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

Mutat Res Genet Toxicol Environ Mutagen. 2015 Jul:786-788:151-7. doi: 10.1016/j.mrgentox.2015.04.002. Epub 2015 Apr 7.

Abstract

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 21 h 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 1000 mg/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.

Keywords: 2,4-Diaminotoluene; In vivo comet assay; JaCVAM validation study; o-Phenylphenol sodium salt; p-Phenylenediamine.

Publication types

  • Validation Study

MeSH terms

  • Administration, Oral
  • Animals
  • Biphenyl Compounds / toxicity*
  • Carcinogens / toxicity
  • Comet Assay / methods*
  • DNA Damage / drug effects
  • Dose-Response Relationship, Drug
  • Liver / drug effects
  • Male
  • Phenylenediamines / toxicity*
  • Rats
  • Rats, Sprague-Dawley
  • Reproducibility of Results
  • Stomach / drug effects

Substances

  • Biphenyl Compounds
  • Carcinogens
  • Phenylenediamines
  • 2-phenylphenol
  • 2,4-diaminotoluene
  • 4-phenylenediamine