Abstract：
:Traditional predictive tests for dermal sensitization in humans use the albino guinea pig as a model. A number of factors make the prospect of an alternative attractive. Guinea pig designs are labor intensive, require significant animal, caging, and husbandry resources, and are expensive. Extensive development and validation was conducted of an alternative using swelling of mouse ears as a quantitative end point. Ten strains of mice, ten age groups, both sexes, induction forms (number, route, timing), the use of an adjuvant, different vehicles and intervals to challenge, two induction sites, and three measurement intervals were evaluated. A methodology was developed for preparing induction sites to increase test sensitivity. A small battery of standard compounds was used to evaluate these design variables and a final test design was developed. The basic process was also demonstrated to occur in rats and guinea pigs and to be dose responsive. The final mouse ear swelling test (MEST) design was used to evaluate 72 materials representing a broad spectrum of chemicals and testing problems. These included 49 known positives and 23 known negatives. Guinea pig maximization test data on 37 of these resulting by studies conducted in our laboratories, along with closed patch guinea pig and human test data on many of these compounds, are also reported here for the first time. The MEST correctly identified 71 of 72 materials as potential human sensitizers or nonsensitizers. Additionally, both the efficacy of an occluded patch induction method and the duration of responsiveness of mice were evaluated. In the studies, the MEST was found to be an accurate, sensitive, and efficient alternative test design for evaluating delayed-contact sensitization.
journal_name
Toxicol Appl Pharmacoljournal_title
Toxicology and applied pharmacologyauthors
Gad SC,Dunn BJ,Dobbs DW,Reilly C,Walsh RDdoi
10.1016/0041-008x(86)90419-9subject
Has Abstractpub_date
1986-06-15 00:00:00pages
93-114issue
1eissn
0041-008Xissn
1096-0333pii
0041-008X(86)90419-9journal_volume
84pub_type
杂志文章abstract：:The effects of the cytochrome P450 inducer beta-naphthoflavone (BNF) on NO2 toxicity were studied in two strains of mice. In one strain (C57B1/6J), cytochrome P450 could be induced by the aromatic hydrocarbon, while in the other strain (DBA/2J) cytochrome P450 was not inducible by this compound. Mice were treated with...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/0041-008x(88)90122-6
更新日期：1988-04-01 00:00:00
abstract：:In order to elucidate the oxidative effects and genotoxicity of nickel on human lymphocytes in vitro, we report the level of intracellular reactive oxygen species (ROS), lipid peroxidation, hydroxyl radical ((*)OH), and DNA damage in human lymphocytes after acute exposure to inorganic nickel. NiCl(2) appeared to incre...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/s0041-008x(03)00086-3
更新日期：2003-06-15 00:00:00
abstract：:Diurnal patterns of eating, drinking, locomotor activity, and rearing in male Fischer-344 rats were examined for 11 days after a single oral dose of triethyltin bromide (TET) at 0, 1.5, 3, or 5 mg/kg. The 5 mg/kg group exhibited a time-related drop in food consumption and body weight until 3 of 10 rats were sacrificed...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/0041-008x(86)90342-x
更新日期：1986-09-30 00:00:00
abstract：:Perfluorooctane sulfonate (PFOS), an emerging persistent contaminant that is commonly encountered during daily life, has been shown to exert toxic effects on the central nervous system (CNS). However, the molecular mechanisms underlying the neurotoxicity of PFOS remain largely unknown. It has been widely acknowledged ...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2015.06.012
更新日期：2015-10-15 00:00:00
abstract：:Polycyclic aromatic hydrocarbons (PAHs) derived from fossil fuels are ubiquitous contaminants and occur in aquatic habitats as highly variable and complex mixtures of compounds containing 2 to 6 rings. For aquatic species, PAHs are generally accepted as acting through either of two modes of action: (1) "dioxin-like" t...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2006.09.018
更新日期：2006-12-15 00:00:00
abstract：:Chronic exposure to low lead concentration produces hypertension; however, the underlying mechanisms remain unclear. We analyzed the role of oxidative stress, cyclooxygenase-2-dependent pathways and MAPK in the vascular alterations induced by chronic lead exposure. Aortas from lead-treated Wistar rats (1st dose: 10 μg...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2015.01.005
更新日期：2015-03-01 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：:Isolated rat lymphocytes in salts-glucose medium (pH 7.2) were incubated with nickel chloride, nickel acetate, nickel sulfate, and a soluble form of nickel subsulfide (0-2 mM) at 37 degrees C for 2 h. The soluble form of nickel subsulfide induced a significant increase in DNA-protein crosslinks (DPXLs) (111%) beginnin...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1006/taap.2000.9097
更新日期：2001-02-01 00:00:00
abstract：:Electrophiles, ubiquitously found in the environment, modify thiol groups of sensor proteins, leading to activation of redox signaling pathways such as the Kelch-like ECH-associated protein 1 (Keap1)/nuclear factor E2 related factor 2 (Nrf2) pathway. Nrf2 activation by exposure to single electrophiles has been establi...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2020.115392
