Toxicity evaluation of petroleum blending streams: Inhalation subchronic toxicity/neurotoxicity study of a light catalytic reformed naphtha distillate in rats

A 13-wk whole-body inhalation study was conducted with Sprague-Dawley CD ra ts (16/ sex/group) exposed to a light catalytic reformed naphtha distillate (LCRN-D, CAS number 64741-63-5) at target concentrations of 0, 750, 2500, and 7500 ppm for 6 h/d, 5 d/wk. Sixteen rats per sex in the control and hig h-dose groups were maintained after final exposure for a 4-wk recovery peri od. The highest exposure concentration was 75% of the lower explosive limit . Standard parameters of subchronic toxicity were measured throughout the s tudy; at necropsy, organs were weighed and tissues processed for microscopi c evaluation. Neurotoxicity evaluations consisted of motor activity (MA) an d a functional operational battery (FOB) measured pretest, throughout expos ure and after the recovery period. Neuropathology was evaluated at terminat ion. No test-related mortality or effects on physical signs, body weight, f ood consumption, or clinical chemistry were observed. In males exposed to 7 500-ppm LCRN-D, a statistically significant decrease in white blood cell co unts and lymphocyte counts was observed at the termination of exposure that was not present in animals after the 4-wk recovery period. However, mean c orpuscular volume was slightly decreased in high-dose males after the recov ery period. Statistically significant increases in kidney weights relative to body weights in 7500-pp m male rats correlated with microscopically obse rved hyaline droplet formation and renal tubule dilation, indicative of lig ht hydrocarbon nephropathy, a condition in male rats that is not toxicologi cally significant for humans. Statistically significant decrease in absolut e and relative spleen weights in 7500-ppm male rats correlated with decreas es in hematologic parameters but had no microscopic correlate and was not o bserved in animals after 4 wk of recovery. This mild, reversible effect in white blood cell populations may relate to the presence of aromatics in the distillate. The only effect of LCRN-D on neurobehavioral parameters was si gnificantly higher motor activity counts among high-dose (7500 ppm) males a fter the 4-wk recovery period, suggesting a possible delayed effect of LCRN -D. However, there was no evidence of hyperactivity or abnormal behavior fr om the functional observational battery evaluations, and there were no micr oscopic changes in neural tissue to support this observation. The no-observ ed-adverse-effects level (NOAEL) for LCRN-D was 2500 ppm for both subchroni c toxicity and neurotoxicity. The no-observed-effects level ( NOEL) was 750 ppm.