RR190 - Inter-individual variability in the interpretation of biological monitoring guidance values
The incorporation of inter-individual differences in the setting of occupational exposure standards such as biological monitoring guidance values has been studied by investigating the possibility of transferring in vitro measurements of variability in metabolism to the in vivo situation. The generation of generic information on the activity of two major enzymes systems considered important in the metabolism of industrial chemicals, was investigated by using 'probe' substrates. Variability in the activities of cytochromes P450 1A2 and 2E1, and the cytosolic glutathione transferases µ and q were measured in human hepatocytes, hepatic microsomes and cytosols. Variability in the metabolism of styrene, a chemical of industrial importance, was also measured for comparison. The ability to use in vitro data to simulate in vivo variability was investigated by incorporating in vitro data into a PBPK model for styrene.
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