ENVIRONMENTAL RISK MANAGEMENT
AUTHORITY DECISION
1 August 2008
Application Code
HSR07054
Application Type
To import or manufacture for release any hazardous
substance under the Hazardous Substances and New
Organisms Act 1996 (“the Act”)
Applicant
Jurox New Zealand Ltd
Date Application Received
20 September 2007
Submission Period
4 October 2007 to 16 November 2007
Consideration Period
5 June 2008 to 7 July 2008
Considered by
A Committee of the Authority
Purpose of the Application
Jurox Domperidone Paste for Horses: to import for
release a veterinary medicine containing 126 g/kg
domperidone, an endocrine agent, for use in horses to
promote ovulation and improve livestock productivity
(Category A).
1 Summary of decision
1.1
The application to import or manufacture Jurox Domperidone Paste for Horses
for release is approved with controls in accordance with the relevant provisions
of the Act, the HSNO Regulations and the HSNO (Methodology) Order 1998
(“the Methodology”).
1.2
The substance has been given the following unique identifier for the ERMA
New Zealand Hazardous Substances Register:
Jurox Domperidone Paste for Horses
2 Legislative criteria for application
2.1
The application was lodged pursuant to section 28. The decision was
determined in accordance with section 29, taking into account matters to be
considered in that section and additional matters specified under Part II of the
Act. Unless otherwise stated, references to section numbers in this decision
refer to sections of the Act.
2.2
Consideration of the application followed the relevant provisions of the
Methodology. Unless otherwise stated, references to clauses in this decision
refer to clauses of the Methodology.
3 Application process
3.1
The application was formally received on 20 September 2007.
3.2
In accordance with sections 53(1) and 53A, and clauses 2(2) (b) and 7, public
notification was made on 9 February 2007.
3.3
Submissions closed on 16 November 2007.
3.4
Various Government departments, Crown Entities and interested parties,
including the New Zealand Food Safety Authority (Agricultural Compounds
and Veterinary Medicines (ACVM) Group), the Ministry of Health and the
Department of Labour Work Place Group, which in the opinion of the
Authority would be likely to have an interest in the application, were notified of
the receipt of the application (sections 53(4) and 58(1)(c), and clauses 2(2)(e)
and 5) and provided with an opportunity to comment or make a public
submission on the application.
3.5
No submissions or comments were received.
3.6
The Agency was commissioned to prepare an Evaluation and Review Report
(“the E&R Report”) to aid the Committee in its decision making process. The
E&R Report consists of the Agency’s review of the application and available
data regarding the substance and/or its constituent components. In the E&R
Report, the Agency proposed a suite of controls considered suitable to manage
the risks associated with the release of Jurox Domperidone Paste for Horses
and has assessed the potential risks the substance may pose to the environment,
human health, Māori, community and to the market economy.
3.7
The ACVM Group, the Ministry of Health, the Department of Labour and the
applicant were given the opportunity to comment on the Agency’s Evaluation
and Review Report (“the E&R Report”) and the controls proposed therein. The
applicant indicated that they did not believe any of the controls to be
impracticable or inappropriate.
3.8
No external experts were used in the consideration of this application (clause
17).
3.9
Due to delays in completing the E&R Report, the Authority, with the
applicant’s consent, postponed the consideration of the application until 5 June
2008.
3.10
The following members of the Authority considered the application (section
19(2) (b)): Helen Atkins (Chair), Dr Deborah Read, Dr Kieran Elborough.
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3.11
The information available to the Committee comprised:

the application;

