Fundamental Toxicological Sciences

Paper Details

Fundamental Toxicological Sciences
Vol. 11 No. 4 July 09, 2024 p.169-181
Data Report
A 90-day repeated oral dose toxicity study of p-cymene in rats
  • Makiko Kuwagata (Division of Cellular and Molecular Toxicology, Center for Biological Safety and Research, National Institute of Health Sciences / kuwagata.m@nihs.go.jp)
Makiko Kuwagata 1) , Yuko Doi 2) 3) , Hirokatsu Saito 1) , Mariko Tsurumoto 1) , Toshime Igarashi 1) , Takuya Nishimura 1) , Yuhji Taquahashi 1) , Yoko Hirabayashi 4) , Satoshi Kitajima 1)
1) Division of Cellular and Molecular Toxicology, Center for Biological Safety and Research, National Institute of Health Sciences , 2) DIMS Institute of Medical Science, Inc. , 3) Toxicological Laboratory for Small Animals, BioSafety Research Center Inc. , 4) Center for Biological Safety and Research, National Institute of Health Sciences
Keywords: p-Cymene, Flavoring agent, Toxicity, Oral treatment, Rats
Abstracts

p-Cymene, is a monocyclic monoterpene hydrocarbon, commonly used as a flavoring agent in food. A 90-day repeated oral toxicological study of p-cymene was conducted to examine the toxicological properties and determine the no-observed-adverse-effect level (NOAEL) of p-cymene in Crl:CD (SD) rats at the following doses: 0 (corn oil), 2.4, 12, and 60 mg/kg/day. No mortality or abnormal clinical signs were observed in the treatment groups. The body weight, food consumption, ophthalmoscopy, and gross pathology of the rats were also not affected by p-cymene treatment. However, in the 60 mg/kg group, certain parameters decreased in males, including hemoglobin and hematocrit, red blood cell count, triglyceride, total protein, and albumin. In females, urine volume and total potassium excretion increased, whereas specific gravity, and sodium, potassium, and chlorine concentrations decreased. Increased liver weight was observed in both males and females. Histopathological observations revealed centrilobular hepatocellular hypertrophy. In the 12 mg/kg group, no adverse effects of p-cymene treatment were observed in both sexes. In conclusion, the NOAEL of p-cymene was 12 mg/kg/day for both sexes under the present experimental conditions, considering the alterations in urinalysis, hematology, clinical biochemistry, and histopathology.