Cytochrome P4502E1 phenotyping by the measurement of the chlorzoxazone metabolic ratio: assessment of its usefulness in workers exposed to styrene.
OBJECTIVE
To analyse the relationship between cytochrome P4502E1 (CYP2E1) activity as assessed by the chlorzoxazone metabolic ratio (CMR) and frequent CYP2E1 genotypes ( CYP2E1*5B, *6, *1B and *1D) and to assess the value of CMR in refining the biomonitoring of exposure to styrene.


METHODS
Thirty-one workers from a fibreglass-reinforced plastics factory took part in the study. Ambient styrene concentration was determined during the whole workshift by passive sampling. Each worker received a 500-mg chlorzoxazone (CZX) tablet at the beginning of the workday, and blood was taken after 2 h for CMR and CYP2E1 genotypes determination. Urine was collected at the end of the shift for the determination of styrene-specific metabolites.


RESULTS
While the only worker heterozygous for CYP2E1*1D allele presented the highest value of CMR, a trend to lower CMR value for individuals possessing at least one mutant CYP2E1*6 allele compared with homozygous wild type was observed. The integration of CMR value as an independent variable to explain inter-individual variability in urinary metabolite excretion was not conclusive.


CONCLUSIONS
Although, in the present population of workers, the CMR test was able to detect a slight influence of some genotypes on the activity of the CYP2E1 enzyme, it must be recognised that this method is not appropriate for refining the biological monitoring of industrial compounds that are metabolised by CYP2E1.
Haufroid
Vincent
V
Industrial Toxicology and Occupational Medicine Unit, Catholic University of Louvain, Clos Chapelle-aux-Champs 30/54, 1200 Brussels, Belgium. haufroid@toxi.ucl.ac.be
Buchet
Jean-Pierre
JP
Gardinal
Sophie
S
Lison
Dominique
D
D000328:Adult; D001530:Belgium; D002753:Chlorzoxazone / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics* / Q000378:metabolism; D004784:Environmental Monitoring; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D016273:Occupational Exposure / Q000009:adverse effects / Q000032:analysis*; D010641:Phenotype; D013050:Spectrometry, Fluorescence; D020058:Styrene / Q000009:adverse effects*
D020058:Styrene; D019392:Cytochrome P-450 CYP2E1; D002753:Chlorzoxazone