SUBCHRONIC TOXICITY OF CYCLOHEXANE IN RATS AND MICE BY INHALATION EXPOSURE

• Published in: Drug and chemical toxicology (New York, N.Y. 1978) N.Y. 1978), 2000-01, Vol.23 (4), p.513-537
• Main Authors: Malley, Linda Angevine, Bamberger, John R., Stadler, Judith C., Elliott, Glenn S., Hansen, John F., Chiu, Taisan, Grabowski, John S., Pavkov, Kenneth L.
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Chemical and industrial products toxicology. Toxic occupational diseases; cyclohexane; Cyclohexanes - pharmacokinetics; Cyclohexanes - toxicity; Erythrocytes - drug effects; Erythrocytes - metabolism; Female; Hematocrit; Hemoglobins - drug effects; Humans; Inhalation Exposure - adverse effects; Liver - drug effects; Liver - pathology; Male; Medical sciences; Mice; Motor Activity - drug effects; No-Observed-Adverse-Effect Level; Random Allocation; Rats; Rats, Sprague-Dawley; Solvents; Species Specificity; Toxicity Tests; Toxicology; United States; United States Environmental Protection Agency
• ISSN: 0148-0545; 1525-6014
• DOI: 10.1081/DCT-100101969

Inhalation studies were conducted to determine the potential toxicity and or potential neurotoxicity of cyclohexane. Groups of rats and mice were exposed to 0, 500, 2000, or 7000 ppm concentrations of cyclohexane vapor 6 hr day, 5 days week for 14 weeks. Subgroups of rats and mice were further observed during a 1-month recovery period. Functional observational battery (FOB) and motor activity (MA) behavioral tests were conducted on rats. These tests were conducted prior to the exposure series and during weeks 4, 8, and 13 on non-exposure days. Clinical pathology evaluations were conducted after approximately 7, 13, and 18 weeks. Approximately 14 and 18 weeks after study initiation, tissues from rats and mice were histologically processed and evaluated by light microscopy. During exposure to 2000 or 7000 ppm, rats and mice had a diminished response or an absent response to delivery of a punctate auditory alerting stimulus. Immediately following removal of rats from the inhalation chambers, 7000 ppm males and females and 2000 ppm females displayed a compound-related increase in the incidence of wet and or stained fur (which occurred in the areas of the mouth, chin, and or perineum). These signs were transient, were not observed during exposure or prior to exposure the following day, and were not associated with any behavioral or morphological changes. During exposure sessions, mice exposed to 7000 ppm exhibited clinical signs of toxicity which included hyperactivity, circling, jumping hopping, excessive grooming, kicking of rear legs, standing on front legs, and occasional flipping behavior. Clinical signs of toxicity observed in 7000 ppm mice immediately after exposure included hyperactivity, hyperreactivity, ruffled fur (females only), gait abnormalities, spasms in both rear legs, and excessive grooming (males only). The clinical signs observed in mice during and immediately after exposure were transient, and were not present prior to the subsequent exposure. A few mice exposed to 2000 ppm appeared hyperactive during exposure in the latter portion of the study. There were no compound-related changes in mean body weights, body weight gains, food consumption, food efficiency, or mortality; and there were no ophthalmological abnormalities in rats or mice. In addition, there were no compound-related effects on 37 different behavioral parameters assessed during the FOB or during motor activity tests in rats. Male and female mice exposed to 7000 ppm had slight i