC 1.4%)
Clay loam
(pH 7.9, OC 1.1%)
Silt loam
(pH 6.4, OC 1.0%)
Silty clay
(pH 7.8, OC 2.9%)
ERMA New Zealand Evaluation and Review Report: Application HSR08124
Page 81 of 149
Soil accumulation
Adsorption/desorption
SAN 582 H
Conclusion:
SAN 582 H is adsorbed weakly by soils of low organic
carbon content. This compound is predicted to have high
to medium mobility in these soils.
Ads
Des
Soil
Kd
Koc
Kd
Koc
Loam (Kenyon)
3.3
150
3.7
168
(pH 7.1, OC 2.2%)
Clay loam
3.5
121
3.9
135
0.7
233
0.7
233
2.0
118
2.1
124
(pH 6.9, OC 2.9%)
Silt Loam
Tong, 1991
Report No.
91/118819
OECD 106
GLP
Klimisch score: 1
(pH 7.4, OC 0.3%)
Sandy clay loam
(pH 6.4, OC 1.7%)
Mobility/leaching
Laboratory
SAN 582 H
Conclusion: SAN 582H is predicted to have high to
medium soil mobility.
Rate: 2.82 ppm soil
Sandy soil (pH 6.90, OC 0.5%)
Cumulative radioactivity in leachate (%AR):
Column A: 24.15%
(AI: 0.09%, M23: 16.66%, M27: 0.96%, M31:1.13%)
König, 1995
Report No.
95/10101
BBA Part IV, 4-2
GLP
Klimisch score: 1
Column B: 23.54%
(AI: --%, M23:16.65%, M27:0.45%, M31: 0.79%)
M31: Thioglycolic acid
The maximum extractable radioactive residues in soil
layer:
Column A: 0-5 cm 14.05%
Column B: 0-5 cm15.36%
Conclusions:
Residues of dimethenamid were only found in one
column (0.09% of AR). Therefore the groundwater
contamination potential of dimethenamid is low.
Oxalamide (M23) was the only transformation product of
significance in the leachate – approximately 17% of AR
in both columns. Therefore the potential for ground water
contamination exists by M23.
Mobility/leaching
Laboratory
SAN 582 H
Rate: 2.82 ppm soil
Loamy sand soil (pH 5.8, OC 2.3%)
Cumulative radioactivity in leachate (%AR):
Column A: 22.41%
(AI: --%, M23: 10.73%, M27: 2.17%, M31: 2.20%)
König, 1994
Report No.
94/10635
BBA Part IV, 4-2
GLP
Klimisch score: 1
Column B: 22.89%
(AI: --%, M23:11.10%, M27:2.54%, M31: 2.34%)
The maximum extractable radioactive residues in soil
layer:
Column A: 0-5 cm 19.13%
Column B: 0-5 cm 24.57%
Conclusions:
No residues of dimethenamid were found in the leachates
ERMA New Zealand Evaluation and Review Report: Application HSR08124
Page 82 of 149
(LOD = 0.1%). Therefore the groundwater contamination
potential of dimethenamid is low.
Oxalamide (M23) was the only transformation product of
significance in the leachate – approximately 11% of AR
in both columns. Therefore a potential for ground water
contamination exists for M23.
Mobility/leaching
Laboratory
SAN 582 H
Rate: 1.6 L/ha (1440 g ai/ha)
Volume
Leachate (mL)
Soil
Sand
A
365
B
370
Total amounts
(%) of
radioactivity in
leachate
A
B
43
37
370
375
5.3
4.5
380
380
11
6.4
375
375
5.8
4.5
375
370
4.9
1.8
König, 1994
Report No.
95/10122
BBA Part IV, 4-2
GLP
Klimisch score: 1
(pH 7.6, OM 0.3%)
Loamy sand
(pH 7.0, OM 2.5%)
Sandy loam
(pH 7.9, OM 1.2%)
Silt loam
(pH 7.0, OM 1.6%)
Sandy clay loam
(pH 8.3, OM 1.3%)
The maximum extractable radioactive residues in soil
layer:
Sand 25-30 cm:
Column A 24%, Column B 24%
Loamy Sand 10-15 cm:
Column A 32%: Column B 40%
Sandy loam 20-25 cm:
Column A 28%, Column B 25%
Silt loam 20-25 cm:
Column A 34%, Column B 34%
Sandy clay loam 20-25 cm:
Column A 20%, Column B 21%
Conclusions:
In the case of sand soil 37% and 30% of the initially
applied amount of dimethenamid had leached whereas no
detectable residues were found in the leachates of the
Loamy sand soil (LOD 0.002% applied amount). Only
one of the two leachates from each of the other soils
contained dimethenamid residues Sandy loam (column
A: 3.27% of the applied amount), Silt loam (column A:
0.59%) and Sandy clay loam (column A: 1.69%),
respectively.
Detectable quantities of metabolites M23, M27 and M31
were measured in the leachates. This observation is
attributed to degradation of the parent molecule in the
test soil.
Mobility/leaching
Outdoor Lysimeters
SAN 582 H
There is a potential for the metabolites M23, M27 and
M31 to leach into groundwater.
Application rate: 1.44 kg ai/ha
Lysimeter 1: one application
Lysimeter 2: two applications one year apart
ERMA New Zealand Evaluation and Review Report: Application HSR08124
Burgener, 1996
Report No.
96/10707
BBA IV, 4-3
Page 83 of 149
Soil Type: Sandy soil
Parameter
pH (KCl)
OC%
Horizon (cm)
0-30
30-60
6.1
5.9
1.05
0.49
GLP
Klimisch score: 1
60-90
6.1
0.14
90-120
7.3
0.00
Determination of movement and degradation of
dimethenamid and its degradation products in a soil
profile of 120 cm and leaching as a function of the
precipitation and vegetation. Normal agricultural
practices such as soil cultivation, crop protection
fertilization and crop rotation were followed.
Distribution of radioactivity
Leachates
First year:
Lysimeter 1: 30.3 μg parent equivalents/L.
Lysimeter 2: 31.5 μg/L
Second year:
Lysimeter 1: 8.9 μg/L
Lysimeter 2: 35.3 μg/L (second treatment)
Third year:
Lysimeter 1: 4.5 μg/L
Lysimeter 2: 15.4 μg/L (second treatment of third year)
Plants - Rape
First year:
Lysimeter 1: 0.41 ppm AR
Lysimeter 2: 0.53 ppm AR
Predominantly found in straw (grain 0.05 ppm)
Second year:
Lysimeter 1: 0.03 ppm AR
Lysimeter 2: 0.15% AR
Third year:
< 0.01 ppm AR
Soil
Lysimeter 1: 22.71% AR present after 3 years
12.3% AR localized in the top 8 cm.
1.62% found below 57 cm.
Lysimeter 2: 26.17% AR present after 3 years
14.65% AR localized in the top 8 cm.
1.64% found below 57 cm.
Total recovery:
Lysimeter 1: 34.72% AR recovered
Lysimeter 2: 40.16% AR recovered
Loss of radioactivity attributed to total degradation to
CO2, conversion to volatile products and biodegradation.
Characterisation of radioactivity
Metabolites
Lysimeter 1: Average annual yield
U1: 3.63AR (6.2 μg/L)
ERMA New Zealand Evaluation and Review Report: Application HSR08124
Page 84 of 149
U8: 0.97 AR (1.7 μg/L)
M27: 0.70 AR (1.2 μg/L)
M23: 0.14 AR (0.2 μg/L)
Dimethenamid was not detected in any leachate.
Lysimeter 2: Average annual yield
U1: 3.34% (5.0 μg/L)
U2: 1.82% (2.9 μg/L)
U5: 1.39% (2.1 μg/L)
U6: 1.67% (2.5 μg/L)
U8: 0.99% (1.5 μg/L)
U10: 1.12% (2.0 μg/L)
M27: 1.61% (2.6 μg/L)
M23: 0.47% (0.7 μg/L)
Dimethenamid was not detected in any leachate.
The chromatographic profile of the leachates changes
throughout the course of the study indicating an
increased formation of polar degradation products with
time. No parent compound was found in the percolation
water.
At least 17 unknown and two known metabolites (M23
and M27) showed a high mobility in the sandy soil of the
lysimeters.
Conclusions:
The metabolites of dimethenamid show the potential to
leach into ground water.
Mobility/leaching
Field
SAN 582 H
Bare soil treated once with 1.6 L/ha (1440 g ai/ha)
Two sites (Germany)
Site 1: R10283
Soil texture (Loamy sand)
Organic matter (%)
0-30 cm: 1.5
30-60 cm: 0.6
pH
0-30 cm: 6.5
30-60 cm: 6.7
Fricker & Hertl,
1995
Report No.
95/10130
BBA IV, 4-1
GLP
Klimisch score: 1
Site 2: R10284
Soil texture (Silty loam)
Organic matter (%)
0-30 cm: 2.1
30-60 cm: 0.8
pH
0-30: 7.6
30-60: 7.4
Dimethenamid
DT50:
3.5 days (R10283)
4.7 days(R10284)
At both sites, dimethenamid was localized exclusively in
the top 10 cm of the soil with the exception of the
samples collected 0, 3 and 7 days after application of one
of the sites (R10283).
ERMA New Zealand Evaluation and Review Report: Application HSR08124
Page 85 of 149
“The findings were demonstrated to be due to cross
contamination during sample collection rather than
leaching of the parent molecule.”
Oxalamide
DT50:
45 days (R10283)
18 days (R10284)
Sulfonate
DT50:
76 days (R10283)
22 days (R10284)
The major fraction of the metabolites was confined to the
uppermost soil layer (0-10 cm). At Site R10283, traces of
oxalamide (0.009 μg/g) were detected at day 90 in the
20-30 cm soil layer indicating possible mobility. This
finding was not confirmed by residues in earlier or later
samples.
Significant quantities of metabolites oxalamide and
sulfonate were measured in the day 0 samples. This
observation is attributed to degradation of the parent in
the time interval between application and freezing.
Mobility/leaching
Field
SAN 582 H
Conclusions:
Although there is some evidence of oxalamide leaching
to the 20-30 cm soil layer, the incidence appears to be
isolated.
Bare soil treated once with 1.6 L/ha (1440 g ai/ha)
Two sites (France)
Site 1: R10242
Soil texture (Sandy loam)
Organic carbon (%)
0-25 cm: 1.50
25-50 cm: 0.70
pH
0-25 cm: 5.9
25-50 cm: 5.6
Fricker & Hertl,
1995
Report No.
95/10133
BBA IV, 4-1
GLP
Klimisch score: 1
Site 2: R10243
Soil texture (Sandy silt loam)
Organic carbon (%)
0-25 cm: 1.10
25-50 cm: 0.50
pH
0-25 cm: 6.00
25-50 cm: 6.50
Dimethenamid
DT50
1.8 days (R10242)
34.7 days (R10243)
The major fraction of dimethenamid was localised in the
upper 10 cm of the soil. Some samples collected during
the first two weeks of the study contained residues (<
0.058 μg/g) in the 10-30 cm layer. No residues were
ERMA New Zealand Evaluation and Review Report: Application HSR08124
Page 86 of 149
detected at depths below 10 cm in any of the samples
collected at day 28 and at the subsequent sampling dates.
No residues were detected below 30 cm throughout the
entire study period.
Oxalamide
DT50:
Not determined (R10242)
41.5 days (R10243)
Sulfonate
DT50:
25.4 days (R10242)
41.7 days (R10243)
Site R10242
Oxalamide residues were detected on four occasions
during the first month of study in the 0-10 cm soil layer
(< 0.031 μg/g). One week after the application 0.012 μg/g
were found in the 10-20 cm layer. After day 28, no
residues were detected below 20 cm throughout the entire
study period.
Sulfonate residues were found on 3 occasions during the
study: day 15 (0.011μg/g in the 10-20 cm layer, day 28
(0.015 μg/g in the 0-10 cm layer) and day 86 (0.010 μg/g
in the 20-30 cm layer). Residues (< 0.01 μg/g were
occasionally detected in the 0-50 cm layer from day 0 to
120 – no sulfonate was detected on the last sampling date
(day 181).
Site R10243
The major fraction of metabolites was found in the 0-10
cm layer. Oxalamide (0.01 μg/g) was found in the 10-20
cm layer at day 21. No residues were detected below 20
cm throughout the entire study period.
Three samples from deeper layers contained sulfonate
residues: two of them in the 10-20 cm layer (0.007 μg/g
and 0.006 μg/g on days 3 and 28, respectively) and one in
the 40-50 cm horizon (0.01 μg/g on day 60). On day 91
and on the subsequent sampling dates no residues were
detected below 10 cm.
Absolute concentrations of metabolites reached
approximately 7% of the initial concentration of
dimethenamid.
Mobility/leaching
Field
SAN 582 H
Conclusions:
Although potential for leaching has been shown for the
metabolites, oxalamide and sulfonate, they appear to be
present at low concentrations (Max: 0.011μg/g soil).
Bare soil treated once with 1.6 L/ha (1440 g ai/ha)
Two sites (France)
Site 1: R10244
Soil texture (loam)
Organic carbon (%)
0-25 cm: 0.5
25-50 cm: 0.3
ERMA New Zealand Evaluation and Review Report: Application HSR08124
Carrier and Blanz,
1997
Report No.
97/11507
BBA IV, 4-1
GLP
Klimisch score: 1
Page 87 of 149
pH
0-25 cm: 6.5
25-50 cm: 6.7
Site 2: R10245
Soil texture (sand)
Organic carbon (%)
0-25 cm: 1.2
25-50 cm: 1.1
pH
0-25 cm: 5.9
25-50 cm: 5.7
Dimethenamid
DT50
16.3 days (R10244)
13.3 days (R10245)
Site R10244
No residues were detected below 10 cm. 98% of residues
were detected in the 0-10 cm layer.
Site R10245
81.7% of residues were detected in the 0-10 cm layer.
Residues were located in the 10-20 cm (11.9%) and 2030 cm (6.4%) layers, respectively.
Residues above the quantitation limit were found in the
layers of 10-20 cm and 20-30 cm depth in the samples
taken at day 0, 57 and 90 and in the layer of 10-20 cm
depth on day 30.
Metabolites
Site R10244
The dissipation of dimethenamid is accompanied by the
transient formation of oxalamide and sulfonate.
Formation is less evident at site R10245, where
metabolites were only detected in trace amounts.
Absolute concentrations of the total of both metabolites
reached approximately 5% of the initial concentration of
dimethenamid.
Conclusions:
Dimethenamid showed the potential to leach beyond both
the 10 cm and 20 cm soil layers.
Mobility/leaching
Field
SAN 582 H
Bare soil treated once with 1.6 L/ha (1440 g ai/ha)
Three sites (Italy)
Site 1: R10246
Soil texture (sandy loam)
Organic carbon (%)
0-30 cm: 0.7
30-50 cm: 0.4
pH
0-30 cm: 7.9
30-50 cm: 8.1
Carrier, 1997
Report No.
97/11508
BBA IV, 4-1
GLP
Klimisch score:
2*
Site 2: R10247
ERMA New Zealand Evaluation and Review Report: Application HSR08124
Page 88 of 149
Soil texture (sandy loam)
Organic carbon (%)
0-30 cm: 0.4
30-50 cm: 0.4
pH
0-30 cm: 8.1
30-50 cm: 8.1
Site 3: R10248
Soil texture (loam)
Organic carbon (%)
0-30 cm: 0.9
30-50 cm: 0.9
pH
0-30 cm: 7.9
30-50 cm: 7.9
Dimethenamid
DT50
4.8 days (R10246)
8.3 days (R10247)
15.2 days (R10248)
Site 1: R10246
At days 0, 3 and 7, some residues of dimethenamid were
detected in the 10 – 40 cm soil layers. No residues were
detected below 10 cm in the samples taken 15 days after
the application – with the exception of the layer 20-30
cm on day 21 (0.003 μg/g).
Site 2: R10247
Samples collected at days 0 and 3 showed residues of
dimethenamid detected down to 50 cm depth.
No dimethenamid above the limit of quantitation was
measured in soil level below 10 cm in any sample taken
after 7 days.
Site 3: R10248
Dimethenamid residues were detected to 30 cm between
days 0 and 7. Day 3 dimethenamid was detected at the
40-50 cm level. No residues were detected below 10 cm
after 14 days – with the exception of the 20-30 cm layer
(day 30).
*Note (Klimisch scoring):
“Since at day 0, the soil was dry and no rain was
recorded in the 24 hours following application and since
the presence of residues of dimethenamid was not
confirmed at later sampling dates and did not increase
with increasing rainfall, the apparent mobility of
dimethenamid to deeper soil layers observed during the
first week at each of the three sites is judged to be an
artefact due to cross-contamination during sampling and
transport of the samples.
These levels were judged to be an artefact due to crosscontamination during sampling and transport of the
samples.”
ERMA New Zealand Evaluation and Review Report: Application HSR08124
Page 89 of 149
Oxalamide
DT50:
97.8 days (R10246)
52.8 days (R10247)
158.5 days (R10248)
Sulfonate
DT50:
24.4 days (R10246)
74.1 days (R10247)
136.6 days (R10248)
Site 1: R10246
Oxalamide was detected only in the upper 10 cm of the
horizon between 14 and 122 days at concentrations
ranging between 0.012 to 0.021 μg/g.
Sulfonate was first detected at day 3. Its concentration
was 0.022 μg/g 14 days after the application and then
decreased to a non-detectable concentration at 93 days.
Concentrations below the limit of quantitation were
measured in the 10-20 cm level 30 and 60 days which
may indicate a slight tendency to migrate to deeper layers
while degrading.
Site 2: R10247
Oxalamide and sulfonate were found only in the upper 10
cm of the soil horizon. Oxalamide was detected at
concentrations above the limit of determination on days
21 and 30. Sulfonate residues were only detected on 4
sampling dates, the concentration increases from 0.03
μg/g (21 days) to 0.039 μg/g (day 30). Residues were
non-detectable 122 days after application.
Site 3: R10248
Oxalamide was only detected in the upper 10 cm level.
The maximum concentration was 0.037 μg/g (5.5% of
the initial concentration of dimethenamid) 122 days after
application. No oxalamide was detected later.
Sulfonate residues were first found only at the 0-10 cm
soil level. The concentration increased from 0.02 μg/g 25
days after application to a maximum concentration of
0.049 μg/g (7.2% of the initial dimethenamid
concentration) 60 and 93 days after initial application.
The concentration decreased following sampling at 186
and 246 days. Sulfonate residues were detected below the
limit of quantitation in the 10-20 cm and 20-30 cm soil
layers, indicating a tendency to migrate deeper with
increasing time whilst degrading.
The peak concentration of both metabolites accounted for
8.2 to 12.7% of the initial concentration of
dimethenamid.
Conclusions:
The data regarding dimethenamid should be treated with
caution with regard to the potential of cross
contamination. The metabolites appear to be not rapidly
degradable for the majority of tested soil types. The
ERMA New Zealand Evaluation and Review Report: Application HSR08124
Page 90 of 149
Mobility/Dissipation
Switzerland 1994-1997
sulfonate metabolite shows the potential for leaching
during the degradation process.
Application rate: 1.6 L/ha (1440 g ai/ha) per year
Soil type: Sandy loam (0-30 cm, pH 7.75, OC 1.1%)
Crop: Corn
Pore water
No dimethenamid residues above 0.1 μg/L were
detectable in any of the pore water samples collected in
suction cups installed at a depth of 1.0-1.2 m or 2.6 – 3.0
m and taken at monthly intervals up to 36 months after
the first application.
Gasser, 1998
Report No.
98/10384
GLP
Klimisch score: 1
