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Description of key information

Key value for chemical safety assessment

Additional information

Animal Information:

One identified key toxicokinetics study was read-across commercial hexane (52 % n-hexane) (API, 1990; Klimisch score = 1). In an animal toxicokinetics metabolism and distribution study commercial n-hexane was metabolized and excreted within 168 hours of iv bolus administration, inhalation exposure or dermal application. Exhaled breath and urine were the two primary routes for the excretion of n-hexane and its metabolites. n-hexane was widely distributed to the body tissues but were not concentrated significantly by any of those tissues. It was extensively metabolized and a number of radio labeled metabolites were excreted in the urine. n-hexane and its radio labeled metabolites disappeared from the blood of rats with a half-life of approximately 9-10 hours. No significant differences between males and females were noted in the rates and routes of metabolism and excretion of the test compounds. Repeated inhalation exposure had no apparent effect on the rates or routes of excretion of either of the test compounds or their metabolites.

Human Information

In a study in which metabolites in urine were measured in workers exposed to n-hexane (Perbellini et al., 1981), mean concentrations of n-hexane metabolites in urine were: 2,5-hexanedione, 5.4 mg/L; 2,5-dimethylfuran, 3.7 mg/L; gamma-valerolactone, 3.3 mg/L; and 2-hexanol, 0.19 mg/L. (2,5-Dimethylfuran and gammavalerolactone are believed to be artifacts of sample preparation and analysis rather than true metabolites of n-hexane (ATSDR, 1999)). The first reaction that takes place is hydroxylation of n-hexane at the 2 position to form 2-hexanol. Further reactions result in 2,5-hexanedione, presumably through transient intermediates, including 2-hexanone, 2,5-hexanediol, and 5-hydroxy-2-hexanone. Correlations between concentrations of n-hexane in air and urinary metabolites were best for total n-hexane metabolites (r=0.7858), followed by 2-hexanol (r=0.6851) and 2,5-hexanedione (r=0.6725).