Validation of alternative methods for developmental toxicity testing.

Abstract:

: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.

journal_name

Toxicol Lett

journal_title

Toxicology letters

authors

Piersma AH

doi

10.1016/j.toxlet.2003.12.029

keywords:

subject

Has Abstract

pub_date

2004-04-01 00:00:00

pages

147-53

issue

1-3

eissn

0378-4274

issn

1879-3169

pii

S0378427403004946

journal_volume

149

pub_type

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