Absence of in vitro genotoxicity of pyrvinium pamoate in sister-chromatid exchange, chromosome aberration, and HGPRT-locus mutation bioassays.
A single preparation of U.S.P. pyrvinium pamoate that exhibited promutagen activity in Salmonella/mammalian microsome reverse mutation assays was subjected to in vitro mammalian cell bioassays. Cytotoxicity limiting doses of dimethyl sulfoxide-solubilized drug were without effect in the absence and/or presence of liver S9 fraction from Aroclor-1254-induced rats in an in vitro Chinese hamster ovary (CHO) cell assay for chromosome aberration and sister-chromatid exchange induction at concentrations of 0.025-0.78 microgram/ml. Forward gene mutation at the hypoxanthine-guanine phosphoribosyl-transferase (HGPRT) locus in Chinese hamster (V-79) cells was studied with and without exogenous metabolic activation at concentrations ranging from 0.3 to 10 micrograms/ml. In concurrent promutagen controls, dimethylnitrosamine, benzo[a]pyrene, and cyclophosphamide caused significant (p less than 0.05) increases over controls in each respective assay endpoint under the metabolic activations used. These results suggest that intrinsic mutagenic activity manifested in lower microbial systems does not have a corresponding effect in mammalian cells. Coupled with the lack of solubility and poor absorption in vivo, we concluded that the drug, when used In the single oral dose mode of administration, possesses a negligible somatic and germinal genotoxicity risk.
D000818:Animals; D000871:Anthelmintics / Q000633:toxicity*; D002478:Cells, Cultured; D002869:Chromosome Aberrations; D006224:Cricetinae; D003412:Cricetulus; D005260:Female; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics; D008099:Liver / Q000378:metabolism; D009153:Mutagens; D010053:Ovary / Q000648:ultrastructure; D011774:Pyrvinium Compounds / Q000633:toxicity*; D012854:Sister Chromatid Exchange / Q000187:drug effects
D000871:Anthelmintics; D009153:Mutagens; D011774:Pyrvinium Compounds; C024631:pyrvinium; D007041:Hypoxanthine Phosphoribosyltransferase