Evaluation of the subacute nephrotoxicity of cyclohexane and other industrial solvents in the female Sprague-Dawley rat.
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 LD50 and the urinary excretion of N-acetyl-beta-D-glucosaminidase, beta 2-microglobulin and albumin was determined. Under these experimental conditions, two solvents, cyclohexane and styrene, were found to cause some tubular injury as evidenced by a statistically significant increase of beta 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 LD50. The increased beta 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.
Bernard
A M
AM
Unit of Industrial Toxicology and Occupational Medicine, Catholic University of Louvain, Brussels, Belgium.
de Russis
R
R
Normand
J C
JC
Lauwerys
R R
RR
D000419:Albuminuria / Q000139:chemically induced; D000818:Animals; D003510:Cyclohexanes / Q000633:toxicity*; D003511:Cyclohexanols / Q000633:toxicity; D005260:Female; D007668:Kidney / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D012997:Solvents / Q000633:toxicity*; D001613:beta 2-Microglobulin / Q000652:urine
D003510:Cyclohexanes; D003511:Cyclohexanols; D012997:Solvents; D001613:beta 2-Microglobulin