Abstract：
:An updated biokinetic model for human exposures to cobalt (Co) was developed based on a comprehensive set of human pharmacokinetics data collected from five male and five female volunteers who ingested ∼1 mg Co/day of a Co supplement for 3 months. Three key experimental observations from the human dosing studies were incorporated into the model: (1) an increase in the measured fraction of large molecular serum protein bound Co from 95% during dosing to 99% after dosing; (2) a linear decrease in Co red blood cell concentration after dosing; and (3) Co renal clearance consistent with estimated glomerular filtration rates and free Co²⁺ concentration. The model was refined by adding compartments accounting for (1) albumin bound Co in intravascular fluid (serum); (2) albumin bound Co in extravascular fluid with physiologic exchange rates of albumin bound Co between extravascular and intravascular fluid; and (3) a novel sequential cascade of compartments representing red blood cell ages between 1 and 120 days. Reasonable agreement between the modeled and measured urine, serum, and whole blood concentrations were observed (r>0.84, slope=0.79-1.0) with gastrointestinal absorption rates between 9% and 66%. In addition, model predictions agreed well with data from several external studies representing healthy human volunteers, dialysis patients, anephric patients, a Co-poisoning incident and whole body retention studies. Our revised model considerably improves the state of knowledge on human Co kinetics, and should be helpful for evaluating elevated blood Co concentrations in currently exposed populations, such as metal-on-metal (MoM) hip implant patients.
journal_name
Chem Biol Interactjournal_title
Chemico-biological interactionsauthors
Unice KM,Kerger BD,Paustenbach DJ,Finley BL,Tvermoes BEdoi
10.1016/j.cbi.2014.04.001subject
Has Abstractpub_date
2014-06-05 00:00:00pages
53-74eissn
0009-2797issn
1872-7786pii
S0009-2797(14)00118-5journal_volume
216pub_type
杂志文章abstract：:In the present study, the inhibition of human glutathione S-transferase P1-1 (GSTP1-1) by the flavonoid quercetin has been investigated. The results show a time- and concentration-dependent inhibition of GSTP1-1 by quercetin. GSTP1-1 activity is completely inhibited upon 1 h incubation with 100 microM quercetin or 2 h...
journal_title：Chemico-biological interactions
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doi：10.1016/s0009-2797(02)00250-8
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journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2018.01.007
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journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2008.05.037
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abstract：:Benzene exposure in occupational settings often occurs with concurrent exposure to toluene, the methyl-substituted derivative of benzene. Toluene is also readily metabolized by CYP450 isozymes although oxidation primarily occurs in the methyl group. While earlier mouse studies addressing co-exposure to benzene and tol...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2010.01.012
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journal_title：Chemico-biological interactions
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doi：10.1016/j.cbi.2018.04.021
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journal_title：Chemico-biological interactions
pub_type： 杂志文章,评审
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journal_title：Chemico-biological interactions
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doi：10.1016/0009-2797(79)90159-5
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journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2012.04.007
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journal_title：Chemico-biological interactions
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doi：10.1016/j.cbi.2018.11.003
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journal_title：Chemico-biological interactions
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doi：10.1016/0009-2797(83)90014-5
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journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/0009-2797(77)90093-x
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journal_title：Chemico-biological interactions
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doi：10.1016/j.cbi.2013.12.004
更新日期：2014-03-05 00:00:00
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journal_title：Chemico-biological interactions
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journal_title：Chemico-biological interactions
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doi：10.1016/j.cbi.2005.10.092
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journal_title：Chemico-biological interactions
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doi：10.1016/j.cbi.2009.06.016
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journal_title：Chemico-biological interactions
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journal_title：Chemico-biological interactions
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journal_title：Chemico-biological interactions
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doi：10.1016/j.cbi.2004.10.007
更新日期：2005-02-10 00:00:00
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journal_title：Chemico-biological interactions
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journal_title：Chemico-biological interactions
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journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2005.10.008
更新日期：2005-12-15 00:00:00
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journal_title：Chemico-biological interactions
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journal_title：Chemico-biological interactions
pub_type： 杂志文章
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journal_title：Chemico-biological interactions
pub_type： 杂志文章
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journal_title：Chemico-biological interactions
pub_type： 杂志文章
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更新日期：1999-12-15 00:00:00
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journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/0009-2797(82)90045-x
更新日期：1982-04-01 00:00:00
abstract：:Aromatic amines are important intermediates in industrial manufacturing. N-oxidation to the N-hydroxyarylamines is a key step determining the genotoxic properties of aromatic amines. N-hydroxyarylamines can form adducts with DNA, with tissue proteins and with the blood proteins albumin and hemoglobin in a dose-depende...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/0009-2797(92)90029-k
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