2. Academic Validation
  3. Initial hazard assessment of benzyl salicylate: In vitro genotoxicity test and combined repeated-dose and reproductive/developmental toxicity screening test in rats

Initial hazard assessment of benzyl salicylate: In vitro genotoxicity test and combined repeated-dose and reproductive/developmental toxicity screening test in rats

  • Regul Toxicol Pharmacol. 2018 Dec:100:105-117. doi: 10.1016/j.yrtph.2018.10.018.
Toshime Igarashi 1,  Hiromasa Takashima 2,  Michihito Takabe 3,  Hiroshi Suzuki 4,  Kazuo Ushida 5,  Tomoko Kawamura 6,  Mariko Matsumoto 7,  Takako Iso 8,  Shihori Tanabe 9,  Kaoru Inoue 10,  Atsushi Ono 11,  Takashi Yamada 12,  Akihiko Hirose 13
Affiliations

Affiliations

  • 1 Division of Risk Assessment, Center for Biological Safety and Research, National Institute of Health Sciences, 3-25-26 Tonomachi, Kawasaki-ku, Kawasaki, Kanagawa, 210-9501, Japan. Electronic address: toshime.igarashi@nihs.go.jp.
  • 2 BoZo Research Center Inc., 1284 Kamado, Gotennba, Shizuoka, 412-0039, Japan. Electronic address: takashima-hiromasa@bozo.co.jp.
  • 3 BoZo Research Center Inc., 1284 Kamado, Gotennba, Shizuoka, 412-0039, Japan. Electronic address: takabe-michihito@bozo.co.jp.
  • 4 Division of Risk Assessment, Center for Biological Safety and Research, National Institute of Health Sciences, 3-25-26 Tonomachi, Kawasaki-ku, Kawasaki, Kanagawa, 210-9501, Japan. Electronic address: hsuzuki@nihs.go.jp.
  • 5 Division of Risk Assessment, Center for Biological Safety and Research, National Institute of Health Sciences, 3-25-26 Tonomachi, Kawasaki-ku, Kawasaki, Kanagawa, 210-9501, Japan. Electronic address: k-ushida@nihs.go.jp.
  • 6 Division of Risk Assessment, Center for Biological Safety and Research, National Institute of Health Sciences, 3-25-26 Tonomachi, Kawasaki-ku, Kawasaki, Kanagawa, 210-9501, Japan. Electronic address: tomoko@nihs.go.jp.
  • 7 Division of Risk Assessment, Center for Biological Safety and Research, National Institute of Health Sciences, 3-25-26 Tonomachi, Kawasaki-ku, Kawasaki, Kanagawa, 210-9501, Japan. Electronic address: mariko@nihs.go.jp.
  • 8 Division of Risk Assessment, Center for Biological Safety and Research, National Institute of Health Sciences, 3-25-26 Tonomachi, Kawasaki-ku, Kawasaki, Kanagawa, 210-9501, Japan. Electronic address: takako.iso@nihs.go.jp.
  • 9 Division of Risk Assessment, Center for Biological Safety and Research, National Institute of Health Sciences, 3-25-26 Tonomachi, Kawasaki-ku, Kawasaki, Kanagawa, 210-9501, Japan. Electronic address: stanabe@nihs.go.jp.
  • 10 Division of Risk Assessment, Center for Biological Safety and Research, National Institute of Health Sciences, 3-25-26 Tonomachi, Kawasaki-ku, Kawasaki, Kanagawa, 210-9501, Japan. Electronic address: k-inoue@nihs.go.jp.
  • 11 Division of Pharmaceutical, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8530, Japan. Electronic address: atsushiono3@okayama-u.ac.jp.
  • 12 Division of Risk Assessment, Center for Biological Safety and Research, National Institute of Health Sciences, 3-25-26 Tonomachi, Kawasaki-ku, Kawasaki, Kanagawa, 210-9501, Japan. Electronic address: t-yamada@nihs.go.jp.
  • 13 Division of Risk Assessment, Center for Biological Safety and Research, National Institute of Health Sciences, 3-25-26 Tonomachi, Kawasaki-ku, Kawasaki, Kanagawa, 210-9501, Japan. Electronic address: hirose@nihs.go.jp.
PMID: 30359701 DOI: 10.1016/j.yrtph.2018.10.018
Abstract

Benzyl salicylate is used as a fragrance ingredient and an ultraviolet light absorber, but its toxicity is unknown. Therefore, toxicity tests and hazard classification were conducted for screening assessment under the Japanese Chemical Substances Control Law. Benzyl salicylate was found to be non-genotoxic in vitro based on the chromosomal aberration test using Chinese hamster lung cells. However, the combined repeated-dose and reproductive/developmental screening toxicity test, in which male and female rats were administered benzyl salicylate by gavage at 0, 30, 100, or 300 mg/kg/day for 42 and 41-46 days, respectively, from 14 days before mating until postnatal Day 4, showed that repeated doses had major effects on the thymus, liver, epididymis, and femur at 100 and/or 300 mg/kg/day. Furthermore, although benzyl salicylate had no effect on the estrus cycle, fertility, corpus lutea, or implantation rate, embryonic resorption, offspring mortality, and neural tube defects were observed at 300 mg/kg/day, and the offspring had lower body weights at 30 and 100 mg/kg/day, suggesting teratogenicity similar to Other salicylates. Based on the developmental toxicity, this chemical was classified as hazard class 2, with a lowest observed adverse effect level (LOAEL) of 30 mg/kg/day and a D-value of 0.003 mg/kg/day.

Keywords

CAS No. 118-58-1; Chemical substances control low; D-value; Embryonic resorption; Existing chemical substance; Hazard class; Low body weight; Neural tube defect; Salicylic acid; Teratogenic potential.

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