Soil
1994
The concentration of dimethenamid found in soil samples
decreased from a maximum concentration of 0.90 μg/g
just after application to < 0.01 μg/g five months after
application.
1995
The concentration of dimethenamid found in soil samples
decreased from a maximum concentration of 0.89 μg/g
just after application to < 0.01 μg/g two months after
application.
Metabolites
Oxalamide
1994
0 – 10 cm
Range 0.01 – 0.03 μg/g (between 3 and 65 days)
Maximum at 65 days
1995
0 – 10 cm
Range 0.01 – 0.02 μg/g (between 0 and 29 days)
Maximum at 16 and 29 days
10-30 cm
0.01 μg/g (16 days)
Sulfonate
1994
0 – 10 cm
Range 0.02 – 0.05 μg/g (between 3 and 65 days)
Maximum at 30 days
1995
0 – 10 cm
Range 0.01 – 0.05 μg/g (between 3 and 29 days)
Maximum at 16 days
10-30 cm
0.03 μg/g (16 days)
Conclusions:
Dimethenamid is not expected to accumulate in soil.
Dimethenamid residues were located in the upper 0 – 10
cm soil layers, no leaching effect could be observed.
Although metabolite residues were found below the 10
ERMA New Zealand Evaluation and Review Report: Application HSR08124
Page 91 of 149
Residues in cropped field
France
cm layer of soil , concentrations are expected to dissipate
to < 0.01 μg/g after 5 months.
Application rate: 1.4 – 1.6 L/ha (1260 – 1440 g ai/ha)
Soil:
Crop: Corn
Ground water samples
No dimethenamid residues were detectable in any of the
ground water samples taken between 5 to 6 months after
application.
Gasser, 1998
Report No.
98/10385
GLP
Klimisch score:
2*
Soil
Site 1
The concentration of dimethenamid found in soil samples
decreased from a maximum concentration of 0.67 μg/g
just after application to < 0.01 μg/g three months after
application.
Site 2
The concentration of dimethenamid found in soil samples
decreased from a maximum concentration of 0.68 μg/g
just after application to < 0.01 μg/g three months after
application.
Dimethenamid residues were located in the upper 0 -12.5
cm soil layers (*Klimisch score: residues found in 4
deeper layers attributed to cross contamination). No
leaching effect was observed during 3 months following
application.
Conclusions:
Data concerning the leaching of dimethenamid to layers
below 12.5 cm should be viewed with caution due to
cross contamination. However, no residues were found in
groundwater samples taken between 5 to 6 months.
Agency’s conclusions:
With regard to ground water contamination, the active ingredient dimethenamid applied at a rate of 1.6 L/ha
shows no leaching potential. The metabolites, oxalamide and sulfonate, appear to be mobile in the soil and
therefore have the potential to leach into groundwater.
Conclusion
Based on these data dimethenamid-P is considered to meet the HSNO criteria for
degradability in soil < 30 days. The metabolites M23 and M27 are not considered to
meet the HSNO criteria for degradability in soil < 30 days (10°C).
Soil toxicity
A summary of the toxicity of dimethenamid-P, dimethenamid, and Frontier-P to soil
dwelling macro-organisms, soil microbial function and terrestrial plants is provided in
Table A2.13, Table A2.13A and table A2.13B, respectively.
Table A2.13: Summary of terrestrial toxicity data for dimethenamid-P (SAN
1289 H).
Test
Test type & Test resultsa, b
Test methodc
[reference number]
species
duration
SAN 1289 H
Metabolites
Soil-dwelling invertebrates
Acute
Earthworm
14 d
Eisenia
Metabolite M23
LC50:
ERMA New Zealand Evaluation and Review Report: Application HSR08124
Krieg, 1998
OECD 207
Page 92 of 149
> 1264
mg/kg soil dry wt
foetida
NOAEC:
1264
mg/kg soil dry wt
Metabolite M27
LC50:
1264
mg/kg soil dry wt
Earthworm
Eisenia
foetida
Report No. 98/10299
GLP
Klimisch score: 1
Krieg, 1998
OECD 207
Report No. 98/10300
GLP
Klimisch score: 1
NOAEC:
632
mg/kg soil dry wt
Terrestrial plants
Acute
Seedling
14 d
emergence
EC50
(Shoot length lettuce):
0.020 lb ai/A
95% CI:
0.0032 – 0.18 lb ai/A
Hoberg, 1997
FIFRA guidelines
122-1, 123-1
Report No. 97/5175
GLP
Klimisch score: 1
SAN 1289 H
EC50 equivalent to:
0.022 kg/ha
0.029 mg/kg soil d. wt
Vegetative
vigour
(Used for
Risk
Assessment
only)
EC50
(Shoot weight ryegrass):
0.082 lb ai/A
95% CI:
0.01 – 0.72 lb ai/A
EC50 equivalent to:
0.092 kg/ha
a
Results are reported on the basis of nominal concentrations except where otherwise stated, Standard
test guidelines provide for reporting of results on a nominal basis where measurements indicate the test
substance remains within 20% of nominal.
b
95% confidence intervals are stated where available
c
Unless otherwise stated, the tests were conducted according to the test method identified
NA= Not applicable
ND= No data provided
Table A2.13A: Summary of terrestrial toxicity data for dimethenamid (SAN 582
H).
Test
Test type & Test results a, b
Test method c
[reference number]
species
duration
Active
Metabolites
Soil-dwelling invertebrates
Acute
Earthworm
14 d
Eisenia
foetida
LC50:
294.4
mg/kg soil dry wt
95% CI:
260.6 – 339.9
mg/kg soil dry wt
van Dijk, 1988
OECD 207 (2)
Report No. 88/11372
GLP
Klimisch score: 1
SAN 582 H
NOEC:
125
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mg/kg soil dry wt
Soil microbial function
28 d
Application rate:
2.4 mg/kg soil
(1.8 kg/ha)
12 mg/kg soil
(9 kg/ha)
Danneberg, 1991
Report No. 91/11908
GLP
Klimisch score:1
SAN 582 H
Soil 1 - Sandy
(pH 6.84, %OC 1.34)
Soil 2 - loamy
(pH 5.50, %OC 3.91)
Carbon
mineralisation
Soils 1 & 2
< 25% deviation from
control at both
application rates
Nitrogen
mineralisation
Soil 1
> 25% deviation from
control (increased
nitrogen in soil) at
both application rates
Soil 2
< 25% deviation from
control at both
application rates
Bacterial
inhibition
16 h
Cell
multiplication
EC50:
> 400 mg/L
Scholtz, 1994
Guideline
ISO 10712:1990 (E)
Report No. 94/11901
NonGLP
SAN 582 H
Table A2.13B: Summary of terrestrial toxicity data for Frontier-P (BAS 656 H).
Test
Test type & Test results a, b
Test method c
[reference number]
species
duration
Formulation
Soil-dwelling invertebrates
Acute
Earthworm
14 d
Eisenia
foetida
LC50:
596.3
mg/kg soil dry wt
95% CI:
544.65 – 650.7
mg/kg soil dry wt
Krieg, 1999
OECD 207 (2)
Report No. 99/10287
GLP
Klimisch score: 1
SAN 656 H
NOEC:
316.5
mg/kg soil dry wt
Soil microbial function
28 d
Soil
Nitrogen
Turnover
Soil
Loamy sand
% - deviation from control
1.4 L/ha
7.0 L/ha
+ 1.7
+ 0.4
ERMA New Zealand Evaluation and Review Report: Application HSR08124
Krieg, 1999
BBA Part VI, 1-1
Report No. 99/10134
GLP
Page 94 of 149
A
Loamy sand
B
- 0.5
- 0.5
Klimisch score: 1
SAN 656 H
Negligible effects.
Soil
Respiration
Soil
Loamy sand
A
Loamy sand
B
% - deviation from control
1.4 L/ha
7.0 L/ha
- 1.5
- 3.0
- 2.4
- 3.6
Krieg, 1999
BBA Part VI, 1-1
Report No. 99/10265
GLP
Klimisch score: 1
SAN 656 H
Negligible effects.
Terrestrial plants
Acute
Seedling
14 d
emergence
EC50
(Shoot length - lettuce):
0.020 lb ai/A
95% CI:
0.0032 – 0.18 lb ai/A
EC50 equivalent to:
0.022 kg/ha
0.029 mg/kg soil d. wt
Hoberg, 1997
FIFRA guidelines
122-1, 123-1
Report No. 97/5175
GLP
Klimisch score: 1
SAN 1289 H
Formulation
EC50
(Shoot weight ryegrass):
0.082 lb ai/A
95% CI:
0.01 – 0.72 lb ai/A
Vegetative
vigour
(Used for
Risk
Assessment
only)
EC50 equivalent to:
0.092 kg ai/ha
Conclusion
Dimethenamid-P and Frontier-P® are classified as 9.2 A due to their toxicity to nontarget plants (Hoberg 1997, Report no. 97/5175).
Sub-class 9.3 Terrestrial vertebrate ecotoxicity
The mammalian toxicity of dimethenamid-P, dimethenamid and Frontier-P has been
addressed under sub-class 6. Key endpoints for both mammalian and avian toxicity
are summarized in Tables A2.14, A2.14A andA2.14B.
Table A2.14: Summary of terrestrial vertebrate toxicity data for dimethenamidP (SAN 1289 H).
Test
species
Mammals
Rat
SpragueDawley rats
Test type
&
duration
Test results a, b
Oral
intubation
LD50:
429 mg/kg bw (males)
Test method c
[reference number]
SAN 1289 H
ERMA New Zealand Evaluation and Review Report: Application HSR08124
Blaszcak, D (1996)
FIFRA Guideline 81Page 95 of 149
LD50:
531 mg/kg bw (females)
Birds
Northern
Bobwhite
Quail
Colinus
virginianus
Acute Oral
14 days
1
GLP
Klimisch score: 1
SAN 1289
LD50:
1068 mg/kg
95% CI:
845 – 1356 mg/kg
Palmer & Beavers,
1996
FIFRA 71-1
Report No. 96/5419
GLP
NOEC:
Klimisch score: 1
< 292 mg/kg
SAN 1289H
Acute
LC50:
Palmer et al, 1996
Northern
Dietary
> 5620 ppm
FIFRA 71-2
Bobwhite
8 days
OECD 205
Quail
NOEC:
Report No. 96/5412
Colinus
1780 ppm
GLP
virginianus
Klimisch score: 1
SAN 1289H
Acute
LC50:
Palmer et al, 1996
Mallard
Dietary
> 5620 ppm
FIFRA 71-2
duck
8 days
OECD 205
Anas
NOEC:
Report No. 96/5419
platyrhynchos
1780 ppm
GLP
Klimisch score: 1
SAN 1289H
a
Results are reported on the basis of nominal concentrations except where otherwise stated, Standard
test guidelines provide for reporting of results on a nominal basis where measurements indicate the test
substance remains within 20% of nominal.
b
95% confidence intervals are stated where available
c
Unless otherwise stated, the tests were conducted according to the test method identified
Table A2.14A: Summary of terrestrial vertebrate toxicity data for dimethenamid
(SAN 582 H).
Test type
&
duration
Test results a, b
Acute Oral
14 days
LD50:
1908 mg/ kg
95% CI:
1486 – 3229 mg/kg
NOEC:
< 292 mg/kg
Northern
Bobwhite
Quail
Colinus
virginianus
Acute
Dietary
8 days
LC50:
> 5620 ppm
Mallard
duck
Anas
platyrhynchos
Acute
Dietary
8 days
Test
species
Birds
Northern
Bobwhite
Quail
Colinus
virginianus
Test method c
[reference number]
SAN 582 H
NOEC:
1780 ppm
LC50:
> 5620 ppm
NOEC:
562 ppm
ERMA New Zealand Evaluation and Review Report: Application HSR08124
Grimes & Jaber,
1988
FIFRA 71-1
Report No. 88/11373
GLP
Klimisch score: 1
SAN 582 H
Hinken et al. 1988
FIFRA 71-2
Report No. 88/11370
GLP
Klimisch score: 1
SAN 582 H
Grimes & Jaber,
1988
FIFRA 71-2
Report No. 88/11369
GLP
Klimisch score: 1
Page 96 of 149
Northern
Bobwhite
Quail
Colinus
virginianus
Reproduction
20 weeks
NOEC
(number of eggs laid per hen)
1800 ppm
NOEL
220.75 mg ai/kg bw/day
NOEC
(mean eggshell thickness)
900 ppm
NOEL
113.52 mg ai/kg bw/day
SAN 582 H
Beavers et al, 1992
FIFRA 71-4
OECD 206
Report No. 94/11900
GLP
Klimisch score: 1
SAN 582 H
NOEC
(proportion of eggs set that are fertile eggs per
hen or number viable embryos over number of
eggs set)
1800 ppm
NOEL
220.75 mg ai/kg bw/day
NOEC
(proportion of fertile eggs hatching per hen or
percent hatching of viable embryos)
1800 ppm
NOEL
220.75 mg ai/kg bw/day
NOEC
(proportion of 14-day old juveniles per number
of hatchlings)
1800 ppm
NOEL
218.05 mg ai/kg bw/day
Mallard
duck
Anas
platyrhynchos
Reproduction
20 weeks
NOEC
(14-day juvenile weights per hen)
1800 ppm
NOEL
218.05 mg ai/kg bw/day
NOEC
(number of eggs laid per hen)
1800 ppm
NOEL
257.86 mg ai/kg bw/day
NOEC
(mean eggshell thickness)
1800 ppm
NOEL
268.83 mg ai/kg bw/day
Beavers et al, 1994
FIFRA 71-4
OECD 206
Report No. 94/11899
GLP
Klimisch score: 1
SAN 582 H
NOEC
(proportion of eggs set that are fertile per hen or
number viable embryos over number of eggs
set)
1800 ppm
NOEL
257.86 mg ai/kg bw/day
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NOEC
(proportion of fertile eggs that hatch per hen or
percent hatching of viable embryos)
1800 ppm
NOEL
257.86 mg ai/kg bw/day
NOEC
(proportion of 14-day old juveniles per number
of hatchlings)
1800 ppm
NOEL
268.83 mg ai/kg bw/day
NOEC
(14-day juvenile weights per hen)
1800 ppm
NOEL
268.83 mg ai/kg bw/day
a
Results are reported on the basis of nominal concentrations except where otherwise stated, Standard
test guidelines provide for reporting of results on a nominal basis where measurements indicate the test
substance remains within 20% of nominal.
b
95% confidence intervals are stated where available
c
Unless otherwise stated, the tests were conducted according to the test method identified
Table A2.14B: Summary of terrestrial vertebrate toxicity data for Frontier-P®
(BAS 656 08 H).
Test
species
Mammals
Rat
Wistar rats
Test type
&
duration
Test results a, b
Oral
LD50:
> 500 - < 2000 mg/kg
bw*
Test method c
[reference number]
BAS 656 08 H
Metabolites
Gamer, A. O. and R.
Lansiedel (2006).
OECD 423
EC Directive
2004/73 No. 1216
B.1 tris.
USEPA OPPTS
870.1100
GLP
Klimisch score: 1
BAS 656 08H
*Note: Acute toxicity studies with a previously tested but very similar formulation of
Frontier-P (BAS 656 07H) have shown an LD50 of 1581 mg/kg bw (See Table A2.8).
As a result, instead of a 9.3B classification being assigned to the product based on the
conservative 500 mg/kg bw value, a 9.3C has been assigned based on the read-across
from the aforementioned data.
Conclusion
Dimethenamid-P is classified as 9.3B due to its toxicity to mammals (Blaszcak, D
(1996), Report No.96-1404).
Frontier-P® is classified as 9.3C due to its toxicity to mammals (Gamer and
Landsiedel, 2006, Table A2.8).
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Sub-class 9.4 Terrestrial invertebrate ecotoxicity
A summary of the data on the toxicity of dimethenamid-P (dimethenamid) and
Frontier-P to honeybees and other non-target terrestrial invertebrates is provided in
Table A2.15 and Table A2.15A.
Table A2.15: Summary of terrestrial invertebrate toxicity data for
dimethenamid.
Test species
Test type &
duration
Test results a, b
Active
Honey bee
Apis
melliferacarnica
Acute
Oral Toxicity
24 h
Oral LD50:
> 1000 μg/bee
Acute
Contact Toxicity
24 h
Contact LD50:
94 μg/bee
Test method c
[Reference number]
Metabolites
Donat, 1986
Report No. 86/11170
Not GLP*
Klimisch score: 4*
Donat, 1990
Report No. 90/11149
Amendment
a
Results are reported on the basis of nominal concentrations except where otherwise stated, Standard
test guidelines provide for reporting of results on a nominal basis where measurements indicate the test
substance remains within 20% of nominal.
b
95% confidence intervals are stated where available
c
Unless otherwise stated, the tests were conducted according to the test method identified
Table A2.15A: Summary of terrestrial invertebrate toxicity data for Frontier-P
(BAS 656 07 H).
Honey bee
Apis
melliferacarnica
Acute
Oral
Toxicity
48 h
Acute
Contact
Toxicity
48 h
Oral LD50:
> 200 μg/bee (205 μg/bee)
NOEC:
< 124.76 μg/bee
Note:
The actual uptaken test substance in the highest
dose was 200 μg/bee and caused 53.3% mortality
after 48h. At 150 μg/bee mortality was 36.7% after
48 h.
Sack, 1999
EPPO No. 170
Report No.
99/10373
GLP
Klimisch score:
1
BAS 656 07 H
Contact LD50:
> 200 μg/bee (1373 μg/bee)
NOEC:
< 200 μg/bee
Note:
In this test neither the highest dose nor lower doses
caused relevant bee mortality (i.e., > 50%). At 200
μg/bee 16.7%, at 150 μg/bee 36.7%.
In the limit test (200 μg/bee) and the multiple dose
tests all bees in the highest doses were negatively
affected 24h. The test bees at the doses of 200, 150
and 100 μg/bee appeared wet and moved only their
legs, unable to reach the feeding tube. They did not
recover until the end of the trial.
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a
Results are reported on the basis of nominal concentrations except where otherwise stated, Standard
test guidelines provide for reporting of results on a nominal basis where measurements indicate the test
substance remains within 20% of nominal.
b
95% confidence intervals are stated where available
c
Unless otherwise stated, the tests were conducted according to the test method identified
Conclusion
Based on the information (Table A2.12 and Table A2.12A), dimethenamid-P and
Frontier–P do not trigger the threshold for toxicity to terrestrial invertebrates.
Table A2.16: Summary of ecotoxicity classifications for dimethenamid-P and
Frontier–P
Sub-class
dimethenamid-P
Frontier–P
9.1 Aquatic ecotoxicity
9.1A highly ecotoxic to the
aquatic environment
9.1A highly ecotoxic to the
aquatic environment
9.2 Soil ecotoxicity
9.2A highly ecotoxic to the soil
environment
9.2A highly ecotoxic to the soil
environment
9.3 Terrestrial vertebrate
ecotoxicity
9.3B ecotoxic to the terrestrial
vertebrates
9.3C harmful to terrestrial
vertebrates
9.4 Terrestrial invertebrate
ecotoxicity
No classification triggered
No classification triggered
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APPENDIX 3: RISK ASSESSMENT
Introduction
Quantitative risk assessments have been carried out to evaluate the level of risk to operators,
bystanders and the environment arising from the use of Frontier-P.
Qualitative assessments have been undertaken for all other stages of the lifecycle. In these
cases, the level of risk has been evaluated on the basis of the magnitude and likelihood of
adverse effects occurring to people or the environment (see Appendix 6 for a description of
the scales used for qualitative assessment).
Human health risk assessment
Assessment of risks to human health – manufacture and packaging
The Agency has qualitatively assessed the risks of Frontier-P to human health and safety
during manufacture and packaging and considers the risks to be negligible.
This assessment is based on the following considerations:

