These studies were supported in part by funds from the Comprehensive Environmental Response, Compensation, and Liability Act trust fund (Superfund) by an interagency agreement with the Agency for Toxic Substances and Disease Registry, U.S. Public Health Service.
Thirteen-week inhalation toxicity studies of n-hexane were conducted with B6C3F1 mice of each sex exposed to 0, 500, 1,000, 4,000, or 10,000 ppm, 6 hours per day, 5 days per week or to 1,000 ppm, 22 hours per day (referred to as 1,000c), 5 days per week. All mice lived to the end of the studies. The final mean body weights of mice exposed to 1,000c ppm or 10,000 ppm were 10% or 17% lower than that of the controls for males and 0% or 6% lower for females.
Hematologic analyses were performed on whole blood samples collected at the end of the 13-week exposure. Segmented neutrophils were significantly increased in male mice exposed to 10,000 ppm.
A battery of behavioral measurements was conducted on mice, and the only parameter affected was locomotor activity, which was decreased in female mice at 1,000c ppm and 10,000 ppm. The test battery performed included forelimb and hind limb grip strength, motor activity and exploratory behavior, acoustic startle response, foot splay, and analgesia response.
Compound-related lesions of the nasal turbinates were seen in all groups of exposed mice except males exposed to 500 or 4,000 ppm. At the 10,000-ppm concentration, nasal lesions included inflammatory, erosive, and regenerative lesions of the olfactory and respiratory epithelium; luminal exudation and metaplastic lesions of the olfactory epithelium; and fibrosis of the submucosa. Lymphoid hyperplasia of the mandibular lymph nodes and neutrophilic hyperplasia of the bone marrow were also seen. At lower concentrations, lesions were not present in all mice and were limited to minimal regeneration or metaplasia of the olfactory epithelium.
A few paranodal swellings in the teased fibers of the tibial nerve were observed in 3/4 males and 3/4 females exposed to 10,000 ppm, 3/4 males and 3/4 females exposed to 1,000c ppm, and 0/4 male and 0/4 female controls; the severity of the lesions was minimal. Neither segmental demyelination nor distal axonal degeneration was seen.
Exposure of mice to n-hexane at concentrations up to 10,000 ppm resulted in only minimal toxicity. Paranodal swellings seen in nerves at 1,000c ppm and at 10,000 ppm were considered to be minimal nerve damage that would not result in paralysis. Exposure-related lesions of the nasal cavity occurred after n-hexane exposure, but minimal or no effects were seen at 1,000 ppm or below.