Display options
Cite
Igarashi T, Suzuki H, Ushida K, et al. Initial hazard assessment of 1,4-dichlorobutane: Genotoxicity tests, 28-day repeated-dose toxicity test, and reproductive/developmental toxicity screening test in rats. Regul Toxicol Pharmacol. 2020;112:104610doi: 10.1016/j.yrtph.2020.104610.
Igarashi, T., Suzuki, H., Ushida, K., Matsumoto, M., Inoue, K., Kanno, T., Miwa, Y., Ishii, T., Nagase, T., Katsumata, Y., Hirose, A., & Ludi, S. (2020). Initial hazard assessment of 1,4-dichlorobutane: Genotoxicity tests, 28-day repeated-dose toxicity test, and reproductive/developmental toxicity screening test in rats. Regulatory toxicology and pharmacology : RTP, 112104610. https://doi.org/10.1016/j.yrtph.2020.104610
Igarashi, Toshime, et al. "Initial hazard assessment of 1,4-dichlorobutane: Genotoxicity tests, 28-day repeated-dose toxicity test, and reproductive/developmental toxicity screening test in rats." Regulatory toxicology and pharmacology : RTP vol. 112 (2020): 104610. doi: https://doi.org/10.1016/j.yrtph.2020.104610
Igarashi T, Suzuki H, Ushida K, Matsumoto M, Inoue K, Kanno T, Miwa Y, Ishii T, Nagase T, Katsumata Y, Hirose A, Ludi S. Initial hazard assessment of 1,4-dichlorobutane: Genotoxicity tests, 28-day repeated-dose toxicity test, and reproductive/developmental toxicity screening test in rats. Regul Toxicol Pharmacol. 2020 Apr;112:104610. doi: 10.1016/j.yrtph.2020.104610. Epub 2020 Feb 04. PMID: 32032664.
Copy Download .nbib Format: NLM
Share it on

Regul Toxicol Pharmacol. 2020 Apr;112:104610. doi: 10.1016/j.yrtph.2020.104610. Epub 2020 Feb 04.

Initial hazard assessment of 1,4-dichlorobutane: Genotoxicity tests, 28-day repeated-dose toxicity test, and reproductive/developmental toxicity screening test in rats.

Regulatory toxicology and pharmacology : RTP

Toshime Igarashi, Hiroshi Suzuki, Kazuo Ushida, Mariko Matsumoto, Kaoru Inoue, Takuya Kanno, Yoshihisa Miwa, Takahiro Ishii, Takahiko Nagase, Yoshihiro Katsumata, Akihiko Hirose, Ludi

Affiliations

  1. Division of Risk Assessment, Center for Biological Safety & Research, National Institute of Health Sciences, 3-25-26 Tonomachi, Kawasaki-ku, Kawasaki-shi, Kanagawa, 210-9501, Japan; Division of Cellular & Molecular Toxicology, Center for Biological Safety & Research, National Institute of Health Sciences, 3-25-26 Tonomachi, Kawasaki-ku, Kawasaki-shi, Kanagawa, 210-9501, Japan. Electronic address: [email protected].
  2. Division of Risk Assessment, Center for Biological Safety & Research, National Institute of Health Sciences, 3-25-26 Tonomachi, Kawasaki-ku, Kawasaki-shi, Kanagawa, 210-9501, Japan. Electronic address: [email protected].
  3. Division of Risk Assessment, Center for Biological Safety & Research, National Institute of Health Sciences, 3-25-26 Tonomachi, Kawasaki-ku, Kawasaki-shi, Kanagawa, 210-9501, Japan. Electronic address: [email protected].
  4. Division of Risk Assessment, Center for Biological Safety & Research, National Institute of Health Sciences, 3-25-26 Tonomachi, Kawasaki-ku, Kawasaki-shi, Kanagawa, 210-9501, Japan. Electronic address: [email protected].
  5. Division of Risk Assessment, Center for Biological Safety & Research, National Institute of Health Sciences, 3-25-26 Tonomachi, Kawasaki-ku, Kawasaki-shi, Kanagawa, 210-9501, Japan. Electronic address: [email protected].
  6. CMIC Pharma Science Co., Ltd., CMIC Bioresearch Center, 10221 Kobuchizawa-cho, Hokuto-shi, Yamanashi, 408-0044, Japan. Electronic address: [email protected].
  7. Nihon Bioresearch Inc., 6-104 Majima, Fukuju-cho, Hashima-shi, Gifu, 501-6251, Japan. Electronic address: [email protected].
  8. BoZo Research Center Inc., 1284 Kamado, Gotennba-shi, Shizuoka, 412-0039, Japan. Electronic address: [email protected].
  9. Nihon Bioresearch Inc., 6-104 Majima, Fukuju-cho, Hashima-shi, Gifu, 501-6251, Japan. Electronic address: [email protected].
  10. BoZo Research Center Inc., 1284 Kamado, Gotennba-shi, Shizuoka, 412-0039, Japan. Electronic address: [email protected].
  11. Division of Risk Assessment, Center for Biological Safety & Research, National Institute of Health Sciences, 3-25-26 Tonomachi, Kawasaki-ku, Kawasaki-shi, Kanagawa, 210-9501, Japan. Electronic address: [email protected].

PMID: 32032664 DOI: 10.1016/j.yrtph.2020.104610

Abstract

1,4-Dichlorobutane (1,4-DCB) is used as raw materials for drugs, pesticides, fragrances, and chemical fibers, and being used as a solvent. Its toxicity data was insufficient for screening assessment under the Japanese Chemical Substances Control Law. We conducted toxicity tests and hazard classification for screening assessment 1,4-DCB showed negative in the Ames test, positive in the in vitro chromosomal aberrations test with metabolic activation, and negative in the in vivo mouse bone-marrow micronucleus test. The 28-day repeated-dose toxicity study, where male and female rats were administered 1,4-DCB by gavage at 0, 12, 60, and 300 mg/kg/day, showed significant effects on the liver and pancreas from 12 mg/kg/day and kidney at 300 mg/kg/day. Based on periportal hepatocellular hypertrophy and decreased zymogen granules in pancreas, the lowest observed adverse effect level (LOAEL) of 12 mg/kg/day was obtained. The reproductive/developmental toxicity screening study, in which male and female rats were administered 1,4-DCB by gavage at dose of 0, 2.4, 12, and 60 mg/kg/day for 42-46 days, showed that the delivery index was decreased at 60 mg/kg/day without maternal toxicity. Based on the general toxicity, we classified this chemical as hazard class 2, with a D-value (Derived No Effect Level) of 0.002 mg/kg/day.

Copyright © 2020 Elsevier Inc. All rights reserved.

Keywords: CAS no. 110-56-5; Chemical substances control low; D-value; Existing chemical substance; Halogenated hydrocarbon; Hazard class

Conflict of interest statement

Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this pa

Substances

MeSH terms

Publication Types