Re-evaluation of the big blue® mouse assay of propiconazole suggests lack of mutagenicity

被引:4
|
作者
Shane, Barbara S. [6 ]
Zeiger, Errol [5 ]
Piegorsch, Walter W. [4 ]
Booth, Ewan D. [3 ]
Goodman, Jay I. [2 ]
Peffer, Richard C. [1 ]
机构
[1] Syngenta Crop Protect LLC, Greensboro, NC 27419 USA
[2] Michigan State Univ, Dept Pharmacol & Toxicol, E Lansing, MI 48824 USA
[3] Syngenta Ltd, Jealotts Hill, England
[4] Univ Arizona, Inst BIO5, Tucson, AZ USA
[5] Errol Zeiger Consulting, Chapel Hill, NC USA
[6] Barbara Shane Consulting, Durham, NC USA
关键词
propiconazole; mutation spectrum; transgenic; in vivo mutation; statistical analysis; CONAZOLE FUNGICIDES; SPONTANEOUS MUTATION; STYRENE OXIDE; DNA-ADDUCTS; MICE; SEQUENCE; INDUCTION; RELEVANCE; FREQUENCY; SPECTRA;
D O I
10.1002/em.20689
中图分类号
X [环境科学、安全科学];
学科分类号
08 ; 0830 ;
摘要
Propiconazole (PPZ) is a conazole fungicide that is not mutagenic, clastogenic, or DNA damaging in standard in vitro and in vivo genetic toxicity tests for gene mutations, chromosome aberrations, DNA damage, and cell transformation. However, it was demonstrated to be a male mouse liver carcinogen when administered in food for 24 months only at a concentration of 2,500 ppm that exceeded the maximum tolerated dose based on increased mortality, decreased body weight gain, and the presence of liver necrosis. PPZ was subsequently tested for mutagenicity in the Big Blue (R) transgenic mouse assay at the 2,500 ppm dose, and the result was reported as positive by Ross et al. ([2009]: Mutagenesis 24:149-152). Subsets of the mutants from the control and PPZ-exposed groups were sequenced to determine the mutation spectra and a multivariate clustering analysis method purportedly substantiated the increase in mutant frequency with PPZ (Ross and Leavitt. [2010]: Mutagenesis 25:231-234). However, as reported here, the results of the analysis of the mutation spectra using a conventional method indicated no treatment-related differences in the spectra. In this article, we re-examine the Big Blue (R) mouse findings with PPZ and conclude that the compound does not act as a mutagen in vivo. (C) Environ. Mol. Mutagen. 2012. Published 2011 Wiley Periodicals, Inc.
引用
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页码:1 / 9
页数:9
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