ATLA::Alternatives to Laboratory Animals

Volume 24, Number 2

An interlaboratory evaluation of five pairs of teratogens and non-teratogens in post-implantation rat embryo culture.

ATLA 24, 201-209, March/April 1996

Aldert H. Piersma,¹ Rudolf Bechter,² Nathalie Krafft,² Beat P. Schmid,³ Jeanne Stadler,⁴ Aart Verhoef,¹ Christian Verseil⁴ and Jacob Zijlstra³

¹National Institute of Public Health and the Environment, P.O. Box 1, 3720 BA Bilthoven, The Netherlands; ²Drug Safety Assessment, Sandoz Pharma Ltd, 4002 Baste, Switzerland; ³Preclinical Development and Drug Safety, Zyma SA, 1260 Nyon, Switzerland; ⁴ Pfizer Research Center, Zl Poce sur Asse BP159, 37401 Amboise, France

SUMMARY

The usefulness of the post-implantation rat embryo culture method in screening xenobiotic compounds for developmental toxicity was validated in four laboratories with five pairs of compounds. This approach was chosen to provide information on the interlaboratory reproducibility of the results and to compare the effects of chemical analogues in embryo culture. By testing analogous compounds which are known to have different embryotoxic potencies in vivo, the discriminating power of the embryo culture method for the compound classes under study could be optimally assessed. The classes selected for testing were triazole antifungals, phthalic ester metabolites, substituted pyridines, sulphonamides and methylated xanthines. In summary, it was possible to distinguish between the compounds in three of the pairs, it was not possible to discriminate between the compounds of one pair, and it was possible to discriminate between the compounds of the other pair at two out of the four laboratories. The embryo culture results generally show a good correspondence with the embryotoxic properties of the compounds tested in vivo, although the embryo culture method appeared to be able to discriminate between only some of the pairs of chemical analogues. Some discrepancies may have arisen among the laboratories, because of methodological differences. These results suggest that the post-implantation rat embryo culture method may be a useful tool for screening xenobiotics within classes of compounds known to interfere with embryogenesis during the period of development represented in culture.

Keywords: embryotoxicity, developmental toxicity, in vitro screening, rat embryo culture, teratogenicity