Abstract：
:When used in the risk assessment process, the output from physiologically based pharmacokinetic (PBPK) models has usually been considered as an exact estimate of dose, ignoring uncertainties in the parameter values used in the model and their impact on model predictions. We have collected experimental data on the variability of key parameters in a PBPK model for tetrachloroethylene (PCE) and have used Monte Carlo analysis to estimate the resulting variability in the model predictions. Blood/air and tissue/blood partition coefficients and the interanimal variability of these data were determined for tetrachloroethylene (PCE). The mean values and variability for these and other published model parameters were incorporated into a PBPK model for PCE and a Monte Carlo analysis (n = 600) was performed to determine the effect on model predicted dose surrogates for a PCE risk assessment. For a typical dose surrogate, area under the blood time curve for metabolite in the liver (AUCLM), the coefficient of variation was 25% and the mean value for AUCLM was within a factor of two of the maximum and minimum values generated in the 600 simulations. These calculations demonstrate that parameter uncertainty is not a significant potential source of variability in the use of PBPK models in risk assessment. However, we did not in this study consider uncertainties as to metabolic pathways, mechanism of carcinogenicity, or appropriateness of dose surrogates.
journal_name
Toxicol Lettjournal_title
Toxicology lettersauthors
Gearhart JM,Mahle DA,Greene RJ,Seckel CS,Flemming CD,Fisher JW,Clewell HJ 3rddoi
10.1016/0378-4274(93)90126-isubject
Has Abstractpub_date
1993-05-01 00:00:00pages
131-44issue
1-2eissn
0378-4274issn
1879-3169pii
0378-4274(93)90126-Ijournal_volume
68pub_type
杂志文章abstract：:The impact of organophosphorus compound (OP) intoxication on the activity of central respiratory circuitry, causing acetylcholinesterase (AChE) inhibition and accumulation of acetylcholine in the respiratory brainstem circuits, is not understood. We investigated the central effect of the OP Crotylsarin (CRS) on respir...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2011.07.005
更新日期：2011-09-25 00:00:00
abstract：:Administration of carcinogenic doses of urethane to male rats (for 30 days) and to females (for 45 days) caused degranulation of microsomes of livers and lungs to approx. 15 and 35%, respectively. The cholesterol levels also declined more than 50% in urethane-treated rats when compared with controls. Studies on struct...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/0378-4274(83)90170-4
更新日期：1983-01-01 00:00:00
abstract：:The industrial solvent dioxane (1,4-diethylene dioxide) was evaluated for teratogenic potential in Sprague-Dawley rats. The compound was administered on days 6-15 of gestation by gavage (0, 0.25, 0.5 and 1.0 ml/kg/day). A slight maternal toxicity, as evidenced by reduced weight gain, was observed with 1.0 ml/kg. Anima...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/0378-4274(85)90189-4
更新日期：1985-07-01 00:00:00
abstract：:Chloropicrin is an aliphatic volatile nitrate compound that is mainly used as a pesticide. It has several toxic effects in animals and can cause irritating and other health problems in exposed humans. Since the mode of chloropicrin action is poorly understood, the aim of this study was to investigate molecular respons...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2012.04.002
更新日期：2012-06-20 00:00:00
abstract：OBJECTIVES:Reactivation of inhibited acetylcholinesterase (AChE) with oximes is a causal therapy of intoxication with organophosphorus compounds (OPs). Maximal oxime effects are expected when effective doses are administered as soon as possible and as long as reactivation can be anticipated. An obidoxime plasma level i...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2010.06.005
更新日期：2010-09-01 00:00:00
abstract：:Toluene, an industrial organic solvent, is voluntarily inhaled as drug of abuse. Because inhibition of N-methyl-d-aspartate (NMDA) receptors is one of the possible mechanisms underlying developmental neurotoxicity of toluene, the purpose of the present study was to examine the effects of toluene exposure during two ma...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2011.06.026
更新日期：2011-09-10 00:00:00
abstract：:Chlordecone is an organochlorine used in the 1970's as a pesticide in banana plantations. It has a long half-life in the soil and can potentially contaminate humans and animals through food. Chlordecone targets, and mainly accumulates in, the liver, leading to hepatomegaly and neurological signs in mammals. Chlordecon...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2018.09.014
更新日期：2018-12-15 00:00:00
