Assessment of cyclohexanone toxicity in inhalation-exposed F344 rats and B6C3F1 mice: applications in occupational health

Background: Cyclohexanone is a chemical used in various industries and many workers are exposed to it. Therefore, in this study, we determined the toxicity of cyclohexanone in inhalation-exposed F344 rats and B6C3F1 mice, so as to apply the findings in hazard and risk assessments.Methods: Ten male and 10 female rats and mice per test group were exposed to cyclohexanone vapors at 0, 100, 250, and 625ppm concentrations for 6h per day, 5d per week, and for 13weeks. All rats and mice were killed after the exposure period. Clinical signs, body weight, feed intake, and ophthalmoscopy findings were recorded during the exposure period, and hematology, blood biochemistry, organ weights, gross findings, and histopathology were evaluated thereafter.Results: The following findings were noted in cyclohexanone-exposed F344 rats: increased alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, increased liver weight, and bile duct hyperplasia in the males exposed to 250 and 625ppm cyclohexanone, increased ALT levels and bile duct hyperplasia in the females exposed to 625ppm cyclohexanone, and increased blood urea nitrogen (BUN) and tubular basophilia in the renal cortex in the males exposed to 625ppm cyclohexanone. On the other hand, B6C3F1 mice exposed to cyclohexanone showed no obvious exposure-related effects.Conclusion: Based on the findings, the no-observed-adverse-effect level (NOAEL) was determined to be 100ppm in F344 rats and >625ppm in B6C3F1 mice. Therefore, 2ppm was revealed as the derived no-effect level (DNEL) for cyclohexanone.