[Excretion kinetics of phenylhydroxyethyl mercapturic acids (PHEMAs), ethanol consumption, and chronic exposure to styrene: preliminary data on humans].
Styrene (S) is a widely used aromatic hydrocarbon, responsible for several adverse effects. In humans, the metabolism of S is well characterized: besides the major metabolites (mandelic and phenylglyoxylic acid), a minor metabolic pathway leads to phenylhydroxyethyl mercapturic acids (PHEMAs) [N-acetyl-S-(1-phenyl-2-hydroxyethyl)-L-cysteine (M1) and N-acetyl-S-(2-phenyl-2-hydroxyethyl)-L-cysteine (M2)], that are potentially useful for biomonitoring purposes. A pilot study on a volunteer exposed under controlled conditions to S, with or without ethanol administration, allowed us to characterize the excretion profile of PHEMAs and the ethanol-induced interference on PHEMAs metabolic pathway. We further considered a group of 9 workers exposed to S during the working week to determine the confounding role of chronic exposure. Our results confirm the wide interindividual variability of both the biotransformation rate of S into PHEMAs and of the excretion rate of these metabolites. Moreover, both the above parameters changed during the working week, suggesting the existence of a large intraindividual variability as a consequence of the exposure to S and to other solvents. As a practical rule, the data indicate that it is necessary to collect samples at the beginning of the working week when studies on the correlation between genotype and phenotype are carried out. Finally, the results emphasise the importance of excluding an even extemporary ethanol assumption when practicing a biological monitoring programme based on the determination of urinary PHEMAs.
Negri
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Laboratorio per lo Studio e il Monitoraggio dell'Esposizione a Inquinanti Aeriformi (LabS-MEIA), Fondazione Salvatore Maugeri I.R.C.C.S., Pavia, Italy. snegri@fsm.it
Ferrari
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M
Maestri
L
L
Ghittori
S
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Imbriani
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D000111:Acetylcysteine / Q000652:urine*; D001711:Biotransformation; D003404:Creatinine / Q000652:urine; D003627:Data Interpretation, Statistical; D004784:Environmental Monitoring; D000431:Ethanol / Q000009:adverse effects*; D006038:Glyoxylates; D006801:Humans; D008333:Mandelic Acids; D008962:Models, Theoretical; D016273:Occupational Exposure / Q000009:adverse effects*; D010865:Pilot Projects; D011102:Polyhydroxyethyl Methacrylate / Q000378:metabolism; D020058:Styrene / Q000009:adverse effects* / Q000378:metabolism*; D013997:Time Factors
D006038:Glyoxylates; D008333:Mandelic Acids; D011102:Polyhydroxyethyl Methacrylate; C012482:phenylglyoxylic acid; D000431:Ethanol; D020058:Styrene; D003404:Creatinine; D000111:Acetylcysteine