Experimental and mathematical modeling methods for the investigation of toxicological interactions.

Abstract:

:While procedures have been developed and used for many years to assess risk and determine acceptable exposure levels to individual chemicals, most cases of environmental contamination can result in concurrent or sequential exposure to more than one chemical. Toxicological predictions of such combinations must be based on an understanding of the mechanisms of action and interaction of the components of the mixtures. Statistical and experimental methods test the existence of toxicological interactions in a mixture. However, these methods are limited to experimental data ranges for which they are derived, in addition to limitations caused by response differences from experimental animals to humans. Empirical methods such as isobolograms, median-effect principle and response surface methodology (RSM) are based on statistical experimental design and regression of data. For that reason, the predicted response surfaces can be used for extrapolation across dose regions where interaction mechanisms are not anticipated to change. In general, using these methods for predictions can be problematic without including biologically based mechanistic descriptions that can account for dose and species differences. Mechanistically based models, such as physiologically based pharmacokinetic/pharmacodynamic (PBPK/PD) models, include explicit descriptions of interaction mechanisms which are related to target tissues levels. These models include dose-dependent mechanistic hypotheses of toxicological interactions which can be tested by model-directed experimental design and used to identify dose regions where interactions are not significant.

journal_name

Toxicol Appl Pharmacol

authors

El-Masri HA

doi

10.1016/j.taap.2006.07.009

subject

Has Abstract

pub_date

2007-09-01 00:00:00

pages

148-54

issue

2

eissn

0041-008X

issn

1096-0333

pii

S0041-008X(06)00261-4

journal_volume

223

pub_type

杂志文章,评审
  • Human exposure to bisphenol A by biomonitoring: methods, results and assessment of environmental exposures.

    abstract::Human exposure to bisphenol A is controversially discussed. This review critically assesses methods for biomonitoring of bisphenol A exposures and reported concentrations of bisphenol A in blood and urine of non-occupationally ("environmentally") exposed humans. From the many methods published to assess bisphenol A co...

    journal_title:Toxicology and applied pharmacology

    pub_type: 杂志文章,评审

    doi:10.1016/j.taap.2007.12.008

    authors: Dekant W,Völkel W

    更新日期:2008-04-01 00:00:00

  • Enhancement of allergic responses in vivo and in vitro by butylated hydroxytoluene.

    abstract::The effect of butylated hydroxytoluene (BHT), which is used widely as an antioxidant, on IgE-dependent allergic responses in vivo and in vitro was investigated. For in vivo study, passive cutaneous anaphylaxis (PCA) was elicited in rats by i.d. injection of anti-DNP IgE and 48 h later by i.v. injection of DNP-HSA. BHT...

    journal_title:Toxicology and applied pharmacology

    pub_type: 杂志文章

    doi:10.1016/j.taap.2007.05.007

    authors: Yamaki K,Taneda S,Yanagisawa R,Inoue K,Takano H,Yoshino S

    更新日期:2007-09-01 00:00:00

  • Arsenic-induced alteration in the expression of genes related to type 2 diabetes mellitus.

    abstract::Chronic exposure to high concentrations of arsenic in drinking water is associated with an increased risk for developing type 2 diabetes. The present revision focuses on the effect of arsenic on tissues that participate directly in glucose homeostasis, integrating the most important published information about the imp...

    journal_title:Toxicology and applied pharmacology

    pub_type: 杂志文章,评审

    doi:10.1016/j.taap.2007.08.019

    authors: Díaz-Villaseñor A,Burns AL,Hiriart M,Cebrián ME,Ostrosky-Wegman P

    更新日期:2007-12-01 00:00:00

  • Effects of pirfenidone in acute and sub-chronic liver fibrosis, and an initiation-promotion cancer model in the mouse.

    abstract::Liver fibrosis results from chronic tissue damage and excessive regeneration with accumulation of extracellular matrix proteins; it is a precursor of liver cirrhosis and hepatocellular carcinoma. Liver fibrosis treatments are primarily directed at inflammation, with few options to combat fibrogenesis. Pirfenidone is a...

    journal_title:Toxicology and applied pharmacology

    pub_type: 杂志文章

    doi:10.1016/j.taap.2017.11.024

    authors: Seniutkin O,Furuya S,Luo YS,Cichocki JA,Fukushima H,Kato Y,Sugimoto H,Matsumoto T,Uehara T,Rusyn I

    更新日期:2018-01-15 00:00:00

  • Prevention of short-term ultraviolet B radiation-mediated damages by resveratrol in SKH-1 hairless mice.