Manufacturing and packaging facilities for Frontier-P will be required to meet the
HSNO requirements for equipment, emergency management and provision of
information (e.g. Safety Data Sheets (SDS)) as well as the requirements of Good
Manufacturing Practice (GMP) and the Health and Safety in Employment Act (H&SE
Act).

The Agency considers that, while Frontier-P has the potential to cause a major adverse
effect through its acute oral toxicity, workers handling the substance will be aware of
the hazards and the measures that need to be undertaken to ensure their own safety and
will not ingest sufficient substance to result in a major adverse effect. Even a
moderate effect is highly improbable.

The Agency considers that it is highly improbable that workers will suffer skin or eye
irritancy from Frontier-P, given requirements for personal protective equipment
(PPE), and compliance with HSNO information provisions (e.g. labels, advertising,
SDS). Furthermore, the magnitude of skin and eye irritancy is considered minimal,
given the temporary nature of effects.

The Agency considers that it is highly improbable that workers will receive skin
sensitisation from Frontier-P, given requirements for PPE and compliance with the
HSNO information provisions (e.g. labels, advertising and SDS). The magnitude of
skin sensitisation is considered minor to moderate based on the sensitivity of the
exposed parties.
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
Quantitative assessment of the chronic risks to human health associated with exposure
to Frontier-P during use, indicated an acceptable level of risk as long as PPE was used.
As workers involved in manufacture and packing of Frontier-P will be required to
comply with the requirements for PPE as well as comply with Department of Labour
(DoL) requirements for health and safety, the Agency considers the level of risk to
workers to be negligible.

The Agency considers the risk of repeated exposure to bystanders during manufacture
is sufficiently remote that it is not necessary to address, given that the general public
are normally excluded from manufacturing facilities.
Assessment of risks to human health – importation, storage and transport
The Agency has qualitatively assessed the risk of Frontier-P to human health and safety
during importation, transportation and storage and considers the risks to be negligible.
This assessment is based on the following considerations:

Workers and bystanders could only be exposed to the substance during transport and
storage in isolated incidents where spillage occurs.

In these circumstances, the Agency considers it highly improbable that workers or
bystanders will ingest sufficient Frontier-P to result in a moderate adverse effect.

The Agency considers that it is highly improbable that a spillage of Frontier-P will
occur during importation, transport or storage and workers or bystanders will suffer
skin or eye irritancy, given adherence to the HSNO controls (e.g. packaging,
identification and emergency management) and the Land Transport Rule 45001, Civil
Aviation Act 1990 and Maritime Transport Act 1994 (as applicable). Furthermore, the
magnitude of skin and eye irritancy is considered minimal, given the temporary nature
of effects.

The Agency considers that it is highly improbable that a spillage of Frontier-P will
occur during importation, transport or storage and workers or bystanders will suffer
skin sensitisation, given adherence to the HSNO controls (e.g. packaging,
identification and emergency management) and the Land Transport Rule 45001, Civil
Aviation Act 1990 and Maritime Transport Act 1994 (as applicable). The magnitude
of skin sensitisation is considered minor to moderate based on the sensitivity of the
exposed parties.

The Agency considers the risk of carcinogenic effects from Frontier-P during
importation, transport or storage to be sufficiently remote that it is not necessary to
address, given that exposure could only occur in isolated spillage incidents.
Assessment of risks to human health - disposal
The Agency has qualitatively assessed the risk to human health and safety during disposal of
Frontier-P, and considers the risks to the health and safety of people to be negligible.
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This assessment is based on the following considerations:

If Frontier-P is disposed of by means other than use, this will be in accordance with
the requirements of the Hazardous Substances (Disposal) Regulations 2001 and the
Resource Management Act 1991.

The Agency considers that it is highly improbable that users or bystanders could
inadvertently ingest sufficient Frontier-P during disposal to result in an acute
moderate effect, given that Frontier-P will generally be disposed of by use or in
accordance with HSNO controls for disposal (e.g. disposal information requirements
on labels and SDS).

The Agency considers that it is highly improbable that workers will suffer skin or eye
irritancy from Frontier-P during disposal, given that Frontier-P will generally be
disposed of by use. Furthermore, the magnitude of skin and eye irritancy is considered
minimal, given the temporary nature of effects.

The Agency considers that it is highly improbable that workers will suffer skin
sensitisation from Frontier-P during disposal, given that Frontier-P will generally be
disposed of by use. The magnitude of skin sensitisation is considered minor to
moderate based on the sensitivity of the exposed parties.

The Agency notes that quantitative assessment of the chronic risks to operators
associated with exposure to Frontier-P during use indicated an acceptable level of risk
as long as PPE is used. This assessment includes the possibility of prolonged and
repeated exposure to Frontier-P during use. The Agency considers it is less likely that
workers or bystanders could be repeatedly exposed to Frontier-P during disposal to
such an extent that carcinogenic effects occur and therefore considers the chronic risk
to human health during disposal of Frontier-P to be negligible.
Assessment of risks to human health - use
The Agency has qualitatively assessed the acute risks of Frontier-P to human health and
safety during use and considers the risks to be negligible.
This assessment is based on the following considerations:

The Agency considers that it is highly improbable that users or bystanders could
inadvertently ingest sufficient Frontier-P during use to result in an acute moderate
effect, given that Frontier-P will be used in accordance with HSNO controls (e.g. PPE,
approved handlers).

The Agency considers that it is highly improbable that users will suffer skin or eye
irritancy from Frontier-P, given the HSNO requirements for PPE, approved handlers
and provision of hazard and precautionary information on the product label.
Furthermore, the magnitude of skin and eye irritancy is considered minimal, given the
temporary nature of the effects.
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
The Agency considers that it is highly improbable that users will suffer skin
sensitisation from Frontier-P, given the HSNO requirements for PPE, approved
handlers and provision of hazard and precautionary information on the product label.
The magnitude of skin sensitisation is considered minor to moderate based on the
sensitivity of the exposed parties.
Operator Exposure Assessment
The Agency has undertaken an assessment of risks to operator health using the United
Kingdom’s Chemicals Regulation Directorate (Pesticides) interpretation of the German BBA
Model to estimate operator exposure to dimethenamid-P during the use of Frontier–P. This
model estimates the exposure of workers to a pesticide during mixing, loading and during
spray application, in mg/kg person/day (http://www.pesticides.gov.uk/approvals.asp?id=697).
The derived values consider both dermal and inhalation exposure routes.
The BBA model provides for a range of different spray applications (tractor-mounted/trailed
sprayers and hand-held sprayers) and formulation types (liquid, wettable powder and wettable
granule). Additionally, the BBA model also allows flexibility to vary protective clothing
(hands, head and body). Six different scenarios were modelled for Frontier–P as shown in
Table A3.1.
The applicant states that the maximum application rate of Frontier–P is as follows:
 1.3 litres formulation/ha, equivalent to 936 g ai/ha pure dimethenamid-P
However, the Agency has considered the purity of the technical grade active ingredient used
in the formulation of Frontier-P so as to take into account the toxicity of the impurities. This
leads to the following application rate:

1.3 litres formulation/ha, equivalent to 999.7 g a.i./ha technical dimethenamid-P
The Agency has used this maximum application rate for conducting an operator exposure
assessment. Table A3.1 details the estimated exposure for each scenario modelled. The
following points have been taken into account for the purposes of calculating the estimated
exposure. For each model only the conservative scenario as described below, has been
addressed:






