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Regul Toxicol Pharmacol. 2019 Jul;105:1-14. doi: 10.1016/j.yrtph.2019.03.012. Epub 2019 Mar 21.

Toxicological evaluation of carcinogenicity of the pyrethroid imiprothrin in rats and mice.

Author information

1
Environmental Health Science Laboratory, Sumitomo Chemical Company, Ltd., 3-1-98 Kasugade-naka, Konohana-ku, Osaka, 554-8558, Japan. Electronic address: yamadat8@sc.sumitomo-chem.co.jp.
2
Environmental Health Science Laboratory, Sumitomo Chemical Company, Ltd., 3-1-98 Kasugade-naka, Konohana-ku, Osaka, 554-8558, Japan.
3
Gradient, 20 University Road, Cambridge, MA, 02138, USA.
4
J.K. Haseman Consulting, Raleigh, NC, USA.
5
Department of Cancer Studies and Molecular Medicine, University of Leicester, Leicester, UK.
6
Technical University of Munich, Munich, Germany.
7
Queen Mary University of London, Mile End Rd, London, E1 4NS, UK.
8
Havlik-Wall Professor of Oncology, Department of Pathology and Microbiology, University of Nebraska Medical Center, 983135, Omaha, NE, 68198-3135, USA.

Abstract

The carcinogenic potential of a non-genotoxic pyrethroid imiprothrin was examined in rats and mice. There was no carcinogenicity in rats up to a maximum dose of 5000 ppm of the diet. There was a higher (p = 0.03) incidence of lung adenocarcinomas at 7000 ppm in males, and females showed an increasing (p < 0.01) trend in the incidence of lung adenomas and combined lung adenoma/adenocarcinomas. Additional step sections of lung demonstrated no significant increases in any tumor at p < 0.05, although an increasing trend with dose was observed among females. We argue that, the 7000 ppm dose exceeded the Maximum Tolerated Dose (MTD) for both sexes, based on systemic toxicity as evidenced by body weight gain reduction (both sexes) and high mortality (females). If the 7000 ppm dose is therefore removed from consideration, there are not significant (p < 0.05) increases in tumor formation. Moreover, a consideration of multiple comparisons reveals that the lung tumor increases observed are totally consistent with what would be expected by chance alone. Based on high susceptibility of this mouse strain for the appearance of lung tumors and the lack of a statistically significant increase in tumors by appropriate analysis, the mouse study does not indicate a carcinogenic effect of imiprothrin, and thus no classification for carcinogenicity is warranted.

KEYWORDS:

Carcinogenicity; Imiprothrin; Long-term bioassays; Lung tumors; Maximum tolerated dose; Mouse; Pyrethroids; Statistical analysis; Step section; Systemic toxicity

PMID:
30905765
DOI:
10.1016/j.yrtph.2019.03.012
[Indexed for MEDLINE]

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