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Triggers for higher-order toxicity testing.

B A Schwetz1, R E Morrissey

  • 1Systemic Toxicology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC.

Toxicology Letters
|December 1, 1989
PubMed
Summary

Selecting chemicals for toxicology testing is crucial due to limited resources. The National Toxicology Program uses specific triggers from animal and in vitro studies to prioritize chemicals for reproductive toxicology, but not developmental toxicology.

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Area of Science:

  • Toxicology
  • Chemical Safety Assessment
  • Risk Assessment

Background:

  • Limited resources necessitate strategic selection of chemicals for comprehensive toxicology testing.
  • The National Toxicology Program (NTP) employs established strategies for prioritizing chemicals for definitive toxicological evaluation.
  • Chemical selection considers human exposure, structure-activity relationships, and existing human health observations.

Purpose of the Study:

  • To outline the strategies used by the NTP for selecting chemicals for definitive toxicology tests.
  • To identify specific triggers derived from animal and in vitro studies that inform chemical selection and study design.
  • To highlight the differences in trigger availability between reproductive and developmental toxicology.

Main Methods:

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  • Review of NTP's chemical selection strategies across various toxicology domains.
  • Identification of specific triggers used in reproductive toxicology, including prechronic study findings (e.g., organ weights, histopathology, sperm parameters, estrus cyclicity).
  • Comparison of trigger availability and utility for reproductive versus developmental toxicology studies.

Main Results:

  • NTP utilizes specific triggers from animal studies and in vitro screens to guide chemical selection for definitive testing.
  • In reproductive toxicology, triggers include observations on reproductive organ health, male reproductive function, and female estrus cyclicity from rodent studies.
  • Currently, comparable tissue-specific triggers are lacking for developmental toxicity, and screening tests are not widely used for prioritizing these studies.

Conclusions:

  • NTP's strategic approach effectively uses specific triggers to prioritize chemicals for reproductive toxicology testing.
  • The absence of similar triggers for developmental toxicology presents a gap in prioritization strategies for these critical studies.
  • Further development of screening methods and tissue-specific triggers is needed to enhance prioritization for developmental toxicity testing.