# Presentation: 179414

## Priority-setting for the Endocrine Disruptor Screening Program:Pesticide Active Ingredients

**Penelope A. Fenner-Crisp**
**Office of Pesticide Programs**
**U.S. Environmental Protection Agency**

## Food Quality Protection Act  Mandates

**EPA MUST:**
**Screen pesticides (both actives and others) for estrogenic effects that may affect human health**** **
**( may include other effects)**
**Develop a screening and testing program by August 1998 **
**Implement the screening and testing program by August 1999**
**Report to Congress by August 2000**

## Proposed Implementation Strategy

**Current Size of the Universe**
**~~ 950 pesticide active ingredients currently registered in U.S.**
**~~ 450 have uses on food/feed**
**(~~ 2500 “other” ingredients (inerts))**

## Proposed Implementation Strategy

**Proposed elements of the strategy**
**Issue exemptions**
**Sort and prioritize “other” (inert) ingredients using the EDPSDB**
**Revise 40 CFR 158 to include EDSP **
**Run Pilot program with 25-50 active ingredient substances**
**Issue orders periodically for groups of substances**

## Proposed Implementation Strategy

**Exemptions-**
**Issue exemptions for those “biological substance(s) or other substance(s) .... anticipated not to produce any effect in humans similar to an effect produced by a naturally occurring estrogen” or other such endocrine effect....**
**Would cover both active and other        (inert) ingredients**

## Currently-registered “Other” Ingredients (Inerts)  

**EPA’s ENDOCRINE DISRUPTOR  SCREENING PROGRAM**
**Currently-registered “Other” Ingredients (Inerts)  **

**SORT**

**Category 1:**
**      ****Hold**

**All other**
** ****Chemicals**

**  ****HTPS**

**Category 2:**
**Insufficient Data,**
**Set Priorities for**
**Tier 1 Screening**

**Tier 1 Screening**

**Tier 2 Testing**

**Hazard**
** ****Assessment**

**Category 4:**
**Adequate **
**    ****Data**

**Category 3:**
**Need Tier 2 **
**Test Data**

**Total Universe of Chemicals**

-    **Est 87,000**

**Commercial Chemicals**
**< 10,000 lbs Production**

**Polymers**

**Exempted **
**Chemicals**

## Proposed Implementation Strategy

**Currently-registered Other Ingredients**
**Formerly known as inerts**
**Will be sorted for priority along with other substances using the EDPSDB**
**Special attention will be given to overlap with chemicals also on TSCA inventory, especially those identified for the HPV and Children’s Chemical Evaluation programs**

## To-be-registered Pesticides-Actives and Others

**EPA’s ENDOCRINE DISRUPTOR  SCREENING PROGRAM****  **
**To-be-registered Pesticides-Actives and Others**

**SORT**

**Category 1:**
**    ****Hold**

**All other**
** ****Chemicals**

**  ****HTPS**

**Category 2:**
**Insufficient Data,**
**Set Priorities for**
**Tier 1 Screening**

- Hazard
- Assessment

**Tier 1 **
**Screening**

**Tier 2 **
**Testing**

**Category 4:**
**Adequate **
** ****Data**

**Category 3:**
**Need Tier 2 **
**Test Data**

**Total Universe of Chemicals**

-    **Est 87,000**

**Commercial Chemicals**
**< 10,000 lbs Production**

**Polymers**

**Exempted **
**Chemicals**

## Proposed Implementation Strategy:To-Be-Registered Active and Other Ingredients

**Amendment of 40 CFR 158 to include EDSP components**
**Requirements may vary with class and use pattern, *****e.g.,***
**Requirements may or may not apply at all**
**Requirements may be required prospectively or triggered**

##    Est 87,000

**EPA’s ENDOCRINE DISRUPTOR  SCREENING PROGRAM**** **
**Already-registered Pesticide Actives**** **

**SORT**

**  ****Category 1:**
**       ****Hold**

**All other**
** ****Chemicals**

**  ****HTPS**

**Category 2:**
**Insufficient Data,**
**Set Priorities for**
**Tier 1 Screening**

**Tier 1 Screening**

**Tier 2 Testing**

**Hazard**
** ****Assessment**

**Category 4:**
**Adequate **
**    ****Data**

**Category 3:**
**Need Tier 2 **
**Test Data**

**      ****Total Universe of Chemicals**

**   ****Est 87,000**

**Commercial Chemicals**
**< 10,000 lbs Production**

**Polymers**

**Exempted **
**Chemicals**** **

## Part 158 Toxicology Data Requirements- Human Health

**Acute oral toxicity **
**Acute dermal**
**Acute inhalation**
**Primary eye irritation**
**Primary dermal irritation**
**Dermal sensitization **
**2 Subchronic feeding studies **
**2 Chronic feeding studies **
**2 Carcinogenicity studies **
***2 Prenatal developmental toxicity studies  ***
***Two-generation reproduction study ***
**General metabolism study **
**Mutagenicity studies **

** **

**Dermal penetration**
**21-day dermal toxicity study***** ***
**Subchronic inhalation or dermal study**
**(2 Immunotoxicity studies)**
**Acute or subchronic delayed neurotoxicity **
**Acute neurotoxicity study**
**Subchronic or chronic neurotoxicity **
***Developmental neurotoxicity***
**Scheduled controlled operant behavior**
**Peripheral nerve function**
**Sensory evoked potential**

