Evaluation of the Potential for Developmental Toxicity in Rats and Mice following Inhalation Exposure to Tetrahydrofuran

Abstract Sprague-Dawley rats and Swiss (CD-1) mice were exposed to 0, 600, 1800, or 5000 ppm THF (a four-carbon cyclic ether, widely used as an industrial solvent) vapors, 6 hr/day, 7 days/week (6–19 days of gestation (DG) for rats; 6–17 DG for mice). Body weights of pregnant rats in the 5000 ppm group were reduced at euthanization. There were no effects on the percentage of live rat fetuses/litter or on the fetal sex ratio. Fetal body weight was significantly reduced for the 5000 ppm group, but the incidence of abnormalities was not increased. Mice in the 1800 and 5000 ppm groups were sedated during exposure; approximately 27% of the mice in the 5000 ppm group died. Mean body and uterine weights of mice were reduced for the 1800 and 5000 ppm groups at euthanization (18 DG), but adjusted maternal weight gain was not affected at 1800 ppm. There was a reduction in the percentage of live fetuses/litter for the mice in 1800 and 5000 ppm groups (95% resorptions in the 5000 ppm group). Fetal weight and sex ratio in mice were not affected. An increase in the incidence of reduced sternebral ossifications was correlated to THF concentration, although differences between groups were not statistically significant. There were no increases in the incidences of other malformations or variations. These results suggest that THF may be embryotoxic in mice, but if the conceptus survives, development as assessed by this experimental design continues in a normal fashion. The no-observable-adverseeffect level (NOAEL) for maternal toxicity was 1800 ppm in both rats and mice. The NOAEL for developmental toxicity was 1800 ppm in rats and 600 ppm in mice.