Changes in n-hexane toxicokinetics in short-term single exposure due to co-exposure to methyl ethyl ketone in volunteers.
OBJECTIVE
Animal studies demonstrate that the formation of the neurotoxic metabolite, 2,5-hexanedione (HD) decreases during co-exposure to methyl ethyl ketone (MEK). The aim of the present study was to describe the influence of co-exposure to MEK on n-hexane toxicokinetics in humans.


METHODS
Four healthy male volunteers were exposed, on different occasions, to three different combinations of vapor of these solvents, namely: 50 ppm n-hexane alone, and in combination with 100 and 200 ppm MEK, for 2 h during light physical exercise (50 W). Arterialized capillary blood, venous blood, and urine were sampled at scheduled intervals before, during, and up to 24 h after the onset of the exposure. HD in venous blood and urine was analyzed by gas chromatography with electron capture detector after derivatization with O-(pentafluorobenzyl) hydroxylamine.


RESULTS
Serum HD decreased with increasing exposure to MEK at 2 h after the onset of the exposure, from an average concentration of 2.2 micromol/l in the n-hexane-alone condition to 1.2 and 0.44 micromol/l in the 100 and 200-ppm MEK conditions, respectively. The area under the concentration-time curve of HD in venous blood and the concentration of HD at 2 and 4 h after the end of exposure decreased with increasing MEK. These results suggest that combined exposure to MEK and n-hexane at occupationally realistic levels depresses the metabolism of n-hexane in a dose-dependent fashion.


CONCLUSIONS
The internal exposure to the toxic metabolite of n-hexane decreased with co-exposure to MEK in a dose-dependent fashion. Estimation of external exposure by HD in serum or urine could be confounded by the co-exposure to MEK.
Shibata
Eiji
E
Department of Medical Technology, Nagoya University School of Health Sciences, 1-1-20 Daiko-minami, Higashi-ku, Nagoya, 461-8673 Japan. eshibata@met.nagoya-u.ac.jp
Johanson
Gunnar
G
Löf
Agneta
A
Ernstgård
Lena
L
Gullstrand
Elisabeth
E
Sigvardsson
Karl
K
D000328:Adult; D019540:Area Under Curve; D002074:Butanones / Q000008:administration & dosage / Q000494:pharmacology*; D002849:Chromatography, Gas; D015986:Confounding Factors, Epidemiologic; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004784:Environmental Monitoring; D005858:Germany; D006586:Hexanes / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D006801:Humans; D019570:Inhalation Exposure; D008297:Male; D008875:Middle Aged; D016273:Occupational Exposure / Q000032:analysis*
D002074:Butanones; D006586:Hexanes; C026385:n-hexane; C005222:methylethyl ketone