Evaluation of the subacute nephrotoxicity of cyclohexane and other industrial solvents in the female Sprague-Dawley rat

Abstract

The subacute nephrotoxicity of more than 20 industrial solvents has been compared in female Sprague-Dawley rats. The animals were given 5 i.p. injections of the solvents per week for 2 weeks at doses ranging from 1 20 to 1 5 of the i.p. or oral LD 50 and the urinary excretion of N-acetyl-β- d-glucosaminidase, β 2-microglobulin and albumin was determined. Under these experimental conditions, two solvents, cyclohexane and styrène, were found to cause some tubular injury as evidenced by a statistically significant increase of β 2-microglobulinuria. At the same dose, styrene was more tubulotoxic than cyclohexane but the opposite was observed when the solvents were administered proportionally to their LD 50. The increased β 2-microglobulinuria caused by cyclohexane was both time- and dose-dependent. It was not accompanied by changes in the glomerular filtration rate and the renal plasma flow, but at the highest dose (1.5 g/kg) the renal concentrating ability was depressed. These renal tubular effects can most likely be ascribed to cyclohexanol, the main metabolite of cyclohexane. As cyclohexane is a widely used industrial solvent with a relatively high threshold limit value (TWA-TLV: 300 ppm) it might represent an underestimated risk for the renal function of exposed populations.