## Part 158 Toxicology Data Requirements- Ecological Effects

_**Avian and Mammalian **_
_**	**__**Species**_
**Avian oral LD50**
**Avian dietary LC50**
**Wild mammal toxicity**
***Avian reproduction***
**Simulated and actual **
**     ****field testing**

_**Aquatic Organisms **_
**Freshwater fish LC50**
**Acute LC50 freshwater**
**	****invertebrates**
**Acute LC50 estuarine and **
**            ****marine organisms**
***Fish early life stage and aquatic***
***	******invertebrate life cycle***
***Fish life cycle***
**Aquatic organism accumulation**
**Simulated or actual field testing**

## Already-registered Pesticide Actives

**Category 3:**
**Need Tier 2**
**Test Data**

**Tier 2 Testing:**
**2-Generation**
** ****Study Designs**

**Category 4**
**Adequate Data**

**Hazard Assessment**

**	****Category 3/4**
**      ****Have Adequate Data pre-EDSP,**
**      ****But Need Refinement of Toxicity **
**      ****Profile for EAT Potential**

**Tailored testing:**
**Screens**
** ****Less Comprehensive tests**
** ****Special Studies**

## PROPOSED SCREENING BATTERY (Tier 1)

**PROPOSED SCREENING BATTERY (Tier 1)**

***In vitro *****Screens**
**ER Binding / Reporter Gene Assay**
**AR Binding / Reporter Gene Assay**
**Steroidogenesis Assay with minced testis**
**In vivo Screens**
**Rodent 3-day Uterotrophic Assay (sc)**
**Rodent 20-day Pubertal Female Assay with Thyroid**
**Rodent 5-7 day Hershberger Assay**
**Frog Metamorphosis Assay**
**Fish Gonadal Recrudescence Assay**

## SCREENING BATTERY  EXAMPLE 1 

**SCREENING BATTERY **** EXAMPLE 1 **

***In vitro***** Screens**
**ER Binding or Reporter Gene Assay***
**AR Binding or Reporter Gene Assay***
**Placental aromatase +**
**Steroidogenesis Assay with minced testis #**
***In vivo***** Screens**
**Rodent 3-day Uterotrophic Assay (sc)**
**Rodent 20-day Pubertal Male Assay with Thyroid +**
**Rodent 20-day Pubertal Female Assay w/ Thyroid #**
**Rodent 5-7 day Hershberger Assay #**
**Frog Metamorphosis Assay**
**Fish Reproduction Screening Assay**
**+ ****Assays in**** ****yellow**** ****may replace**** ****assays in**** ****red #**** **

## SCREENING BATTERY  EXAMPLE 2

**SCREENING BATTERY **** EXAMPLE 2**

***In vitro***** Screens**
**ER Binding or Reporter Gene Assay***
**AR Binding or Reporter Gene Assay***
**Steroidogenesis Assay with minced testis #**
***In vivo***** Screens**
**Rodent 3-day Uterotrophic Assay (sc) #**
**In-utero Assay +**
**Rodent 20-day Pubertal Female Assay w/ Thyroid #**
**Rodent 5-7 day Hershberger Assay #**
**Frog Metamorphosis Assay**
**Fish Reproduction Screening Assay**
**+ ****Assay in**** ****yellow ****may replace assays in**** ****red #**

## TIER 2 TESTING BATTERY

**TIER 2 TESTING BATTERY**

**Multi-generation studies of reproduction and development in:**
**Mammals**
**Birds **
**Fish**
**Invertebrates**
**Amphibians**

## TIER 2 TESTING BATTERY:LESS COMPREHENSIVE TESTS

**Alternative or Single-generation studies of reproduction and development in:**
**Mammals  **
**(Alternative test could be *****in utero***** assay ****	****	****	****     described in Screening Battery Example #2)**
**Birds **
**Fish**
**Invertebrates**
**Amphibians**

## Proposed Implementation Strategy:Already-Registered Active Ingredients

**Original Proposal**
**Implement EDSP on timetable for FIFRA Reregistration and/or FQPA Tolerance Reassessment mandates**

## Proposed Implementation Strategy:Already-Registered Active Ingredients

**Current Proposal-**
**Phase 1- Pilot Program with 25-50 “potentially high EAT hazard concern” substances**
**Later Phases**
**Periodic issuance of FFDCA Section 408p orders for additional substances**
**May make use of EDPSDB**
**May integrate with timetable for Registration Renewal**

## Proposed Implementation Strategy:Already-Registered Active Ingredients

**Selection process for Phase 1**
**Will identify chemicals of potential concern **
**from both a human health *****and *****ecological effects perspective**
**using existing published hazard/risk assessments (*****e.g.*****, REDs), internal databases, Data Evaluation Records (*****i.e.*****, study reviews), open literature and expert scientific judgment**

## Summary:Proposed Implementation Strategy

**Issue exemptions**
**Sort and prioritize “other” (inert) ingredients using EDPSDB**
**Revise 40 CFR 158 to include EDSP (for to-be-registered substances) **
**Run Pilot program for 25-50 (already-registered) active ingredient substances**
**Issue orders periodically for groups of (already-registered) substances**