    abstract::Nonmelanoma skin cancer is the most common cancer among humans and solar UV radiation, particularly its UVB component (290-320 nm), is its major cause. One way to reduce the occurrence of the cancer is via the use of substances (often antioxidants) termed "photochemopreventive agents". Resveratrol (trans-3,4',5-trihyd...

    journal_title:Toxicology and applied pharmacology

    pub_type: 杂志文章

    doi:10.1016/s0041-008x(02)00014-5

    authors: Afaq F,Adhami VM,Ahmad N

    更新日期:2003-01-01 00:00:00

  • Induction of endoplasmic reticulum stress might be responsible for defective autophagy in cadmium-induced prostate carcinogenesis.

    abstract::Earlier, we reported that chronic cadmium (Cd)-exposure to prostate epithelial (RWPE-1) cells causes defective autophagy, which leads to the transformation of a malignant phenotype in both in vitro and in vivo models. However, the upstream events responsible for defective autophagy are yet to be delineated. The presen...

    journal_title:Toxicology and applied pharmacology

    pub_type: 杂志文章

    doi:10.1016/j.taap.2019.04.012

    authors: Kolluru V,Tyagi A,Chandrasekaran B,Ankem M,Damodaran C

    更新日期:2019-06-15 00:00:00

  • In utero and lactational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induces genital dysmorphogenesis in the female rat.

    abstract::Recently, Gray and Ostby (Toxicol. Appl. Pharmacol. 133, 285-294, 1995) reported that in utero and lactational TCDD exposure causes striking abnormalities in the rat female reproductive system, including reduced fecundity and vaginal threads. The mechanism by which TCDD induces such abnormalities is unknown. Thus, we ...

    journal_title:Toxicology and applied pharmacology

    pub_type: 杂志文章

    doi:10.1006/taap.1997.8295

    authors: Flaws JA,Sommer RJ,Silbergeld EK,Peterson RE,Hirshfield AN

    更新日期:1997-12-01 00:00:00

  • Activation of Nrf2 by arsenite and monomethylarsonous acid is independent of Keap1-C151: enhanced Keap1-Cul3 interaction.

    abstract::Drinking water contaminated with arsenic, a human carcinogen, is a worldwide health issue. An understanding of cellular signaling events in response to arsenic exposure and rational designing of strategies to reduce arsenic damages by modulating signaling events are important to fight against arsenic-induced diseases....

    journal_title:Toxicology and applied pharmacology

    pub_type: 杂志文章

    doi:10.1016/j.taap.2008.03.003

    authors: Wang XJ,Sun Z,Chen W,Li Y,Villeneuve NF,Zhang DD

    更新日期:2008-08-01 00:00:00

  • Methoxychlor induces estrogen-like alterations of behavior and the reproductive tract in the female rat and hamster: effects on sex behavior, running wheel activity, and uterine morphology.

    abstract::The current investigation was designed to determine if the pesticide methoxychlor (M) mimicked the effects of estrogen in the brain and on behavior. Running wheel activity (RWA) and sex behaviors were evaluated in this study because the role of estrogen in the regulation of these behaviors has been thoroughly establis...

    journal_title:Toxicology and applied pharmacology

    pub_type: 杂志文章

    doi:10.1016/0041-008x(88)90012-9

    authors: Gray LE Jr,Ostby JS,Ferrell JM,Sigmon ER,Goldman JM

    更新日期:1988-12-01 00:00:00

  • On the cytotoxicity of chrysotile asbestos fibers toward pulmonary alveolar macrophages. II. Effects of nicotinamide on the cell metabolism.

    abstract::Since it was recently shown that the addition of nicotinamide (NAM) to pulmonary alveolar macrophages (PAM) cell monolayers significantly altered their ATP pools (Nadeau and Lane, 1988), the effects of the vitamin on the metabolism of the cells, exposed or not to very short chrysotile asbestos fibers (VSF), were evalu...

    journal_title:Toxicology and applied pharmacology

    pub_type: 杂志文章

    doi:10.1016/0041-008x(89)90142-7

    authors: Nadeau D,Lane DA

    更新日期:1989-03-15 00:00:00

  • Studies with 1,1'-ethylidenebis(tryptophan), a contaminant associated with L-tryptophan implicated in the eosinophilia-myalgia syndrome.

    abstract::L-Tryptophan binds to a rat liver nuclear envelope protein, and this binding is saturable, stereospecific, and of high affinity. Utilizing an in vitro assay of [3H]tryptophan binding to rat hepatic nuclear envelopes, we have previously determined that the L-tryptophan obtained from Showa Denko and which was implicated...