the concentration of technical grade dimethenamid-P in Frontier–P = 769 g/L
1.3 L of Frontier–P is applied per hectare
the substance is sprayed using a tractor mounted boom sprayer with hydraulic nozzles;
a work rate of 20 hectares per day (the default value for boom sprayers used in the
German BBA model) is used in the absence of specific work rate data in the New
Zealand context;
a 4% percutaneous absorption value was used for dimethenamid-P (see dermal
penetration studies summary, Table A2.7) from both the formulated product and the
diluted spray; and
the bodyweight for operators is set at 70 kg.
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Table A3.1: Estimated exposure to dimethenamid-P for 70 kg operator under five
different exposure scenarios as predicted from the UK CRD’s interpretation of the BBA
Model
Exposure scenario
No personal protective clothing
and equipment (PPE) during
mixing, loading and
application
Gloves only during mixing and
loading
Gloves only during application
Gloves during mixing/loading
and application
Full PPE during mixing,
loading and application
(excluding respirator)
Full PPE during mixing,
loading and application
(including respirator)
Estimated operator Exposure
(mg/kg bw/day)
0.051
0.024
0.047
0.020
0.002
0.001
Calculation of Acceptable Operator Exposure Level (AOEL)
The toxicological endpoint for assessment of occupational (worker) and bystander risks is the
AOEL (Acceptable Operator Exposure Level). The AOEL is the maximum daily dose
considered to be without adverse health effect for operators, workers and bystanders. It is
based on the most appropriate NOAEL from relevant studies and is calculated by dividing the
NOAEL by one or more uncertainty (safety) factors selected on the basis of the extent and
quality of the available data, the species for which data are available and the nature of the
effects observed.
AOEL = NOEL (most relevant study)
Safety Factors
Selection of NOEL:
The Agency has established the following NOAEL to consider as the basis for the AOEL for
dimethenamid:
 13 week oral toxicity study in beagle dogs, 5 mg/kg bw/day
 52 week oral toxicity study in beagle dogs, 1.95 mg/kg bw/day
With respect to assigning an appropriate NOAEL to calculate the AOEL, the Agency has
taken the likely duration and frequency of worker exposure into consideration. Given these
factors, the Agency considers it appropriate to use the NOAEL of 1.95 mg/kg bw/day from
the study detailed above.
In calculating the AOEL, the Agency has used a combined safety factor of 100 to account for
intra- and interspecies variation. Additionally, an oral absorption factor of 90% (see ADME
summary in Table A2.7) has been applied by the Agency.
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AOEL = 1.95 mg/kg bw/day x 90% = 0.018 mg/kg bw/day.
100
Calculation of Risk Quotients and operator risk assessment
To assess the risks to operators the Agency has divided the estimated exposure values as
calculated from the exposure modelling by the AOEL to derive a risk quotient (RQ) for each
exposure scenario modelled (Table A3.2).
RQ = Estimated Operator (or Bystander) Exposure
AOEL
A RQ > 1 indicates the likelihood of a risk to the operator (or bystander).
Table A3.2: Risk quotients determined for each exposure scenario for Frontier–P.
Exposure scenario
Estimated operator
RQ
Exposure (mg/kg bw/day)
No personal protective
0.051
2.83
clothing and equipment
(PPE) during mixing,
loading and application
Gloves only during mixing
0.024
1.33
and loading
Gloves only during
0.047
2.61
application
Gloves during
0.020
1.11
mixing/loading and
application
Full PPE during mixing,
0.002
0.11
loading and application
(excluding respirator)
Full PPE during mixing,
0.001
0.06
loading and application
(including respirator)
The only exposure situations in which risks to operators is considered to be acceptable
(RQ < 1) is when full PPE is worn during mixing, loading and applying the substance, either
with or without a respirator. This indicates full PPE should be worn by operators when
mixing, loading and/or applying Frontier–P. The Agency notes that PPE is triggered as a
default control for Frontier–P as a result of its 6.1D, 6.5B and 6.7B classifications.
Re-entry exposures
In respect of potential re-entry exposures, these were not estimated for Frontier–P. Since the
substance is applied pre-emergence or early post-emergence, there is no likelihood of
extensive contact between a re-entry worker and treated foliage during re-entry operations.
Public health exposure and risk assessment
The main potential source of exposure to the general public from Frontier–P (other than via
food residues which will be considered as part of the registration of this substance under the
Agricultural Compounds and Veterinary Medicines (ACVM) Act 1997) is via spray drift.
ERMA New Zealand Evaluation and Review Report: Application HSR08124
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The results from the quantitative modelling of operator exposure indicate there is an
unacceptable risk to operators from Frontier–P unless full PPE (with or without respirator) is
worn. The Agency notes that although any potential bystanders will not be wearing PPE, they
will not be directly handling the substance.
By-stander Exposure
The Agency has undertaken an assessment of risks to public/bystander health using the
United Kingdom Chemicals Regulation Directorate, Pesticides (CRD) current formula to
assess public/bystander exposure for pesticides which are of low volatility and which are
typically applied as sprays either by boom sprayers, broadcast air assisted sprayers or hand
held sprayers
http://www.pesticides.gov.uk/applicant_guide.asp?id=1246&link=%2Fuploadedfiles%2FWeb
%5FAssets%2FPSD%2FBystander%2520exposure%2520guidance%5Ffinal%2520version%
2Epdf
The CRD guidance document considers a number of scenarios for bystander exposure.
The Agency has undertaken the assessment of risks to public/bystander health using the
formula that estimates the exposure of the public/bystanders at the time of application (spray
drift) which is:
Systemic exposure = {(PDE x SC x %absorbed) + (PIE x SC x 100%)}/BW
Tractormounted/trailed
boom sprayer:
hydraulic nozzles
PDE (potential
dermal
exposure)
SC (concentration
of dimethenamid-P
in spray)
0.1 ml spray
3.33 mg/ml
% absorbed
(percentage
dermal
absorption)
4%
PIE (potential
inhalation
exposure)
BW
(bodyweight
70 kg).
0.006 ml spray
70 kg
SC calculation:
 recommended maximum application rate = 1300 ml product/ha with 300 L of
water/ha;
 concentration of technical grade dimethenamid-P technical in Frontier-P = 769 g/l,
therefore amount in 1.3 L = 1.3 X 769 = 999.7 g;
 This implies that 300 L of spray contains 999.7g dimethenamid-P technical;
 Therefore, concentration of dimethenamid-P technical in spray = 999.7/300 g/L =
3.33 mg/ml
The following measurements are default values used by the CRD and have been adopted by
the Agency for the purposes of calculating the estimated exposure from spray drift:
 For boom spray, the average potential dermal exposure for a bystander, positioned 8
meters downwind from the sprayer and the average estimated amount of spray passing
through the breathing zone are 0.1 and 0.006 ml spray/person, respectively.
Using these data, exposure to dimethenamid-P from the use of FRONTIER-P can be
estimated as follows assuming no protection from clothing and 100% inhalation, retention and
absorption of PIE:
Systemic exposure
= [(PDE x SC x % absorbed) + (PIE x SC x 100%)]/BW
= [(0.1 x 3.33 x 0.04) + (0.006 x 3.33 x 1)]/70
ERMA New Zealand Evaluation and Review Report: Application HSR08124
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= 0.0005 mg/kg bw/day
RQ = Bystander Exposure/AOEL = 0.0005/0.018 = 0.03
Therefore, risks to the general public are considered to be at acceptable levels (RQ < 1) from
ground based applications.
Risks from Aerial Application
The Chemicals Registration Directorate (CRD)’s Bystander Model does not consider risk
arising from aerial application of a substance. The Agency acknowledges that spray drift from
aerial applications is likely to be greater than for ground based applications, potentially
increasing bystander exposure. The Agency notes that although any potential bystanders will
not be wearing PPE, they will not be directly handling the substance. Applying a drift factor
of 13% (aerial spray - default) determined in the GENEEC 2 environmental exposure
modeling, the Agency estimates the exposure of bystanders to be 13% of the calculated
operator exposure (no PPE) given in Table A3.2:
Exposure from aerial application
= 0.13 x 0.051
= 0.007 mg/kg bw
RQ = Bystander Exposure/AOEL = 0.007/0.018 = 0.37.
Since RQ < 1, the Agency considers that aerial application of Frontier-P is unlikely to pose
unacceptable risk to bystanders.
Exposure of Children
It is also possible that spray drift fallout from applications may be deposited in gardens
adjacent to treated areas and individuals in such locations may become exposed through
contact with such deposits. Total children’s exposure is estimated using the CRD Bystander
Exposure Guidance as detailed below.
a) Spray Drift fallout:
Allowing for an untreated headland of 1 m, the fallout from spray drift at the boundary with a
neighboring area is predicted to be equivalent to 2.77% of the applied dose, declining to
0.57% at a distance of 5m from the boundary. The total level of fallout over the whole area
from boundary to a point 3 m outside is estimated to be about 1%.
b) Children’s Dermal Exposure:
Systemic dermal exposure SE(d) can be calculated using the fallout values and the equation
SE(d)
= (AR x DF x TTR x TC x H x DA)/BW
Where,
 Field application rate (AR) = 0.9997 kg/ha or ~1 kg / 10,000 m2 = 1kg/108 cm2
= 1000000000 / 108 mg cm-2
= 10 μg / cm2
 Drift fallout (DF) is assumed to average 1% from field crop (boom) sprayer applications
 Turf transferable residues (TTR) is estimated at 5%, the EPA default value
 Transfer coefficient (TC) = 5200 cm2/h, the standard EPA value
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


Exposure duration (H) in hours for a typical day is assumed to be 2 hours, which matches
the 75th percentile for toddlers playing on grass in the EPA Exposure Factors Handbook
DA = percent dermal absorption
BW = body weight – assumed to be 15kg for a 2-3 year old toddler
Therefore,
SE(d)
= (10 x 0.01 x 0.05 x 5200 x 2 x 0.04)/15
= 0.14 μg /kg bw
c) Children’s hand-to-mouth exposure:
Systemic dermal exposure via the hand-to-mouth route, SE(h), can be calculated using the
fallout values and the equation
SE(h)
= (AR x DF x TTR x SE x SA x Freq x H)/BW
Where,
 Field application rate (AR) = 10 μg / cm2
 Drift fallout (DF) is assumed to average 1% from field crop (boom) sprayer
applications
 Turf transferable residues (TTR) is estimated at 5%, the EPA default value
 Saliva extraction factor (SE) = 50%, the default value
 SA = surface area of the hands, the assumption used here is that 20 cm2 of skin area is
contacted each time a child puts a hand into their mouth (this is equivalent to the
palmer surface of three fingers and is also related to the next parameter)
 Freq = frequency of hand to mouth events per hour – for short term exposures the
value of 20 events /hour is used, this is the 90th percentile of observations that range
from 0 to 70 events / hour
 Exposure duration (H) in hours for a typical day is assumed to be 2 hours, which
matches the 75th percentile for toddlers playing on grass in the EPA Exposure Factors
Handbook
 BW = body weight – assumed to be 15kg for a 2-3 year old toddler
Therefore,
SE(h)
= (10 x 0.01 x 0.05 x 0.5 x 20 x 20 x 2)/15
= 0.13 μg /kg bw
d) Children’s object-to-mouth exposure:
Systemic exposure arising from object to mouth events, SE(o), can be calculated using the
equation
SE(o)
= (AR x DF x TTR x IgR)/BW
Where,
 Field application rate (AR) = 10 μg / cm2
 Drift fallout (DF) is assumed to average 1% from field crop (boom) sprayer
applications
 Turf transferable residues (TTR) is estimated at 5%, the EPA default value
 IgR is the ingestion rate for mouthing grass/day. This was assumed to be equivalent to
25cm2 of grass / day
 BW = body weight – assumed to be 15kg for a 2-3 year old toddler
ERMA New Zealand Evaluation and Review Report: Application HSR08124
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Therefore,
SE(h)
= (10 x 0.01 x 0.05 x 25)/15
= 0.008 μg /kg bw
e) Children-as-bystander’s total exposure:
Children’s total exposure (TE) is estimated as the sum of the dermal, hand-to-mouth and
object to mouth exposures i.e.
TE
= SE(d) + SE(h) + SE(o)
= 0.14 + 0.13 + 0.008 μg /kg bw
= 0.28 μg /kg bw
Risk quotient for children
= Total Exposure / AOEL
= 0.00028 mg/kg bw / 0.018 mg/kg bw/day
= 0.02
Therefore, the Agency considers that the risk to children as bystanders arising out of
Frontier-P application is low.
Summary and conclusions of the human risk assessment
The outcome of the quantitative assessment of risks posed to operators and bystanders from
the use of Frontier-P indicates that there is a significant risk to operators if full personal
protective clothing is not used. This risk is addressed by appropriate labeling requirements
and the T5 control.
Bystander risk assessment indicates that Frontier-P, when used as directed on the draft label,
does not pose a significant risk to members of the public.
Environmental exposure and risk assessment
Assessment of environmental risks - manufacture, importation, transport and storage
The Agency has qualitatively assessed the risks to the environment of Frontier-P during
manufacture, importation, transportation and storage and considers the risks to be negligible.
This assessment is based on the following considerations:

The magnitude of adverse effects on the environment from a spillage during
manufacture, importation, transport or storage are considered by the Agency to be
moderate, as although the substance is very toxic to the aquatic environment, very
toxic to the soil environment and harmful to terrestrial vertebrates, any spill would
involve small quantities which would lead to localised effects only.
ERMA New Zealand Evaluation and Review Report: Application HSR08124
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
The Agency also considers such an event to be highly improbable given adherence to
the HSNO controls (e.g. packaging, identification and emergency management) and
the Land Transport Rule 45001, Civil Aviation Act 1990 and Maritime Transport Act
1994 (as applicable).
Assessment of environmental risks – disposal
The Agency has qualitatively assessed the risks to the environment of disposal of Frontier-P
and considers the risks to be negligible.
This assessment is based on the following considerations:

Frontier-P will generally be disposed of by normal use as a herbicide.

