Current situation with the
development of the endocrine
disruption criteria
13 March 2014
Markus Griesser (BASF SE)
Chair ECPA ED Expert Group
Outline
Introduction
Proposals for ED criteria and further scientific input
State of play and way forward
Potential impact on agriculture, innovation and trade
Summary
Definition
WHO/IPCS (2002)
„An endocrine disruptor is an exogenous substance or
mixture that alters function(s) of the endocrine system
and consequently causes adverse effects in an intact
organism, or ist progeny, or (sub)populations.“
Widely accepted definition, but…
The WHO definition is not a regulatory definition!
What is the concern about?
WHO/ UNEP report 2012
– Many ED-related diseases are on the rise
– Human and wildlife populations are
exposed to EDCs
– Numerous laboratory studies support the
idea that chemical exposures contribute to
endocrine disorders
– Internationally agreed and validated test
methods capture only a limited range of
the known spectrum of ED effects
The 2012 report raises a global concern on EDCs
Critique of the WHO report
Critical review by Jim Lamb et al (February 2014)
– Summary is not a true representation of the main report
– Disease trends are attributed to ED without evidence of
their causes or discussion of other possible factors
– Dose-response and potency are addressed poorly
The report does not provide a balanced
perspective and is not an accurate reflection of
the state of the science on endocrine disrupters
ED regulation in the EU
Horizontal ED criteria for all sectors
Pesticides
Biocides
REACH
Hazard-based cut-off
Hazard-based cut-off
ED may be SVHC
Limited derogations
possible
Derogations possible
Authorisation based
on risk assessment
ED criteria: proposal
by December 2013
ED criteria: adoption
by December 2013
ED criteria: no legal
requirements
Harmonized criteria, but consequences differ
6
ED in EU pesticides legislation
Regulation 1107/2009
• Annex II, Article 3.6.5 (Human Health)
–
“An active substance, safener or synergist shall only be approved if …. it is not
considered to have endocrine disrupting properties that may cause adverse effect in
humans, unless the exposure … is negligible, that is, the product is used in closed
systems or in other conditions excluding contact with humans and where residues of the
active substance, safener or synergist concerned on food and feed do not exceed the
default value set in accordance with … Regulation (EC) No 396/2005.”
• Annex II, Article 3.8.2 (Environment)
–
“An active substance, safener or synergist shall only be approved if … it is not
considered to have endocrine disrupting properties that may cause adverse effects on
non-target organisms unless the exposure of non-target organisms … is negligible.”
No criteria defined despite legislative deadline
ED in EU pesticides legislation
Interim criteria
• Pending the adoption of these criteria, substances that are or have to be classified, in
accordance with the provisions of Regulation (EC) No 1272/2008, as carcinogenic category 2
and toxic for reproduction category 2, shall be considered to have endocrine disrupting
properties.
– Interim criteria not scientifically justified (not all substances
classified as C2 and R2 are automatically endocrine disrupters)
– No interim criteria and legislative deadline for the environment
– Interim criteria are beeing applied for the CfS list
– Some member states want to apply interim criteria for AIR2
– ECPA position: interim criteria should not be applied for
regulatory decision making
Provision is a poor substitute for scientific criteria
Outline
Introduction
Proposals for ED criteria and further scientific input
State of play and way forward
Potential impact on agriculture, innovation and trade
Summary
Industry proposal to regulate ED
First detailed proposal for ED criteria
Original work published in 2009 as technical report
Detailed assessment scheme to identify EDs of regulatory
concern for human health and wildlife
In 2013, the American Society of Toxicology (SOT)
awarded it “Best Published Paper Advancing the
Science of Risk Assessment”
Source:R. Bars et al. Regulatory Toxicology
and Pharmacology 64 (2012), 143–154
Industry plays a proactive and constructive role
BfR/ CRD proposal (human health)
Source: JOINT DE – UK POSITION PAPER.
REGULATORY DEFINITION OF AN ENDOCRINE
DISRUPTER IN RELATION TO POTENTIAL
THREAT TO HUMAN HEALTH. May 2011.