    journal_title:Toxicology and applied pharmacology

    pub_type: 杂志文章

    doi:10.1006/taap.1994.1096

    authors: Sidransky H,Verney E,Cosgrove JW,Latham PS,Mayeno AN

    更新日期:1994-05-01 00:00:00

  • Ovarian mitochondrial and oxidative stress proteins are altered by glyphosate exposure in mice.

    abstract::Glyphosate (GLY) usage for weed control is extensive. To investigate ovarian impacts of chronic GLY exposure, female C57BL6 mice were orally administered saline as vehicle control (CT) or GLY at 0.25 (G0.25), 0.5 (G0.5), 1.0 (G1.0), 1.5 (G1.5), or 2 (G2.0) mg/kg for five days per wk. for 20 wks. Feed intake increased ...

    journal_title:Toxicology and applied pharmacology

    pub_type: 杂志文章

    doi:10.1016/j.taap.2020.115116

    authors: Ganesan S,Keating AF

    更新日期:2020-09-01 00:00:00

  • Edible plant-derived exosomal microRNAs: Exploiting a cross-kingdom regulatory mechanism for targeting SARS-CoV-2.

    abstract:BACKGROUND:The current COVID-19 pandemic is caused by SARS-CoV-2 which belongs to coronaviridae family. Despite the global prevalence, there are currently no vaccines or drugs. Dietary plant derived exosome-like vesicles are known as edible nanoparticles (ENPs). ENPs are filled with microRNAs (miRNAs), in bioavailable ...

    journal_title:Toxicology and applied pharmacology

    pub_type: 杂志文章

    doi:10.1016/j.taap.2021.115425

    authors: Kalarikkal SP,Sundaram GM

    更新日期:2021-01-28 00:00:00

  • Alterations in biodistribution of cocaine may explain differential toxicity in pregnant and postpartum rats.

    abstract::Biodistribution of cocaine in female rats before and after delivery of litters was studied in order to provide an explanation for the observed differences in cocaine-induced toxicity in pregnant and postpartum rats. Cocaine (20 mg/kg, ip) given to female rats at 16 days of gestation or 20 days of gestation did not hav...

    journal_title:Toxicology and applied pharmacology

    pub_type: 杂志文章

    doi:10.1006/taap.1993.1018

    authors: Dwivedi C,Engineer FN,Vaughan SL

    更新日期:1993-01-01 00:00:00

  • Differential effects of arsenic species on Nrf2 and Bach1 nuclear localization in cultured hepatocytes.

    abstract::Arsenic is a ubiquitous metalloid element present in both inorganic and organic forms in the environment. The liver is considered to be a primary organ of arsenic biotransformation and methylation, as well as the main target of arsenic toxicity. Studies have confirmed that Chang human hepatocytes have an efficient ars...

    journal_title:Toxicology and applied pharmacology

    pub_type: 杂志文章

    doi:10.1016/j.taap.2021.115404

    authors: Liu D,Xu G,Bai C,Gu Y,Wang D,Li B

    更新日期:2021-01-09 00:00:00

  • Ethambutol-induced toxicity is mediated by zinc and lysosomal membrane permeabilization in cultured retinal cells.

    abstract::Ethambutol, an efficacious antituberculosis agent, can cause irreversible visual loss in a small but significant fraction of patients. However, the mechanism of ocular toxicity remains to be established. We previously reported that ethambutol caused severe vacuole formation in cultured retinal cells, and that the addi...

    journal_title:Toxicology and applied pharmacology

    pub_type: 杂志文章

    doi:10.1016/j.taap.2008.11.006

    authors: Chung H,Yoon YH,Hwang JJ,Cho KS,Koh JY,Kim JG

    更新日期:2009-03-01 00:00:00

  • Effects of chronic exposure to ozone on collagen in rat lung.

    abstract::Pulmonary fibrosis is a consequence of severe injury from some toxic agents including high doses of ozone. It is not known, however, whether chronic exposure to low doses of ozone, such as those encountered in polluted ambient atmospheres, could also result in abnormal accumulations of lung collagen. Rats were exposed...

    journal_title:Toxicology and applied pharmacology

    pub_type: 杂志文章

    doi:10.1016/0041-008x(88)90184-6

    authors: Wright ES,Kehrer JP,White DM,Smiler KL

    更新日期:1988-03-15 00:00:00

  • Sex-related differences in mouse renal metabolism and toxicity of acetaminophen.

