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 language | English |
|---|---|
| Pages (from-to) | 105-117 |
| Number of pages | 13 |
| Journal | Regulatory Toxicology and Pharmacology |
| Volume | 100 |
| DOIs | |
| Publication status | Published - Dec 1 2018 |
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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
Cite this
Initial hazard assessment of benzyl salicylate : In vitro genotoxicity test and combined repeated-dose and reproductive/developmental toxicity screening test in rats. / Igarashi, Toshime; Takashima, Hiromasa; Takabe, Michihito; Suzuki, Hiroshi; Ushida, Kazuo; Kawamura, Tomoko; Matsumoto, Mariko; Iso, Takako; Tanabe, Shihori; Inoue, Kaoru; Ono, Atsushi; Yamada, Takashi; Hirose, Akihiko.
In: Regulatory Toxicology and Pharmacology, Vol. 100, 01.12.2018, p. 105-117.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Initial hazard assessment of benzyl salicylate
T2 - In vitro genotoxicity test and combined repeated-dose and reproductive/developmental toxicity screening test in rats
AU - Igarashi, Toshime
AU - Takashima, Hiromasa
AU - Takabe, Michihito
AU - Suzuki, Hiroshi
AU - Ushida, Kazuo
AU - Kawamura, Tomoko
AU - Matsumoto, Mariko
AU - Iso, Takako
AU - Tanabe, Shihori
AU - Inoue, Kaoru
AU - Ono, Atsushi
AU - Yamada, Takashi
AU - Hirose, Akihiko
PY - 2018/12/1
Y1 - 2018/12/1
N2 - 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.
AB - 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.
KW - CAS No. 118-58-1
KW - Chemical substances control low
KW - D-value
KW - Embryonic resorption
KW - Existing chemical substance
KW - Hazard class
KW - Low body weight
KW - Neural tube defect
KW - Salicylic acid
KW - Teratogenic potential
UR - http://www.scopus.com/inward/record.url?scp=85055672369&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85055672369&partnerID=8YFLogxK
U2 - 10.1016/j.yrtph.2018.10.018
DO - 10.1016/j.yrtph.2018.10.018
M3 - Article
C2 - 30359701
AN - SCOPUS:85055672369
VL - 100
SP - 105
EP - 117
JO - Regulatory Toxicology and Pharmacology
JF - Regulatory Toxicology and Pharmacology
SN - 0273-2300
ER -