EURION Regulatory Affairs WG

Andreas Kortenkamp

Brunel University London

athena

EU Regulations dealing with endocrine disruptors

• Plant Protection Products (pesticides) EU Reg 1107/2009• Authorisation NOT granted unless exposure is negligible

• Biocidal Products EU Reg 528/2012• Authorisations NOT granted unless risk is negligible

• Industrial chemicals REACH EU Reg 1907/2006• Requires authorisation (Annex XIV)

EDC criteria - the definition: what is an EDC?• it shows an adverse effect in an intact organism or its progeny, which is a

change in the morphology, physiology, growth, development, reproduction or life span of an organism, system or (sub)population that results in an impairment of functional capacity, an impairment of the capacity to compensate for additional stress or an increase in susceptibility to other influences

• it has an endocrine mode of action, i.e. it alters the function(s) of the endocrine system

• the adverse effect is a consequence of the endocrine mode of action

Delegated Reg 2017/2100, Section A, (1)

Identification of EDC

• Based on available scientific data (in vitro, in vivo, in silico from internationally agreed study protocols) by systematic review methodology

• …on assessment of data by weight of evidence approaches

• …on establishing a link between adversity and endocrine mode of action

Delegated Reg 2017/2100 Section A (2)

Endocrine disrupter tests are poorly implemented in EU

regulations on data requirements

PPPR: active substances Reg 283/2013, specified in Comm communication

2013/C95/01

Testing only if indications for endocrine disruption from repeated dose studies

Estrogenicity: ToxCast ER models OR uterotrophic assay (OECD TG 440)Anti-androgenicity: Hershberger assay (OECD TG 441)Thyroid disruption: Standard studies for repeated dose toxicitySteroidogenesis: H295R assay (OECD TG 456)

No in vitro mode of action screens on androgen receptor antagonism or thyroid relevant assays

No testing strategy

Environ Health Perspect 119, 794 (2011)

Nine previously untested pesticide AS identified as in vitro AR antagonists:

dimethomorph, fenhexamid, quinoxyfen, cyprodinil, λ-cyhalothrin, pyrimethanil, fludioxonil, azinphos-methyl, pirimiphos-methyl

Work group aims and programme (1)

• Characterise the regulatory status quo – how are triggers for further ED testing interpreted?

• Suggest ways of improving Reg 283/2013, specified in Comm communication 2013/C95/01, and other equivalent directives

• Which OECD validated EDC tests can (should) be implemented NOW?

• Which test methods should be implemented to capture wildlife ED effects?

• Development of testing strategies

Work group aims and programme (2)

• How are ED test data used to establish ADI, TDI?

• Impact of improvements in EU on other legislations?

• New EURION test methods – implementation?

Interaction with other work groups

• Overlap with:

• IATA work group

• AOP work group