1. Effects on Animals: n-Hexane is a neurotoxin, a narcotic, and an irritant of the eyes, skin, and mucous membranes [Hathaway et al. 1991]. n-Hexane also causes productive and embryotoxic effects and is cytotoxic in mammalian and human test systems [NIOSH 1991]. The oral LD(50) in rats is 28,710 mg/kg, and the lowest lethal concentration in mice is 120 g/m(3) [NIOSH 1991]. Mice exposed to concentrations ranging from 1,000 to 2,000 ppm 24 hours/day for 6 days/week for 1 year developed atrophy and degeneration of hind leg muscle fibers [NLM 1992]. Mice exposed to 2,500 to 3,000 ppm n-hexane for 4 days developed liver enlargement within 24 hours of exposure onset [NLM 1992]. Rabbits exposed by inhalation to 3,000 ppm 8 hours/day for 8 days showed changes in the lungs, emphysema, necrosis of the bronchial epithelium, and atelectasis [NLM 1992]. Rats continuously exposed to 400 ppm developed anoxapathy, although intermittent exposure to 10,000 ppm 6 hours/day, 5 days/week for 13 weeks caused only mild paranodol axonal swelling [Hathaway et al. 1991]. The offspring of rats and mice exposed orally or by inhalation to n-hexane during gestation showed depressed weight gain after birth [Hathaway et al. 1991]. This agent also affects male and female reproductive capacity [Amdur 1991].
2. Effects on Humans: n-Hexane is a narcotic agent; an irritant to the eyes, upper respiratory tract, and skin; and a neurotoxin. Exposure of humans to 5,000 ppm n-hexane for 10 minutes causes marked vertigo; exposure to 1,500 ppm results in headache and slight nausea [Hathaway et al. 1991; Clayton and Clayton 1982]. In industrial settings, exposure to levels exceeding 1,000 ppm have been reported to cause mild symptoms of narcosis [Hathaway et al. 1991]. Eye and upper respiratory tract irritation has been reported to occur in humans exposed to 880 ppm n-hexane for 15 minutes [Clayton and Clayton 1982]. Dermal contact with n-hexane results in immediate irritation characterized by erythema and hyperemia; exposed subjects developed blisters 5 hours following dermal exposure to n-hexane [Hathaway et al. 1991]. The neuropathic toxicity of n-n-hexane in humans is well documented; cases of polyneuropathy have typically occurred in humans chronically exposed to levels of n-hexane ranging from 400 to 600 ppm, with occasional exposures up to 2,500 ppm [Hathaway et al. 1991]. Distal symmetrical motor weakness is common in most cases; however, in severely affected individuals, motor weakness may extend to the pelvic and high musculature [Rom 1992]. Nerve biopsies in affected individuals show swelling of the nerve and thinning of the myelin sheath. Functional neurological disturbances usually progress for a few months after termination of exposure. Although recovery is expected to occur within a year, clinical polyneuropathy has been reported in some cases to remain after 2 years [Hathaway et al. 1991]. Blurred vision, restricted visual field, and optic nerve atrophy has been reported to occur in association with n-hexane-induced polyneuropathy. Twelve of 15 individuals working with hexane for 12 years were found to have abnormal color discrimination [Grant 1986].
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