Determination of S-phenylmercapturic acid in the urine—an improvement in the biological monitoring of benzene exposure

Abstract

In an inhalation study rats were exposed to different doses of benzene, ranging from 1 to 500 p.p.m. The urine was sampled during the inhalation period of 8 h and for 24 h after exposure. S-Phenylmercapturic acid (S-PMA) in the urine was determined by amino acid analysis. Phenol was measured by gas chromatography/mass spectrometry. In both cases the correlation between benzene uptake and the excretion of the urinary metabolites was significant at the level of P = 0.01. The same significant correlation (P = 0.01) was demonstrable after i.p. administration of benzene at doses between 0.7 and 140.0 microliters/kg body weight. In the case of two collectives of workers who were exposed to air concentrations of up to 0.15 p.p.m. for 8 h and of up to 1.13 p.p.m. for 12 h respectively, the amount of S-PMA in the first urine samples after the shift was significantly higher than in samples collected at the beginning of the shift (P = 0.01). In the first collective the mean values and the standard deviations of the S-PMA concentrations in the samples at the beginning of the shift were 12.0 +/- 16.7 compared with 48.5 +/- 64.5 micrograms/g creatinine at shift end. In the second collective they were 25.1 +/- 25.1 compared with 70.9 +/- 109.2 micrograms/g creatinine. The level of significance of the difference between the concentration values of S-PMA at the beginning and end of the shift was P = 0.01. The phenol concentration did not differ significantly. These results suggest that S-PMA can be regarded as a useful indicator for monitoring individuals and collectives exposed to benzene at levels even less than 1 p.p.m.

Urinary Phenylmercapturic Acid as a Marker of Occupational Exposure to Benzene.

“…This study group has been studying on urinary biomarkers of occupational exposure to benzene such as catechol 10) , quinol 10) , 1,2,4-benzenetriol 11,12) as well as t,t-muconic acid 13) in addition to a traditional marker of phenol 14) . Urinary phenylmercapturic acid (PMA; N-acetyl-S-phenyl-L-cysteine), a N-acetylcysteine conjugate of benzene, has also been evaluated as a marker of exposure to low-level benzene 8,9,[15][16][17][18][19][20] , but the analytical methods employed are rather complex, e.g., requiring derivatization or clean-up through columns before instrumental analysis [21][22][23][24][25] such as gas chromatography-mass spectrometry 15) or liquid chromatography-mass spectrometry 26) , and application of the methods to routine occupational health services appear to be not practical.…”

Biological monitoring of occupational exposure to low levels of benzene.

“…Methods based on its urinary metabolites, such as phenol and the newly proposed trans, trans-muconic acid (4,5), are nonspecific because these compounds are also generated from sources other than benzene. S-phenylmercapturi c acid in urine is reported to be useful in monitoring exposures even below benzene concentrations of I cm 3 • m-3 (6). The analytical method is, however, too complicated for routine monitoring purposes .…”

On cancer risk estimation of urban air pollution

“…In epidemiological studies, exposure to motor exhausts has been associated with a raised incidence of tumors other than lung cancer, mainly bladder cancer (possibly with nitroarenes in diesel exhausts as a causative factor) and multiple myeloma (56). Chimney sweeps exhibit a raised incidence of cancer of several types, with inhaled PAH being assumed to be a main etiological factor (57 (63, unpublished data from this laboratory), and DNA and hemoglobin adducts have been observed only recently (64,65). One reason for these difficulties may be that genotoxic metabolites are bound predominantly to S9 proteins in the test medium because of high reactivity, as seen when radiolabeled benzene is used (unpublished data).…”