title: Re-analysis results using medians of the data from the JaCVAM-organized international validation study of the in vivo rat alkaline comet assay.
abstract: The data from the JaCVAM-organized international validation study of the in vivo rat alkaline comet assay were reported and analyzed statistically using the simple means of % tail DNA. However, OECD test guideline TG 489 recommends use of the median for data analysis due to the hierarchical nature of the data. Comparison between the simple mean approach and the median based approach for positive/negative/equivocal chemical calls was conducted using the % tail DNA data for the 40 chemicals tested in the JaCVAM-organized international validation study of the in vivo rat alkaline comet assay, using liver and stomach as target organs. In the liver, two genotoxic chemicals, o-anisidine and 9-aminoacridine hydrochloride monohydrate, were positive using the median based approach but negative using the simple mean approach, and two genotoxic chemicals, 2-acetylaminofluorene and busulfan were equivocal using the median based approach but negative using the simple mean approach. In contrast, cadmium chloride (genotoxic carcinogen) was equivocal in both organs using the median based approach, while positive and equivocal in liver and stomach, respectively, using the simple mean approach. Two data sets of sodium arsenite showed equivocal and negative results for liver using the median based approach, although both data sets were equivocal using the simple mean approach. Overall, there are no large differences in terms of the genotoxic call between both approaches. However, the median based approach recommended in OECD TG 489 has an advantage toward higher precision within the groups treated with a test chemical, whereas the approach might show the lower values for the effect.
authors.affiliation: Mitsubishi Tanabe Pharma Co., Chiba, Japan. Electronic address: Uno.Yoshifumi@ma.mt-pharma.co.jp.
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Uno
authors.affiliation: Kobe University Hospital, Kobe, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Omori
mesh_terms: D015073:2-Acetylaminofluorene / Q000633:toxicity; D000284:Administration, Oral; D000585:Aminacrine / Q000633:toxicity; D000814:Aniline Compounds / Q000633:toxicity; D000818:Animals; D002273:Carcinogens / Q000633:toxicity; D020552:Comet Assay / Q000379:methods*; D004249:DNA Damage / Q000187:drug effects; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results
chemical_list: D000814:Aniline Compounds; D002273:Carcinogens; D000585:Aminacrine; D015073:2-Acetylaminofluorene; C003898:2-anisidine
keywords: Comet assay; JaCVAM; Mean; Median; Validation study; in vivo