Exposure-Based Validation List for Developmental Toxicity Screening Assays

  • Publication Date :
  • Publication Type : Journal Article
  • Author(s) : Daston GP, Beyer BK, Carney EW, Chapin RE, Friedman JM, Piersma AH, Rogers JM, Scialli AR
  • Journal Name : Birth Defects Research Part B: Developmental and Reproductive Toxicology

Birth Defects Research Part B: Developmental and Reproductive Toxicology. 2014;101:423-428

Abstract: Validation of alternative assays requires comparison of the responses to toxicants in the alternative assay with in vivo responses. Chemicals have been classified as “positive” or “negative” in vivo, despite the fact that developmental toxicity is conditional on magnitude of exposure. We developed a list of positive and negative developmental exposures, with exposure defined by toxicokinetic data, specifically maternal plasma Cmax. We selected a series of 20 chemicals that caused developmental toxicity and for which there were appropriate toxicokinetic data. Where possible, we used the same chemical for both positive and negative exposures, the positive being the Cmax at a dose level that produced significant teratogenicity or embryolethality, the negative being the Cmax at a dose level not causing developmental toxicity. It was not possible to find toxicokinetic data at the no-effect level for all positive compounds, and the negative exposure list contains Cmax values for some compounds that do not have developmental toxicity up to the highest dose level tested. This exposure-based reference list represents a fundamentally different approach to the evaluation of alternative tests and is proposed as a step toward application of alternative tests in quantitative risk assessment.

To download an open-access PDF copy, click here.

Contact Us

Health and Environmental Sciences Institute (HESI)

Phone: +1-202-659-8404
Fax: +1-202-659-3859

740 15th Street NW, Suite 600
Washington, DC 20005

Stay Informed

Sign up for our monthly e-newsletter.