EPA Resumes Testing Under the Endocrine Disruptor Screening Program

EPA's call for testing expected to reach beyond 30 identified chemicals

The Environmental Protection Agency (EPA) is on the cusp of issuing data call-ins (DCIs) to screen 30 pesticide active ingredients for endocrine-disrupting properties under the Endocrine Disruptor Screening Program (EDSP). The full list of highest-priority chemicals for EPA EDSP data call-ins can be downloaded at Regulations.gov. 

These DCIs are expected to be issued this summer or shortly thereafter and will be the second round of EDSP-related DCIs issued by EPA. Before this, EPA released its first round of DCIs for EDSP Tier 1 screening in 2009, when test orders were issued for the first list of chemicals identified based on exposure potential.

Potential impact for pesticide registrants and other stakeholders

The EDSP was developed to fulfill requirements of the 1996 Food Quality Protection Act (FQPA) to assess how pesticides and other chemicals may affect the estrogen, androgen, and thyroid hormonal pathways. Testing under EDSP involves a two-tiered approach: 

• Tier 1 screening uses a battery of in vitro and in vivo assays to identify substances with the potential to interact with endocrine pathways. 
• Tier 2 testing involves definitive in vivo studies intended to identify any adverse endocrine-related effects and to establish dose-response relationships for those outcomes. 

The 30 chemicals to be screened are pesticide active ingredients for which an updated (post-1998) two-generation reproductive toxicity (OPPTS 870.3800) study or extended one-generation reproductive toxicity (EOGRT; OECD 443) study are not available and for which ToxCast Pathway Model scores for the estrogen or androgen receptor show activity (i.e., model AUC scores ≥ 0.1).  

Pending evaluation of available thyroid data, additional DCIs could be issued for additional chemicals with an updated two-generation reproduction study and sufficient ToxCast Pathway Model data (≤82 chemicals). However, EPA has not stated what thyroid data would be considered sufficient to satisfy an endocrine evaluation or if an evaluation for the comparative thyroid assays would be required.

Future DCIs are also expected to be issued for another 126 pesticide active ingredients that have neither updated reproductive studies nor ToxCast Pathway Model data, although the endocrine disrupting potential for some of these chemicals may be addressed during the registration review process instead. For new chemicals, endocrine data requirements will be addressed during the registration process. 

Testing Challenges

If EDSP Tier 1 screening is triggered, EPA is likely to request assays, including: 

• In vitro steroidogenesis and aromatase assays 
• Hershberger assay in male rats 
• Male and female rat pubertal assays 

Performing these assays poses some challenges. Because the pubertal assays have not been conducted regularly since the last round of EDSP Tier 1 screening, contemporaneous historical control data are not available, which will affect interpretation. Additionally, there will be challenges with lab capacity for some of these assays. This will likely be compounded by growing European ED testing obligations precipitated by an update to the EU REACH regulatory requirements. 

Other possible data for addressing potential endocrine disruption

In lieu of Tier 1 assays, EPA is expected to alternatively allow registrants to submit an updated two-generation reproductive or EOGRT study, which will generally provide conclusive data for potential estrogen and androgen effects. 

In addition, other scientifically relevant information (OSRI) may be accepted by EPA to fulfil EDSP Tier 1 screening requirements. This is contrary to 2009, when registrants were encouraged to submit OSRI to fulfil EDSP Tier 1 screening requirements, but EPA was nonetheless restrictive in their acceptance of these data for the initial list of 52 chemicals identified for Tier 1 screening. This time around, EPA will more likely consider existing data, when possible, to make endocrine decisions. 

It is also possible that risk-based approaches for determining the need for endocrine data may be acceptable as a similar approach was previously taken in assessing the need for comparative thyroid assays. Alternatively, data on estrus cyclicity/sperm parameters, pubertal development, and reproductive organ weights/histopathology available from other studies may be sufficient to fulfil EDSP requirements.

Next steps for stakeholders

Seek out EDSP strategic guidance to determine best approaches for addressing forthcoming DCIs, including: 

• Whether existing data may be sufficient to fulfill testing requirements or whether an endocrine-related effect is likely to be a driving endpoint for chemical risk assessment
• Whether the development of new data would be beneficial, including risk-based assessments to determine whether the requested data will impact EPA's overall risk evaluations

OSRI development: Prepare and submit OSRI, including the evaluation of whether existing data are likely to trigger or satisfy EDSP testing requirements and the potential impact of new data on the risk evaluation.

EDSP study: In addition to EDSP Tier 1 assay placement and monitoring, develop weight-of-evidence evaluations of EDSP and OSRI to assess a chemical's potential to interact with the estrogen, androgen, thyroid, and steroidogenesis (EATS) hormonal systems based on data derived from EDSP screening studies.