CYP2E1 phenotype in Mexican workers occupationally exposed to low levels of toluene

Abstract

CYP2E1, an inducible enzyme present in different human tissues, metabolizes several potentially toxic substances including many volatile organic compounds (VOCs). One indirect way to monitor exposure to VOCs may be, therefore, the assessment of CYP2E1 activity in vivo using the chlorzoxazone (CHZ) test.

Goal: To compare CYP2E1 activity in two groups of workers: one with a known occupational exposure to VOCs (exposed group) and the other employed in administrative tasks at two universities (control group) from the city of León, Guanajuato, México.

Material and methods: (1) Passive diffusion monitors were used to evaluate individual levels of exposure to toluene, benzene and ethylbenzene in 48 persons (24 tannery workers and 24 administrative controls) during a 8h work shift; (2) after 12h fasting 500mg CHZ, a selective probe for assessing CYP2E1 activity, was orally administered and, after 2h, a venous blood sample was collected for HPLC plasmatic quantitative determination of CHZ and its mean metabolite 6-hydroxychlorzoxazone.

Results: Toluene mean exposure levels were higher in the exposed group (2.86±2ppm vs. 0.05±0.005ppm; p<0.001). Also, in this group CYP2E1 activity was lower (p<0.05) and it decreased as the accumulated months of labor exposure increased (negative correlation, p<0.05). These results are in line with previous findings obtained from shoemakers exposed to various solvents but, interestingly, they are partly in contrast with those of another study in printers.

Conclusion: In spite of the relatively low levels of toluene exposure found for tannery workers, an effect on CYP2E1 activity was evident. Although the mechanism of this interaction is still unknown, the decrease in CYP2E1 activity per se might represent a health risk, considering that these workers may be less protected against other CYP2E1 substrates present in the labor setting or derived from an intentional exposure.