Investigation of sodium arsenite, thioacetamide, and diethanolamine in the alkaline comet assay: Part of the JaCVAM comet validation exercise
2015
Abstract As part of the Japanese Center for the Validation of Alternative Methods (JaCVAM)-initiative
international validationstudy of the in vivo rat alkaline
comet assay(
comet assay), we examined
sodium arsenite,
thioacetamide, and
diethanolamine. Using the JaCVAM approved study protocol version 14.2, each chemical was tested in male rats up to
maximum tolerated doselevels and DNA damage in the liver and
stomachwas assessed approximately 3 h after the final administration by gavage. Histopathology assessments of liver and
stomachsections from the same animals were also examined for evidence of cytotoxicity or necrosis. No evidence of DNA damage was observed in the
stomachof animals treated with
sodium arseniteat 7.5, 15, or 30 mg/kg/day. However, equivocal findings were found in the liver, where increases in DNA migration were observed in two independent experiments, but not in all treated animals and not at the same dose levels.
Thioacetamidecaused an increase in DNA migration in the
stomachof rats treated at 19, 38, and 75 mg/kg/day, but not in the liver, despite evidence of marked hepatotoxicity following histopathology assessments. No evidence of DNA damage was observed in the
stomachor liver of animals treated with
diethanolamineat 175, 350, or 700 mg/kg/day.
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