Abstract
DMF, NMF and their major metabolites were investigated for their developmental toxicity in the mouse limb bud assay. We found that neither DMF, NMF nor the predominant urinary metabolite HMFF exhibited developmental activity. In contrast, all metabolites resulting from the glutathione binding pathway, SMG, SMC and AMCC showed potent developmental activity. Under the chosen exposure conditions, the developmental toxicity of DMF in different species appears to be related to the magnitude of glutathione binding. The results further show the value of using an in vitro system which is incapable of metabolic transformation of exogenous compounds for the identification of ultimate teratogenic species.
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