abstract：:This study was designed to compare the pulmonary cellular proliferative effects of inhaled, size-separated preparations of chrysotile asbestos fibres with similar aerosol fibre concentrations of para-aramid fibrils. Following fibre preparation, rats were exposed for 2 weeks to aerosols of p-aramid fibrils or chrysotil...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/0378-4274(96)03751-4
更新日期：1996-11-01 00:00:00
abstract：:Regions with heavy industry are in many ways regions of crisis. The health of the population is primarily affected by the different air pollutants. Dust, with all its organic (dioxins and furans) and inorganic (heavy metals) contents, makes up the greatest part of the air-borne pollutants. The influence on health of e...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/0378-4274(96)03731-9
更新日期：1996-11-01 00:00:00
abstract：:Organophosphate flame retardants (OPFRs) have been used in a wide variety of applications and detected in several environmental matrices, including indoor air and dust. Continuous human exposure to these chemicals is of growing concern. In this study, the agonistic and/or antagonistic activities of 12 primary OPFR-met...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2016.01.004
更新日期：2016-03-14 00:00:00
abstract：:Guidelines concerning the preclinical safety assessment of therapeutic proteins are available, e.g. in the European Community (EC Notes for Guidance). Unlike rather rigidly prescribing test systems such as those known for chemical substances, it is agreed that for biotechnologically-produced products, testing may be q...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/0378-4274(92)90206-y
更新日期：1992-12-01 00:00:00
abstract：:This study demonstrates an intraspecies difference in elimination of methylmercury between two genetic variant strains of mice. Following a single non-toxic dose of 203Hg labeled methylmercury (0.5 mg Hg/kg i.p.), the half-time of 203Hg elimination in the CBA/J inbred strain was 7.4 days compared to 3.0 days in the CF...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/0378-4274(80)90114-9
更新日期：1980-10-01 00:00:00
abstract：:Chronic exposure to arsenic increases the risk of developing a variety of human cancers including lung carcinomas. However, the exact molecular mechanism underlying arsenic carcinogenicity remains largely unknown. Autophagy is a conserved catabolic process for maintaining cellular protein homeostasis whose defects mig...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2020.06.006
更新日期：2020-10-10 00:00:00
abstract：:The clinical use of gentamicin (G) is limited because of its nephrotoxic potential. The administration of G (50 mg/kg) to rats in a 10-day daily treatment gave a biphasic pattern of lactate dehydrogenase (LDH) and N-acetyl-beta-D-glucosaminidase (NAG) excretion. Alkaline phosphatase (ALP) was highly elevated during th...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/0378-4274(94)03163-2
更新日期：1995-01-01 00:00:00
abstract：:The binding of bisphenol A (BPA) and its halogenated derivatives (halogenated BPAs) to mouse peroxisome proliferator-activated receptor α ligand binding domain (mPPARα-LBD) was examined by a combination of in vitro investigation and in silico simulation. Fluorescence polarization (FP) assay showed that halogenated BPA...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2017.11.004
更新日期：2018-02-01 00:00:00
abstract：:Goniothalamin, a styryllactone, has been shown to induce cytotoxicity via apoptosis in several tumor cell lines. In this study, we have examined the potential role of several genes, which were stably transfected into T-cell lines and which regulate apoptosis in different ways, on goniothalamin-induced cell death. Over...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2009.08.012
更新日期：2009-12-15 00:00:00
abstract：:Two groups of C57BL/6J mice received a single oral dose of 1 nmol/kg 2,3,7,8-[3H]tetrachlorodibenzo-p-dioxin (TCDD) alone or in combination with 300 mumol/kg 2,2',4,4',5,5'-hexachlorobiphenyl (HxCB). The disposition of TCDD in liver, fat, skin, spleen, lung and blood was studied at days 3, 7, 13 and 34 after dosage. H...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/0378-4274(95)03387-z
更新日期：1995-10-01 00:00:00
abstract：:The effect of sodium selenite administered acutely or repeatedly on the biochemical components of the hepatic microsomal monooxygenase enzyme system was examined in male rats. 72 h following acute administration of selenium (2.4 mg Se/kg, i.p.), there was a significant decrease in ethylmorphine-N-demethylase activity ...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/0378-4274(83)90057-7
更新日期：1983-06-01 00:00:00
abstract：:Sulfur dioxide (SO2) is a ubiquitous air pollutant, presents in low concentrations in the urban air, and in higher concentrations in the working environment. In the present study, male Wistar rats were housed in exposure chambers and treated with 14.00+/-1.53, 28.00+/-2.12 and 56.00+/-4.28 mg/m3 SO2 for 6 h/day for 7 ...
