N-Hexane (CAS No. 110-54-3) Inhalation Developmental Toxicology Studies in Mice
Report Date: May 1988
The following abstract presents results of a study conducted by a contract laboratory for the National Toxicology Program. The findings may not have been peer reviewed and were not evaluated in accordance with the levels of evidence criteria established by NTP in March 2009. For more information, see the Explanation of Levels of Evidence for Developmental Toxicity. The findings and conclusions for this study should not be construed to represent the views of NTP or the U.S. Government.
Timed-pregnant (~33 females per group) and virgin (10 females per group) Swiss (CD-1) mice were exposed to 0 (filtered air), 200, 1000, and 5000 ppm n-hexane (99.2% purity) vapor in inhalation chambers, 20 h/day, for a period of 12 consecutive days. Plug-positive females were exposed on 6-17 days of gestation. Maternal body weight at sacrifice (18 dg) and total cumulative weight gain for dams in the 5000-ppm exposure group were significantly reduced with respect to controls; however, this waa due to an exposure correlated reduction in gravid uterine weight, not to a decrease in extragestational gain. An exposure-correlated decrease in the gravid uterine weight to extragestational weight gain ratio (significant for the 5000-ppm group) occurred in the absence of an effect on placental weight.
Gestational exposure to n-hexane resulted in an increase in the number of resorbed fetuses for all exposure groups relative to the control group; however, the increases were not directly correlated to exposure concentration. The differences were statistically significant for the 200-ppm group with respect to total intrauterine death (early plus late resorptions), and with respect to late resorptions for the 5000-ppm group. A small, but statistically significant, reduction in female (but not male) fetal body weight relative to the control group was observed at the 5000-ppm exposure level. There were no exposure-related increases in any individual fetal malformation or variation, nor was there any increase in the incidence of combined malformations or variations.
Gestational exposure of CD-1 mice to n-hexane vapors appeared to cause a degree of concentration-related developmental toxicity in the absence of overt maternal toxicity, but the test material was not found to be teratogenic. This developmental toxicity was manifested as an increase in the number of resorptions per litter for all exposure levels, and as a decrease in the uterine: extra-gestational weight gain ratio at the 5000-ppm exposure level. Because of the significant increase in the number of resorptions at the 200-ppm exposure level, a no observed effect level for developmental toxicity was not established for exposure of mice to 200, 1000, or 5000-ppm n-hexane vapors.