Objective: Ethylbenzene is an important constituent of widely used solvent
mixtures in industry. The objective of the present study was to provide inf
ormation about biological monitoring of occupational exposure to ethylbenze
ne, and to review the biological limit values corresponding to the threshol
d limit value of ethylbenzene. Methods: A total of 20 male workers who had
been exposed to a mixture of ethylbenzene and xylene, through painting and
solvent mixing with commercial xylene in a metal industry, were recruited i
nto this study. Environmental and biological monitoring were performed duri
ng an entire week. The urinary metabolites monitored were mandelic acid for
ethylbenzene and methylhippuric acid for xylene. Correlations were analyze
d between urinary metabolites and environmental exposure for ethylbenzene a
nd xylene. The interaction effects of a binary exposure to ethylbenzene and
xylene were also investigated using a physiologically based pharmacokineti
c (PBPK) model. Results: The average environmental concentration of organic
solvents was 12.77 ppm for xylene, and 3.42 ppm for ethylbenzene. A signif
icant correlation (R-2 = 0.503) was found between environmental xylene and
urinary methylhippuric acid. Urinary level of methylhippuric acid correspon
ding to 100 ppm of xylene was 1.96 g/g creatinine in the worker study, wher
eas it was calculated as 1.55 g/g creatinine by the PBPK model. Urinary lev
el of mandelic acid corresponding to 100 ppm of ethylbenzene was found to b
e 0.7 g/g creatinine. PBPK results showed that the metabolism of ethylbenze
ne was highly depressed by co-exposure to high concentrations of xylene lea
ding to a non-linear behavior. Conclusions: At low exposures, both methylhi
ppuric acid and mandelic acid can be used as indicators of commercial xylen
e exposures. However at higher concentrations mandelic acid cannot be recom
mended as a biological indicator due to the saturation of mandelic acid pro
duced by the co-exposure to xylene.