Application of an integrated testing strategy to the U.S. EPA endocrine disruptor screening program

Toxicol Sci. 2011 Sep;123(1):15-25. doi: 10.1093/toxsci/kfr145. Epub 2011 Jun 3.

Abstract

New approaches to generating and evaluating toxicity data for chemicals are needed to cope with the ever-increasing demands of new programs. One such approach involves the use of an integrated testing and evaluation strategy based on the specific properties and activities of a chemical. Such an integrated strategy, whether applied to existing or future programs, can promote efficient use of resources and save animals. We demonstrate the utility of such a strategy by applying it to the current U.S. Environmental Protection Agency Endocrine Disruptor Screening Program (EDSP). Launched in October 2009, the EDSP utilizes a two-tiered approach, whereby each tier requires a battery of animal-intensive and expensive tests. Tier 1 consists of five in vitro and six in vivo assays that are intended to determine a chemical's potential to interact with the estrogen (E), androgen (A), or thyroid (T) hormone pathways. Tier 2 is proposed to consist of multigenerational reproductive and developmental toxicity tests in several species and is intended to determine whether a chemical can cause adverse effects resulting from E, A, or T modulation. In contrast to the existing EDSP structure, we show, using the pesticide atrazine as an example, that a multilevel testing framework combined with an integrated evaluation process would significantly increase efficiency by minimizing testing.

MeSH terms

  • Animal Use Alternatives
  • Animals
  • Endocrine Disruptors / toxicity*
  • Endocrine System / drug effects*
  • Environmental Monitoring / economics
  • Environmental Monitoring / methods*
  • Environmental Monitoring / standards
  • Female
  • Male
  • Program Evaluation
  • Rats
  • Toxicity Tests / economics
  • Toxicity Tests / methods*
  • Toxicity Tests / standards
  • United States
  • United States Environmental Protection Agency*
  • Xenobiotics / toxicity*

Substances

  • Endocrine Disruptors
  • Xenobiotics