If Frontier-P is disposed of by means other than use, this will be in accordance with
the requirements of the Hazardous Substances (Disposal) Regulations 2001 and the
Resource Management Act 1991. The Agency considers the likelihood of adverse
effects to the environment arising from disposal to be highly improbable and the
magnitude of such effects minor.
Assessment of environmental risks - use
For Class 9 substances, irrespective of the intrinsic hazard classification, the ecological risk
can be assessed for a substance by calculating a risk quotient based on an estimated exposure
concentration. Such calculations incorporate toxicity values, exposure scenarios (including
spray drift, application rates and frequencies), and the half lives of the component(s) in soil
and water. The calculations provide an Estimated Environmental Concentration (EEC) which,
when divided by the LC50 or EC50, gives a risk quotient (RQ).
Acute RQ =
EECshort term
LC50 or EC50
Chronic RQ = EEClong term
NOEC
If the RQ exceeds a predefined level of concern, this suggests that it may be appropriate to
refine the assessment or to apply the approved handler control (AH) control and/or other
controls to ensure that appropriate matters are taken into account to minimize off-site
movement of the substance. Conversely, if a worst-case scenario is used, and the level of
concern is not exceeded, then in terms of the environment, there is a presumption of low risk
which is able to be adequately managed by such things as label statements (warnings,
disposal). The AH control can then be removed on a selective basis.
Levels of concern (LOC) developed by the USEPA (Urban and Cook 1986) and adopted by
ERMA New Zealand, to determine whether a substance poses an environmental risk are
provided in Table A3.3.
Table A3.3: Levels of concern as adopted by ERMA New Zealand.
Endpoint
LOC
Presumption
Aquatic (fish, invertebrates)
Acute RQ≥
0.5
High acute risk
Acute RQ
0.1-0.5 Risk can be mitigated through restricted use
Acute RQ<
0.1
Low risk
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Chronic RQ≥
1
High chronic risk
Plants (aquatic and terrestrial)
Acute RQ≥
1
High acute risk
Mammals and birds
Acute dietary
0.5
RQ≥
Acute oral dose 0.5
[granular
products] RQ≥
Chronic RQ≥
1
High acute risk
High acute risk
High chronic risk
Aquatic risk
Assessment of Expected Environmental Concentration
The Agency has used the Generic Estimated Environmental Concentration Model v2
(GENEEC2) surface water exposure model (USEPA 2001) to estimate the EEC of
dimethenamid-P in surface water which may potentially arise as a result of spray drift and
surface runoff from the applicant’s proposed New Zealand use pattern.
The parameters used in the GENEEC2 modelling are listed in Table A3.4 and represent the
recommended use on maize (highest rate) as a conservative estimate.
Table A3.4: Input parameters for GENEEC2 analysis.
Application rate
Dimethenamid-P Reference
1.3 L/ha
Product label
(1 kg ai/ha)
Application frequency
1
Application interval
N/A
Kd
1.23*
Aerobic soil DT50
28.69**
Pesticide wetted in?
No
Product label
Methods of application
Aerial
Ground –
(low boom)
Product label
‘No spray’ zone
NA
Water solubility
1149
Product label
Tong & Su, 1997
Report No. 97/5180
Sabat & Yu, 1992
Report No. 92/12387
Krueger & Bade, 1990
Report No. 90/11105
König, 1995
Report No. 95/10128
Nietschmann & Yu, 1997
Report No. 97/5181
Laster, 1996
Report No.
96/5411
ERMA New Zealand Evaluation and Review Report: Application HSR08124
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Aerobic aquatic DT50
33.4 days***
Aqueous photolysis
DT50
25.7
(noon sunlight at
40°N latitude)
Wyss-Benz & Völkel 1994
Report No. 94/10641
Guirguis, 1997
Report No.
97/5195
*The lowest of the Kd values measured in a non-sand textured soil (i.e. not sand, coarse sand,
fine sand, loamy sand) (USEPA, 2001).
**The soil DT50 value of 28.69 for dimethenamid-P follows the GENEEC2 calculation of the
upper 90% confidence limit on the mean value (n≥2) of the four aerobic laboratory values
(USEPA, 2001).
***Longest value taken in accordance with GENEEC2 guidance document (USEPA, 2001).
Output from the GENEEC2 model.
Aerial application
RUN No.
1 FOR DimethenamidP
ON
maize
* INPUT VALUES *
-------------------------------------------------------------------RATE (#/AC)
No.APPS &
SOIL SOLUBIL
APPL TYPE NO-SPRAY INCORP
ONE(MULT)
INTERVAL
Kd
(PPM )
(%DRIFT)
ZONE(FT) (IN)
-------------------------------------------------------------------.890(
.890)
1
1
1.2 1149.0
AERL_B( 13.0)
.0
.0
FIELD AND STANDARD POND HALFLIFE VALUES (DAYS)
-------------------------------------------------------------------METABOLIC DAYS UNTIL HYDROLYSIS
PHOTOLYSIS
METABOLIC COMBINED
(FIELD)
RAIN/RUNOFF
(POND)
(POND-EFF)
(POND)
(POND)
-------------------------------------------------------------------28.69
2
N/A
25.70- 3186.80
33.40
33.05
GENERIC EECs (IN MICROGRAMS/LITER (PPB))
Version 2.0 Aug 1, 2001
-------------------------------------------------------------------PEAK
MAX 4 DAY
MAX 21 DAY
MAX 60 DAY
MAX 90 DAY
GEEC
AVG GEEC
AVG GEEC
AVG GEEC
AVG GEEC
-------------------------------------------------------------------44.41
43.68
39.56
31.92
27.39
Low boom application
RUN No.
2 FOR DimethenamidP
ON
Maize
* INPUT VALUES *
-------------------------------------------------------------------RATE (#/AC)
No.APPS &
SOIL SOLUBIL
APPL TYPE NO-SPRAY INCORP
ONE(MULT)
INTERVAL
Kd
(PPM )
(%DRIFT)
ZONE(FT) (IN)
-------------------------------------------------------------------.890(
.890)
1
1
1.2 1149.0
GRLOFI( 2.9)
.0
.0
FIELD AND STANDARD POND HALFLIFE VALUES (DAYS)
-------------------------------------------------------------------METABOLIC DAYS UNTIL HYDROLYSIS
PHOTOLYSIS
METABOLIC COMBINED
(FIELD)
RAIN/RUNOFF
(POND)
(POND-EFF)
(POND)
(POND)
-------------------------------------------------------------------28.69
2
N/A
25.70- 3186.80
33.40
33.05
GENERIC EECs (IN MICROGRAMS/LITER (PPB))
Version 2.0 Aug 1, 2001
-------------------------------------------------------------------PEAK
MAX 4 DAY
MAX 21 DAY
MAX 60 DAY
MAX 90 DAY
ERMA New Zealand Evaluation and Review Report: Application HSR08124
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GEEC
AVG GEEC
AVG GEEC
AVG GEEC
AVG GEEC
-------------------------------------------------------------------41.15
40.43
36.60
29.52
25.33
The Estimated Environmental Concentration (EEC) for dimethenamid-P as estimated by
GENEEC2 are:
Aerial application
Peak EEC: 0.04441 mg/L
Chronic EEC: 0.03956 (21 days)
Chronic EEC: 0.02739 (90 days)
Low boom application
Peak EEC: 0.04115 mg/L
Chronic EEC: 0.03660 (21 days)
Chronic EEC: 0.02533 (90 days)
Assessment of acute risk
Table A3.5: Aquatic ecotoxicity endpoints to be used in risk assessment
(formulation data was used where possible).
Exposure
Species
Acute
Onchorynchus mykiss
Daphnia magna
Lemna gibba
Chronic
Onchorynchus mykiss*
Daphnia magna*
LC50 or EC50
(mg formulation/L)
7.94
17.1
0.054
LC50 or EC50
(mg a.i./L)
5.40
11.63
0.037
0.12
1.36
*data from active ingredient
The Estimated Environmental Concentration (EEC) for dimethenamid-P as estimated by
GENEEC2 are shown in Table 3.6, along with the aquatic data for dimethenamid-P for the
most sensitive species tested (further details on these toxicity data are included in Table
A2.7).
Table A3.6: Acute risk quotients derived from the GENEEC2 model and toxicity data
(Aerial application).
Peak EEC from
LC50 or EC50
RQ (Acute)
GENEEC2 (mg/L)
(mg ai/L)
EEC/ LC50 or EC50
Fish
0.04441
5.40
< 0.01
Crustacea
11.63
< 0.01
Algae
0.037
1.20
Table A3.6A: Acute risk quotients derived from the GENEEC2 model and toxicity data
(Low boom application).
Peak EEC from
LC50 or EC50
RQ (Acute)
GENEEC2 (mg/L)
(mg ai/L)
EEC/ LC50 or EC50
Fish
Crustacea
0.04115
6.11
< 0.01
13.15
< 0.01
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Algae
0.037
1.11
When compared against the relevant acute levels of concern (Table A3.1), the acute RQs
derived from the GENEEC2 modeling for dimethenamid-P indicate the following:
Aerial application
For fish and crustacean:
the acute risk is low
For algae and aquatic plants: the acute risk is high
Low boom
For fish and crustacean:
the acute risk is low
For algae and aquatic plants: the acute risk is high
Assessment of chronic risk
Table A3.7: Chronic risk quotients derived from the GENEEC2 model and chronic
aquatic toxicity data (Aerial application).
EEC from GENEEC2 NOEC
RQ (Chronic)
(mg/L)
(mg/L)
EEC/ NOEC
0.02739 (90 days)
Fish
0.12
0.23
Crustacea
0.03956 (21 days)
1.36
0.03
Table A3.7A: Chronic risk quotients derived from the GENEEC2 model and chronic
aquatic toxicity data (Low boom application).
EEC from GENEEC2 NOEC
RQ (Chronic)
(mg/L)
(mg/L)
EEC/ NOEC
0.02533 (90 days)
Fish
0.12
0.21
Crustacea
0.03660 (21 days)
1.36
0.03
When compared against the relevant chronic levels of concern (Table A3.3), the chronic RQs
derived from the GENEEC2 modelling for dimethenamid-P indicate the following:
Aerial application
For fish and crustacean:
For algae:
Low boom
For fish and crustacean:
For algae:
the chronic risk is low
the levels of concern to estimate chronic risks to algae are not
currently defined
the chronic risk is low
the levels of concern to estimate chronic risks to algae are not
currently defined
Terrestrial risk - Aerial Application
Soil exposure - Seedling Emergence
Dimethenamid-P is sprayed at a maximum application rate of 1 kg a.i./ha or 100 mg a.i./m2.
ERMA New Zealand Evaluation and Review Report: Application HSR08124
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If it assumed that the dimethenamid-P is dispersed to a depth of 0.05 m and the density of soil
is 1500 kg/m3, then the 100 mg a.i./m2 dimethenamid-P will be dispersed within 75 kg of
soil/m2 giving 1.333 mg/kg.
If it is assumed that 13% of the dimethenamid-P will be uniformly distributed over a 1 ha area
outside the target area (an assumption based on GENEEC2 modelling), then the concentration
of dimethenamid-P adjacent to a sprayed field would be 0.1733 mg/kg soil.
Dimethenamid-P generates an EC50 value of 0.029 mg/kg, (see Table A2.13B for further
details of this study) for lettuce. Consequently, dimethenamid-P results in a risk quotient of
5.98. The risk to non-target plants is high.
Foliar deposition – Vegetative Vigour
Dimethenamid-P is sprayed at a maximum application rate of 1 kg a.i./ha.
If it is assumed that 13% of the dimethenamid-P will be uniformly distributed over a 1 ha area
outside the target area (an assumption based on GENEEC2 modelling), then the concentration
of dimethenamid-P adjacent to a sprayed field would be 0.13 kg ai/ha.
Dimethenamid-P generates an EC50 value of 0.092 kg ai/ha, (see Table A2.13B for further
details of this study) for lettuce. Consequently, dimethenamid-P results in a risk quotient of
1.41. The risk to non-target plants is high.
Terrestrial risk – Low Boom
Soil exposure - Seedling Emergence
Dimethenamid-P is sprayed at a maximum application rate of 1 kg a.i./ha or 100 mg a.i./m2.
If it assumed that the dimethenamid-P is dispersed to a depth of 0.05 m and the density of soil
is 1500 kg/m3, then the 100 mg a.i./m2 dimethenamid-P will be dispersed within 75 kg of
soil/m2 giving 1.333 mg/kg.
If it is assumed that 2.9% of the dimethenamid-P uniformly distributed over a 1 ha area
outside the target area (an assumption based on GENEEC2 modelling), then the concentration
of dimethenamid-P adjacent to a sprayed field would be 0.039 mg/kg soil.
Dimethenamid-P generates an EC50 value of 0.029 mg/kg, (see Table A2.13B for further
details of this study) for lettuce. Consequently, dimethenamid-P results in a risk quotient of
1.333. The risk to non-target plants is high.
Foliar deposition – Vegetative Vigour
Dimethenamid-P is sprayed at a maximum application rate of 1 kg a.i./ha.
If it is assumed that 2.9% of the dimethenamid-P will be uniformly distributed over a 1 ha
area outside the target area (an assumption based on GENEEC2 modelling), then the
concentration of dimethenamid-P adjacent to a sprayed field would be 0.029 kg ai/ha.
Dimethenamid-P generates an EC50 value of 0.092 kg ai/ha, (see Table A2.13B for further
details of this study) for lettuce. Consequently, dimethenamid-P results in a risk quotient of
0.32. The risk to non-target plants is low.
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Avian Toxicity - Dimethenamid-P
The avian toxicity assessment was performed according to “Risk Assessment to Birds and
Mammals (EFSA 2008)”.
For practical reasons it is useful to conduct the risk assessment in two stages. The screening
step contains simple procedures for the calculation of the TERs (Toxicity Exposure Ratios).
These procedures involve standard scenarios and default values for the exposure estimate
which can be performed with a low input of effort. The tier 1 standard scenarios include
intake via feed and represent a realistic worst case assessment where the exposure scenarios
are selected to reflect a situation where the total daily feed is contaminated. The aim is to
avoid doing detailed evaluations for low risk scenarios while excluding, with sufficient
certainty, false negatives (= risk remains undetected).
Acute toxicity
Screening step
Step 1
Identify which of the indicator species listed in Table I.1 (Annex I) is relevant to the crop.
Step 2
Calculate the daily dietary dose (DDD) for a single application by multiplying the shortcut value
presented in Table I.1 with the application rate in kg/ha.
The DDD is defined by the food intake rate of the species of concern (i.e., the indicator species,
the generic focal species or the focal species), the body weight of the species of concern, the
concentration of a substance in/on fresh diet (appendix 14) and the fraction of the diet obtained in
the treated area.
The estimated food intake rates are based on the daily energy expenditure of the species of
concern, the energy in the food, the ‘energy’ assimilation efficiency of the species of concern, and
the moisture content of the food.
The above information is combined into a single value for a specific species-crop-combination
and termed a ‘short cut value’.
DDD single application = application rate [kg/ha] x short cut value
Step 3
Multiply the daily dietary dose for a single application with an appropriate multiple application
factor for 90th percentile residue data (MAF90) when the substance is applied two or more times.
Or calculate a specific MAF90 according to Appendix 15 for non-standard application intervals.
DDD multiple applications = DDD single application x MAF90
Step 4
Take the appropriate LD50 (mg/kg bw/d) for birds.
Step 5
Calculate the toxicity-exposure-ratio
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TER = LD50 / DDD
Step 6
Compare the TER to the respective trigger value.
TER ≥ 10
No refinement required
TER < 10
Go to first-tier risk assessment (step 7)
Acute toxicity
Table A3.8: Acute avian risk assessment – screening step.
Crop1
Indicator
Short-cut
LD504
Application
(mg/kg)
Species2
value3
rate (kg/ha)
MAF905 TER6
Trigger
value
1
43.25
<10
6.73
<10
(90th percentile RUD)
Bulbs and
onion like
crops
Small
granivorous
bird
Small
omnivorous
bird
24.7
1068
0.9997
158.8
1
Crop type Table I.1 (Annex 1) and Appendix 10
Species type Table I.1 (Annex 1) and Appendix 10
3
Residue Unit Dose (90th percentile) Table I.1 (Annex 1)
4
Geometric mean if multiple species tested
5
Multiple application factor (90th percentile) Table 11 and Appendix 15
6
Toxicity-exposure ratio = LD50 / Estimated environmental concentration
2
Based upon the acute toxicity screening step, dimethenamid-P as a component of Frontier-P
applied according to the manufacturer’s instructions, may be acutely toxic to birds. The risk
assessment requires the refinement of a tier 1 assessment.
First-tier risk assessment
Step 7
Identify all of the generic focal species listed in Table I.3 (annex I) that are relevant for the
crop.
Step 8
Calculate the daily dietary dose (DDD) for a single application for each generic focal species
by multiplying the shortcut value presented in Table I.3 with the application rate in kg/ha.
DDD single application = application rate [kg/ha] x short cut value
Step 9
Multiply the DDD for a single application with an appropriate multiple application factor for
90th percentile residue data (MAF90) when the substance is applied two or more times (see
Table 11). Or calculate a specific MAF90 according to Appendix 15 for non-standard
application intervals.
DDD multiple applications = DDD single application x MAF90
Step 10
Take the appropriate LD50 for birds (as in step 4).
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Step 11
Calculate the toxicity exposure ratio:
TER = LD50 / DDD
Step 12
Compare the TER to the respective trigger.
All TERs ≥ 10
One or more of the TERs < 10
No refinement required
Higher tier risk assessment required.
Acute avian risk assessment – Refining step (Tier 1)
Table A3.9: Summary of values applied in the phase specific approach
(bulbs and onion-like crops).
Crop
Indicator
Short-cut
LD504
Application MAF905 TER6
(mg/kg)
Stage
Species
value
rate (kg/ha)
Trigger
value
(Mean RUD)
BBCH
10-39
BBCH
10-19
BBCH
10-19
Finch
24.7
Lark
Wagtail
1068
0.9997
1
43.25
<10
24
44.51
<10
26.8
39.86
<10
Based upon the refined risk assessment for acute toxicity (Tier 1), dimethenamid-P as a
component of Frontier-P applied according to the manufacturer’s instructions, is unlikely to
be acutely toxic to birds.
Chronic toxicity
Steps to determine the reproductive risk to birds
It should be noted that the initial steps are based on worst-case assumptions and should be
used to identify those substances and associated uses that do not pose a risk to birds and hence
for which no further reproductive risk assessment is required.
Step 1
Determine if breeding birds will be exposed to either the active substance or the associated
product.
Step 2
If exposure is possible, the lowest NOAEL from the avian reproduction study/studies should
be determined. It should be noted that the endpoints from the current guidelines are presented
as ppm diet or mg a.s./kg diet. Therefore, it is necessary to convert the endpoints to daily
doses, i.e. mg a.s./kg bw/d. In the first instance a generic factor of 0.1 can be used and applied
to the ppm or mg a.s./kg food endpoint.
Step 3
Identify the appropriate indicator species and mean shortcut value for the crop under
assessment from Table I.1 in Annex 1 and multiply this by the application rate in kg a.s./ha. If
multiple applications are to be made, then the appropriate ‘multiple application factor’ or
MAFm should be used.
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DDD = application rate x short-cut value x MAFm
Step 4
Compare the lowest NOAEL to the DDD generated.
TER ≥ 5
TER< 5
No refinement required
Go to phase-specific approach (step 5)
Chronic toxicity
Table A3.10: Chronic avian risk assessment – screening step.
Crop1
Indicator
Short-cut NOAEL4
Application
2
3
mg
ai/kg
bw/d
Species
value
rate (kg/ha)
MAFm5
TER6
Trigger
value
1
15.33
<5
(Mean RUD)
Bulbs and
onion like
crops
Small
granivorous
bird
Small
omnivorous
bird
11.4
174.69
0.9997
64.8
2.69
1
Crop type Table I.1 (Annex 1) and Appendix 10
Species type Table I.1 (Annex 1) and Appendix 10
3
Residue Unit Dose (Mean) Table I.1 (Annex 1)
4
Most sensitive reproductive parameter (Geometric mean if multiple species tested)
5
Multiple application factor (Mean) Table 11 and Appendix 15
6
Toxicity-exposure ratio = LD50 / Estimated environmental concentration
2
Based upon the chronic toxicity screening step, dimethenamid-P as a component of Frontier-P
applied according to the manufacturer’s instructions, may be chronically toxic to birds. The
risk assessment requires the refinement of a tier 1 assessment.
Chronic avian risk assessment – Refining step (Tier 1)
Step 5
In the phase-specific approach the breeding cycle of birds is divided into five phases, namely:
1) pair formation and establishing site selection;
2) copulation and egg laying ranging from 5 days pre-laying through to the end of the egg-laying
period;
3) incubation and hatching;
4) juvenile growth and survival until fledging; and
5) post-fledging.
Extract the following toxicity endpoints from the avian reproduction studies:
 NOAEL for the number of eggs laid per hen;
 NOAEL for mean eggshell thickness;
 NOAEL for the proportion of fertile eggs per eggs set per hen or number
viable embryos over number of eggs set;
 NOAEL for the proportion of hatching per fertile eggs per hen or percent
hatching of viable embryos;
 NOAEL for the proportion of 14-day old juveniles per number of hatchlings;
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
NOAEL for 14-day juvenile weights per hen.
If more than one avian reproduction study is available, then the above endpoints should be
extracted for each study.
Step 6
Once the above endpoints have been extracted then the endpoints need to be converted to daily
dose using the mean value for food consumption over the whole study and average body weight
over the duration of the study at the NOAEL.
Step 7
If more than one study is available, then the datasets can be either merged or the geometric mean
of the endpoints used.
Step 8
In addition to the above reproductive endpoints, it is also necessary to determine an endpoint to
assess the risk to the phases relevant to chick survival. In order to calculate this endpoint, the LD50
value used in the acute assessment (see section 3.1) should be divided by 10.
Step 9
In order to address uncertainty about the appropriate exposure scenario for the phase-specific
approach, two exposure scenarios are assessed, namely:
1) A scenario where the residue on treated food is assumed to be based on a 1- to 3-day
Period;
2) A scenario where the residue on treated food is assumed to be based on a 21-day period.
For the first scenario, it is assumed that a short exposure could lead to reproductive effects,
whereas in the second scenario it is assumed that long-term exposure could lead to reproductive
effects.
Identify the appropriate crop and generic focal species in Tables I.3 (Annex I). Where more than
one generic focal species is highlighted, the one that is relevant in terms of time of application or
growth stage should be selected. Where there is more than one generic focal species in terms of
timing etc, then it is proposed that risk assessment should be carried out with all relevant generic
focal species and then refined as necessary.
Step 10
Once an appropriate generic focal species has been selected, then the daily dietary dose (DDD)
based on 1-, 2-, 3- and 21-day exposure should be determined. The 1-day DDD uses the initial
exposure estimate. In order to calculate the 2-, 3- and 21-d DDDs it is necessary to multiply by a
time-weighted average (TWA) factor to the initial exposure. For 2 days, the factor is 0.93; for 3
days 0.90 and for 21 days 0.53.
DDD = application rate x short-cut x TWA x MAFm
Step 11
In order to have an exposure estimate for chick survival stage, it is necessary to calculate a 3-day
DDD assuming a shortcut value of 22.7 for chicks fed foliar dwelling insects, and 3.8 for those
fed ground dwelling insects. In the first instance both scenarios should be assessed, unless it can
be justified that one scenario is not relevant to the proposed use.
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Step 12
Compare the above DDD to the relevant phase-specific NOAEL.
Step 13
Interpret the risk assessment following the below table.
Scenario
1 to 3-day ETE
(Effects are based
on short-term
exposure)
21-day ETE
scenarios (i.e.,
effects are based on
long-term
exposure)
Next steps
Assessment outcome
TER ≥ 5
TER < 5
TER < 5
TER ≥ 5
TER ≥ 5
TER < 5
No further
refinement
required.
Further refinement is
required. The outcome
of the risk assessment
indicates that one
possible refinement
step is to try to
determine if the effects
are the result of shortterm exposure.
Further refinement is required.
However, the outcomes of the risk
assessment indicates that little will
be gained by additional effects
data and hence trying to determine
if the effects are the result of shortterm exposure. It is recommended
that refinements should
concentrate on refining the
exposure as well as the potential
consequences of effects.
Chronic avian risk assessment – Refining step (Tier 1)
Table A3.11: Summary of values applied in the phase specific approach.
Species
Short-cut
value
Application
rate (kg/ha)
MAFm
TWA
2 days
TWA
3 days
TWA
21 days
0.9997
1
0.93
0.9
0.53
(Mean RUD)
Finch
Lark
