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

Toshime Igarashi, Hiromasa Takashima, Michihito Takabe, Hiroshi Suzuki, Kazuo Ushida, Tomoko Kawamura, Mariko Matsumoto, Takako Iso, Shihori Tanabe, Kaoru Inoue, Atsushi Ono, Takashi Yamada, Akihiko Hirose

Research output: Contribution to journalArticle

1 Citation (Scopus)

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.

Original languageEnglish
Pages (from-to)105-117
Number of pages13
JournalRegulatory Toxicology and Pharmacology
Volume100
DOIs
Publication statusPublished - Dec 2018

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

ASJC Scopus subject areas

  • Toxicology

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  • Cite this

    Igarashi, T., Takashima, H., Takabe, M., Suzuki, H., Ushida, K., Kawamura, T., Matsumoto, M., Iso, T., Tanabe, S., Inoue, K., Ono, A., Yamada, T., & Hirose, A. (2018). Initial hazard assessment of benzyl salicylate: In vitro genotoxicity test and combined repeated-dose and reproductive/developmental toxicity screening test in rats. Regulatory Toxicology and Pharmacology, 100, 105-117. https://doi.org/10.1016/j.yrtph.2018.10.018