Abstract：
:The goodness of fit of three PBPK models to data for inhalation uptake of 1,3-butadiene by mice from closed chambers were compared. These models included a classical flow-limited model with blood consolidated into arterial and venous compartments, a flow-limited model with implicit blood and alveolar compartments, and a model with an actual alveolar compartment and blood distributed among compartments for arterial, venous, and capillary spaces. Using physiological and biochemical parameters from the literature, all three models reproduced observed steady-state blood butadiene concentrations. However, the first two models predicted more rapid uptake of butadiene than was observed. Assumptions such as ignoring extrahepatic metabolism or reducing the ventilation rate by 75% were required to enable these models to fit the butadiene uptake data. The behavior of the third model resembled that of the other two models when the single-pass extraction ratio of butadiene for all tissues was close to 1, but the model did reproduce observed butadiene uptake when an extraction ratio of 0.5 was used. The difference in predictions of the three models was traced to smaller computed blood:tissue gradients and tissue butadiene concentrations, hence reduced rates of metabolic clearance, when the blood is distributed. These results suggest that the common assumption of flow limitation in the disposition of an inhaled gas may not always be appropriate. Because structurally different models can reproduce the same uptake data and all these models cannot be correct, the assumptions on which these models were based must be investigated experimentally to ensure that they are physiologically realistic.
journal_name
Toxicol Appl Pharmacoljournal_title
Toxicology and applied pharmacologyauthors
Kohn MCdoi
10.1006/taap.1997.8289subject
Has Abstractpub_date
1997-12-01 00:00:00pages
448-58issue
2eissn
0041-008Xissn
1096-0333pii
S0041-008X(97)98289-2journal_volume
147pub_type
杂志文章abstract：:Our previous studies in mice revealed that two weeks short-term toxicity of sodium selenosulfate was significantly lower than that of sodium selenite, but selenium repletion efficacy of both compounds was equivalent. In addition, we showed that sodium selenosulfate reduced nephrotoxicity of cisplatin (CDDP) without co...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2011.11.020
更新日期：2012-02-01 00:00:00
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journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1006/taap.2000.9036
更新日期：2000-11-01 00:00:00
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journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2017.12.010
更新日期：2018-01-15 00:00:00
abstract：:Organophosphorus esters (OP) are highly toxic chemicals used as pesticides and nerve agents. Their acute toxicity is attributed to inhibition of acetylcholinesterase (AChE, EC 3.1.1.7) in nerve synapses. Our goal was to find a new therapeutic for protection against OP toxicity. We used a gene therapy vector, adeno-ass...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2005.12.008
更新日期：2006-07-15 00:00:00
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journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
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journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1006/taap.1993.1105
更新日期：1993-06-01 00:00:00
abstract：:Speciation of arsenicals in biological samples is an essential tool to gain insight into its distribution in tissues and its species-specific toxicity to target organs. Biological samples (urine, hair, fingernail) examined in the present study were collected from 41 people of West Bengal, India, who were drinking arse...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2003.10.030
更新日期：2004-08-01 00:00:00
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journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/0041-008x(89)90111-7
更新日期：1989-06-01 00:00:00
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journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/s0041-008x(03)00259-x
更新日期：2003-10-01 00:00:00
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journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
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更新日期：2018-10-01 00:00:00
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journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2008.07.022
更新日期：2008-11-01 00:00:00
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journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
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更新日期：2005-02-15 00:00:00
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journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1006/taap.1996.0173
更新日期：1996-08-01 00:00:00
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journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1006/taap.1996.0078
更新日期：1996-04-01 00:00:00
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journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/0041-008x(86)90107-9
更新日期：1986-09-15 00:00:00
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journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2008.05.022
更新日期：2008-09-15 00:00:00
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journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1006/taap.1993.1150
更新日期：1993-08-01 00:00:00
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journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2006.12.035
更新日期：2007-04-15 00:00:00
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journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/0041-008x(87)90058-5
更新日期：1987-12-01 00:00:00
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journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/0041-008x(83)90186-2
更新日期：1983-08-01 00:00:00
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journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
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更新日期：2020-07-15 00:00:00
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journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1006/taap.1993.1039
更新日期：1993-03-01 00:00:00
abstract：:The present study examined the activation of protein kinase C (PKC) and disruption of Ca2+ homeostasis as potential mechanisms underlying effects of the polychlorinated biphenyl (PCB) congener 2,2'-dichlorobiphenyl (DCB) on inositol phosphate (IP) signaling in cerebellar granule cells. DCB (100 microM) increased basal...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1006/taap.1996.0311
更新日期：1996-12-01 00:00:00
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journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2007.08.015
更新日期：2008-01-01 00:00:00
abstract：:Triaryl phosphates including tricresyl phosphate (TCP) and butylated triphenyl phosphate (BTP) are organophosphates used in the commercial manufacture of plastics, lubricants, and hydraulic fluids. Rat steroidogenic tissues such as adrenocortical (AC), ovarian interstitial (OI), and Leydig cells use an intracellular p...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1006/taap.1993.1197
更新日期：1993-10-01 00:00:00
abstract：UNLABELLED:Acetaminophen (APAP) overdose causes severe hepatotoxicity in animals and humans. However, the mechanisms underlying the gender differences in susceptibility to APAP overdose in mice have not been clarified. In our study, APAP (300mg/kg) caused severe liver injury in male mice but 69-77% lower injury in fema...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2014.09.002
更新日期：2014-11-15 00:00:00
abstract：:The issue of Elongated Mineral Particles (EMP) in building materials has been revealed during roadworks in 2013 in France. In fact, road coating aggregates are made of specific rock gravels that can contain Naturally Occurring Asbestos (NOA), which is mainly actinolite. The legislation refers to six regulatory asbesto...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2018.04.027
更新日期：2018-12-15 00:00:00
abstract：:The sensory irritation potential of a series of saturated and unsaturated aliphatic and cyclic aldehydes was investigated in B6C3F1 and Swiss-Webster mice. With the reflex decrease in respiratory rate as the endpoint response, alpha, beta-unsaturated aliphatic aldehydes yielded RD50 values (concentration which elicits...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/0041-008x(84)90126-1
更新日期：1984-03-15 00:00:00
abstract：:4-Aminobiphenyl (4-ABP), an aromatic amine present in tobacco smoke, is an animal and human carcinogen. 4-ABP can undergo several biotransformation reactions to yield DNA-binding species. The role of acetylation in the biotransformation of 4-ABP to reactive intermediates was investigated by determining mutagenicity in...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1006/taap.1999.8727
更新日期：1999-09-01 00:00:00
abstract：:Biphasic dose-response relationship induced by environmental agents is often characterized with the effect of low-dose stimulation and high-dose inhibition. Some studies showed that arsenite may induce cell proliferation and apoptosis via biphasic dose-response relationship in human cells; however, mechanisms underlyi...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2006.12.021
更新日期：2007-04-01 00:00:00
