The relationship between occupational exposure to methyl ethyl ketone (MEK) and its concentration in urine and blood was studied in a group of 72 workers in a printing factory. Personal exposure monitoring was carried out with passive samplers during the workshifts. The time weighted average (TWA) concentration of MEK ranged from 1.3 to 223.7 ppm, with a mean concentration of 47.6 ppm. In addition to MEK, toleuene, xylene, isopropyl alcohol, and ethyl acetate were detected as the main contaminants in all samples.

In this study, we evaluated the effects of ALDH2, CYP1A1, and CYP2E1 genetic polymorphisms and smoking and drinking habits on the toluene metabolism. The study subjects were 92 male workers who handle toluene in a printing factory, an electrical parts factory, and a painting workplace in Japan. Their exposure levels to toluene were monitored using the diffusion-type sampler. Benzyl alcohol concentrations in their blood and hippuric acid (HA) and creatinine concentrations in their urine at the end of a workshift were determined. The genotype of ALDH2 was classified into the homozygous genotype of a normal ALDH2 gene (NN), the homozygous genotype of an inactive ALDH2 gene (DD), and the heterozygous genotype of normal and inactive ALDH2 genes (ND). The genetic polymorphism of CYP1A1 and CYP2E1 were also determined by restriction fragment length polymorphism (RFLP). A strong correlation between the personal exposure level and the urinary HA concentration was observed. Regression lines were calculated after being divided by the five factors, i.e., ALDH2, CYP1A1, CYP2E1, smoking, and drinking. The HA formation from toluene was significantly (p < 0.001) different among the genotypes of ALDH2. The slopes of the regression lines decreased from NN to ND to DD in this order. The benzyl alcohol concentration in the blood of the DD group was significantly higher than that found in the NN and ND groups. This result demonstrates that ALDH2 polymorphism affects the oxidation of benzyl alcohol to benzoic acid. The toluene metabolism was also affected by CYP1A1 polymorphism. The slope for the Ile/Ile (the predominant homozygous allele) group was significantly lower than that for the Ile/Val (the heterozygous allele) and Val/Val (the rare homozygous allele) group after correction for creatinine. A drinking habit significantly (p < 0.05) reduced urinary HA concentration in the NN group. A smoking habit also significantly (p < 0.05) reduced urinary uncorrected HA concentration in both the NN and ND groups. In a multiple regression analysis, ALDH2 and the drinking habit were significantly (p < 0.01) associated with HA excretion after toluene exposure with and without correction for creatinine, and the corrected HA concentration was also significantly (p < 0.01) increased in the Ile/Val and Val/Val group of CYP1A1. The smoking habit reduced the corrected HA concentration (p < 0.05); however, the polymorphism in the 5′-flanking region of CYP2E1 did not affect HA appearance in urine.

In this study, we evaluated the effects of the genetic polymorphism of ALDH2 (low Km aldehyde dehydrogenase) on toluene metabolism and determined biological exposure indices (BEIs) of the genotypes of ALDH2. The study subjects included 45 toluene workers and 122 nonexposed students. The genotype of ALDH2 was classified into the homozygous genotype of normal ALDH2 (NN), the homozygous genotype of an inactive one (DD), and the heterozygous genotype of normal and inactive ones (ND) by means of artificial-RFLP. The personal exposure levels to toluene were monitored, using diffusion type samplers and urinary hippuric acid (HA) and creatine concentrations were determined. The urinary HA levels of the three genotypes of ALDH2 of nonexposed students did not differ. In the toluene workers, positive correlations between the personal exposure to toluene and urinary HA levels were observed in the NN, ND, and DD groups. The urinary HA level of the DD group was significantly lower than that of the NN or ND group. Regression lines were used to estimate the BEIs of the NN, ND, and DD groups, which were approximately 2.9 g/g creatinine, 3.3 g/g creatinine, and 1.9 g/g creatinine, respectively.