    abstract::The objective of this study is to elucidate the role of cytochrome P450 2E1 in the metabolic activation of acetaminophen (APAP) in mouse kidneys. With the kidney microsomes from C3H/HeJ mice, a significant sex-related difference was observed in the NADPH-dependent formation of a reactive APAP metabolite which was trap...

    journal_title:Toxicology and applied pharmacology

    pub_type: 杂志文章

    doi:10.1006/taap.1993.1167

    authors: Hu JJ,Lee MJ,Vapiwala M,Reuhl K,Thomas PE,Yang CS

    更新日期:1993-09-01 00:00:00

  • Refinement and verification of the physiologically based dosimetry description for acrylonitrile in rats.

    abstract::The physiologically based dosimetry description for acrylonitrile (ACN) and its mutagenic epoxide metabolite 2-cyanoethylene oxide (CEO) in F-344 rats (M. L. Gargas, M. E. Anderson, S.K.O. Teo, R. Batra, T. R. Fennell, and G. L. Kedderis, 1995, Toxicol. Appl. Pharmacol. 134, 185-194) has been refined to include a phys...

    journal_title:Toxicology and applied pharmacology

    pub_type: 杂志文章

    doi:10.1006/taap.1996.0239

    authors: Kedderis GL,Teo SK,Batra R,Held SD,Gargas ML

    更新日期:1996-10-01 00:00:00

  • Testicular dysgenesis syndrome and the development and occurrence of male reproductive disorders.

    abstract::Patients with 45,X0/46XY karyotype often present with intersex phenotype and testicular dysgenesis. These patients may also have undescended testes (cryptorchidism), hypospadias and their spermatogenesis is severely disrupted. They have a high risk for testicular cancer. These patients have the most severe form of tes...

    journal_title:Toxicology and applied pharmacology

    pub_type: 杂志文章,评审

    doi:10.1016/j.taap.2005.01.058

    authors: Virtanen HE,Rajpert-De Meyts E,Main KM,Skakkebaek NE,Toppari J

    更新日期:2005-09-01 00:00:00

  • Effect of JP-8 jet fuel on molecular and histological parameters related to acute skin irritation.

    abstract::Organic chemicals such as jet fuels and solvents can cause skin irritation after dermal exposure. The molecular responses to these chemicals resulting in acute irritation are not understood well enough to establish safe exposure limits. Male F-344 rats were dermally exposed to JP-8 jet fuel for 1 h using Hill Top Cham...

    journal_title:Toxicology and applied pharmacology

    pub_type: 杂志文章

    doi:10.1006/taap.2001.9248

    authors: Kabbur MB,Rogers JV,Gunasekar PG,Garrett CM,Geiss KT,Brinkley WW,McDougal JN

    更新日期:2001-08-15 00:00:00

  • Allylamine and beta-aminopropionitrile-induced vascular injury: an in vivo and in vitro study.

    abstract::Toxic cardiovascular effects of allylamine and beta-aminopropionitrile were studied in adult male Sprague-Dawley rats given allylamine alone (AA), 100 mg/kg/day, beta-aminopropionitrile alone (beta APN), 1 g/kg/day, or both chemicals (AA + beta APN) by gavage. Rats were given a total of 10 doses in 11 days. Rats given...

    journal_title:Toxicology and applied pharmacology

    pub_type: 杂志文章

    doi:10.1016/0041-008x(90)90231-i

    authors: Kumar D,Hysmith RM,Boor PJ

    更新日期:1990-04-01 00:00:00

  • JBP485 improves gentamicin-induced acute renal failure by regulating the expression and function of Oat1 and Oat3 in rats.

    abstract::We investigated the effects of JBP485 (an anti-inflammatory dipeptide and a substrate of OAT) on regulation of the expression and function of renal Oat1 and Oat3, which can accelerate the excretion of accumulated uremic toxins (e.g. indoxyl sulfate) in the kidney to improve gentamicin-induced ARF in rats. JBP485 cause...

    journal_title:Toxicology and applied pharmacology

    pub_type: 杂志文章

    doi:10.1016/j.taap.2013.04.029

    authors: Guo X,Meng Q,Liu Q,Wang C,Sun H,Peng J,Ma X,Kaku T,Liu K

    更新日期:2013-09-01 00:00:00

  • Synergistic interaction between nitrogen dioxide and respirable aerosols of sulfuric acid or sodium chloride on rat lungs.

    abstract::We examined interactions in rats between NO2 gas and respirable aerosols of sulfuric acid (H2SO4) or sodium chloride (NaCl). Rats were exposed for 1, 3, or 7 days to 5 ppm of NO2 gas, alone or in combination with 1 mg/m3 of H2SO4 or NaCl aerosols. The apparent rate of collagen synthesis by lung minces was measured aft...

