Assessment of the toxicity of cyclohexanone administered intravenously to Wistar and Gunn rats

Abstract

The toxicity of cyclohexanone, used as a solvent cement in polyvinyl chloride medical devices, was assessed in Wistar and Gunn rats. The Gunn rat was used because it has a negligible activity of UDP glucuronosyltransferase toward bilirubin and certain other aglycones. Cyclohexanone was administered iv for 28 consecutive days to Wistar and Gunn rats in two doses (50 and 100 mg/kg), using solutions containing 0.25 and 0.50 g per 100 ml, respectively, at a constant volume of 20 mg/kg. Saline (0.9% NaCI) was used as the control. Daily observations for signs of toxicity showed no adverse effects in Wistar or Gunn rats injected with either dose. Daily weight changes of control and test animals were similar. Ophthalmologic examinations revealed no treatment‐related structural lesions. No adverse effects were noted when the data from the hemogram or clinical chemistry parameters were evaluated. Gross pathological and histopathologic assessment showed no alterations due to cyclohexanone treatment. Urinary excretions of total and glucuronide conjugates of cyclohexanol were similar for Wistar and Gunn rats; less than 1% was excreted as free cyclohexanone and cyclohexanol. It is concluded that the Gunn rat is capable of forming glucuronides of cyclohexanol and that cyclohexanone at these doses has a negligible toxic potential.