Bacterial Mutagenesis and Cell Transformation Assays of Pyrvinium Pamoate (Povan),An Antiparasitic Agent

Abstract

Mutagenicity of pyrvinium pamoate formulations was determined in various Salmonella typhimurium strains in a well test and plate incorporation assays in the presence and absence of liver homogenate (S9) from Aroclor-1254-induced rats or from normal human liver. Strains TA98 and TA100 were reverted to histidine independence by bulk pyrvinium pamoate over a concentration range of 500 to 2500 μg/plate, particularly in the presence of rat S9. Purified pyrvinium pamoate was mutagenic over a concentration range of 5.0 to 25 μg/plate in the presence of both rat and human liver S9. Urine concentrates from human subjects given 10 mg/kg and mice given drug up to 100 mg/kg were not significantly mutagenic even after S9 activation and/or β-glucuronidase-sulfatase treatment. These results confirm earlier observations of mutagenic activity in Salmonella, but, unlike several antiparasitic agents, mutagenic metabolites do not appear in urine. In vitro mouse cell (C₃H10T1/2) transformation assays of pyrvinium pamoate were negative. The effects of pyrvinium pamoate in Salmonella are not paralleled by effects in mammalian cell systems. In the absence of quantitative human population data for risk assessments, the evidence of carcinogenic potential of Povan is not defined.

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