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A Different Approach to Validating Screening Assays for Developmental Toxicity
Citation:
Daston, G. P., R. E. Chapin, A. R. Scialli, A. H. Piersma, E. W. Carney, J. M. ROGERS, AND J. M. Friedman. A Different Approach to Validating Screening Assays for Developmental Toxicity. BIRTH DEFECTS RESEARCH PART B: DEVELOPMENTAL AND REPRODUCTIVE TOXICOLOGY. John Wiley & Sons, Ltd., Indianapolis, IN, 89(6):526-530, (2010).
Impact/Purpose:
This paper describes an approach to validating in vitro tests for developmental toxicity. It is the first step in an effort to develop a list of exposures to be used to validate and calibrate such tests.
Description:
BACKGROUND: There continues to be many efforts around the world to develop assays that are shorter than the traditional embryofetal developmental toxicity assay, or use fewer or no mammals, or use less compound, or have all three attributes. Each assay developer needs to test the putative assay against a set of performance standards, which traditionally has involved testing the assays against a list of compounds that are generally recognized as "positive" or "negative" in vivo. However, developmental toxicity is highly conditional, being particularly dependent on magnitude (i.e., dose) and timing of exposure, which makes it difficult to develop lists of compounds neatly assigned as developmental toxicants or not. APPROACH: Here we offer a new approach for the evaluation of developmental toxicity assays based on exposures. Exposures are classified as "positive" or "negative" in a system, depending on the compound and the internal concentration. Although this linkage to "internal dose" departs from the recent approaches to validation, it fits well with widely-accepted principles of developmental toxicology. CONCLUSIONS: This paper introduces this concept, discusses some of the benefits and drawbacks of such an approach, and lays out the steps we propose to implement it for the evaluation of developmental toxicity assays.