更新日期：2021-01-09 00:00:00
abstract：:There is a growing recognition of the need to identify when exposures to specific combinations of chemicals result in toxicological effects of concern. In order to meet this need new tools are required to evaluate the doses of multiple chemicals that occur from the concurrent exposures to multiple sources of the chemi...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.taap.2006.11.032
更新日期：2007-09-01 00:00:00
abstract：:The putative neurotoxicity of the organophosphorus compound triphenyl phosphite (TPP) was examined in Long Evans, adult male rats. Animals were exposed to two 1.0 ml/kg (1184 mg/kg) injections (sc) of TPP spaced 1 week apart and sampled for biochemical and neuropathological examination. At the time of sampling, rats d...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/0041-008x(86)90297-8
更新日期：1986-04-01 00:00:00
abstract：:6-Hydroxy-trans,trans-2,4-hexadienal (CHO-M-OH) is a metabolite of trans,trans-muconaldehyde (muconaldehyde or MUC), a microsomal hematotoxic ring-opened metabolite of benzene. In the present study, the toxicity of CHO-M-OH was examined. In order to assess potential toxic effects of CHO-M-OH on the maturation of eryth...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1006/taap.1995.1101
更新日期：1995-06-01 00:00:00
abstract：:A previously developed PBPK model for ethylene glycol and glycolic acid was extended to include glyoxylic acid, oxalic acid, and the precipitation of calcium oxalate that is associated with kidney toxicity in rats and humans. The development and evaluation of the PBPK model was based upon previously published pharmaco...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2010.10.011
更新日期：2011-02-01 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：:Occupational exposure to nickel (Ni), chromium (Cr), and arsenic (As) containing compounds has been associated with lung cancer and other adverse health effects. Their carcinogenic properties may be attributable in part, to activation and/or repression of gene expression induced by changes in the DNA methylation statu...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2009.01.009
更新日期：2009-04-01 00:00:00
abstract：:The disposition and metabolism of 2,3,7,8-tetrachlorodibenzofuran (TCDF) was investigated in rainbow trout (Oncorhynchus mykiss) in order to better understand the metabolic and physiological factors that modulate the fate of this extremely toxic compound in rainbow trout compared to other species. The fish were dosed ...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1006/taap.1996.0183
更新日期：1996-08-01 00:00:00
abstract：:Catechol-O-methyltransferase (COMT) acts as a 'gate-keeper' to prevent DNA damage during estrogen metabolism. Both experimental and epidemiological studies suggest the role of COMT in pathogenesis of human breast cancer (BCa). It was previously reported that inhibition of COMT enzyme activity in estradiol-treated huma...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2019.01.016
更新日期：2019-03-15 00:00:00
abstract：:Erionite, a naturally occurring fibrous zeolite, is associated with the development of nonmalignant and malignant lung diseases and is more carcinogenic than asbestos fibers in man and rodent inhalation models of disease. To investigate the possible molecular mechanisms of erionite-induced toxicity and carcinogenesis ...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1006/taap.1998.8450
更新日期：1998-07-01 00:00:00
abstract：:As an edible traditional Chinese herb, Fructus psoraleae (FP) has been widely used in Asia for the treatment of vitiligo, bone fracture and osteoporosis. Several cases on markedly elevated bilirubin and acute liver injury following administration of FP and its related proprietary medicine have been reported, but the m...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2015.09.003
更新日期：2015-11-15 00:00:00
abstract：:Assessment of toxic or mutagenic risks associated with phosphorothioate oligonucleotides (PTO) is important. In vitro and in vivo data have shown that PTOs are nontoxic and nonmutagenic. However, these studies do not address interactions between PTOs and other compounds. The sulfur on PTOs may provide a novel reactive...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1006/taap.1995.1126
更新日期：1995-07-01 00:00:00
abstract：:Exposure of intact cultured Chinese hamster ovary (CHO) cells to water-soluble nickel (Ni) salts and to relatively water-insoluble crystalline nickel subsulfide (Ni3S2) resulted in an increased formation of the fluorescent oxidized compound, dichlorofluorescein (DCF) from the parent nonfluorescent compound, 2,7-dichlo...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1006/taap.1993.1083
更新日期：1993-05-01 00:00:00
abstract：:Inoculation of metallic tin powder produced marked proliferation of plasma cells and Russell body cells in draining lymph nodes. Prior, but not concurrent, administration of a soluble tin salt in the drinking water prevented the plasma cell hyperplasia. Various Na, Zn, Ag, and Cu salts were not inhibitory. The inhibit...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/0041-008x(83)90359-9
更新日期：1983-03-30 00:00:00
abstract：:The present study investigates the effects of nicotine treatment on exocrine pancreatic function. