Oral gavage subchronic neurotoxicity and inhalation subchronic immunotoxicity studies of ethylbenzene in the rat

• Published in: Neurotoxicology (Park Forest South) Vol. 31; no. 3; pp. 247 - 258
• Main Authors: Li, Abby A., Maurissen, Jacques P.J., Barnett, John F., Foss, John, Freshwater, Les, Garman, Robert H., Peachee, Vanessa L., Hong, Sandra J., Stump, Donald G., Bus, James S.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 01-06-2010; Elsevier
• Subjects: Administration, Inhalation; Administration, Oral; Analysis of Variance; Animals; Benzene Derivatives - administration & dosage; Benzene Derivatives - toxicity; Biological and medical sciences; Body Weight - drug effects; Disease Models, Animal; Dose-Response Relationship, Drug; Eating - drug effects; Ethylbenzene; Female; Immunotoxicity; Inhalation; Kidney Diseases - chemically induced; Liver Diseases - etiology; Male; Medical sciences; Motor Activity - physiology; Neurologic Examination - methods; Neurotoxicity; Neurotoxicity Syndromes - complications; Neurotoxicity Syndromes - etiology; Neurotoxicity Syndromes - immunology; Neurotoxicity Syndromes - mortality; Neurotoxins - toxicity; No-Observed-Adverse-Effect Level; Ophthalmology; Oral; Rat; Rats; Rats, Sprague-Dawley; Sex Factors; Toxicology; Ethylbenzene; Neurotoxicity; Oral; Rat; Immunotoxicity; Inhalation; Immunopathology; Nervous system diseases; Subchronic; Toxicity; Rodentia; Oral administration; Vertebrata; Mammalia; Animal
• ISSN: 0161-813X; 1872-9711
• DOI: 10.1016/j.neuro.2010.02.001

The potential for neurotoxicological and immunotoxicological effects of ethylbenzene was studied in young adult Crl:CD(SD) rats following 90-day oral (neurotoxicity) or 28-day inhalation (immunotoxicity) exposures. In the neurotoxicity study, ethylbenzene was administered orally via gavage twice daily at 0, 25, 125, or 250
mg/kg per dose (total daily dosages of 0, 50, 250, or 500
mg/kg bwt/day [mg/kg bwt/day]) for 13 weeks and the functional observational battery (FOB), automated tests for motor activity and neuropathological examination were conducted. In the immunotoxicity study, animals were exposed by inhalation to 0, 25, 100, or 500
ppm ethylbenzene (approximately 26, 90, or 342
mg/kg bwt/day as calculated from physiologically based pharmacokinetic modeling). Immunotoxicity was evaluated in female rats using the splenic antibody-forming cell plaque-forming assay in sheep red blood cell sensitized animals. The no-observed-effect level for the oral gavage study was 50
mg/kg bwt/day based on increased relative weights of the liver and kidneys in the male rats. The no-observed-adverse-effect level (NOAEL) for adult neurotoxicity was the highest dose tested 500
mg/kg bwt/day. The NOAEL for the immunotoxicity evaluation was the highest tested exposure concentration, 500
ppm (342
mg/kg bwt/day).