Lack of in vivo and in vitro genotoxicity with the nonsteroid, antiinflammatory agent sodium meclofenamate.
Sodium meclofenamate (Meclomen), CI-583, is an anthranilic acid salt developed as a nonsteroidal, antiinflammatory agent. A multitest battery of short-term tests was employed to characterize the genotoxic and mutagenic potential of the compound by measuring point mutations in bacteria, induction of sister-chromatid exchange, chromosome aberrations, and gene mutations in mammalian cells in vitro. In vitro assays included metabolic activation. The in vivo assay was for chromosome aberrations in bone marrow cells from rats. At toxicity-limited doses for each assay, no activity was detected in the bacterial or mammalian cell mutation assays, and sister-chromatid exchange frequencies were not increased over control rates. When sodium meclofenamate was evaluated in vitro, chromosome aberrations were induced under metabolic activation in CHO cells. Chromosome aberrations and clastogenic activity were not demonstrated after oral administration of Meclomen to male rats. It was concluded that sodium meclofenamate does not possess overt mutagenic potential under these conditions. The activity seen in vitro with CHO cells after metabolic activation did not correlate with the results from the other tests and was attributed to the formation of reactive metabolites not present or formed in in vivo systems.
D000818:Animals; D001711:Biotransformation; D002478:Cells, Cultured; D002869:Chromosome Aberrations; D006224:Cricetinae; D003412:Cricetulus; D005260:Female; D008469:Meclofenamic Acid / Q000633:toxicity*; D009152:Mutagenicity Tests; D009154:Mutation / Q000187:drug effects*; D010053:Ovary; D051381:Rats; D012854:Sister Chromatid Exchange / Q000187:drug effects; D062367:ortho-Aminobenzoates / Q000633:toxicity*
D062367:ortho-Aminobenzoates; D008469:Meclofenamic Acid