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Description of key information

One key repeat dose oral toxicity (Krasavage, 1980; Klimisch score =2) and two key repeat dose inhalation studies (Takeuchi, 1980; Klimisch score =2 and (Dunnick, 1991; Klimisch score =2) were identified for n-hexane.   No studies were identified for repeat dose toxicity dermal endpoint for n-hexane.
The NOAEL for repeat dose oral toxicity = 568 mg/kg bw/day.
The LOAEC for sub-chronic inhalation exposures was 10800 mg/m3 (Takeuchi, 1980; Klimisch score =2).
The LOAEC for female mice was 1760 mg/m3 based on nasal lesions. No NOAEC was found for female mice. (Dunnick, 1991; Klimisch score =2).

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Dose descriptor:
NOAEL
568 mg/kg bw/day
Study duration:
subchronic
Species:
rat

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion
Dose descriptor:
LOAEC
1 760 mg/m³
Study duration:
subchronic
Species:
mouse

Additional information

In a key repeat dose oral toxicity study ((Krasavage, 1980; Klimisch score =2) the effect of oral exposure to the test substance n-hexane was examined. 5 male rats were exposed to concentrations of 6.60, 13.2, and 46.2 mmol/kg bw (568, 1135, 3973 mg/kg) by oral gavage for 90 to 120 days. Neurological effects were only seen at the highest dose level after an average of 101.3 days of exposure. The LOAEL for neurological effects is 46.2 mmol/kg bw (37973 mg/kg), and the NOAEL is 13.2 mmol/kg bw (1135 mg/kg). Reduced body weight gain was seen at all three dose levels, however was only considered treatment related in the 13.2 and 46.2 mmol/kg bw groups. The NOAEL is therefore 6.60 mmol/kg bw.

 

In a key repeat dose inhalation study (Takeuchi, 1980; Klimisch score =2) 7 rats were exposed to 3000 ppm of hexane vapors for 12 hrs a day for 16 weeks. Two animals died before the end of the exposure period. All animals showed reduced weight gain after 4 weeks of exposure. Neurological effects were seen beginning at 10 weeks exposure. Motor nerve conduction velocity and distal latency were significantly affected after 4 weeks exposure. Examination of neural tissue showed damage to the tibial nerve and dorsal trunk of the tail nerve. The LOAEC for sub-chronic exposure was 3000 ppm.

In another key repeat dose inhalation study (Dunnick, 1991; Klimisch score =2) the effect of 13 weeks inhalation exposure of n-hexane to mice was examined. Groups of 18 female and 18 male mice were exposed to concentrations of 0, 500, 1000, 4000, or 10,000 ppm of test substance for 6 hrs/day, 5 days/week, for 13 weeks. An additional group was exposed to 1000 ppm of test substance for 22 hrs/day, 5 days/week, for 13 weeks. 8 mice of each sex in each exposure group were examined for neurobehaviour. No animals died during the study, and the only neurological effects were decreased locomotion in females exposed to 10000 ppm. Nasal lesions were seen in females in all exposure groups, and in males exposed to 1000 ppm of test substance. The LOAEC for females was therefore 500 ppm (1760 mg/m3), with no NOAEC found. The NOAEC for males was 500 ppm (1760 mg/m3), with an LOAEC of 1000 ppm (3520 mg/m3) based on nasal lesions.

Justification for classification or non-classification

n-Hexane is classified as a Category 2 toxicant for single target organ repeated exposure.