INVITRO TERATOGENICITY OF RETINOIDS

  • 1 April 1987
    • journal article
    • research article
    • Vol. 68  (2) , 215-223
Abstract
Mid-gestation rat conceptuses were cultured for 48 h in serum containing the retinoids all-trans-retinoic acid (TRA), 13-cis-retinoic acid (13-CRA), etretinate (ETR), etretin or one of six retinamides at concentrations ranging from 0.5 to 400 .mu.g/ml. TRA was toxic at a concentration of 0.5 .mu.g/ml. 13-CRA and etretin caused abnormal development at 1.0 .mu.g/ml. However, the six retinamides were less toxic and adverse developmental effects were only evident at concentrations of 50 to 100 .mu.g/ml. ETR was without effect at 100 .mu.g/ml, the highest dose level of this compound tested. In vivo, TRA, 13-CRA and ETR are highly teratogenic. In this culture system, TRA and 13-CRA caused abnormal development at very low concentrations but in contrast, ETR was non-toxic at 100 .mu.g/ml. Therefore these findings indicate that in vivo, maternal pharmacokinetics, and bioactivation in particular, play a major role in inducing abnormal development. Cis/trans isomerization was not a major determinant of toxicity. However, there appeared to be a relationship between abnormal development and the actual or estimated pKa values of the 10 retinoids tested.

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