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.
The straight chain hydrocarbon, n-hexane, is a volatile, ubiquitous solvent used in industrial, academic, and smaller commercial environments. The significant opportunity for women of child-bearing age to be exposed to this chemical prompted the undertaking of a study to assess the developmental toxicity of n-hexane in an animal model. Timed-pregnant (30 animals per group) and virgin (10 animals per group) Sprague-Dawley rats were exposed to 0 (filtered air), 200, 1000, and 5000 ppm n-hexane (99.9% purity) vapor in inhalation chambers for 20 hours per day for a period of 14 consecutive days. Spermpositive females were exposed for 6-19 days of gestation and virgins were exposed concurrently for 14 consecutive days. The day of sperm detection was designated as 0 dg for mated females. Adult female body weights were monitored prior to, throughout the exposure period, and at sacrifice. Uterine, placental, and fetal body weights were obtained for gravid females at sacrifice. Implants were enumerated and their status recorded as live fetus, early or late resorption, or dead. Live fetuses were sexed and examined for gross, visceral, skeletal, and soft-tissue craniofacial defects.
Maternal toxicity manifested as a reduction in extra-gestational maternal weight gain was observed at all exposure levels, and was statistically significant for the 5000 ppm exposure group. Extra-gestational maternal weight gain (calculated from 0 dg to 20 dg) relative to control animals was reduced by 20, 23, and 45% for the 200, 1000, and 5000 ppm exposure groups, respectively. Cumulative weight gain for dams in the 1000 and 5000 ppm exposure groups was significantly reduced with respect to controls by 20 dg. The CWG for the 5000 ppm was also significantly reduced with respect to controls by 13 dg.
Comparison of n-hexane exposed groups with the control group (0 ppm) indicated that gestational exposure to n-hexane did not result in an increase in the incidence of intrauterine deaths or in the incidence of fetal malformations. A statistically significant reduction in fetal body weight relative to controls was observed for males at the 1000 and 5000 ppm exposure levels (7 and 15% reduction, respectively). Female weights were also reduced with respect to controls for these exposure levels (3 and 14% reduction, respectively), but the reduction was statistically significant for only the 5000 ppm group. Gravid uterine weight was also significantly less than controls for the 5000 ppm exposure groups. A statistically significant increase in the mean percent incidence per litter of reduced ossification of sternebrae 1-4 was observed for the 5000 ppm group, and was positively correlated with exposure concentration. This increased incidence of reduced ossification in the sternebrae, and the reduction in fetal body weight at the 5000 ppm level, may have been inter-related manifestations of a slight growth retardation.
No major abnormalities were found in any of the fetuses. Variations observed included dilated ureter, renal pelvic cavitation, supernumerary ribs, and reduced skeletal ossifications at several sites. The increase in mean percent incidence per litter of reduced ossification of sternebrae 1-4 was statistically significant for the highest exposure concentration, and the increase was positively correlated with increasing exposure concentration. The lowest n-hexane exposure concentration, 200 ppm, proved to be a no observable effect level for developmental toxicity.