A 13-week vapor inhalation study of 3,3-dimethyl-2-butanol in Sprague-Dawley rats

Four groups of male and female Sprague-Dawley rats were exposed for 13 weeks to 3,3-dimethyl-2-butanol (PA) at concentrations of 0.00, 0.20, 1.00 or 5.00 mg/l (1 mg/l = 240 ppm). Exposures were for 6 hr per day, 5 days per week with sacrifices at 7 and 13 weeks of exposure, and at 4 weeks after exposure. The test animals were evaluated for abnormalities in physiology, behaviour, clinical laboratory parameters, and gross and microscopic morphology. No abnormalities were detected in electrocardiograms, respiratory indices, spontaneous activity, passive avoidance activity and open-field behaviour. Clinical signs related to PA exposure included alopecia, ataxia and lacrimation. There were no biologically significant between-group differences in body-weights during the study. The clinical laboratory data demonstrated a 30% increase in serum cholesterol and bilirubin at 7 weeks in high-dose males and an increase in urea nitrogen in intermediate and high-dose males at 13 weeks. There were no abnormalities in hematologic or coagulation parameters. At necropsy there were no significant gross abnormalities; however, examination of organ weights revealed enlarged kidneys in high-dose male rats at 13 weeks, enlarged ovaries in high-dose female rats at 13 weeks, and microscopic study of tissue sections revealed minimal to mild renal tubular injury in high and possibly intermediate dose males at several sacrifices. These findings suggest that the primary target organ of PA, when given by inhalation, is the kidney in male rats and possibly the ovary in female rats. The renal changes in the high-dose males were not fully reversible during the recovery period.(ABSTRACT TRUNCATED AT 250 WORDS)