The effects of prolonged exposure to low concentrations of halothane (151677) and nitrous-oxide (10024972) on tumor incidence were studied in Fischer-344-rats. Group 1 rats were exposed to filtered air only; group 2 was exposed to 1 part per million (ppm) of halothane and 50ppm of nitrous-oxide, and group 3 was exposed to 10ppm of halothane and 500ppm of nitrous-oxide. Exposures lasted for 6 hours per day, 5 days per week for 104 weeks. Individual body weights were recorded periodically, and gross signs of systemic toxicity and incidences, sizes, and location of tissue masses were recorded. Complete blood counts also were determined. Survival rates at 104 weeks among males were 74, 76 and 72 percent, respectively, for groups 1, 2 and 3. Corresponding survival rates for females were 86, 78 and 84 percent. Heart weight, kidney weight, and the kidney to body weight ratio for group 3 males were slightly but significantly lower than for comparisons. Spleen weights and spleen to body weight ratios for group 2 and 3 females were significantly lower than for comparisons. Values for males did not differ between the three groups. No exposure related lesions were observed at necropsy. Microscopic examination revealed a variety of nonneoplastic, nontreatment related lesions in all groups. No exposure related pattern of malignancy was evident for any organ system in any of the groups. The authors conclude that prolonged exposure to such low concentrations of halothane and nitrous-oxide does not affect body weight, appearance, behavior, survival, or hematology, and does not increase the incidence of reticuloendothelial tumors.
Dr. Coate, Inhalation Toxicology Department, Hazleton Laboratories America, Inc., 9200 Leesburg Turnpike, Vienna, Virginia 22180