Wagtail
11.4
10.9
11.3
Chick
short-cut
value
3 days
3.8
Chick
short-cut
value
21 days
22.7
Table A3.12: Summary of toxicity values applied in the phase specific approach.
LD50
NOAEL1 NOAEL2 NOAEL3 NOAEL4 NOAEL5 NOAEL6
Geometric
Mean
NOAEL1
NOAEL2
NOAEL3
NOAEL4
NOAEL5
NOAEL6
1068
238.58
174.69
238.58
238.58
242.11
242.11
number of eggs laid per hen
mean egg shell thickness
proportion of viable eggs set per hen
proportion of hatchling per viable eggs per hen
proportion of 14 day old juveniles per number of hatchlings per hen
14 day juvenile weights per hen
Note: Geometric mean of data used (where more than one study available).
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Table A3.13: Pair formation and establishing site selection.
Short term
Long term
LD50/10 and 1 day DDD
LD50/10 and 21 day TWA DDD
Finch TER
9.37
17.68
Lark TER
9.80
18.49
Wagtail TER 9.45
17.84
Trigger level < 5
Table A3.14: Copulation and egg laying.
Short term
NOAEL1 and 1
NOAEL2 and 1
day DDD
day DDD
Finch
20.93
15.33
TER
Lark
21.90
16.03
TER
Wagtail 21.12
15.46
TER
Trigger < 5
level
Table A3.15: Incubation and hatching.
Short term
LD50/10
NOAEL3
NOAEL4
and 1 day and 1 day and 1 day
DDD
DDD
DDD
Finch
TER
Lark
TER
Wagtail
TER
Trigger
level
Long term
NOAEL1 and 21
day TWA DDD
39.50
NOAEL2 and 21
day TWA DDD
28.92
41.31
30.25
39.85
29.18
9.37
20.93
23.26
Long term
LD50/10
and 21
day TWA
DDD
17.68
9.80
21.90
24.33
18.49
41.31
41.31
9.45
21.12
23.47
17.84
39.85
39.85
NOAEL3
and 21
day TWA
DDD
39.5
NOAEL4
and 21
day TWA
DDD
39.5
<5
Table A3.16: Juvenile growth and survival.
Short term
LD50/10
and 2
day
TWA
DDD
Finch
TER
Lark
NOAEL5
and 3
day
TWA
DDD
LD50/10
and 1
day
DDD
LD50/10
and 1
day
DDD
Chick
ground
dwelling
insects
value
Chick
foliar
dwelling
insects
value
10.08
28.11
4.71
23.60
10.54
28.11
4.71
24.69
Long term
LD50/10
LD50/10
and 21
and 21
day
day
TWA
DDD
Chick
DDD
LD50/10
and 21
day
DDD
NOAEL5
and 21
day
TWA
DDD
ground
dwelling
insects
value
Chick
foliar
dwelling
insects
value
17.68
53.04
8.88
40.08
18.49
53.04
8.88
41.92
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TER
Wagtail 10.17
TER
Trigger
level
28.11
4.71
23.81
53.04
8.88
40.44
<5
Table A3.17: Post-fledgling survival.
Short term
LD50/10 and LD50/10
NOAEL6
1 day DDD
and 1 day and 3 day
Chick ground
DDD
DDD
Finch
TER
Lark
TER
Wagtail
TER
Trigger
level
17.84
Long term
LD50/10
and 21
day TWA
DDD
LD50/10
and 21
day TWA
DDD
Chick ground
dwelling
insects value
Chick foliar
dwelling
insects value
NOAEL6
and 21
day TWA
DDD
dwelling insects
value
Chick foliar
dwelling
insects value
28.11
4.71
23.60
53.04
8.88
40.08
28.11
4.71
24.69
53.04
8.88
41.92
28.11
4.71
23.81
53.04
8.88
40.44
<5
Based upon the refined risk assessment for chronic toxicity (Tier 1), dimethenamid-P as a
component of Frontier-P applied according to the manufacturer’s instructions, may be
chronically toxic to chicks and post-fledgling birds. However, the use pattern of the product is
limited to one application per year and output of the modelling shows that the risk appears to
be evident for a short duration only. It has been noted by the Agency that the TERs for shortterm juvenile survival and short-term fledgling survival feeding exclusively on foliar dwelling
insects are based on the daily dietary dose (DDD) which assumes the initial exposure
estimate.
To calculate the 2 day DDD it is necessary to multiply the initial exposure (DDD) by a timeweighted average (TWA) factor. For 2 days, the factor is 0.93 – when this value is factored into
the equation the TER for the above-described scenarios is > 5 indicating no risk to juvenile or
fledgling birds. This calculation indicates that the risk to these birds is transient to the day of
application only.
In addition, the above calculation assumes that the proportion of an animal’s daily diet
obtained in habitat treated with pesticide = 1. In reality, birds may visit a variety of habitats
may obtain their food from a variety of fields rather than the specifically treated field. Given
the closeness of the TER to the cut-off, it is not unreasonable to assume that a small variation
in dietary source will also equate to the low risk threshold being achieved.
Further, registrations in other jurisdictions (EU, USA, Australia and Canada), using different
assessment modelling, have not predicted any chronic effects to birds. However, as a
precautionary measure, the Agency considers that the application rate proposed by the
applicant and used in the modelling should be set as a maximum application rate.
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Risk to Terrestrial Invertebrates (Bees)
The terrestrial invertebrate risk assessment for agricultural pesticides determines whether or
not the proposed application poses an unacceptable risk to terrestrial invertebrates (bees).
The following European model has been adopted by ERMA New Zealand to assess the risk to
bees [Guidance Document on terrestrial ecotoxicology under Council Directive 91/414/EEC,
SANCO/ 10329/2002 rev. 2 final, 17 October 2002].
Hazard Quotient (HQ) = Application Rate / LD50
4.88 = 1000 / 205
Application rate: the maximum single application rate (g active ingredient/ha).
LD50: µg active ingredient/bee.
Conclusion:
Based on the HQ, when dimethenamid-P is applied at 1 kg a.i./ha the risk to bees will be
negligible.
Risk to Beneficial Invertebrates
Table A3.18: Summary of terrestrial invertebrate (beneficial insects) toxicity data for
Frontier-P (BAS 656 07 H).
Test species
Test methodc
[Reference
number]
Test resultsa, b
Formulation
Predatory mite
Typhlodromus
pyri
Effect
Mortality [%]
Mortality corrected
[%]
Mean no.
offspring/female
(+7 to +14)
Mean no.
offspring/female/day
Total Effect [%]
Control
9.0
-
BAS 656 07 H [L/ha]
0.0084 0.14
1.4
9.0
10.0
19.0
0.0
1.1
11.0
8.3
7.4
6.4
6.1
1.19
1.06
0.91
0.87
10
20.9
37.7
Kühner, 1998
Louis/Ufer 1995
(ESCORT 1994)
Report No. 98/1127
GLP
Klimisch score: 1
Conclusion:
Not expected to cause adverse effects up to 1.4 L/ha
application rate.
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Ground beetle
Poecilus cupreus
Effect
Mortality [%]
Mortality corrected
[%]
Feeding capacity
(Mean/replicate)
R in %
Control
0
-
BAS 656 07 H
[L/ha]
1.4
0
0
4.40
3.93
-
10.61
Kühner, 1998
BBA VI 23-2.1.8
ESCORT 1994
Report No. 98/1127
GLP
Klimisch score: 1
Conclusion:
Not expected to cause adverse effects up to 1.4 L/ha
application rate.
Green lacewing
Chrysoperla
carnea
Effect
Mortality [%]
Mortality corrected
[%]
Mean no. fertile
eggs/female/day
Control
4.4
-
BAS 656 07 H
[L/ha]
1.4
8.9
4.7
23.8
25.5
Kühner, 1998
Bigler 1988
ESCORT 1994
Report No. 98/11334
GLP
Klimisch score: 1
-7.1
Reproductive effect
in %
Total Effect [%]
-2.0
Conclusion:
Not expected to cause adverse effects up to 1.4 L/ha
application rate.
Wolf spider
Pardosa spec.
Effect
Mortality corrected
[%]
Food consumption
[%]
Control
6.7
BAS 656 07 H
[L/ha]
1.4
-7.2
100
106
Schmitzer, 1999
BBA draft 1994
Report No. 99/10751
GLP
Klimisch score: 1
Conclusion:
Not expected to cause adverse effects up to 1.4 L/ha
application rate.
Staphylinid
beetle
Aleochara
bilineata
Effect
Mean no offspring
per replicate
Reproductive effect
[%]
Control
680 + 33.8
BAS 656 07 H
[L/ha]
1.4
659 + 75.9
-
3
Kemmeter, 1999
Moreth & Naton
1992
ESCORT 1994
Report No. 99/10856
GLP
Klimisch score: 1
Conclusion:
Not expected to cause adverse effects up to 1.4 L/ha
application rate.
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Parasitic wasp
Aphidius
rhopalosiphi
Tier 1 Test
Effect
Mortality [%]
Mortality corrected
[%]
BAS 656 07 H
[L/ha]
1.4
100
100
Control
2.5
-
Kühner, 1998
Polgar 1988
Mead-Briggs1992
ESCORT 1994
Report No. 98/11334
GLP
Klimisch score: 1
Conclusion:
Frontier-P has significant effects on the mortality of the
parasitic wasp Aphidius rhopalosiphi. Due to the high
mortality a reproductive test was not conducted.
Parasitic wasp
Aphidius
rhopalosiphi
Tier 2 Test
Effect
Control
BAS 656 07 H [L/ha]
0.14
1.4
Mortality [%]
Mortality corrected
[%]
Mean no. mummies
/female
Reproduction factor
5.0
-
2.8
-2.3
5.0
0
10.0
7.7
5.41
-
0.77
0.54
Schuld, 1999
Mead-Briggs (1996)
ESCORT 1994
Report No. 99/10669
GLP
Klimisch score:
1
significantly different to the control (p<0.05)
46 % reduction in reproductive potential.
Conclusion:
As the reduction in reproductive potential is < 50%, Frontier-P
is not expected to cause adverse effects up to 1.4 L/ha (1 kg
ai/ha) application rate.
Risk assessment
In tier 1 testing, Frontier-P caused 100% mortality to the parasitic wasp, Aphidius
rhopalosiphi at the maximum recommended application rate of 1.4 L/ha. Higher tier testing
using a natural substrate resulted in < 10% mortality and < 50% reduction in reproductive
potential. Therefore, Frontier-P is not expected to cause significant adverse effects to
beneficial insects at the New Zealand application rates of 1.4 1.3 L/ha (1 kg a.i/ha).
Tier 1 testing of Typhlodromus pyri, Poecilus cupreus, Chrysoperla carnea, Pardosa spec.,
and Aleochara bilineata at application rates ≤ 1.4L/ha showed negligible adverse effects.
Volatilisation/Evaporation
Final remaining soil radioactivity (SAN 582 H) at the end of the pre-plant incorporated study
was 97.7%. 0.84% of the applied labeled dimethenamid volatilised from the soil (30 days).
Final remaining soil radioactivity at the end of topical (surface applied) study was 96.6%.
1.18% of the applied labeled dimethenamid volatilized from the soil (30 days).
Volatility is an insignificant route in the degradation and environmental dissipation of SAN
582 H.
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Chen & Hsieh, 1993
Report No. 93/11472
Internal protocol
GLP
Klimisch score: 1
The volatilisation rate of dimethenamid (SAN 582 H) from soil or plants was below 20% of
the applied dose. The total amount of volatilised test substance amounted to 6.61% of applied
radiocarbon for soil, and 14.1% of applied radiocarbon for plants. The main portion of
evaporated dimethenamid was found in the condensate, 4.95% and 13.01%, respectively.
Jonas, 1994
Report No. 94/10642
BBA Part IV, 6-1
GLP
Klimisch score: 1
Conclusion:
Based on the above studies the risk of long range transport of dimethenamid would be
negligible.
Summary and conclusions of the ecological risk assessment
Based on the risk assessment for the aquatic and terrestrial environment as set out above, risks
to the following species groups have been identified.
Aerial application
Aquatic plants (Acute risk)
Based on the acute RQs for algae, the Agency considers it is appropriate to retain the
approved handler controls for Frontier–P when it is used in a wide dispersive manner, or by a
commercial contractor for aerial operations.
Terrestrial plants (Soil and foliar deposition)
Based on the RQs for both soil and foliar deposition on plants, the Agency considers it is
appropriate to retain the approved handler controls for Frontier–P when it is used in a wide
dispersive manner, or by a commercial contractor for aerial operations.
Low boom application
Aquatic plants (Acute risk)
Based on the acute RQs for algae, the Agency considers it is appropriate to retain the
approved handler controls for Frontier–P when it is used in a wide dispersive manner, or by a
commercial contractor for ground applications.
Terrestrial plants (Soil deposition)
Based on the RQs for soil deposition effects on plants, the Agency considers it is appropriate
to retain the approved handler controls for Frontier–P when it is used in a wide dispersive
manner, or by a commercial contractor for ground applications.
Further to the approved handler control, the Agency considers that the application rate
proposed by the applicant and used in the modelling should be set as a maximum application
rate.
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For specific information on the controls set see Appendix 4.
References
EPPO 2001. Guideline on the test methods for evaluating the side-effects of plant protection
products. No PP 1/170(3)
EPPO 2002. Environmental risk assessment scheme for plant protection products. Chapter 10
honeybees. EPPO Bulletin 33
http://archives.eppo.org/EPPOStandards/PP3_ERA/pp3-10(2).pdf
ERMA New Zealand 2008a. User Guide to HSNO Thresholds and Classifications. ERMA
New Zealand, Wellington.
European Commission, Guidance Document on terrestrial ecotoxicology under Council
Directive 91/414/EEC, SANCO/ 10329/2002 rev. 2 final, 17 October 2002.
http://ec.europa.eu/food/plant/protection/evaluation/guidance/wrkdoc09_en.pdf
Urban DJ, Cook, NJ 1986. Hazard Evaluation Division Standard Evaluation Procedure:
Ecological Risk Assessment. EPA 540/9-85-001. United States Environmental Protection
Agency Office of Pesticide Programs, Washington DC, USA.
USEPA 2001. Generic Estimated Environmental Concentration Model v2 (GENEEC2).
United States Environmental Protection Agency Office of Pesticide Programs, Washington
DC, USA http://www.epa.gov/oppefed1/models/water/index.htm#geneec2
ERMA New Zealand Evaluation and Review Report: Application HSR08124
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APPENDIX 4: DISCUSSION ON CONTROLS
Based on the hazard classification as shown in Table 6.1, the set of associated controls has
been identified. These default controls, expressed as control codes12, are listed in Table A4.1.
Table A4.1: List of default controls for Frontier-P
Toxicity Controls
T1
Limiting exposure to toxic substances through the setting of TELs
T2
Controlling exposure in places of work through the setting of WESs
T4
Requirements for equipment used to handle substances
T5
Requirements for protective clothing and equipment
T7
Restrictions on the carriage of toxic or corrosive substances on passenger service vehicles
Ecotoxicity Controls
E1
Limiting exposure to ecotoxic substances through the setting of EELs
E2
Restrictions on use of substances in application areas
E5
Requirements for keeping records of use
E6
Requirements for equipment used to handle substances
E7
Approved handler/security requirements for certain ecotoxic substances
Identification Controls
I1
Identification requirements, duties of persons in charge, accessibility, comprehensibility,
clarity and durability
I3
Priority identifiers for ecotoxic substances
I8
Priority identifiers for toxic substances
I9
Secondary identifiers for all hazardous substances
I11
Secondary identifiers for ecotoxic substances
I16
Secondary identifiers for toxic substances
I17
Use of generic names
I18
Requirements for using concentration ranges
I19
Additional information requirements, including situations where substances are in
multiple packaging
I20
Durability of information for class 6.1 substances
I21
General documentation requirements
I23
Specific documentation requirements for ecotoxic substances
I28
Specific documentation requirements for toxic substances
I29
Signage requirements
I30
Advertising corrosive and toxic substances
Packaging Controls
P1
General packaging requirements
P3
Criteria that allow substances to be packaged to a standard not meeting Packing Group I,
II or III criteria
P13
Packaging requirements for toxic substances
P15
Packaging requirements for ecotoxic substances
PG3
Packaging requirements equivalent to UN Packing Group III
PS4
Packaging requirements as specified in Schedule 4
12
Control codes are those assigned by ERMA NZ to enable easy cross reference with the regulations. A
detailed list of these codes is contained in the ERMA New Zealand User Guide to the Controls
Regulations.
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Disposal Controls
D4
Disposal requirements for toxic or corrosive substances
D5
Disposal requirements for ecotoxic substances
D6
Disposal requirements for packages
D7
Information requirements for manufacturers, importers and suppliers, and persons in
charge
D8
Documentation requirements for manufacturers, importers and suppliers, and persons in
charge
Emergency Management Controls
EM1
Level 1 information requirements for suppliers and persons in charge
EM6
Information requirements for toxic substances
EM7
Information requirements for ecotoxic substances
EM8
Level 2 information requirements for suppliers and persons in charge
EM11
Level 3 emergency management requirements: duties of person in charge, emergency
response plans
EM12
Level 3 emergency management requirements: secondary containment
EM13
Level 3 emergency management requirements: signage
Tracking Controls
TR1
General tracking requirements
Approved Handler Controls
AH1
Approved Handler requirements (including test certificate and qualification requirements)
Tank Wagon and Transportable Containers Controls
The Hazardous Substance (Tank Wagons and Transportable Containers) Regulations 2004
prescribe a number of controls relating to tank wagons and transportable containers.
Those controls which require calculations, derivations or extended discussion are considered
in the following sections.
Toxicity Controls
Setting of TELs (Control Code T1)
Tolerable Exposure Limits (TELs) are designed to limit the extent to which the general public
is exposed to hazardous (toxic) substances. A TEL represents the maximum concentration of
a substance legally allowable in a particular medium, and can be set as either a guideline
value or an action level that should not be exceeded. For the purposes of setting TELs, an
environmental medium is defined as air, water, soil or a surface that a hazardous substance
may be deposited onto.
TELs are established from PDE (Potential Daily Exposure) values, which are themselves
established from ADE (Acceptable Daily Exposure) values or reference doses (RfD) which
are similar to ADE but are used to protect against a specific toxic effect of concern.
Human exposure may also occur through food or drinking water. Exposure through food is
managed via the establishment of Maximum Residue Limits (MRLs) as set by the Minister of
Food Safety on the advice of the New Zealand Food Safety Authority (NZFSA). Exposure
through drinking water is managed via the establishment of Maximum Acceptable Values
(MAVs) as set by the Ministry of Health. MRLs and MAVs are also established from ADE
values.
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Setting of PDEs
If an ADE or RfD value is set for a substance, or component of a substance, a PDE value for
each relevant exposure route must also be set. A PDE is an amount of substance (mg/kg
bodyweight/day), calculated in accordance with Regulation 23, that estimates the relative
likelihood of particular exposures. A PDE for any single exposure route is a fraction of the
ADE or RfD, and the sum of all PDE values from all possible exposures must be less than or
equal to the ADE or RfD.
The main routes of exposure considered are ingestion (food, water, air, soil), inhalation (air)
and skin contact (surface deposition, water, soil).
Setting of ADEs
An ADE is an amount of a hazardous substance (mg/kg bodyweight/day), that, given a
lifetime of daily exposure, would be unlikely to result in adverse human health effects. An
RfD (reference dose) is a similar measure that can be used to protect against a specific toxic
effect of concern.
Regulation 11(1) of the Hazardous Substances (Classes 6, 8, and 9 Controls) Regulations
2001 determines when an ADE/RfD is required to be set:
(1)
This regulation applies to a class 6 substance if(a)
it is likely to be present in(i) 1 or more environmental media; or
(ii) food; or
(iii) other matter that might be ingested; AND
(b)
it is a substance to which a person is likely to be exposed on 1 or more
occasions during the lifetime of the person; AND
(c)
exposure to the substance is likely to result in an appreciable toxic
effect.
If all three requirements of regulation 11(1) are met, then an ADE/RfD should be set for the
relevant component(s), and PDE and TEL values subsequently established for each relevant
exposure route.
Where a substance is a pesticides or veterinary medicines active ingredient that is new to New
Zealand and it is intended for use on a food crop or animal, the Agency will propose an ADE
regardless of whether the requirements of Regulation 11 are met as this information may be of
use to NZFSA in setting MRLs.
The Agency considers that the active meets the requirements of Regulation 11(1)(a), (b) and
(c), and therefore notes that an ADE, and subsequently PDEs and TELs are required to be set
for this component.
However, the Agency is intending to review the setting of ADEs, PDEs and TELs under
section 77B of the Act, and until this review is complete, the Agency proposes not to set
TELs for Frontier–P. Noting that Frontier–P is intended for use on food crops and contains
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dimethenamid-P, a new active ingredient to New Zealand, an ADE and PDEfood value are
calculated for this component which will enable the NZFSA to set MRLs is needed.
On review of the relevant toxicology data, the Agency considers that an ADE of 0.018 mg/kg
bw/day should be adopted for dimethenamid-P. Based on this value, and considering the main
ingestion exposure to dimethenamid-P would be via food stuff (70%), drinking water (20%)
and other non-foodstuffs (10%), the Agency proposes that PDEfood = 0.013 mg/kg bw/day
and PDEdrinking water = 0.004 mg/kg bw/day should be set for dimethenamid-P.
Setting of WES (Control Code T2)
Workplace Exposure Standards (WES) are designed to protect persons in the workplace from
the adverse effects of toxic substances. A WES is an airborne concentration of a substance
(expressed as mg substance/m3 of air, or ppm in air), which must not be exceeded in a
workplace and only applies to places of work (Regulation 29(2), Hazardous substances
(Classes 6, 8 and 9 Controls) Regulations 2001).
Regulation 29(1) of the Hazardous Substances (Classes 6, 8, and 9 Controls) Regulations
2001 determines when a WES is required to be set. If all three of the requirements of this
regulation are met then a WES is required to be set.
Regulation 29 states:
(1) This regulation and regulation 30 apply to a class 6 substance if,(a) under the temperature and pressure the substance is to be used in, it can become
airborne and disperse in air in the form of inspirable or respirable dust, mists,
fumes, gases or vapours; AND
(b) human exposure to the substance is primarily through the inhalation or dermal
exposure routes; AND
(c) the toxicological and industrial hygiene data available for the substance is
sufficient to enable a standard to be set.
When setting WES, the Authority must either adopt a value already proposed by the
Department of Labour or already set under HSNO or derive a value by taking into account the
matters described in Regulation 30(2) of the Hazardous Substances (Classes 6, 8, and 9
Controls) Regulations.
The Agency typically adopts WES values listed in the Workplace Exposure Standards
(Effective from 2002) document (refer to the link below).
http://www.osh.govt.nz/order/catalogue/pdf/wes2002.pdf
The Agency notes that at this time Department of Labour WES values have been set for
components C2 and C6 in Frontier–P. Both values are set at 52 mg/m3 air (time-weighted
average). However, the Agency notes that these WES values are of little relevance to
Frontier-P as their concentration is too low for the WES to be applicable.
The Agency further notes that a WES value of 100 mg/m3 has bee set in the European Union
for component A3. Again this WES is not relevant to Frontier-P as the component is present
at a low concentration.
No WES values have been set for the active by any overseas body monitored by the Agency.
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Setting of EELs (Control code E1)
Regulation 33 of the Hazardous Substances (Classes 6, 8, and 9 Controls) Regulations 2001
specify that an environmental exposure limit (EEL) may be set for a class 9 substance for one
or more environmental media if organisms that live in that environment may be exposed to the
substance. An EEL is the (maximum) concentration of a substance in an environmental
medium that will present a negligible risk of adverse environmental effects to organisms
(excluding humans) in non-target areas.
As specified by regulation 32, a default EEL of 0.1 µg/L water is set for any class 9.1
substance, and 1 µg/kg soil (dry weight) for any class 9.2 substance.
For the purposes of setting EELs, an environmental medium is defined as water, soil or
sediment where these are in the natural environment, or a surface onto which a hazardous
substance may be deposited.
An EEL can be established by one of three means:

