Effect of coexposure to methyl ethyl ketone (MEK) on n-hexane toxicokinetics in human volunteers.
In order to study the effects of methyl ethyl ketone (MEK) on the toxicokinetics of n-hexane and, in particular, the formation of 2,5-hexanedione from n-hexane in humans, volunteers were exposed to n-hexane (approx. 60 ppm, 2.4 microM in the inhaled air) with or without simultaneous inhalatory coexposure to MEK for 15.5 min. The concentration-time course of n-hexane (in exhaled alveolar air) and its neurotoxic metabolite, 2,5-hexanedione (in serum), were studied. The concentration-time courses obtained after exposure to n-hexane alone were compared with those obtained after coexposure to 200 or 300 ppm MEK in the same volunteer on the same day. No effect of MEK was observed on the concentration-time course of exhaled n-hexane. The concentration-time course of the metabolite, 2,5-hexanedione, revealed a decrease in the rate of formation of 2,5-hexanedione (about three-fold) after coexposure to MEK. Furthermore, the time to reach the peak concentration was increased from 18 to 30 min after the start of exposure. These changes in the concentration-time course of 2,5-hexanedione caused by MEK are most likely the result of inhibition of the biotransformation of one of the intermediate steps in the conversion of n-hexane to 2,5-hexanedione. These results indicate that the interaction of n-hexane and MEK leads to a decreased concentration of the neurotoxic metabolite 2,5-hexanedione (after short-term, acute exposure).
van Engelen
J G
JG
Division of Human Toxicology, University of Amsterdam, Academic Medical Centre, The Netherlands.
Rebel-de Haan
W
W
Opdam
J J
JJ
Mulder
G J
GJ
D000280:Administration, Inhalation; D000328:Adult; D001711:Biotransformation / Q000187:drug effects; D001774:Blood Chemical Analysis; D001944:Breath Tests; D002074:Butanones / Q000008:administration & dosage / Q000494:pharmacology*; D004347:Drug Interactions; D005260:Female; D006586:Hexanes / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity*; D006801:Humans; D008297:Male; D008452:Maximum Allowable Concentration; D008954:Models, Biological
D002074:Butanones; D006586:Hexanes; C026385:n-hexane; C005222:methylethyl ketone