171113 Update on recent developments in the ed regulatory landscape in Europe REACh (1907/2006): potential EDs as substances of very high concern (SVHC), equiv. level of concern CMR or PBT (art. 57(f)), authorization 
 Biocides (528/2012): non-approval of EDs, exceptions: demonstration of negligible risk
or necessity to combat serious pests
or disproportionate negative impacts on society 
 PPPs (1107/2009): non-approval of EDs, exceptions: demonstration of negligible exposure or necessity to combat serious pests 
 Cosmetics (1223/2009): regulation under review, so far EDs not yet restricted (possibly via REACh) 


Plant Protection Products and Biocides in Europe Plant Protection Products Regulation (PPPR) (EC1107/2009) (EU 283/2013 sets data requirements) Includes endocrine disruption as an exclusion criteria Based solely on hazard Unless the exposure of humans to that active substance, safener or synergist in a plant protection product, under realistic proposed conditions of use, is negligible (EC1107/2009 Annex II, paragraph 3.6.5); or It is necessary to control a serious danger to plant health which cannot be contained by other available means (for a maximum period of 5 years).

Plant Protection Products and Biocides in Europe EU Biocides Product Regulation (BPR) (528/2012) Article 5: Proposal similar to PPPR above Unless risks negligible, particularly in closed systems or in conditions excluding human contact and environmental release; or essential to prevent or control serious dangers to human, animal or environmental health; or Not approving would have disproportionate negative impacts on society compared to the risks. No substance with ED properties allowed for use as biocide by general public. PPPR (EC 1107/2009) includes endocrine disruption as an exclusion criterion. Approval only possible if no “endocrine disrupting properties that may cause adverse effects” in humans or environment unless negligible exposure Similar wording is under consideration in the BPR and the EU REACH regulation requires that endocrine disruptors progress to the stage of authorisation as substances of very high concern. Overall, being labeled as a potential endocrine disruptor based on screening results alone, without confirmatory tier 2 testing could result in regulatory action. (From Bars et al., 2010) In the regulations on plant protection and biocidal products, active substances considered to have endocrine disrupting properties that may be of toxicological significance in humans or non-target organisms will not be granted market approval. This represents exclusion from commerce based solely on hazard and does not allow for the fact that safe uses may be demonstrated by a risk based approach. Moreover, hazard based classification makes no distinction regarding the potency of substances. As such, a hazard based approach to the regulation of chemicals, requires a robust and scientifically defensible method for identifying endocrine disrupters. However, the fundamental scientific criteria, necessary to define ‘endocrine disrupting properties’, are not described in any of these legislative texts. Therefore, there is a possibility that different interpretations of what constitutes ‘endocrine disrupting effects’ might lead to inappropriate categorization of certain substances as endocrine disrupters.

EU Commission DG Environment originally charged with developing criteria for the identification of endocrine disrupting properties across EU regulations. A policy and technical group to discuss the issue and inform the criteria was formed Member States, NGOs and industry also provided their proposals ECHA now has role in the classification of potential EDs as SVHCs (EU expert group established in 2014) EC published in 2014 potential criteria and policy options – the ‘road map’

Road Map Options for criteria to Identify EDs Details/Comments 1 No criteria specified; the interim criteria for PPPR to apply (C2 and R2 or R2 with adverse endocrine effects) 2 A single category (‘known or presumed’) based on the WHO/IPCS definition. 3 A multiple category approach based on the WHO/IPCS definition. Category 1: endocrine disruptors ; Category 2: suspected endocrine disruptors; Category 3: endocrine active substances; 4 WHO/IPCS definition to identify EDs and inclusion of potency as an element of hazard characterization (hazard identification and characterization)

Road Map Approaches for Regulatory Decision Making Option Details/Comments A No policy change required (Baseline). The hazard based provisions in PPPR on regulatory decision making not changed. B Introduction of elements of risk assessment into sectorial legislation as opposed to basing on hazard alone. Introduction of negligible risk to replace negligible exposure? C Introduction of further socio-economic considerations, including risk-benefit analysis, into sectorial legislation. Exemption from the ban for cases where not approving the substance would have a disproportionate negative impact on society?

Impact Assessment European Commission engaged JRC to perform an impact assessment Substance by substance assessment for the different policy options specified in the roadmap Joint Research Centre developed a screening methodology –(http://ec.europa.eu/health/endocrine_disruptors/events/ev_20151106_em.htm) JRC screened the evidence available for about 700 chemical substances and determined if and where they fell under each of the 4 options outlined in the Roadmap. Specifically stated that it was a screening exercise only. Should not be used for a regulatory conclusion.

Development of ED Criteria in Europe Scientific criteria to define ED were approved by the Member States in July 2017 for plant protection products (PPP) and August 2017 for biocides The European Parliament voted to reject the draft criteria for PPP in October. Rejection based on Commission exceeding their powers by excluding pesticides that specifically target hormones (e.g. insect growth regulators (IGR)) A new draft may be put forward as early as the end of November without the IGR exemption The European Parliament adopted the draft criteria for biocides in early November The exemption for insect growth regulators is included but is only relevant for “non-target” effects on humans and there is no exemption if it is for consumer uses. ECHA and European Food Safety Agency (EFSA) drafting guidance on how the criteria would be implemented Target completion before the May 2018 formal adoption of the biocide criteria

EU Draft Endocrine Criteria Based on the WHO/IPCS 2002 definition Causal link between an observed adverse effect and the endocrine mode of action Use of weight of evidence Criteria apply to both human health and wildlife Use of human and animal data for human health assessment Hazard-based Substances that are identified as ED will not be approved for use (or will be severely restricted)

Endocrine Assessments in Japan Japan is currently developing assays with which to evaluate endocrine properties Many are part of the OECD test guideline development program The government is also testing selected materials (some based on effects, some based on detection in monitoring programs) SPEED 98 and ExTEND Programs Considering two-tiered approach that still includes ecological risk assessment Considering in vitro assays used to prioritize to enhance efficiency

Endocrine Assessments in China Draft of an agro-industrial standard ‘Evaluation Methods for Pesticide Endocrine Disruptors became available in late 2014 Final version implemented April 2016 Focus on in vivo mammalian tests

Endocrine Assessments in China 2 tier system (similar to US-EPA) Phase 1 In vitro tests: ER Transcriptional activation and Steroidogenesis assays In vivo tests: Uterotrophic, Hershberger and Pubertals Phase 2 Extended One-Generation Reproductive Toxicity Triggered by ‘positives’ at phase 1

Elsewhere in the Asia Pacific Region Most APAC countries are monitoring developments elsewhere in the world Australia publically stated that from a regulatory perspective they consider “endocrine disruption” no different than other modes of action suggesting it will be regulated using a risk-based approach Some APAC countries are beginning to request additional OECD endocrine studies if reproductive effects are noted in the standard pesticide submissions

Endocrine Assessments in Latin America Brazil and Chile are the primary Latin American countries where the endocrine issue has been under discussion by the regulators Brazil appears to be evaluating both hazard and risk-based approaches as they move forward with new chemical legislation Chile, so far, does not appear to be considering a hazard-based approach