Predicting cancer risk from vinyl chloride exposure with a physiologically based pharmacokinetic model
| Autor: | W.M. Provan, Michael L. Gargas, Melvin E. Andersen, Richard H. Reitz, Trevor Green |
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| Rok vydání: | 1996 |
| Předmět: |
Male
Physiologically based pharmacokinetic modelling medicine.medical_specialty Hemangiosarcoma Vinyl Chloride Mice Inbred Strains Pharmacology Toxicology Models Biological Risk Assessment Vinyl chloride Rats Sprague-Dawley chemistry.chemical_compound Mice Pharmacokinetics Predictive Value of Tests Neoplasms medicine Toxicokinetics Animals Humans Angiosarcoma Chemistry Incidence Liver Neoplasms Reproducibility of Results Neoplasms Experimental Stimulation Chemical Surgery Rats Toxicity Carcinogens Female Rabbits Cancer risk Liver Angiosarcoma |
| Zdroj: | Toxicology and applied pharmacology. 137(2) |
| ISSN: | 0041-008X |
| Popis: | A physiologically based pharmacokinetic (PBPK) model capable of describing the metabolism of vinyl chloride (VC) in rats, mice, and humans has been developed and validated by comparison with experimental data from experiments not used in model development. This PBPK model has been used to predict measures of delivered dose (reactive VC metabolites produced in the livers of the affected species) hypothesized to be involved in the induction of liver angiosarcoma in rats, mice, and human populations exposed to VC. Measures of delivered dose in rats were fit to an empirical dose-response model (the linearized multistage model of Crump et al.) and used to make predictions of liver angiosarcoma incidence in mice and human populations exposed to VC. This procedure gave a good prediction of angiosarcoma incidence in mice. Predictions of angiosarcoma incidence in humans were more than two orders of magnitude lower than risk estimations which did not utilize pharmacokinetic data, but were still almost an order of magnitude higher than actually observed in exposed human populations. |
| Databáze: | OpenAIRE |
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