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

Horizontal ED criteria for all sectors

Pesticides

Hazard-based cut-off

Limited derogations possible

ED criteria: proposal by December 2013

Biocides

Hazard-based cut-off

Derogations possible

ED criteria: adoption by December 2013

REACH

ED may be SVHC

Authorisation based on risk assessment

ED criteria: no legal requirements

6

ED regulation in the EU

Harmonized criteria, but consequences differ

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.”

ED in EU pesticides legislation

No criteria defined despite legislative deadline

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

ED in EU pesticides legislation

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

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”

Industry proposal to regulate ED

Industry plays a proactive and constructive role

Source:R. Bars et al. Regulatory Toxicology and Pharmacology 64 (2012), 143–154

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.

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

DK EPA proposal

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

Expert Advisory Group (EAG)

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

EFSA Scientific Opinion

EDs can be treated like most other substances of concern for human health and 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)

Proposal by DG Environment

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)

Industry view on the ED criteria

Hazard idenfication (WHO definition; adverse effect and ED MoA)

Hazard characterization

Exposure characterization

Risk assessment

DG Envi proposal Some MS 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

2014 20152013

DG Envi to develop horizontal ED criteria

Impact assessment process ?

public consultation roadmap

COM to review REACH (thresholds for ED)

Election EP New COM

DG Sanco drafting pesticides criteria

DG Envi drafting biocides criteria

?

?

2016

DG Envi work on ED strategy ?

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

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

ECPA impact assessment

Impact has to be considered in drafting the criteria

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 %

CRD impact assessment (I)

Based on the BfR/ CRD proposal (human health) and the CRD proposal (environment)The Proposal by DG Environment would have an even higher impact

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)

CRD impact assessment (II)

Actual impact is likely to be underestimated

Impact on innovationCurrent situation in the EU

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

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

Impact on international trade

8.4 billion €

7.9 billion €

6.9 billion €

6.9 billion €

24.3 billion €

Huge potential impact on international trade

ECPA welcomes the impact assessment, but is concerned about the significant delays

ECPA view on the impact assessmentImpacts 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

Commission impact assessment

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 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 cha-racterization 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

Summary

THANK YOUFOR YOUR ATTENTION