Abstract:
:Environmental risk assessment requires models for estimating the bioaccumulation of untested compounds. So far, bioaccumulation models have focused on lipophilic compounds, and only a few have included hydrophilic compounds. Our aim was to extend an existing bioaccumulation model to estimate the oral uptake efficiency of pollutants in mammals for compounds over a wide K(ow) range with an emphasis on hydrophilic compounds, i.e. compounds in the lower K(ow) range. Usually, most models use octanol as a single surrogate for the membrane and thus neglect the bilayer structure of the membrane. However, compounds with polar groups can have different affinities for the different membrane regions. Therefore, an existing bioaccumulation model was extended by dividing the diffusion resistance through the membrane into an outer and inner membrane resistance, where the solvents octanol and heptane were used as surrogates for these membrane regions, respectively. The model was calibrated with uptake efficiencies of environmental pollutants measured in different mammals during feeding studies combined with human oral uptake efficiencies of pharmaceuticals. The new model estimated the uptake efficiency of neutral (RMSE=14.6) and dissociating (RMSE=19.5) compounds with logK(ow) ranging from -10 to +8. The inclusion of the K(hw) improved uptake estimation for 33% of the hydrophilic compounds (logK(ow)<0) (r(2)=0.51, RMSE=22.8) compared with the model based on K(ow) only (r(2)=0.05, RMSE=34.9), while hydrophobic compounds (logK(ow)>0) were estimated equally by both model versions with RMSE=15.2 (K(ow)&K(hw)) and RMSE=15.7 (K(ow) only). The model can be used to estimate the oral uptake efficiency for both hydrophilic and hydrophobic compounds.
journal_name
Toxicol Appl Pharmacoljournal_title
Toxicology and applied pharmacologyauthors
O'Connor IA,Huijbregts MA,Ragas AM,Hendriks AJdoi
10.1016/j.taap.2012.10.015subject
Has Abstractpub_date
2013-01-01 00:00:00pages
150-6issue
1eissn
0041-008Xissn
1096-0333pii
S0041-008X(12)00457-7journal_volume
266pub_type
杂志文章abstract::Hexachlorobenzene (HCB) induces hepatic porphyria and liver cancer in female rats, whereas toxicity is minimal in male rats. HCB is biotransformed to sulfur-containing metabolites originating from conjugation to glutathione (GSH). This study aimed to assess differences in GSH conjugation of HCB between male and female...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/0041-008x(92)90192-u
更新日期:1992-02-01 00:00:00
abstract::T-2 toxin, a trichothecene mycotoxin, is a potently cytotoxic and immunosuppressive secondary metabolite produced by Fusarium fungi. Young male white Swiss mice were fed a diet supplemented with T-2 toxin at levels of 5, 10, or 20 ppm, control diet ad libitum, or control diet at a restricted rate for 1, 2, 3, 4, and 6...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/0041-008x(83)90304-6
更新日期:1983-06-30 00:00:00
abstract::Previous work in our laboratory has shown that the continuous administration of alpha-difluoromethylornithine (DFMO), a highly specific irreversible inhibitor of ornithine decarboxylase (ODC), which is the rate-limiting enzyme in polyamine biosynthesis, prevented the development of pulmonary hypertension and right ven...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/0041-008x(85)90124-3
更新日期:1985-10-01 00:00:00
abstract::The threshold hemodynamic changes associated with the cardiovascular (CV) toxicity of minoxidil (MNX) in the dog, characterized by subendocardial necrosis, right atrial hemorrhagic lesions, and coronary vascular medial hemorrhage and necrosis, have not been defined. To determine the relationship between serum concentr...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1006/taap.1996.0229
更新日期:1996-10-01 00:00:00
abstract::Pyrrolizidine alkaloids such as monocrotaline (MCT) are toxic plant constituents which poison livestock and humans. Low doses of MCT given to rats result in cardiopulmonary pathophysiologic sequelae similar to forms of chronic pulmonary hypertension in man. This provides a useful model of human disease. The toxicology...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章,评审
doi:10.1016/0041-008x(88)90050-6
更新日期:1988-05-01 00:00:00
abstract::Jaridonin, a novel diterpenoid from Isodon rubescens, has been shown previously to inhibit proliferation of esophageal squamous cancer cells (ESCC) through G2/M phase cell cycle arrest. However, the involved mechanism is not fully understood. In this study, we found that the cell cycle arrest by Jaridonin was associat...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2014.11.003
