Effect of buprenorphine on genotoxicity evaluation of chemicals by the rat liver micronucleus test with partial hepatectomy

The Journal of Toxicological Sciences
Satoru ItohWataru Takasaki

Abstract

In the view of animal welfare considerations, we investigated the suitability of modifying the rat liver micronucleus test with partial hepatectomy to include administration of an analgesic drug to minimize pain and distress as much as possible. The effects of the analgesic, buprenorphine, on the genotoxicity evaluation of structural chromosome aberration inducers (cyclophosphamide, diethylnitrosamine and 1,2-dimethylhydrazine) and numerical chromosome aberration inducers (colchicine and carbendazim) were examined. The genotoxicants were given orally to 8-week-old male F344 rats a day before or after partial hepatectomy and hepatocytes were isolated 4 days after the partial hepatectomy. Buprenorphine was injected subcutaneously twice a day with at least a 6-hr interval for 2 days from just after partial hepatectomy. As results, buprenorphine caused neither change in clinical signs (except for one animal death) nor increase in the incidence of micronucleated hepatocytes of vehicle treated animals. In the case of concomitant treatment of buprenorphine and a genotoxicant, one out of 8 animals died in each group given buprenorphine with cyclophosphamide, carbendazim or colchicine (lower dose level only). Slight changes in clinical ...Continue Reading

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Citations

Mar 19, 2016·Chemosphere·Cássio Resende MoraisEdimar Olegário Campos Júnior
Apr 14, 2015·Mutation Research. Genetic Toxicology and Environmental Mutagenesis·Satoru ItohChiharu Hattori

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