Fundam. Toxicol. Sci. Comprehensive toxicity evaluation of cyclopentyl methyl ether (CPME) for establishing a permitted daily exposure level

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    • Inoue Kaoru
    • Division of Risk Assessment, National Institute of Health Sciences
    • Suzuki Hiroshi
    • Division of Risk Assessment, National Institute of Health Sciences
    • Yamada Takashi
    • Division of Risk Assessment, National Institute of Health Sciences


<p>Cyclopentyl methyl ether (CPME, CAS No. 5614-37-9) is used as an alternative to other ethereal solvents in pharmaceutical chemical process development. Although brief summaries on the repeated dose toxicity or genotoxicity of CPME are available, no detailed toxicity information has been reported. This study performed a detailed hazard characterization of CPME using new reproductive/developmental toxicity data and existing data for a 28-day repeated dose toxicity and genotoxicity study of CPME. Sprague-Dawley (SD) rats were treated with CPME by gavage at doses of 50, 150, or 450 mg/kg/day in the reproductive/developmental toxicity study or at doses of 15, 150, and 700 mg/kg/day in the 28-day study. In the reproductive/developmental toxicity study, lower body weight in males and longer gestational lengths were observed in the F0 animals receiving the 450 mg/kg/day dose. In the F1 animals, lower body weight gain during days 1-7 of life was detected in the 450 mg/kg/day groups in both sexes. In the 28-day study, 6 of 10 males showed poor clinical conditions, resulting in unscheduled deaths in the 700 mg/kg/day group. Based on these findings, the NOAELs for both the reproductive/developmental and 28-day repeated dose toxicity studies were estimated at 150 mg/kg/day. The results of all genotoxicity studies including the bacterial reverse mutation test, <i>in vitro</i> mammalian cell chromosome aberration test, and <i>in vivo</i> mouse micronucleus test were negative. A permitted daily exposure (PDE) of 15 mg/day was suggested based on the present findings to help determine the PDE for the ICH guidelines on impurities in pharmaceuticals.</p>


  • Fundamental Toxicological Sciences

    Fundamental Toxicological Sciences 6(5), 145-165, 2019

    The Japanese Society of Toxicology


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