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

Sprague-Dawley rats and Swiss (CD-1) mice were exposed to 0,600, 1800, or 5000 ppm THF (a four-carbon cyclic ether, widelyused as an industrial solvent) vapors, 6 hr/day, 7 days/week(6–19 days of gestation (DG) for rats; 6–17 DG formice). Body weights of pregnant rats in the 5000 ppm group werereduced at euthanization. There were no effects on the percentageof live rat fetuses/litter or on the fetal sex ratio. Fetalbody weight was significantly reduced for the 5000 ppm group,but the incidence of abnormalities was not increased. Mice inthe 1800 and 5000 ppm groups were sedated during exposure; approximately27% of the mice in the 5000 ppm group died. Mean body and uterineweights of mice were reduced for the 1800 and 5000 ppm groupsat euthanization (18 DG), but adjusted maternal weight gainwas not affected at 1800 ppm. There was a reduction in the percentageof live fetuses/litter for the mice in 1800 and 5000 ppm groups(95% resorptions in the 5000 ppm group). Fetal weight and sexratio in mice were not affected. An increase in the incidenceof 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 malformationsor variations. These results suggest that THF may be embryotoxicin mice, but if the conceptus survives, development as assessedby this experimental design continues in a normal fashion. Theno-observable-adverse-effect level (NOAEL) for maternal toxicitywas 1800 ppm in both rats and mice. The NOAEL for developmentaltoxicity was 1800 ppm in rats and 600 ppm in mice.