Estimating Chemical Developmental Hazard in a Chicken Embryo Limb Bud Micromass System

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Abstract
A chicken limb bud micromass system measuring the production of cartilage proteoglycans and the incorporation of radiolabelled thymidine and leucine was used to calculate potential developmental hazard. This hazard index was based upon the 50% inhibitory concentration (IC50) for these parameters and enabled classification of substances according to their intrinsic ability to inhibit differentiation at concentrations which were not cytotoxic. All-trans-retinoic acid, a potent teratogen, inhibited cartilage proteoglycan synthesis at a concentration which was more than 100 times lower than those affecting the incorporation of 14C-thymidine and 14C-leucine. On the other hand, sodium valproate, salicylate and isoniazid inhibited cartilage proteoglycan synthesis only near concentrations which were also cytotoxic. The results from testing with chicken limb bud micromass compared favorably, both with respect to effective concentrations and ratios describing developmental hazard to those from rodent micromass systems.