title: 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.
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.
authors.affiliation: Janssen Research & Development, a Division of Janssen Pharmaceutica N.V., Discovery Sciences, Beerse, Belgium. Electronic address: mdboeck@its.jnj.com.
authors.forename: Marlies
authors.initials: M
authors.lastname: De Boeck
authors.affiliation: Janssen Research & Development, a Division of Janssen Pharmaceutica N.V., Discovery Sciences, Beerse, Belgium.
authors.forename: Bas-jan
authors.initials: BJ
authors.lastname: van der Leede
authors.affiliation: Janssen Research & Development, a Division of Janssen Pharmaceutica N.V., Discovery Sciences, Beerse, Belgium.
authors.forename: Kathleen
authors.initials: K
authors.lastname: De Vlieger
authors.affiliation: Janssen Research & Development, a Division of Janssen Pharmaceutica N.V., Biometrics Reporting, Nonclinical Statistics and Computing, Beerse, Belgium.
authors.forename: Helena
authors.initials: H
authors.lastname: Geys
authors.affiliation: Janssen Research & Development, a Division of Janssen Pharmaceutica N.V., Discovery Sciences, Beerse, Belgium.
authors.forename: An
authors.initials: A
authors.lastname: Vynckier
authors.affiliation: Janssen Research & Development, a Division of Janssen Pharmaceutica N.V., Discovery Sciences, Beerse, Belgium.
authors.forename: Jacky
authors.initials: J
authors.lastname: Van Gompel
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001713:Biphenyl Compounds / Q000633:toxicity*; D002273:Carcinogens / Q000633:toxicity; D020552:Comet Assay / Q000379:methods*; D004249:DNA Damage / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D008099:Liver / Q000187:drug effects; D008297:Male; D010655:Phenylenediamines / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D013270:Stomach / Q000187:drug effects
chemical_list: D001713:Biphenyl Compounds; D002273:Carcinogens; D010655:Phenylenediamines; C004369:2-phenylphenol; C010914:2,4-diaminotoluene; C029728:4-phenylenediamine
keywords: 2,4-Diaminotoluene; In vivo comet assay; JaCVAM validation study; o-Phenylphenol sodium salt; p-Phenylenediamine