Toxicity evaluation of petroleum blending streams: inhalation subchronic toxicity/neurotoxicity study of a light catalytic reformed naphtha distillate in rats
| Autor: | D. Burnett, R. Breglia, F. Koschier, C Schreiner, Gary M. Hoffman, Paula Podhasky, E. Lapadula, R. Mandella, Russell White, Q. Bui |
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| Rok vydání: | 2003 |
| Předmět: |
Male
No-observed-adverse-effect level Health Toxicology and Mutagenesis Physiology Motor Activity Toxicology Kidney Rats Sprague-Dawley White blood cell Administration Inhalation Alkanes medicine Animals Lymphocyte Count Mean corpuscular volume No-Observed-Adverse-Effect Level medicine.diagnostic_test Inhalation Behavior Animal Dose-Response Relationship Drug Chemistry Neurotoxicity Organ Size medicine.disease Rats Dose–response relationship medicine.anatomical_structure Petroleum Toxicity Female Spleen |
| Zdroj: | Journal of toxicology and environmental health. Part A. 60(7) |
| ISSN: | 1528-7394 |
| Popis: | A 13-wk whole-body inhalation study was conducted with Sprague-Dawley CD rats (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 high-dose groups were maintained after final exposure for a 4-wk recovery period. The highest exposure concentration was 75% of the lower explosive limit. Standard parameters of subchronic toxicity were measured throughout the study; at necropsy, organs were weighed and tissues processed for microscopic evaluation. Neurotoxicity evaluations consisted of motor activity (MA) and a functional operational battery (FOB) measured pretest, throughout exposure and after the recovery period. Neuropathology was evaluated at termination. No test-related mortality or effects on physical signs, body weight, food consumption, or clinical chemistry were observed. In males exposed to 7500-ppm LCRN-D, a statistically significant decrease in white blood cell counts and lymphocyte counts was observed at the termination of exposure that was not present in animals after the 4-wk recovery period. However, mean corpuscular volume was slightly decreased in high-dose males after the recovery period. Statistically significant increases in kidney weights relative to body weights in 7500-ppm male rats correlated with microscopically observed hyaline droplet formation and renal tubule dilation, indicative of light hydrocarbon nephropathy, a condition in male rats that is not toxicologically significant for humans. Statistically significant decrease in absolute and relative spleen weights in 7500-ppm male rats correlated with decreases in hematologic parameters but had no microscopic correlate and was not observed 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 significantly higher motor activity counts among high-dose (7500 ppm) males after the 4-wk recovery period, suggesting a possible delayed effect of LCRN-D. However, there was no evidence of hyperactivity or abnormal behavior from the functional observational battery evaluations, and there were no microscopic changes in neural tissue to support this observation. The no-observed-adverse-effects level (NOAEL) for LCRN-D was 2500 ppm for both subchronic toxicity and neurotoxicity. The no-observed-effects level (NOEL) was 750 ppm. |
| Databáze: | OpenAIRE |
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