更新日期:2015-01-15 00:00:00
abstract::Azole derivatives are teratogenic in rats and mice in vitro and in vivo. The postulated mechanism for the dysmorphogenetic effects is the inhibition of retinoic acid (RA)-degrading enzyme CYP26. Azole-related abnormalities are confined to structures controlled by RA, especially the neural crest cells, hindbrain, crani...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2008.09.025
更新日期:2009-01-01 00:00:00
abstract::Recent studies have demonstrated that macrophages are the cell types capable of metabolizing benzo[a]pyrene (B(a)P) within the spleens of untreated mice. Since repeated exposure to B(a)P results in immunosuppression and B(a)P is known to induce cytochrome P450 levels, the first objective of this study was to investiga...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/0041-008x(92)90305-c
更新日期:1992-10-01 00:00:00
abstract::Heavy metals in the environment originate from both human activities and natural processes. Exposure to these metals can result in important changes to immune activity. Depending on the metal and dose, these changes can result in enhanced immune function, diminished immune responses, or altered responses that produce ...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.taap.2005.04.021
更新日期:2006-01-01 00:00:00
abstract::Benzene is a potent hematotoxin and has been shown to cause leukemia in man. Chronic toxicity studies indicate that B6C3F1 mice are more susceptible than F334/N rats to benzene toxicity. The purpose of the studies presented in this paper was to determine if there were metabolic differences between F344/N rats and B6C3...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/0041-008x(88)90343-2
更新日期:1988-06-15 00:00:00
abstract::Triclosan (TCS) is an antimicrobial agent commonly found in a variety of personal care products and cosmetics. TCS readily enters the environment through wastewater and is detected in human plasma, urine, and breast milk due to its widespread use. Studies have implicated TCS as a disruptor of thyroid and estrogen sign...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2016.08.013
更新日期:2016-10-01 00:00:00
abstract::We have studied the effects of opiates on ATP and acetylcholine (ACh) release from cholinergic nerve terminals isolated from the electric organ of Torpedo marmorata. The release of ATP was inhibited by morphine and this action was reversed by naloxone. Morphine, [D-Met2-Pro5]enkephalinamide and [D-Ala2-Leu5]enkephalin...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/0041-008x(90)90101-y
更新日期:1990-10-01 00:00:00
abstract::1,3-butadiene (BD) has been classified as a human carcinogen, however, the relationship between chromosomal damage and its metabolic polymorphisms is not clear. The present study used the CBMN assay to detect chromosomal damage in the peripheral lymphocytes of 166 exposed workers and 41 non-exposed healthy individuals...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2010.07.006
更新日期:2010-09-15 00:00:00
abstract::The results of a series of screening tests to determine the potential teratogenicity and neurotoxicity of developmental exposure to TBTO in rats are presented in this paper. For prenatal exposure, pregnant Long Evans rats were intubated with 0-16 mg/kg/day bis(tri-n-butyltin)oxide TBTO from Days 6 to 20 of gestation (...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/0041-008x(89)90060-4
更新日期:1989-01-01 00:00:00
abstract::For highly water soluble and reactive gases, such as formaldehyde, the reported distribution of nasal lesions in rats and rhesus monkeys following inhalation exposure may be attributable, at least in part, to regional gas uptake patterns that are a consequence of nasal airflow characteristics. Inspiratory nasal airflo...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/s0041-008x(05)80005-5
更新日期:1991-09-01 00:00:00
abstract::Glucose feeding can markedly exacerbate the toxicity of the anticholinesterase insecticide, parathion. We determined the effects of parathion on brain nitric oxide and its possible role in potentiation of toxicity by glucose feeding. Adult rats were given water or 15% glucose in water for 3 days and challenged with ve...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2006.11.005
更新日期:2007-03-01 00:00:00
abstract::This study was designed to evaluate the developmental toxicity of nitrazepam (NZ) in Sprague-Dawley rats and ICR mice and to determine the metabolic factors which modulate susceptibility to the developmental effects of NZ. Rats were treated orally with a single dose of NZ at 300 mg/kg on Day 12 of gestation. Mice rece...
