Abstract:
:Studies conducted by the National Toxicology Program on the chronic toxicity of benzene indicated that B6C3F1 mice were more sensitive to the carcinogenic effects of benzene than were F344 rats. A physiological model was developed to describe the uptake and metabolism of benzene in rats and mice. Our objective was to determine if differences in toxic effects could be explained by differences in pathways for benzene metabolism or by differences in total uptake of benzene. Compartments incorporated into the model included liver, fat, a poorly perfused tissue group, a richly perfused tissue group, an alveolar or lung compartment and blood. Metabolism of benzene was assumed to take place only in the liver and to proceed by four major competing pathways. These included formation of hydroquinone conjugates (HQC), formation of phenyl conjugates (PHC), ring-breakage and formation of muconic acid (MUC), and conjugation with glutathione with subsequent mercapturic acid (PMA) formation. Values for parameters such as alveolar ventilation, cardiac output, organ volumes, blood flow, partition coefficients, and metabolic rate constants were taken from the literature. Model simulations confirmed that during and after 6-hr inhalation exposures mice metabolized more benzene on a mumole per kilogram body weight basis than did rats. After oral exposure, rats metabolized more benzene than mice at doses above 50 mg/kg because of the more rapid absorption and exhalation of benzene by mice. Model simulations for PHC and PMA, generally considered to be detoxification metabolites, were similar in shape and dose-response to those for total metabolism.(ABSTRACT TRUNCATED AT 250 WORDS)
journal_name
Environ Health Perspectjournal_title
Environmental health perspectivesauthors
Medinsky MA,Sabourin PJ,Henderson RF,Lucier G,Birnbaum LSdoi
10.1289/ehp.898243subject
Has Abstractpub_date
1989-07-01 00:00:00pages
43-9eissn
0091-6765issn
1552-9924journal_volume
82pub_type
杂志文章abstract::Scaling of the quantified dispositional parameters of xenobiotics from animals to man is of interest from the standpoint of toxicology (e.g., poisoning and risk assessment). Scaling is also important from the standpoint of therapeutics because it represents a strategy for predicting first-use-in-human doses in clinica...
journal_title:Environmental health perspectives
pub_type: 杂志文章,评审
doi:10.1289/ehp.96104400
更新日期:1996-04-01 00:00:00
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journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.7826275
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journal_title:Environmental health perspectives
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doi:10.1289/ehp.961041084
更新日期:1996-10-01 00:00:00
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更新日期:1999-06-01 00:00:00
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journal_title:Environmental health perspectives
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更新日期:2006-05-01 00:00:00
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journal_title:Environmental health perspectives
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doi:10.1289/ehp.02110721
更新日期:2002-07-01 00:00:00
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journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.782337
更新日期:1978-04-01 00:00:00
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journal_title:Environmental health perspectives
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doi:10.1289/ehp.814245
更新日期:1981-12-01 00:00:00
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更新日期:2004-07-01 00:00:00
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pub_type: 杂志文章
doi:10.1289/ehp.834819
更新日期:1983-02-01 00:00:00
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doi:10.1289/ehp.99107s4605
更新日期:1999-08-01 00:00:00
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journal_title:Environmental health perspectives
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doi:10.1289/ehp.7826121
更新日期:1978-10-01 00:00:00
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doi:10.1289/ehp.834993
更新日期:1983-03-01 00:00:00
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更新日期:2012-05-01 00:00:00
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journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.11367
更新日期:2008-12-01 00:00:00
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更新日期:1998-06-01 00:00:00
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更新日期:2009-07-01 00:00:00
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journal_title:Environmental health perspectives
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doi:10.1289/ehp.8353169
更新日期:1983-11-01 00:00:00
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journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.97105734
更新日期:1997-07-01 00:00:00
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journal_title:Environmental health perspectives
pub_type: 杂志文章
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更新日期:1996-05-01 00:00:00
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journal_title:Environmental health perspectives
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doi:10.1289/ehp.8454249
更新日期:1984-03-01 00:00:00
abstract::Polychlorinated biphenyls (PCBs) are important environmental contaminants, and their toxicity to wildlife and humans are of major concern. PCBs form persistent and abundant metabolites, PCB methyl sulfones, that accumulate in biota. We now report that certain hydroxylated PCB metabolites show a strong and selective ac...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.94102464
更新日期:1994-05-01 00:00:00
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doi:10.1289/ehp.011091145
更新日期:2001-11-01 00:00:00
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更新日期:2005-08-01 00:00:00
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journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/EHP6301
更新日期:2020-05-01 00:00:00
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journal_title:Environmental health perspectives
pub_type: 杂志文章,评审
doi:10.1289/ehp.95103s729
更新日期:1995-10-01 00:00:00