VALIDATION OF POSTIMPLANTATION RODENT WHOLE EMBRYO CULTURE FOR IN VITRO TERATOGENICITY TESTING

KIYOHITO NAKASHIMA
Department of Chemistry Asahi University School of Dentistry, 1851-1 Hozumi, Hozumi-cho, Motosu-gun, Gifu 501-02, Japan

Regular article :AATEX3(1):9-16

Abstract
Teratogenicity data obtained from rat and mouse whole embryo culture (WEC) concerning the agents compiled in the Smith list were collected from the literature. Following analysis of these data, each technique for an in vitro teratogenicity testing was validated for its ability to evaluate teratogenic potential.
The rodent WEC techniques were variable between investigators with regard to culture medium, exogenous metabolizing source, and endpoint measurements. Of 34 agents tested in cultured rat embryos, two showed variable results. The remaining 32 agents had accuracy values of 90.0, 84.4, and 66.7% when the teratogenic potentials in vitro were compared with those available from rats, mammals, and humans in vivo, respectively. Of 15 known mammalian teratogens in vivo tested in cultured mouse embryos, 14 were positive and one was variable.
The results indicated that the rat WEC assay has poorer predictive value of teratogenic potential in vivo in mammals or humans than in rats. Also, the validity of the results obtained by the mouse WEC assay is unknown because agents known to be nonteratogenic in mammals in vivo have not been tested. Standardization of rodent WEC techniques is critically important before further validation efforts are made.


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