CYP2E1 expression in bone marrow and its intra- and interspecies variability: approaches for a more reliable extrapolation from one species to another in the risk assessment of chemicals.

When characterizing the health risks for man by exposure to chemicals, species-specific differences have to be taken into consideration, otherwise extrapolation from animal data to the human situation would be inadequate. The site-specific toxicity of chemicals may be explained by the following alternatives: (1) reactive metabolites are generated in the liver and subsequently transported to the target tissue(s); (2) metabolism of the parent compound occurs in the target tissue, a pathway by which the enzymes necessary for activation must be expressed in the target tissue. Cytochrome P450 2E1 (CYP2E1) is an important phase-I enzyme activating several chemicals.

CYP2E1-dependent benzene toxicity: the role of extrahepatic benzene metabolism.

Benzene, a ubiquitous environmental pollutant, is haematotoxic and myelotoxic. As has been shown earlier, cytochrome P450 2E1 (CYP2E1)-dependent metabolism is a prerequisite for the cytotoxic and genotoxic effects of benzene, but which of the benzene metabolites produces toxicity is still unknown. The observed differences between the toxicity of benzene and that of phenol, a major metabolite of benzene, could be explained by alternative hypotheses.

Quantitation of R- and S-propafenone and of the main metabolite in plasma.

Several methods for the determination of racemic propafenone or its enantiomers as well of the main metabolite R,S-5-hydroxypropafenone are known from the literature. The method described here enables the simple simultaneous quantification of R- and S-propafenone and of R,S-5-hydroxypropafenone in human plasma. The method is based on an HPLC separation using a Chiralpak AD column.