the E&R Report including confidential appendices.
3.12
During the consideration the Committee was concerned about lack of data
regarding the effect of potential metabolites excreted by the treated horse and
the potential effects of these metabolites on human health and the general lack
of data on human health and environmental adverse effects. Accordingly, the
Committee requested that additional information be provided on the potential
adverse effects and benefits of the substance and how similar applications have
been treated by the Authority in the past.
3.13
The Agency requested further information on adverse effects and benefits from
the applicant.
3.14
In response, the applicant supplied the following:
 Calculations of environmental concentration of domperidone in soil
 A letter to the US Food and Drug Administration (US FDA)
 A report from the US FDA
 Comments on the need to conduct an environmental impact assessment
 Further Information on the benefits of Jurox Domperidone.
3.15
The Agency provided a report to the Committee for consideration on 27 June
2008 and the Committee concluded its consideration of the application for
approval on 7 July 2008.
.
4 Consideration
Purpose of the application
4.1
To import for release a veterinary medicine Jurox Domperidone Paste for
Horses containing 126 g/kg domperidone, an endocrine agent, for use in horses
to promote ovulation and improve livestock productivity (Category A).
Information Review
4.2
In the E&R Report, the Agency noted that there are data gaps for many of the
hazard subclasses for Jurox Domperidone Paste for Horses.
4.3
As indicated above, the Committee requested further information from the
applicant and the Agency on the potential adverse effects and benefits of the
substance and how similar applications have been treated by the Authority in
the past.
4.4
The additional information included a predicted environmental concentration
(PEC) in soil of between 0.06 and 0.08 µg/kg. This level is well below the
VICH (International Cooperation on Harmonisation of Technical Requirements
for Registration of Veterinary Medicinal Products) Guideline trigger value of
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100 µg/kg for requiring an environmental risk assessment. (See Fig 1. Phase 1
Decision Tree, E&R Report Page 40).
4.5
Although the calculations relate to a predicted concentration in soil not faeces,
it means that it is highly improbable that the amount of domperidone in
soil/faeces will pose a risk to humans.
4.6
The additional information also made it clear that international practice does
not require environmental risk assessments for products such as Jurox
Domperidone. It also appears that risks to human health by exposure to manure
etc. have not been considered. However, given the concentration that would be
required to cause an adverse health effect, this is does not appear to be
unreasonable.
4.7
The additional benefits identified by the applicant relate to “off-label” uses of
the substance in treating agalactia in mares and the prevention of fescue
toxicosis in peripaturient mares. As no alternative substances have been
identified, these additional benefits would appear to be potentially significant in
New Zealand.
4.8
The Agency also identified three approvals under Part V and two transferred
approvals for similar substances. The Agency noted that these substances have
been approved and are being used without any additional controls being applied
to cover uncertainties in information on their human health and environmental
effects. Furthermore, the Agency is not aware of any reports that indicate that
the use of these substances has caused any concerns about human health or
environmental adverse effects.
4.9
Having reviewed the application, the E&R Report and the additional
information supplied by the applicant and the Agency, the Committee considers
that the information available constitutes an adequate and appropriate basis for
considering the application (clause 8).
Sequence of the consideration
4.10
In accordance with clause 24, the approach to the consideration adopted by the
Committee was to:

establish the hazard classifications for the substances and derive the
default controls that are prescribed under section 77 for each classification.

identify potentially non-negligible risks, costs, and benefits.

assess the potentially non-negligible risks and costs. Risks were assessed
in accordance with clause 12, and costs in accordance with clause 13.

consider the adequacy of the default controls, prescribed under section 77,
and exposure limits alongside the assessment of risks and costs to
determine whether those controls or limits should be varied or set and
identify where additional controls need to be applied, under section 77A,
to mitigate any unacceptable risks.

vary and add controls in accordance with sections 77 and 77A.
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
undertake a combined consideration of all the risks and costs and
determine whether the combined risks and costs are negligible or nonnegligible. The combined risks and costs for this application were
determined to be negligible.

consider the cost-effectiveness of the application of controls in accordance
with clause 35 and sections 77 and 77A.

determine whether it was evident that the identified potential benefits
outweighed the costs.

confirm and set the controls.

approve or decline the application under section 29 and clause 26.

assess the benefits associated with this application in accordance with
clauses 9, 11, 13 and 14 and section 6(e).

taking into account the risk characteristics established under clause 33,
evaluate the risks, costs and benefits in accordance with clause 34 and
section 29 and determine whether the application should be approved or
declined.

