Mechanisms of benzene carcinogenesis: application of a physiological model of benzene pharmacokinetics and metabolism.
A physiological pharmacokinetic model for benzene, incorporating metabolic transformations, is used to explore why benzene, but not phenol--its primary metabolite--is carcinogenic at many sites in rats. The model has been parametrized using in vitro or in vivo experimental data. Ranges, rather than fixed values, were assigned to the parameters. The model-predicted levels of phenol and hydroquinone in the tissues are consistently higher when phenol, rather than benzene, is administered. This result demonstrates that the differential carcinogenicity of the two compounds is not explainable in the context of this pharmacokinetic analysis. It also indicates that the phenol-hydroquinone pathway alone is unlikely to account for the carcinogenic effects of benzene. Other metabolites must therefore also be involved.
Bois
F Y
FY
Biomedical and Environmental Health Sciences, School of Public Health, University of California, Berkeley 94720.
Smith
M T
MT
Spear
R C
RC
D000280:Administration, Inhalation; D000818:Animals; D001554:Benzene / Q000378:metabolism / Q000493:pharmacokinetics / Q000633:toxicity*; D002138:Calibration; D006873:Hydroquinones / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008297:Male; D008954:Models, Biological; D009010:Monte Carlo Method; D009374:Neoplasms, Experimental / Q000139:chemically induced; D010636:Phenols / Q000493:pharmacokinetics; D051381:Rats; D011916:Rats, Inbred F344; D011919:Rats, Inbred Strains
D006873:Hydroquinones; D010636:Phenols; D001554:Benzene; C031927:hydroquinone