Evaluation of p-phenylenediamine, o-phenylphenol sodium salt, and 2,4-diaminotoluene in the rat comet assay as part of the Japanese Center for the Validation of Alternative Methods (JaCVAM)-initiated international validation study of in vivo rat alkaline comet assay

• Published in: Mutation research. Genetic toxicology and environmental mutagenesis 2015-07, Vol.786-788, p.151-157
• Main Authors: De Boeck, Marlies, van der Leede, Bas-jan, De Vlieger, Kathleen, Geys, Helena, Vynckier, An, Van Gompel, Jacky
• Format: Article
• Language: English
• Subjects: 2,4-Diaminotoluene; Administration, Oral; Animals; Bioassays; Biphenyl Compounds - toxicity; Carcinogens; Carcinogens - toxicity; Cells; Comet Assay - methods; DNA damage; DNA Damage - drug effects; Dose-Response Relationship, Drug; In vivo comet assay; JaCVAM validation study; Liver - drug effects; Male; o-Phenylphenol sodium salt; p-Phenylenediamine; Phenylenediamines - toxicity; Rats; Rats, Sprague-Dawley; Reproducibility of Results; Rodents; Stomach - drug effects
• ISSN: 1383-5718; 1879-3592
• DOI: 10.1016/j.mrgentox.2015.04.002

•Three coded compounds were evaluated in the in vivo rat alkaline comet assay.•Contribution to JaCVAM comet assay validation trial in rat liver and stomach.•PPD and OPP were negative up to 100 and 1000mg/kg/day, respectively.•2,4-DAT (genotoxic carcinogen) was weak positive in liver and negative in stomach. As part of the Japanese Center for the Validation of Alternative Methods (JaCVAM)-initiated international validation study of in vivo rat alkaline comet assay (comet assay), p-phenylenediamine dihydrochloride (PPD), o-phenylphenol sodium salt (OPP), and 2,4-diaminotoluene (2,4-DAT), were analyzed in this laboratory as coded test chemicals. Male Sprague–Dawley rats (7–9 weeks of age) were given three oral doses of the test compounds, 24 and 21h apart and liver and stomach were sampled 3h after the final dose administration. Under the conditions of the test, no increases in DNA damage were observed in liver and stomach with PPD and OPP up to 100 and 1000mg/kg/day, respectively. 2,4-DAT, a known genotoxic carcinogen, induced a weak but reproducible, dose-related and statistically significant increase in DNA damage in liver cells while no increases were observed in stomach cells.