confirm and set the controls.
Hazard classification
4.11
The Agency reviewed the hazard classification for Jurox Domperidone Paste
for Horses on the basis of its composition and the properties of its components.
4.12
The Agency was unable to assess the ecotoxicity hazards associated with the
Jurox Domperidone Paste for Horses since the applicant had not provided any
formulation studies; providing instead a literature survey on the hazardous
properties of domperidone.
4.13
Additional information provided by the applicant after the consideration
reduced this uncertainty but did not provide sufficient information to allow the
reassessment of the hazard classifications.
4.14
The Agency has classified Jurox Domperidone Paste for Horses as follows:
Hazardous Property
Target Organ Toxicity
Jurox Domperidone
Paste for Horses
6.9B
Default controls
4.15
In the E&R Report, the Agency assigned default controls for Jurox
Domperidone Paste for Horses based on its hazardous property as set out in the
HSNO Regulations. The default controls were used as a reference for
evaluation of the application in the E&R Report. The default controls are listed
in section 8 of the E&R Report and have not been reproduced here.
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Identification of the potentially non-negligible risks, costs and benefits
of the substance
4.16
In its evaluation of Jurox Domperidone Paste for Horses, the Agency identified
potentially significant, and therefore non-negligible, risks, costs and benefits
associated with the substance.
Potentially non-negligible risks
4.17
The Committee considers that the potentially non-negligible risks associated
with Jurox Domperidone Paste for Horses relate to the substance’s
classification of 6.9B indicating its potential to cause target organ toxicity
Potentially non-negligible costs
4.18
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”.
Accordingly, the costs were assessed in an integrated fashion together with the
risks in the Agency’s assessment.
Potentially non-negligible benefits
4.19
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.
4.20
The Committee considers that the major benefit associated with the substance
is the improvement of mare fertility in the early stages of the breeding season to
provide better control of reproduction in mares and less wastage of stallion time
covering mares during low fertility periods.
4.21
The Committee also noted that the availability of the Jurox Domperidone Paste
for Horses ready-to- use formulation will avoid the current situation where the
human medicine is used off-label. It is possible that the risks associated with
the off-label process, particularly the likelihood of human exposure to the
active ingredient, outweigh those of production in a Good Manufacturing
Practice compliant facility and administration of a ready-to-use paste.
Assessment of the potentially non-negligible risks and costs of the
substance
4.22
The Agency was unable to assess the ecotoxicity hazards associated with the
Jurox Domperidone Paste for Horses due to a lack of data and the Committee
considers that there is some uncertainty surrounding the magnitude of potential
adverse effects. Taking this into account and after consideration of the
additional information the Committee considers that, since the Jurox
Domperidone Paste for Horses will be available in small quantities (pre
packaged in 5 g syringes) and will only be available with a veterinary
prescription any potential adverse environmental effects will be negligible.
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4.23
The Agency classified Jurox Domperidone Paste as a target organ toxicant. The
Committee considers that the risks to human health and safety are negligible
since there is no dust associated with the formulation of the paste, reducing the
hazards via the inhalation route, and its use will be limited to veterinarians or
those under the direction off a veterinarian. The Committee noted that the dose
at which human toxicity would be reached was equivalent to the repeated daily
ingestion of 5 syringes of paste and that this is highly improbable.
4.24
Significant adverse impacts on the social or economic environment are not
anticipated with the controlled use of Jurox Domperidone Paste for Horses.
4.25
The overall level of risk to Māori culture or traditional relationships with
ancestral lands, water, sites, wāhi tapu, valued flora and fauna or other taonga
is described as negligible.
4.26
There is no evidence to suggest that the controlled use of Jurox Domperidone
Paste for Horses will provide significant risks to New Zealand’s international
obligations.
5 Controls
5.1
A number of variations to the default controls for Jurox Domperidone Paste for
Horses were proposed in the E&R Report in accordance with clause 35 and
sections 77 and 77A. These variations and the setting of exposure limits and
applications rates are discussed below.
5.2
The applicant was given an opportunity to comment on the proposed controls
as set out in the E&R Report (clause 35(b)).
5.3
In response, the applicant indicated that they did not believe any of the controls
to be impracticable or inappropriate.
Setting of exposure limits and application rates
5.4
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.
5.5
The Committee notes that domperidone is intended for use in horses which are
not specifically excluded from use to produce meat for human consumption.
However, given the limited information supplied the Committee is unable to
determine an appropriate ADE and subsequent PDEfood and TEL values.
Consequently no ADE or TEL values are set at this time.
5.6
Control T2 relates to the requirement to limit worker exposure to toxic
substances by the setting of Workplace Exposure Standards (WESs). The
Committee has deleted this control as Jurox Domperidone Paste for Horses will
not become airborne and disperse in air.
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Proposed additional controls
5.7
Under section 77A, the Authority may impose as controls any obligations and
restrictions as the Authority thinks fit. Under section 77A(4), the Authority
must be satisfied that, against any other specified controls that apply to the
substance,

