Validation of alternative methods for developmental toxicity testing.
Developmental toxicity testing according to current international guidelines involves exposure of pregnant animals, mostly rats and rabbits, and subsequent assessment of toxic effects in their fetuses. Alternative methods have been developed since the early 1980s. They include cell differentiation assays using either primary cell cultures or immortalized cell lines. At a higher integration level the development of organ anlagen in vitro has been employed in assays for developmental toxicity. The most complex assays in this area make use of isolated postimplantation rodent embryos which are cultured in vitro during the phase of major organogenesis. The possibilities for their application as toxicity screens have been investigated in various validation studies. The most elaborate validation study of embryotoxicity assays carried out to date included the embryonic stem cell test EST, the limb bud micromass MM, and whole embryo culture WEC. In each test 20 chemical compounds were tested in four independent laboratories. The results have shown a marked success in the reproducibility of results. The extrapolation of these results of a limited set of chemicals to a generalized judgment of the tests for the world of chemicals remains a matter for further discussion.
Piersma
Aldert H
AH
Department of Reproductive Toxicology, Laboratory for Toxicology, Pathology and Genetics, National Institute for Public Health and the Environment RIVM, P.O. Box 1, 3720 BA Bilthoven, The Netherlands. ah.piersma@rivm.nl
D000014:Abnormalities, Drug-Induced / Q000473:pathology*; D000818:Animals; D023381:Endpoint Determination; D005260:Female; D005544:Forecasting; D006801:Humans; D011247:Pregnancy; D011817:Rabbits; D051381:Rats; D015203:Reproducibility of Results; D013723:Teratogens / Q000633:toxicity*; D018675:Toxicity Tests / Q000592:standards
D013723:Teratogens