    journal_title:Toxicology and applied pharmacology

    pub_type: 杂志文章

    doi:10.1016/0041-008x(87)90303-6

    authors: Last JA,Warren DL

    更新日期:1987-08-01 00:00:00

  • In vitro effects of benzene metabolites on mouse bone marrow stromal cells.

    abstract::Benzene exposure can result in bone marrow myelotoxicity. We examined the effects of benzene metabolites on bone marrow stromal cells of the hemopoietic microenvironment. Male B6C3F1 mouse bone marrow adherent stromal cells were plated at 4 X 10(6) cells per 2 ml of DMEM medium in 35-mm tissue culture dishes. The grow...

    journal_title:Toxicology and applied pharmacology

    pub_type: 杂志文章

    doi:10.1016/0041-008x(84)90027-9

    authors: Gaido K,Wierda D

    更新日期:1984-10-01 00:00:00

  • Effect of dietary acid or aluminum on growth and growth-related hormones in young chickens.

    abstract::The effect of two concentrations of dietary acid (sulfuric acid) or aluminum (aluminum sulfate) on growth and growth-related hormones was examined in a heavy (broiler) strain of chicken between 4 and 18 days old. Growth (body weight, average daily gain, and tibial length) in chicks receiving either dietary acid or alu...

    journal_title:Toxicology and applied pharmacology

    pub_type: 杂志文章

    doi:10.1006/taap.1995.1137

    authors: Capdevielle MC,Scanes CG

    更新日期:1995-07-01 00:00:00

  • Cholinergic systems in brain development and disruption by neurotoxicants: nicotine, environmental tobacco smoke, organophosphates.

    abstract::Acetylcholine and other neurotransmitters play unique trophic roles in brain development. Accordingly, drugs and environmental toxicants that promote or interfere with neurotransmitter function evoke neurodevelopmental abnormalities by disrupting the timing or intensity of neurotrophic actions. The current review disc...

    journal_title:Toxicology and applied pharmacology

    pub_type: 杂志文章,评审

    doi:10.1016/j.taap.2003.06.001

    authors: Slotkin TA

    更新日期:2004-07-15 00:00:00

  • A QSAR study that compares the ability of bisdioxopiperazine analogs of the doxorubicin cardioprotective agent dexrazoxane (ICRF-187) to protect myocytes with DNA topoisomerase II inhibition.

    abstract::The cardiotoxicity caused by doxorubicin and extravasation injury caused by anthracyclines is reduced by the clinically approved bisdioxopiperazine drug dexrazoxane. Dexrazoxane is a rings-closed analog of EDTA and is hydrolyzed in vivo to a form that strongly binds iron. Its protective effects were originally thought...

    journal_title:Toxicology and applied pharmacology

    pub_type: 杂志文章

    doi:10.1016/j.taap.2020.115038

    authors: Hasinoff BB,Patel D,Wu X

    更新日期:2020-07-15 00:00:00

  • Dioxin-like effects observed in male rats following exposure to octachlorodibenzo-p-dioxin (OCDD) during a 13-week study.

    abstract::Octachlorodibenzo-p-dioxin (OCDD) is a ubiquitous environmental pollutant which has been reported to be nontoxic following acute exposure but has recently been shown to accumulate upon repeated exposure. To determine if this accumulation results in toxic effects, male Fischer 344 rats were treated with 50 micrograms/k...

    journal_title:Toxicology and applied pharmacology

    pub_type: 杂志文章

    doi:10.1016/0041-008x(88)90023-3

    authors: Couture LA,Elwell MR,Birnbaum LS

    更新日期:1988-03-30 00:00:00

  • Effects of dimethylarsinic and dimethylarsinous acid on evoked synaptic potentials in hippocampal slices of young and adult rats.

    abstract::In this study, the effects of pentavalent dimethylarsinic acid ((CH(3))(2)AsO(OH); DMA(V)) and trivalent dimethylarsinous acid ((CH(3))(2)As(OH); DMA(III)) on synaptic transmission generated by the excitatory Schaffer collateral-CA1 synapse were tested in hippocampal slices of young (14-21 day-old) and adult (2-4 mont...

    journal_title:Toxicology and applied pharmacology

    pub_type: 杂志文章

    doi:10.1016/j.taap.2007.07.007

    authors: Krüger K,Repges H,Hippler J,Hartmann LM,Hirner AV,Straub H,Binding N,Musshoff U

    更新日期:2007-11-15 00:00:00