Support: TSCA Health and Safety Study Cover Sheet with Preliminary Results from 4-Week Inhalation Toxicity Study of Cyclopropanemethanol in Rats, with Cover Letter dated 05/171/1998

摘要

In this study, male and female Sprague-Dawley rats were exposed to nominal concentrations of 0, 0.1, 0.3, or 1.0 mg/1 of CPMO for 6 hours per day, 5 days per week for 4 weeks. Animals were observed during and after exposure and daily on non-exposure days. Body weights and feed consumption were measured weekly. Minimal signs of toxicity such as reduced activity during exposure, reduced feces, and porphyrin discharge from the nose were obsesved in animals exposed to 1.0 mg/1. Porphyrin discharge from the nose was also seen in mid-dose female rats. No other unusual or remarkable effects were seen at the lower concentrations. After 4 weeks of exposure, animals were fasted and sacrificed. Blood was collected and analyzed for clinical chemistry and hematology. White blood cell count was decreased in the male and female high-dose animals. Red blood cell count, hematocrit, and hemoglobin were reduced in the high-dose females. Prothrombin time was increased in the male and female high- dose animals. Blood urea nitrogen (BUN) was increased in the high-dose treatment groups. Glucose was increased in the mid- and high-dose males. Triglycerides were increased in the high-dose females. Cholesterol was decreased in all male test groups. Mean relative (to body weight) heart weights for female rats exposed to 0.1 and 1.0 mg/1 were significantly higher than for the control groups. Liver weights for the mid- and high-dose male group, and for all treated female groups were significantly higher than for the control group. Testes and epididymides weights were significantly decreased in the high-dose males. Histopathologic examinations indicated that the target organs were liver and heart (all animals), testes and epididymides (males) and sternal bone marrow (females). Lesions in the heart included myocarditis, muscle fiber vacuolation, and muscle fiber degeneration. These heart lesions were observed at all exposure levels for both male and female rats. Lesions in the liver included hepatocellular eytoplasmic vacuolation, which was observed at all exposure levels for both males and females. Lesions in the testes were spermatid degeneration, which was seen only in the 1.0 mg/1 male group. Seminiferous tubule degeneration was also seen in the high dose male group. There was a mild decrease in cellularity within the sternal bone marrow in the 1.0 mg/1 female group.