DK EPA proposal
Category 1: Confirmed ED
- Adverse in vivo effects & ED MoA highly plausible
- ED MoA in vivo clearly linked to adverse effects in vivo
(e.g. by read across)
Category 2a: Suspected ED
- Some evidence, mainly based on in vivo data
Category 2b: Indicated ED
- Some in vitro/ in silico evidence indicating an ED potential
Expert Advisory Group (EAG)
Members
- Experts from member states authorities, industry and NGOs
- EU agencies (EFSA, ECHA) & COM services as observers
- Chaired by the Joint Research Centre (JRC)
Final Report
- Hazard identification: Consideration of mode of action and
adversity in parallel applying weight of evidence
- Human health: Potency, severity, irreversibility and lead
toxicity are relevant for hazard characterization
- Environment: Adverse effects must be population relevant
EFSA Scientific Opinion
Joint work with experts from EMA, ECHA, EEA
Mandate by COM, published in March 2013
- Reasonably complete set of standardised assays for EATS
in mammals and fish are available
- Critical effect, severity, (ir)reversibility and potency are part
of hazard characterization of EDs
- Mixture toxicity and low-dose effects
are not unique for EDs
- Risk assessment makes best use
of available information
EDs can be treated like most other substances
of concern for human health and environment
Proposal by DG Environment
Presented to the ED Ad hoc meeting (Feb. 2013)
Category 1: Endocrine Disruptors
- Evidence mainly based in vivo data
Category 2: Suspected EDs
- Less evidence than Cat 1 (incl. in vitro and in silico data)
ECPA has severe concerns with the proposal
-
Categorization scheme (not required by any EU legislation)
Category 1 goes beyond the WHO definition
Focus on hazard identification
Elements of hazard characterization not considered
(e.g. potency, severity of effects, irreversibilty)
Industry view on the ED criteria
The criteria should…
-
be based on the widely accepted WHO definition
include elements of hazard characterization
(e.g. potency, severity, lead toxic effect, irreversibility)
be a single set of criteria as required by the legislation
(and not a categorization)
Hazard idenfication
(WHO definition;
adverse effect
and ED MoA)
Hazard
characterization
DG Envi proposal
Some MS
Exposure
Risk assessment
characterization
US EPA, Industry
Outline
Introduction
Proposals for ED criteria and further scientific input
State of play and way forward
Potential impact on agriculture, innovation and trade
Summary and conclusions
State of play and way forward
Anticipated timelines
Election EP
2013
DG Envi to develop horizontal
ED criteria
New COM
2014
roadmap
2015
2016
public consultation
Impact assessment process
?
?
DG Sanco drafting pesticides criteria
?
DG Envi drafting biocides criteria
DG Envi work on ED strategy
?
COM to review REACH (thresholds for ED)
ED strategy and criteria should be „one package“
Outline
Introduction
Proposals for ED criteria and further scientific input
State of play and way forward
Potential impact on agriculture, innovation and trade
Summary
ECPA impact assessment
Scope
• Based on the proposal by DG Environment (February 2013)
• Impact on agriculture, trade and future innovation
Key messages
– 35 - 45 % of the European crop protection market will be affected
(3 – 4 billion €)
– Fungicides are particularly vulnerable: The ten most important cereal
fungicides in Germany would be lost, in France 7 out of the top 10 products
would be removed
– Yield losses on key crops would be 10-20 % in an average year
and up to 50 % in years of high disease pressure
– Significant impact on innovation and international trade
Impact has to be considered in drafting the criteria
CRD impact assessment (I)
Category
Tox Assessment
(98 substances)
Ecotox Assessment
(20 substsances)
ED more likely to pose a
risk
5%
35 %
ED less likely to pose a risk 9 %
5%
Potential EDs requiring
further information
26 %
55 %
Not considered ED
59 %
5%
Based on the BfR/ CRD proposal (human health)
and the CRD proposal (environment)
The Proposal by DG Environment
would have an even higher impact
CRD impact assessment (II)
Prepared by the Food and Environment
Research Agency (fera)
Agronomic and economic impact
– Loss of „Category 1“: 225 Mio GBP (260 Mio €)
– Loss of „Category 1 & 2“ : 440 Mio GBP (510 Mio €)
Based on the assumption that all other ais
remain available (which is unrealistic)
Production of many crops will not be viable
anymore in the UK (e.g. lettuce, soft fruit)
Actual impact is likely to be underestimated
Active ingredients in development (worldwide)
Share of active ingredients
introduced or in development
ED criteria have the potential to further
hinder innovation and research in the EU
Source: R&D trends for chemical crop protection products and the
position of the European Market. A consultancy study undertaken
for ECPA. Phillips McDougall, September 2013
Impact on innovation
Current situation in the EU
Impact on international trade
6.9 billion €
6.9 billion €
8.4 billion €
24.3 billion €
7.9 billion €
Source: Potential Trade Effects on World
Agricultural Exporters of European Union
Regulations on Endocrine Disruptors.
Prepared by Kyd D. Brenner LLC for
CropLife International, February 2014.
Based on the assumption that all MRLs will be
set at the default value of 0.01 mg/kg
Imports worth 65 billion € would be affected by
ED cut-off criteria alone
Huge potential impact on international trade
Commission impact assessment
ECPA welcomes the impact assessment,
but is concerned about the significant delays
ECPA view on the impact assessment
- Impacts on sectors should be assessed separately
- All existing impact assessments should be considered
- Assessment should be robust and detailed
enough to provide a meaningful conclusion
- Intended and unintended impacts should be considered:
agronomic impacts, impacts on human health and
environment, socio-economic impacts, trade impacts and
global competitiveness of European agriculture
- Assessment should consider a risk assessment option
Outline
Introduction
Proposals for ED criteria and further scientific input
State of play and way forward
Potential impact on agriculture, innovation and trade
Summary
Summary
ECPA takes ED-related concerns seriously and
believes that they can be addressed using a
science and risk-based approach
The WHO definition and elements of hazard characterization should be the basis for the criteria
DG Environments‘s proposal would have had a
significant negative impact on European
agriculture, innovation and international trade
The Commission impact assessment offers the
chance to provide a more solid basis for the ED
criteria and the revision of the ED strategy
THANK YOU
FOR YOUR ATTENTION