journal_title：Toxicology letters
pub_type： 杂志文章,随机对照试验
doi：10.1016/j.toxlet.2005.06.002
更新日期：2005-12-30 00:00:00
abstract：:In the olfactory epithelium the primary olfactory neurons are in contact with the environment in the nasal cavity and they are also connected to the olfactory bulbs of the brain. These neurons may therefore provide a pathway by which foreign materials may reach the brain. Inhalation of cobalt-containing dust or fumes ...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/s0378-4274(03)00266-2
更新日期：2003-11-01 00:00:00
abstract：:Elevated urinary trehalase activity was observed in the inhabitants of the Jinzu River basin. Urinary trehalase activity was correlated with other urinalysis components, such as beta 2-microglobulin, glucose, amino nitrogen, and cadmium, of which a high level was observed in cadmium-polluted areas as compared with the...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/0378-4274(86)90206-7
更新日期：1986-12-01 00:00:00
abstract：:This paper reviews the results from past regulatory and mechanistic inhalation studies in rats with the type II pyrethroid Cyfluthrin. Apart from many chemical irritants, Cyfluthrin was shown to be a neuroexcitatory agent without any inherent tissue-destructive or irritant property. Thus, any Cyfluthrin-induced neuroe...
journal_title：Toxicology letters
pub_type： 杂志文章,评审
doi：10.1016/j.toxlet.2017.10.003
更新日期：2018-01-05 00:00:00
abstract：:Two groups, each of 4 rabbits, 17 and 4 months old, respectively, were given s.c. administrations of cadmium (Cd) at a dose level of 0.5 mg/kg/day 6 times per week for up to 32 weeks. In 17-month-old rabbits, low-molecular-weight proteinuria appeared in the 3rd week, proteinuria, glycosuria and anemia in the 6th week;...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/0378-4274(80)90123-x
更新日期：1980-09-01 00:00:00
abstract：OBJECTIVE:The aim of this investigation was to identify pathways involved in pneumoconiosis susceptibility, clarify their potential mechanisms, and generate SNP-to-gene to pathway hypotheses using an analytical pathway-based approach. METHODS:The identify candidate causal SNPs and pathways (ICSNPathway) was used to pe...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2014.10.028
更新日期：2015-01-05 00:00:00
abstract：:This study describes two phases of a multi-phase project aiming to validate a mouse model for cow's milk allergy to assess the potential allergenicity of hydrolysed cow's milk based infant formulas (claim support EC-directive 2006/141/E). The transferability and the discriminatory power of this model was evaluated in ...
journal_title：Toxicology letters
pub_type： 杂志文章,多中心研究
doi：10.1016/j.toxlet.2013.04.008
更新日期：2013-06-20 00:00:00
abstract：:The disposition of methanol and its putative toxic metabolite formate has been studied in humans, non-human primates, and rodents after exposure to high, neurotoxic doses. The rate at which rodents detoxify formate is more rapid than that of primates. Formate, an endogenous biological substrate, is detoxified by metab...
journal_title：Toxicology letters
pub_type： 杂志文章,评审
doi：10.1016/0378-4274(95)03515-x
更新日期：1995-12-01 00:00:00
abstract：:In the present study, the emetic effect of the anticancer drug cisplatin, and protective effects of 5-HT3 receptor antagonists against cisplatin emesis were investigated in the pigeon. The experimental setting involved the i.v. administration of drugs and subsequent observation of the percentage of vomiting animals an...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/0378-4274(92)90256-j
更新日期：1992-12-01 00:00:00
abstract：:Sister-chromatid exchanges (SCEs) were analyzed from peripheral lymphocyte cultures of 8 men and 16 women who had been exposed to environmental cadmium (Cd), and 6 controls. Average Cd concentrations in blood of the Cd-polluted group were 8.9 micrograms/l for men and 10.0 micrograms/l for women. These were no signific...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/0378-4274(86)90120-7
更新日期：1986-09-01 00:00:00
abstract：:Interstitial pulmonary fibrosis is characterized by an abnormal accumulation of fibroblasts with a resultant increase in lung collagen content. Previous research has implied a possible involvement of the T-lymphocyte in this process. We used cyclosporin A (Cy A), a known immunosuppressant, to deplete T-lymphocyte-depe...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/0378-4274(85)90162-6
更新日期：1985-08-01 00:00:00
abstract：:Aim of this pilot study was to correlate the human exposure to formaldehyde (F) with N-methylenvaline, a molecular adduct formed by addiction of F to the N-terminal valine in hemoglobin. A group of 21 subjects employed in a plywood factory and a laminate factory, and occupationally exposed to F, together with a group ...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2005.07.016
更新日期：2006-02-08 00:00:00
