Relation between schedules of exposure to hexane and plasma levels of 2,5-hexanedione.
Male Fischer rats were exposed repeatedly to high concentrations of hexane for 10 minutes in a pattern resembling human solvent abuse or to low concentrations of hexane continuously for 8 or 24 hours daily. Concentrations of hexane in blood and brain were linearly related to the concentrations of hexane in the chamber after a 10-minute exposure, and declined thereafter, with half lives of about 2 1/2 and 4 minutes in blood and brain, respectively. Despite the rapid elimination of hexane, neurotoxic levels of 2,5-hexanedione (2,5-HD) were formed from repeated 10-minutes exposures to a high concentration of hexane when the interexposure interval was 20 minutes. Neurotoxic levels of 2,5-HD also resulted from continuous exposure to much lower concentrations of hexane. Both exposure schedules caused an increase in 2,5-HD concentrations in blood after repeated daily treatments, suggesting induction of liver microsomal enzymes synthesizing 2,5-HD from hexane. The minimal sustained plasma 2,5-HD concentration that will result in neurotoxicity appears to be less than 50 micrograms/ml in the rat.
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006586:Hexanes / Q000633:toxicity*; D006588:Hexanones / Q000097:blood*; D007659:Ketones / Q000097:blood*; D008297:Male; D008657:Metabolic Clearance Rate; D051381:Rats; D011916:Rats, Inbred F344
D006586:Hexanes; D006588:Hexanones; D007659:Ketones; C011269:2,5-hexanedione