Applying the default EELs specified in regulation 32

Adopting an established EEL as provided by regulation 35(a)

Calculating an EEL from an assessment of available ecotoxicological data as
provided by regulation 35(b).
The Hazardous Substances and New Organisms (Approvals and Enforcement) Act 2005
added a new section (s77B) to the HSNO Act, which, amongst other things provided the
Authority with the ability to set EELs as guideline values, rather than the previous pass/fail
values.
However, until the Agency has developed formal policy on the implementation of s77B, it
proposes not to set EELs for any components of Frontier–P at this time. It is also proposed
that the default EEL water and soil values be deleted until the policy has been established.
Approved Handler Controls- Highly ecotoxic substances (AH1, E7)
Approved handler requirements have been triggered for Frontier–P as a result of its 9.1A and
9.2A classifications. The outcome of the ecological risk assessment (refer Appendix 3)
indicates that there is potential for adverse environmental effects on aquatic and terrestrial
plants if the substance moves off-target. The Agency considers it is therefore appropriate to
retain the approved handler control.
This approach is consistent with the Authority’s policy on approved handler and tracking
controls for class 9 substances (November 2003).
Tracking control- Highly ecotoxic substances (TR1)
Tracking requirements have been triggered for Frontier–P as a result of its 9.1A and 9.2A
classifications. However, for substance where the tracking control has been triggered solely as
a result of ecotoxicity, it is considered that any risk that may arise during its life-cycle are
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adequately managed by other controls such as approved handler packaging, labelling and
emergence management requirements. The Agency therefore considers the tracking control
can be deleted as provided by section 77(4)(b).
This approach is consistent with the Authority’s policy on approved handler and tracking
controls for class 9 substances (November 2003).
Setting of Application Rate (Control Code E2)
These regulations relate to the requirement to set an application rate for a class 9 substance
that is to be sprayed or applied to an area of land (or air or water) and for which an EEL has
been set.
Although no EEL has been set for Frontier–P, the Agency proposes setting the application
rate of 1 kg ai/ha*, once per season as the application rate for Frontier–P. This rate was used
in the ecological risk assessment.
*Note: the Agency has assumed that the purity of the active ingredient to be 100% to take the
toxicity of any impurities into account considered the purity of the technical grade active
ingredient used in the formulation of Frontier-P so as to take into account the toxicity of the
impurities.
Other controls required as a result of the ecological risk assessment.

