CARCINOGENESIS STUDIES OF TETRAHYDROFURAN VAPORS IN RATS AND MICE

Tetrahydrofuran (THF) is a widely used industrial solvent and was sele cted for carcinogenesis studies by the National Toxicology Program (NT P) because of its potential for widespread occupational exposure in hu mans and a lack of information on animal toxicity and carcinogenicity. Groups of 50 male and 50 female F344/N rats and B6C3F(1) mice were ex posed to 0, 200, 600, or 1800 ppm THF by inhalation, 6 h per day, 5 da ys per week, for 105 weeks. Survival and mean body weights of male and female rats exposed to THF were comparable to that of the controls. N o clinical findings or nonneoplastic lesions related to THF exposure w ere observed in male or female rats. The incidences of renal tubule ep ithelial adenoma or carcinoma (combined) in exposed male rats occurred with a positive trend, and in males exposed to 600 and 1800 ppm excee ded the historical range for controls in 2-year NTP inhalation studies . There were no other neoplastic lesions related to THF exposure obser ved in male or female rats. After week 36, the survival of male mice e xposed to 1800 ppm was significantly lower than that of the controls. Mean body weights of male and female mice exposed to THF were similar to those of the controls throughout the study. Male mice exposed to 18 00 ppm were observed in a state of narcosis during and up to 1 h after the exposure periods. Nonneoplastic lesions related to THF exposure w ere not observed in male or female mice. The neoplastic lesions relate d to THF exposure were seen in female mice only. In female mice expose d to 1800 ppm, the incidences of hepatocellular neoplasms were signifi cantly greater than those in the controls. In conclusion, there was so me evidence of carcinogenic activity of THF in male F344/N rats due to increased incidences of adenoma or carcinoma (combined) of the kidney at the 600 and 1800 ppm exposure levels. There was clear evidence of carcinogenic activity in female B6C3F(1) mice based on increased incid ences of hepatocellular neoplasms at the 1800 ppm exposure level. THF was not carcinogenic in female rats or male mice exposed at 200, 600, or 1800 ppm.