A retrospective evaluation method for in vitro mammalian genotoxicity tests using cytotoxicity index transformation formulae

Mutation Research. Genetic Toxicology and Environmental Mutagenesis
Yurika FujitaHiroshi Honda

Abstract

Although in vitro chromosomal aberration tests and micronucleus tests have been widely used for genotoxicity evaluation, false-positive results have been reported under strong cytotoxic conditions. To reduce false-positive results, the new Organization for Economic Co-operation and Development (OECD) test guideline (TG) recommends the use of a new cytotoxicity index, relative increase in cell count or relative population doubling (RICC/RPD), instead of the traditionally used index, relative cell count (RCC). Although the use of the RICC/RPD may result in different outcomes and require re-evaluation of tested substances, it is impractical to re-evaluate all existing data. Therefore, we established a method to estimate test results from existing RCC data. First, we developed formulae to estimate RICC/RPD from RCC without cell counts by considering cell doubling time and experiment time. Next, the accuracy of the cytotoxicity index transformation formulae was verified by comparing estimated RICC/RPD and measured RICC/RPD for 3 major chemicals associated with false-positive genotoxicity test results: ethyl acrylate, eugenol and p-nitrophenol. Moreover, 25 compounds with false-positive in vitro chromosomal aberration (CA) test resul...Continue Reading

References

Mar 19, 2014·Mutation Research. Genetic Toxicology and Environmental Mutagenesis·Paul FowlerStefan Pfuhler

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Citations

May 14, 2016·Mutation Research. Genetic Toxicology and Environmental Mutagenesis·Yurika FujitaHiroshi Honda
Mar 21, 2018·Genes and Environment : the Official Journal of the Japanese Environmental Mutagen Society·Eiji YamamuraYoshifumi Uno
Jan 18, 2018·Genes and Environment : the Official Journal of the Japanese Environmental Mutagen Society·Hiroshi HondaOsamu Morita

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