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

Barbara S. Shane, Errol Zeiger, Walter W Piegorsch, Ewan D. Booth, Jay I. Goodman, Richard C. Peffer

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

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® 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® mouse findings with PPZ and conclude that the compound does not act as a mutagen in vivo.

Original languageEnglish (US)
Pages (from-to)1-9
Number of pages9
JournalEnvironmental and Molecular Mutagenesis
Volume53
Issue number1
DOIs
StatePublished - Jan 2012

Fingerprint

Mutagenesis
Mutation
Mutagenicity Tests
Maximum Tolerated Dose
Liver
Mutagens
Chromosome Aberrations
Carcinogens
Transgenic Mice
DNA Damage
Weight Gain
Cluster Analysis
Spectrum Analysis
Necrosis
Multivariate Analysis
Body Weight
propiconazole
Food
Mortality
DNA

Keywords

  • In vivo mutation
  • Mutation spectrum
  • Propiconazole
  • Statistical analysis
  • Transgenic

ASJC Scopus subject areas

  • Health, Toxicology and Mutagenesis
  • Epidemiology
  • Genetics(clinical)

Cite this

Re-evaluation of the big blue® mouse assay of propiconazole suggests lack of mutagenicity. / Shane, Barbara S.; Zeiger, Errol; Piegorsch, Walter W; Booth, Ewan D.; Goodman, Jay I.; Peffer, Richard C.

In: Environmental and Molecular Mutagenesis, Vol. 53, No. 1, 01.2012, p. 1-9.

Research output: Contribution to journalArticle

Shane, Barbara S. ; Zeiger, Errol ; Piegorsch, Walter W ; Booth, Ewan D. ; Goodman, Jay I. ; Peffer, Richard C. / Re-evaluation of the big blue® mouse assay of propiconazole suggests lack of mutagenicity. In: Environmental and Molecular Mutagenesis. 2012 ; Vol. 53, No. 1. pp. 1-9.
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