This substance is not to be applied onto or into water.
Identification controls
Identification of Toxic Components on Labels/Documentation (SDS)
The Hazardous Substances (Identification) Regulations 2001 specify that certain toxic
components are required to be specified on the product label and on SDS documentation.
Identification of toxic components on labels
Regulations 25(e) and 25(f) require that certain toxic components are required to be specified
on the product label.
Regulation 25(e) states:
...a toxic substance must be identified by...
'information identifying, by its common or chemical name, every ingredient, that would,
independently of any other ingredient, give the substance a hazard classification of 6.1A,
6.1B, 6.1C, 6.5, 6.6, 6.7, 6.8 or 6.9, and the concentration of that ingredient in the substance."
Regulation 25(f) states:
...a toxic substance must be identified by...
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"information identifying (other than an ingredient referred to in paragraph (E)) that would,
independently of any other ingredient, give the substance a hazard classification of 6.1D, and
the concentration of the ingredient that would contribute the most to that classification."
Identification of toxic components on SDS
Regulation 39(5) of the Hazardous Substances (Identification) Regulations 2001, states that
certain corrosive and toxic components are required to be specified on documentation.
Regulations 39(5) states:
"The requirements of regulation 25(e) apply to all documentation; but any ingredient
required by that provision to be identified (other than an ingredient to which regulation 26
applies) must also be identified by any Chemical Abstract Services number allocated to it."
Concentration cut-offs for component identification
Consistent with the guidance provided by GHS, the Hazardous Substances Standing
Committee (HSSC) agreed that the concentration cut-offs triggering the requirement for
identification of components on labels and documentation are:
HSNO Classification
6.5A, 6.5B, 6.6A, 6.7A
6.6B
6.7B
6.8A, 6.8C
6.8B
6.9A, 6.9B
Cut-off for label (% w/w)
0.1
1
1
0.3
3
10
Cut-off for SDS (% w/w)
0.1
1
0.1
0.1
0.1
1
Frontier–P - Components requiring identification
Under these regulations, as determined by the HSSC (March 2006), the name and
concentration of the following components need to be specified on the label and
documentation:
Label
Dimethenamid-P,
Documentation
Dimethenamid-P, A6
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APPENDIX 5: LIST OF PROPOSED CONTROLS FOR
FRONTIER-P
Table A5.1: Proposed controls for Frontier-P – codes, regulations and variations.
Control Regulation Topic
Variations
14
Code13
Hazardous Substances (Classes 6, 8, and 9 Controls) Regulations 2001
T1
11-27
Limiting exposure to toxic
substances
No TEL values are set at this time.
The following ADE and PDE values
are set for dimethenamid-P:
ADE = 0.018 mg/kg bw/day
PDEfood = 0.013 mg/kg bw/ day
PDEwater = 0.004 mg/kg bw/day
T2
29, 30
Controlling exposure in places of
work
No WES values are set for
components in this substance at this
time.
T4/E6
7
Requirements for equipment used to
handle hazardous substances
Controls T4 and E6 are combined.
T5
8
Requirements for protective clothing
and equipment
T7
10
Restrictions on the carriage of toxic
or corrosive substance on passenger
service vehicles
The maximum quantity of substance
allowed is varied from 0.1 L to 1 L.
E1
32-45
Limiting exposure to ecotoxic
substances
No EEL values are set at this time and
the default EELs are deleted.
E2
46-48
Restrictions on use within
application area
As no EELs have been set, no
application rate is required to be set
under this control at this time.
However, an application rate is set as
an additional control under section
77A.
E5
5(2), 6
E7
9
Requirements for keeping records of
use.
Approved handler requirements
The following control is substituted
for Regulation 9(1) of the Hazardous
Substances (Classes 6, 8, and 9
Controls) Regulations 2001:
(1). The substance must be under the
personal control of an approved
Note: The numbering system used in this column relates to the coding system used in the ERMA New Zealand Controls Matrix. This links the
hazard classification categories to the regulatory controls triggered by each category. It is available from the ERMA New Zealand website
www.ermanz.govt.nz/resources and is also contained in the ERMA New Zealand User Guide to the HSNO Control Regulations.
14 These Regulations form the controls applicable to this substance. Refer to the cited Regulations for the formal specification, and for definitions
and exemptions.
13
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Control
Code13
Regulation
Topic
Variations
14
handler when the substance is (a) applied in a wide
dispersive manner; or
(b) used by a commercial
contractor.
Hazardous Substances (Identification) Regulations 2001
I1
6, 7, 32-35,
36 (1)-(7)
General identification requirements
Regulation 6 – Identification duties
of suppliers
Regulation 7 – Identification duties
of persons in charge
Regulations 32 and 33 –
Accessibility of information
Regulations 34, 35, 36(1)-(7) –
Comprehensibility, Clarity and
Durability of information
I3
9
Priority identifiers for ecotoxic
substances
I8
14
Priority identifiers for toxic
substances
I9
18
Secondary identifiers for all
hazardous substances
I11
20
Secondary identifiers for ecotoxic
substances
I16
25
Secondary identifiers for toxic
substances
I17
26
Use of Generic Names
I18
27
Use of Concentration Ranges
Revised cut-offs for component
labelling required by Regulation 25(e)
HSNO
Classification of
Component
Concentration
Cut-off for
Label (%)
6.5A, 6.5B
0.115
6.6A, 6.7A
0.1
6.6B, 6.7B
1
6.8A, 6.8C
0.3
6.8B
3
6.9A, 6.9B
10
For more information about this
variation see paragraph 10.8 of the
main document.
15
Identification of sensitising components may be required below the 0.1% level if a lower value has been
used for classification.
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Control
Code13
I19
Regulation
Topic
Variations
14
29-31
Alternative information in certain
cases
Regulation 29 – Substances in fixed
bulk containers or bulk transport
containers
Regulation 30 – Substances in
multiple packaging
Regulation 31 – Alternative
information when substances are
imported
I20
36(8)
I21
37-39, 4750
Durability of information for class
6.1 substances
Documentation required in places of
work
Regulation 37 – Documentation
duties of suppliers
Regulation 38 – Documentation
duties of persons in charge of places
of work
Regulation 39 – General content
requirements for documentation
Regulation 47 – Information not
included in approval
Regulation 48 – Location and
presentation requirements for
documentation
Regulation 49 – Documentation
requirements for vehicles
Regulation 50 – Documentation to be
supplied on request
I23
41
Specific documentation requirements
for ecotoxic substances
I28
46
Specific documentation requirements
for toxic substances
I29
51-52
Duties of persons in charge of places
with respect to signage
I30
53
Advertising corrosive and toxic
substances
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Control Regulation Topic
14
Code13
Hazardous Substances (Packaging) Regulations 2001
P1
5, 6, 7 (1), 8
Variations
General packaging requirements
Regulation 5 – Ability to retain
contents
Regulation 6 – Packaging markings
Regulation 7(1) – Requirements
when packing hazardous substance
Regulation 8 – Compatibility
P3
9
Regulation 9A and 9B – Large
Packaging
Packaging requirements for
substances packed in limited
quantities
P13
P15
19
21
Packaging requirements for FrontierP
PG3
Schedule 3
The tests in Schedule 3 correlate to
the packaging requirements of UN
Packing Group III (UN PGIII).
PS4
Schedule 4
This schedule describes the
minimum packaging requirements
that must be complied with when a
substance is packaged in limited
quantities
Controls P13 and P15 are combined.
Hazardous Substances (Disposal) Regulations 2001
D4
D5
D6
D7
D8
8
9
10
11, 12
13, 14
Disposal requirements for Frontier-P
EM1
6, 7, 9-11
EM6
8(e)
EM7
8(f)
EM8
EM11
12-16, 1820
25-34
EM12
35-41
Level 1 emergency management
information: General requirements
Information requirements for toxic
substances
Information requirements for
ecotoxic substances
Level 2 emergency management
documentation requirements
Level 3 emergency management
requirements – emergency response
plans
Level 3 emergency management
requirements – secondary
containment
Controls D4 and D5 are combined
Disposal requirements for packages
Disposal information requirements
Disposal documentation
requirements
Hazardous Substances (Emergency Management) Regulations 2001
The following subclauses shall be
added after subclause (3) of
regulation 36:
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Control
Code13
Regulation
Topic
Variations
14
(4)
(5)
For the purposes of this
regulation, and regulations
37 to 40, where this
substance is contained in
pipework that is installed and
operated so as to manage any
loss of containment in the
pipework it—
(a) is not to be taken into
account in determining
whether a place is
required to have a
secondary containment
system; and
(b) is not required to be
located in a secondary
containment system.
In this clause, pipework—
(a) means piping that—
(i) is connected to a
stationary
container; and
(ii) is used to transfer a
hazardous
substance into or
out of the stationary
container; and
(b) includes a process
pipeline or a transfer line.
The following subclauses shall be
added after subclause (1) of
regulation 37:
(2) If pooling substances that do not
have class 1 to 5 hazard
classifications are held in a place
above ground in containers each
of which has a capacity of 60
litres or less—
ERMA New Zealand Evaluation and Review Report: Application HSR08124
(a)
if the place’s total pooling
potential is less than
20,000 litres, the
secondary containment
system must have a
capacity of at least 25% of
that total pooling potential:
(b)
if the place’s total pooling
potential is 20,000 litres or
more, the secondary
containment system must
have a capacity of the
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Control
Code13
Regulation
Topic
Variations
14
greater of—
(i)
5% of the total
pooling potential; or
(ii)
5,000 litres.
(3) Pooling substances to which
subclause (2) applies must be
segregated where appropriate to
ensure that leakage of one
substance may not adversely
affect the container of another
substance.
The following subclauses shall be
added after subclause (1) of
regulation 38:
(2) If pooling substances which do
not have class 1 to 5 hazard
classifications are held in a place
above ground in containers 1 or
more of which have a capacity of
more than 60 litres but none of
which have a capacity of more
than 450 litres—
(a)
if the place’s total pooling
potential is less than
20,000 litres, the
secondary containment
system must have a
capacity of either 25% of
that total pooling potential
or 110% of the capacity of
the largest container,
whichever is the greater:
(b)
if the place’s total pooling
potential is 20,000 litres or
more, the secondary
containment system must
have a capacity of the
greater of—
(i)
5% of the total
pooling potential; or
(ii)
5,000 litres
(3) Pooling substances to which
subclause (2) applies must be
segregated where appropriate to
ensure that the leakage of one
substance may not adversely
affect the container of another
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Control
Code13
Regulation
Topic
Variations
14
substance.
EM13
42
Level 3 emergency management
requirements – signage
Hazardous Substances (Personnel Qualification) Regulations 2001
AH1
4-6
Approved Handler requirements
See E7.
Hazardous Substances (Tank Wagons and Transportable Containers) Regulations 2004
Regulations 4 to 43
where applicable
The Hazardous Substances (Tank Wagons and Transportable Containers)
Regulations 2004 prescribe a number of controls relating to tank wagons and
transportable containers and must be complied with as relevant.
Section 77 and 77A Additional Controls
The controls relating to stationary container systems, as set out in Schedule 8 of the Hazardous
Substances (Dangerous Goods and Scheduled Toxic Substances) Transfer Notice 2004 (Supplement to
the New Zealand Gazette, 26 March 2004, No. 35, page 767), as amended, apply to this substance,
notwithstanding clause 1(1) of that schedule.
Addition of subclauses after subclause (3) of Regulation 36, subclause (1) of Regulation 37 and
subclause (1) of Regulation 38 of the Hazardous Substances (Emergency Management Controls)
Regulations, refer control EM12.
Frontier-P shall not be applied onto or into water.
The maximum application rate for Frontier-P shall be 1.3 L/ha (0.936 kg dimethenamid-P/ha)
with a maximum application frequency of 1 application per year.
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APPENDIX 6: SCALES FOR QUALITATIVE RISK
ASSESSMENT
Qualitative descriptors are indicative only and they are primarily intended to be used to rank
risks and benefits for the purposes of balancing risks and costs against benefits, and so that
risks can be prioritised for management. The ‘descriptor’ words should not be seen in any
absolute senses – they are simply a means of differentiating levels of significance.
Assessing risks, costs and benefits qualitatively
This section describes how the Agency staff and the Authority address the qualitative
assessment of risks, costs and benefits.
Risks and benefits are assessed by estimating the magnitude and nature of the possible effects
and the likelihood of their occurrence. For each effect, the combination of these two
components determines the level of the risk associated with that effect, which is a two
dimensional concept. Because of lack of data, risks are often presented as singular results.
In reality, they are better represented by ‘families’ of data which link probability with
different levels of outcome (magnitude).
Describing the magnitude of effect
The magnitude of effect is described in terms of the element that might be affected. The
qualitative descriptors for magnitude of effect are surrogate measures that should be used to
gauge the end effect or the ‘what if’ element.
Tables A6.1 and A6.2 contain generic descriptors for magnitude of adverse and beneficial
effect. These descriptors are examples only, and their generic nature means that it may be
difficult to use them in some particular circumstances. They are included here to illustrate
how qualitative tables may be used to represent levels of adverse and beneficial effect.
Table A6.1: Magnitude of adverse effect (risks and costs)
Descriptor Examples of descriptions - ADVERSE
Minimal
Mild reversible short term adverse health effects to individuals in highly localised area
Highly localised and contained environmental impact, affecting a few (less than ten) individuals
members of communities of flora or fauna, no discernible ecosystem impact
Local/regional short-term adverse economic effects on small organisations (businesses,
individuals), temporary job losses
No social disruption
Minor
Mild reversible short term adverse health effects to identified and isolated groups
Localised and contained reversible environmental impact, some local plant or animal communities
temporarily damaged, no discernible ecosystem impact or species damage
Regional adverse economic effects on small organisations (businesses, individuals) lasting less
than six months, temporary job losses
Potential social disruption (community placed on alert)
Moderate
Minor irreversible health effects to individuals and/or reversible medium term adverse health
effects to larger (but surrounding) community (requiring hospitalisation)
Measurable long term damage to local plant and animal communities, but no obvious spread
beyond defined boundaries, medium term individual ecosystem damage, no species damage
Medium term (one to five years) regional adverse economic effects with some national
implications, medium term job losses
Some social disruption (e.g. people delayed)
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Major
Significant irreversible adverse health effects affecting individuals and requiring hospitalisation
and/or reversible adverse health effects reaching beyond the immediate community
Long term/irreversible damage to localised ecosystem but no species loss
Measurable adverse effect on GDP, some long term (more than five years) job losses
Social disruption to surrounding community, including some evacuations
Significant irreversible adverse health effects reaching beyond the immediate community and/or
deaths
Extensive irreversible ecosystem damage, including species loss
Significant on-going adverse effect on GDP, long term job losses on a national basis
Major social disruption with entire surrounding area evacuated and impacts on wider community
Massive
Table A6.2: Magnitude of beneficial effect (benefits).
Descriptor Examples of descriptions -BENEFICIAL
Minimal
Mild short term positive health effects to individuals in highly localised area
Highly localised and contained environmental impact, affecting a few (less than ten)
individuals members of communities of flora or fauna, no discernible ecosystem impact
Local/regional short-term beneficial economic effects on small organisations (businesses,
individuals), temporary job creation
No social effect
Minor
Mild short term beneficial health effects to identified and isolated groups
Localised and contained beneficial environmental impact, no discernible ecosystem impact
Regional beneficial economic effects on small organisations (businesses, individuals)
lasting less than six months, temporary job creation
Minor localised community benefit
Moderate Minor health benefits to individuals and/or medium term health impacts on larger (but
surrounding) community and health status groups
Measurable benefit to localised plant and animal communities expected to pertain to
medium term.
Medium term (one to five years) regional beneficial economic effects with some national
implications, medium term job creation
Local community and some individuals beyond immediate community receive social
benefit.
Major
Significant beneficial health effects to localised community and specific groups in wider
community
Long term benefit to localised ecosystem(s)
Measurable beneficial effect on GDP, some long term (more than five years) job creation
Substantial social benefit to surrounding community, and individuals in wider community.
Massive
Significant long term beneficial health effects to the wider community
Long term, wide spread benefits to species and/or ecosystems
Significant on-going effect beneficial on GDP, long term job creation on a national basis
Major social benefit affecting wider community
Determining the likelihood of the end effect
Likelihood in this context applies to the composite likelihood of the end effect, and not either
to the initiating event, or any one of the intermediary events. It includes:

the concept of an initiating event (triggering the hazard), and

the exposure pathway that links the source (hazard) and the area of impact
(public health, environment, economy, or community).
Thus, the likelihood is the likelihood of the specified adverse effect16 resulting from that
initiating event. It will be a combination of the likelihood of the initiating event and several
16 The specified effect refers to scenarios established in order to establish the representative risk, and may
be as specific as x people suffering adverse health effects, or y% of a bird population being adversely
affected. The risks included in the analysis may be those related to a single scenario, or may be defined as a
combination of several scenarios.
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intermediary likelihoods17. The best way to determine the likelihood is to specify and analyse
the complete pathway from source to impact.
Likelihood may be expressed as a frequency or a probability. While frequency is often
expressed as a number of events within a given time period, it may also be expressed as the
number of events per head of (exposed) population. As a probability, the likelihood is
dimensionless and refers to the number of events of interest divided by the total number of
events (range 0–1). (See Table A6.3).
Table A6.3: Using magnitude and likelihood to construct the level of risk and benefit
Descriptor
Description
Highly improbable
Almost certainly not occurring but cannot be totally ruled out
Very unlikely
Unlikely (occasional)
Considered only to occur in very unusual circumstances
Could occur, but is not expected to occur under normal operating conditions.
Likely
A good chance that it may occur under normal operating conditions.
Highly likely
Almost certain, or expected to occur if all conditions met
Using the magnitude and likelihood tables a matrix representing a level of effect can be
constructed.
Determining the level or risk/benefit
In the example shown in Table 6.4, four levels of risk/benefit are allocated: A (negligible), B
(low), C (medium), and D (high). These terms have been used to avoid confusion with the
descriptions used for likelihood and magnitude, and to emphasise that the matrix is a tool to
help decide which risks/benefits require further analysis to determine their significance in the
decision making process.
For negative effects, the levels are used to show how risks can be reduced by the application
of additional controls. Where the table is used for positive effects it may also be possible for
controls to be applied to ensure that a particular level of benefit is achieved, but this is not a
common approach. The purpose of developing the tables for both risk and benefit is so that
the risks and benefits can be compared.
Table A6.4: Level of risk.
Magnitude of effect
Likelihood
Highly improbable
Minimal
A
Minor
A
Moderate
A
Major
B
Massive
B
Very unlikely
A
A
B
B
C
Unlikely
A
B
B
C
C
Likely
B
B
C
C
D
Highly likely
B
C
C
D
D
17 Qualitative event tree analysis may be a useful way of ensuring that all aspects are included.
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APPENDIX 7: GOVERNMENT DEPARTMENTS,
CROWN ENTITIES AND INTERESTED PARTIES
NOTIFIED
Aakland Chemicals (1997) Limited
AgBio Research Limited
Agcarm Incorporated
AgResearch Limited
Agronica New Zealand Limited
ARPPA
BALDWINS
BASF New Zealand Limited
Bayer New Zealand Limited
BOC Limited
Chancery Green
Chemagro New Zealand Limited
Chemsafety Limited
Crown Public Health
CSD Consultancy Ltd
DuPont (New Zealand) Limited
Far North District Council
Federated Farmers of New Zealand
(Incorporated)
Fish and Game Eastern Region
Greater Wellington - The Regional Council
Green Party of Aotearoa New Zealand
Hawkes Bay Regional Council
IMCD New Zealand Limited
Kaipara District Council
Kawerau District Council
Landcorp Farming Limited
Lowndes Associates
MAF Biosecurity New Zealand (MAFBNZ)
Ministry of Research Science and Technology
(MoRST)
Napier Health Centre - Public Health Unit
New Zealand Bee Industry Group - Federated
Farmers
New Zealand Chemical Industry Council Inc
New Zealand Customs Service
New Zealand Meatworkers Union
New Zealand Press Association
New Zealand Society of Gunsmiths Inc
Ngati Kahungunu Iwi Incorporated
Northland Health
Nufarm New Zealand Limited
Pacific Building Steel Group
Pacific Growers Supplies Limited
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Pesticide Action Network Aotearoa New
Zealand
PharmVet Solutions
Physicians and Scientists for Global
Responsibility (PSGR)
Rangitikei District Council
Reckitt Benckiser
South Taranaki District Council
Sustainability Council of New Zealand
Syngenta Crop Protection Limited
Taranaki Regional Council
Tasman District Council
Technical Strategy Group Limited
Television New Zealand
The National Beekeepers Association of New
Zealand
The New Zealand Institute for Plant and Food
Research Limited
TMP Consultancy
Wellington City Council
Zelam Limited
6 Private Individuals
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APPENDIX 8: CONFIDENTIAL MATERIAL
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