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
abstract::Eicosanoids released after ozone exposure of a human bronchial epithelial cell line, BEAS-S6, were analyzed by high-pressure liquid chromatography (HPLC) of supernatants from exposed cells prelabeled with [3H]arachidonic acid. BEAS cells released thromboxane B2 (TxB2), prostaglandin E2 (PGE2), leukotriene C4 (LTC4), L...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1006/taap.1993.1027
更新日期:1993-02-01 00:00:00
abstract::Partition coefficients (PCs) are chemical-specific parameters used in physiologically based pharmacokinetic models to describe chemical solubility in tissues. Tissue:air PCs for volatile chemicals can be estimated using vial equilibration techniques in which the chemical concentration in the vial headspace is measured...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1006/taap.1994.1184
更新日期:1994-09-01 00:00:00
abstract::This study investigated the protective effects of curcumin on tetrachloro-p-benzoquinone (TCBQ)-induced hepatotoxicity in mice. TCBQ-treatment causes significant liver injury (the elevation of serum AST and ALT activities, histopathological changes in liver section including centrilobular necrosis and inflammatory cel...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2014.08.003
更新日期:2014-10-15 00:00:00
abstract::Kynurenic acid (KYNA) is a recognized broad-spectrum antagonist of excitatory amino acid receptors with a particularly high affinity for the glycine co-agonist site of the N-methyl-D-aspartate (NMDA) receptor complex. KYNA is also a putative endogenous neuroprotectant. Recent studies show that KYNA strongly blocks alp...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2009.07.011
更新日期:2009-10-15 00:00:00
abstract::To examine the magnitude of human variability across the entire transcriptome after chemical challenge, we profiled gene expression responses to three different prototypic chemical inducers in primary human hepatocyte cultures from ten independent donors. Correlation between basal expression in any two hepatocyte dono...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2008.04.024
更新日期:2008-09-01 00:00:00
abstract::3-Methylindole (3-MI) is a pneumotoxic metabolite of L-tryptophan that can form in the digestive tracts of humans and ruminants as a result of microbial protein metabolism. Alternatively, human lungs can be directly exposed to 3-MI formed during protein pyrolysis and inhalation of tobacco smoke. 3-MI has been shown to...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/0041-008x(91)90001-u
更新日期:1991-07-01 00:00:00
abstract::Neuropathy target esterase (NTE) is a membrane-bound protein with high esterase catalytic activity. The physiological function of the protein is not known and the catalytic activity is not essential to health of nerve axons. Nevertheless there is overwhelming evidence that modification of the structure of NTE by coval...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章,评审
doi:10.1016/0041-008x(90)90036-t
更新日期:1990-03-01 00:00:00
abstract::Ethanolic extract of Casearia sylvestris is thought to be antimutagenic. In this study, we attempted to determine whether this extract and casearin X (a clerodane diterpene from C. sylvestris) are protective against the harmful effects of airborne pollutants from sugarcane burning. To that end, we used the Tradescanti...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2012.09.005
更新日期:2012-12-15 00:00:00
abstract::Mast cells reside at interfaces with the environment, including the mucosa of the respiratory and gastrointestinal tracts. This localization exposes mast cells to inhaled, or ingested, environmental challenges. In the airways of smokers, resident immune cells will be in contact with the condensed components of cigaret...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2004.09.003
更新日期:2005-04-15 00:00:00
abstract::Dietary consumption of phytoestrogens like genistein has been linked with lower incidence of prostate cancer. The estradiol-like benzopyran core of genistein confers estrogen receptor-β (ER-β) selectivity that imparts weak anti-proliferative activity against prostate cancer cells. DL-2-[4-(2-piperidinoethoxy)phenyl]-3...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2015.01.017
更新日期:2015-03-15 00:00:00
abstract::Marijuana or synthetic cannabinoids and alcohol are often used together, with these combinations causing motor impairments that can subsequently lead to motor vehicle accidents. This study investigated the combined use of both synthetic cannabinoids and ethanol and their effect on motor coordination in mice in additio...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2020.115283
更新日期:2020-12-01 00:00:00
abstract::The toxicokinetics of deltamethrin and its metabolite 4'-HO-deltamethrin after single doses of 26 mg of deltamethrin/kg (oral) or 1.2 mg of deltamethrin/kg (intravenous) were studied in male Wistar rats. Serial blood samples were obtained after oral and intravenous administration. Brain, vas deferens, and anococcygeus...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1006/taap.1996.0254
更新日期:1996-11-01 00:00:00
abstract::The immunoreactivity and pharmacokinetics of a new horse F(ab')2 scorpion antivenom and its effect on Buthus occitanus mardochei venom plasma disposition in the rabbit were studied. The scorpion venom-specific F(ab')2 affinity constant determined by immunoradiometric assay was 1.6 +/- 0.6 10(8) M-1. One group received...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1006/taap.1996.0284
更新日期:1996-11-01 00:00:00