PERINATAL TOXICITY AND METABOLISM OF NORMAL-HEXANE IN FISCHER-344 RATS AFTER INHALATION EXPOSURE DURING GESTATION

Repeated exposure of adult rats to n-hexane produces a central and peripheral neuropathy which may be mediated through metabolic activation to methyl n-butyl ketone (MBK) and 2,5-hexanedione (2,5-HD). The perinatal toxicity of n-hexane and its metabolism in the pregnant rat have not been investigated. Pregnant rats were exposed for 6 hr per day to 1000 ppm n-hexane on Days 8-12, 12-16, or 8-16 of gestation. No significant alterations in fetal resorptions, body weights, visible anomalies, and the incidence of soft tissue and skeletal anomalies were noted in any of the treatment groups. The postnatal growth of pups born from dams exposed to 1000 ppm n-hexane 6 hr/day on Days 8-16 of gestation was significantly depressed compared to controls up to 3 weeks after birth (mean treated litter weight 13.9% less than control at 3 weeks). Litter weights of treated pups had returned to control values by 7 weeks after birth. n-Hexane was metabolized to MBK and 2,5-HD in pregnant rats exposed to 1000 ppm n-hexane on Day 20 of gestation. Concentrations of the three compounds in the fetus were approximately equal to those in maternal blood at all times after exposure. The half-life of 2,5-HD in maternal blood was significantly greater than n-hexane and MBK (3.90 hr vs 1.24 and 0.99 hr, respectively). Thus, n-hexane and its metabolites MBK and 2,5-HD may have only a minimal potential to alter perinatal development of rats. © 1979.