Is there any place for nonmammalian in vitro tests?
In vitro developmental toxicity testing procedures have two potential uses: 1) prediction of Adult/Developmental Ratios (A/D Ratios); and 2) study of the mechanisms of embryo development. Historically there has been an incorrect emphasis on malformation as the most relevant endpoint of developmental toxicity, as well as an incorrect assumption that this endpoint alone could be identified by an in vitro procedure. The literature is filled with tests that have later been shown to be inaccurate predictors of mammalian developmental toxicity. In addition, industrial experience with in vitro tests used to predict bimodal responses (e.g., potential carcinogenicity) has produced a basic mistrust of the results of these tests and an unwillingness to perform a test because of fear of inappropriate delays in the regulatory process. Because no single test has been identified as one that can replace mammalian testing procedures, there is also little need seen for these procedures, although some tests are used, not necessarily correctly, to prioritize testing. Better understanding of the utility of these tests would increase their use in the prioritizing process, possibly allow their use when remarkable acute environmental hazards occur, and assist in identifying the mechanism underlying the observed effect.
Christian
M S
MS
Argus Research Laboratories, Horsham, Pennsylvania 19044.
D000014:Abnormalities, Drug-Induced; D000818:Animals; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D006801:Humans; D066298:In Vitro Techniques; D012098:Reproduction / Q000187:drug effects*; D014116:Toxicology / Q000379:methods*