the proposed control is more effective in terms of its effect on the
management, use and risks of the substance; or

the proposed control is more cost-effective in terms of its effect on the
management, use and risks of the substance; or

the proposed control is more likely to achieve its purpose.

5.8
The Committee notes that the risk assessment has been based solely upon the
substance being used as a veterinary medicine but none of the specified
(default) controls limit how the substance may be used. Additionally, with the
uncertainty associated with the toxic properties of Jurox Domperidone Paste for
Horses, the Committee considers that the potential for contact with people
involved in administering the substance should be minimised. Accordingly, the
Committee has applied the following controls so that the suite of controls for
Jurox Domperidone Paste for Horses will be more effective than the specified
controls in terms of their effect on the management, use and risks of the
substance (section 77A(4)(a)):
“This approval relates to the importation only of Jurox Domperidone Paste for
Horses in the form of syringes”.
“Jurox Domperidone Paste for Horses shall only be used as a veterinary
medicine”
Proposed modification of controls
5.9
Under section 77, the default controls triggered for the substance may be
varied. Under section 77(3), controls may be substituted or added. Under
section 77(4), controls may be substituted or deleted. Under section 77(5),
where a substance triggers more than one hazard classification, controls may be
combined.
5.10
No modifications are proposed to the default controls for Domperidone Paste
for Horses.
6 Overall evaluation of risks and costs
6.1
The Committee considers that, despite the uncertainties, there are no significant
risks to the environment, human health, society or the community, the
relationship of Maori to the environment, the market economy, or to New
Zealand’s international obligations from Jurox Domperidone Paste for Horses
with the proposed controls in place.
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7 Assessment of the potentially non-negligible benefits
7.1
The Committee is unable to place an expected value on the benefits (clause
13(b)) but is satisfied that the ability of the substance to enter the market could
give rise to the associated benefits detailed in paragraphs 4.11 and 4.12 above.
However, the Committee considers that the benefits associated with the release
of Jurox Domperidone Paste for Horses are potentially significant.
7.2
In accordance with sections 29(1) (a) (iii) and 29(1) (b) (iii), the Committee
considers that if Jurox Domperidone Paste for Horses were not made available,
the benefits offered would not be realised and users would continue to use the
human medicine.
8 Comparison of risks, cost and benefits
8.1
As discussed above, the Committee considers that due to its packaging and
mode of application Jurox Domperidone Paste for Horses poses negligible risks
to human health and safety.
8.2
The Committee considers that, while Jurox Domperidone Paste for Horses
presents negligible risks to the environment, with any effects being reversible
localised around the area of application.
8.3
The Committee also considers that Jurox Domperidone Paste for Horses offers
a significant level of benefit to users.
8.4
As there are potentially non-negligible benefits associated with the import or of
Jurox Domperidone Paste for Horses, the Committee is satisfied that it is
evident that the benefits associated with the substance outweigh the costs.
9 Recommendations
9.1
The Committee recommends that, should inappropriate or accidental use,
transport or disposal of Jurox Domperidone Paste for Horses result in the
contamination of waterways, the appropriate authorities, including the relevant
iwi authorities in the region, should be notified. This action should include
advising them of the contamination and the measures taken in response.
10 Environmental User Charges
10.1
The Committee considers that the use of controls is the most effective way of
managing risks throughout the lifecycle of Jurox Domperidone Paste for
Horses. The imposition of an environmental user charge instead of, or in
combination, with controls is therefore not required at this time.
11 Decision
11.1
The Committee determines that Jurox Domperidone Paste for Horses triggers
the 6.9B Target organ systemic toxicity hazard classifications.
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11.2
Pursuant to section 29 and clause 26, the positive effects (benefits) of the
substance outweigh the adverse effects (risks and costs).
11.3
The application for importation and release of the hazardous substance, Jurox
Domperidone Paste for Horses, is thus approved with controls as listed in
Appendix 1.
11.4
In accordance with clause 36(2) (b), the Committee records that, in reaching
this conclusion, it has applied the balancing tests in section 29 and clause 26.
11.5
It has also applied the following criteria in the Methodology:

