New approaches to the metabolism of xylenes: verification of the formation of phenylmercapturic acid metabolites of xylenes.
It was the aim of this study to ascertain whether xylenes form phenylmercapturic acids via aromatic epoxides in the human metabolism. Aromatic epoxides are suspected to exert mutagenic properties. Therefore we developed an LC/MS/MS procedure for the determination of these mercapturic acids. Using this method we were able to detect dimethylphenylmercapturic acid (DPMA) in urine samples of persons occupationally exposed to xylenes. The unequivocal LC/MS/MS detection of phenylmercapturic acid metabolites of xylene thanks to authentic standards was verified with an independent GC/MS method. Xylene concentrations in the air of the workplaces ranged between 0.7 and 58.1 ppm (median 12.6 ppm). The excretion of methylhippuric acid in the urine samples of the workers (n=27) ranges from 19.8 to 2332.5 mg/l (median 450.9 mg/l). DPMA was detected in only 9 samples of 27 exposed persons. According to a rough calculation DPMA is only formed in a ratio of 0.0003% respective to the xylene main metabolite MHA. That means that even under occupationally relevant xylene exposure potential mutagenic potencies should be negligible. DPMA in urine is not sensitive enough for general biomonitoring purposes due to the low ratio of excretion. MHA should therefore be used for biomonitoring from now on. Furthermore, our results show that irrespective of the structure of xylene isomers there is no preferences in metabolism.
Gonzalez-Reche
Luis Mariano
LM
Institut und Poliklinik für Arbeits-, Sozial- und Umweltmedizin, Friedrich-Alexander Universität Erlangen-Nürnberg, Schillerstrasse 25, Germany.
Schettgen
Thomas
T
Angerer
Jürgen
J
D000111:Acetylcysteine / Q000031:analogs & derivatives* / Q000032:analysis / Q000378:metabolism*; D000328:Adult; D000395:Air Pollutants, Occupational / Q000032:analysis / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D004784:Environmental Monitoring / Q000379:methods*; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D008297:Male; D008875:Middle Aged; D016273:Occupational Exposure; D015203:Reproducibility of Results; D014992:Xylenes / Q000378:metabolism*
D000395:Air Pollutants, Occupational; D014992:Xylenes; C053003:S-phenyl-N-acetylcysteine; D000111:Acetylcysteine