Urinary excretion of mandelic, phenylglyoxylic, and specific mercapturic acids in rats exposed repeatedly by inhalation to various concentrations of styrene vapors

Adult male Sprague-Dawley rats were exposed by inhalation to various concentrations of styrene vapors (25, 50, 100, or 200 ppm) 6 h/day, 5 days/week, for 4 consecutive weeks. The concentrations were varied from day to day according to a random pattern allowing treated animals to be exposed five times to each concentration of styrene. Each day, the following urinary metabolites were analysed from samples collected during exposure (0-6 h) and after exposure (6-24 h): mandelic acid; phenylglyoxylic acid; and two mercapturic acids, N-acetyl-S-(1-phenyl-2-hydroxyethyl)-L-cysteine (M1) and N-acetyl-S-(2-phenyl-2-hydroxyethyl)-L-cysteine (M2). Various parameters of renal toxicity and hepatic microsomal and cytosolic enzyme activities were also measured. The results show that there is a very good relationship between the excretion of all four styrene metabolites and the degree of daily exposure to styrene over the entire period of urine collection, with correlation coefficients ranging from 0.82 to 0.98. The correlation was poor for mandelic acid during the 0-6 h period. There was no evidence that repeated exposure to styrene caused renal toxicity, nor induced hepatic microsomal enzyme activities; cytosolic glutathione S-transferase activity was increased moderately by 1.5 times. Thus, under conditions of exposure to styrene likely to be found in the workplace, all four metabolites measured were good indicators of styrene exposure throughout the length of the experiment. Since mercapturic acids result from the conjugation of styrene oxide with glutathione, the data suggest that measurement of these metabolites offers the possibility to monitor internal exposure to a toxic electrophilic compound more directly.