clause 9 – equivalent of sections 5, 6 and 8;

clause 11 – characteristics of substance;

clause 12 – evaluation of assessment of risks;

clause 13 – evaluation of assessment of costs and benefits;

clause 14 – costs and benefits accruing to New Zealand

clause 21 – the decision accords with the requirements and regulations;

clause 22 – the evaluation of risks, costs and benefits – relevant
considerations;

clause 24 – the use of recognised risk identification, assessment,
evaluation and management techniques;

clause 25 – the evaluation of risks;

clause 33 – risk characteristics;

clause 34 – the aggregation and comparison of risks, costs and benefits;
and

Clause 35 – the costs and benefits of varying the default controls.
signed
Helen Atkins
Date: 1 August 2008
Chair
ERMA New Zealand Approval Code:
ERMA New Zealand Decision: Application HSR07054
HSR007947
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APPENDIX 1: CONTROLS FOR JUROX
DOMPERIDONE PASTE FOR HORSES
Table A5.1: Controls for Jurox Domperidone Paste for Horses – codes, regulations and
variations.
Control Regulation2 Topic
Variations
Code1
Hazardous Substances (Classes 6, 8, and 9 Controls) Regulations 2001
T1
11-27
Limiting exposure to toxic substances
T4
7
T5
8
Requirements for equipment used to
handle hazardous substances
Requirements for protective clothing and
equipment
No ADE or TEL values are set for Jurox
Domperidone Paste for Horses at this
time.
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
I9
18
I16
25
I17
I18
I19
26
27
29-31
Regulations 34, 35, 36(1)-(7) –
Comprehensibility, Clarity and
Durability of information
Secondary identifiers for all hazardous
substances
Secondary identifiers for toxic
substances
Use of Generic Names
Use of Concentration Ranges
Alternative information in certain cases
Regulation 29 – Substances in fixed bulk
containers or bulk transport containers
Regulation 30 – Substances in multiple
packaging
I21
37-39, 47-50
Regulation 31 – Alternative information
when substances are imported
Documentation required in places of
work
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.
2
These Regulations form the controls applicable to this substance. Refer to the cited Regulations for the formal
specification, and for definitions and exemptions. The accompanying explanation is intended for guidance only.
1
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Control
Code1
Regulation2
Topic
Variations
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
I28
46
Regulation 50 – Documentation to be
supplied on request
Specific documentation requirements for
toxic substances
Hazardous Substances (Packaging) Regulations 2001
P1
5, 6, 7 (1), 8
General packaging requirements
Regulation 5 – Ability to retain contents
Regulation 6 – Packaging markings
Regulation 7(1) – Requirements when
packing hazardous substance
Regulation 8 – Compatibility
Regulation 9A and 9B – Large
Packaging
P3
9
PS4
Schedule 4
Packaging requirements for substances
packed in limited quantities
This schedule describes the minimum
packaging requirements that must be
complied with when a substance is
packaged in limited quantities
Hazardous Substances (Disposal) Regulations 2001
D4
8
Disposal requirements for Jurox
Domperidone Paste for Horses
D6
D7
D8
10
11, 12
13, 14
Disposal requirements for packages
Disposal information requirements
Disposal documentation requirements
Hazardous Substances (Emergency Management) Regulations 2001
EM8
12-16, 18-20
Level 2 emergency management
documentation requirements
Hazardous Substances (Tank Wagons and Transportable Containers) Regulations 2004
Regulations 4 to 43 where
The Hazardous Substances (Tank Wagons and Transportable Containers) Regulations
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Control
Code1
applicable
Regulation2
Topic
Variations
2004 prescribe a number of controls relating to tank wagons and transportable
containers and must be complied with as relevant.
Section 77A Additional Controls
This approval relates to the importation only of Jurox Domperidone Paste for Horses in the form of syringes
Jurox Domperidone Paste for Horses shall only be used as a veterinary medicine.
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