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Regul Toxicol Pharmacol. 2014 Dec;70(3):711-9. doi: 10.1016/j.yrtph.2014.10.011. Epub 2014 Oct 27.

Development of a category approach to predict the testicular toxicity of chemical substances structurally related to ethylene glycol methyl ether.

Author information

1
Chemical Management Center, National Institute of Technology and Evaluation, 2-49-10, Nishihara, Shibuya-ku, Tokyo 151-0066, Japan. Electronic address: yamada-takashi@nite.go.jp.
2
Chemical Management Center, National Institute of Technology and Evaluation, 2-49-10, Nishihara, Shibuya-ku, Tokyo 151-0066, Japan.
3
Food Safety Commission of Japan, 5-2-20, Akasaka, Minato-ku, Tokyo 107-6122, Japan.
4
Biological Safety Research Center, National Institute of Health Sciences, 1-18-1, Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan.
5
Biosafety Research Center, 582-2, Shioshinden, Iwata, Shizuoka 437-1213, Japan.

Abstract

We propose a category approach to assessing the testicular toxicity of chemicals with a similar structure to ethylene glycol methyl ether (EGME). Based on toxicity information for EGME and related chemicals and accompanied by adverse outcome pathway information on the testicular toxicity of EGME, this category was defined as chemicals that are metabolized to methoxy- or ethoxyacetic acid, a substance responsible for testicular toxicity. A Japanese chemical inventory was screened using the Hazard Evaluation Support System, which we have developed to support a category approach for predicting the repeated-dose toxicity of chemical substances. Quantitative metabolic information on the related chemicals was then considered, and seventeen chemicals were finally obtained from the inventory as a shortlist for the category. Available data in the literature shows that chemicals for which information is available on the metabolic formation of EGME, ethylene glycol ethyl ether, methoxy- or ethoxyacetic acid do in fact possess testicular toxicity, suggesting that testicular toxicity is a concern, due to metabolic activation, for the remaining chemicals. Our results clearly demonstrate practical utility of AOP-based category approach for predicting repeated-dose toxicity of chemicals.

KEYWORDS:

Adverse outcome pathway; Category approach; Methoxyacetic acid; Repeated-dose toxicity; Testicular toxicity

PMID:
25444998
DOI:
10.1016/j.yrtph.2014.10.011
[Indexed for MEDLINE]

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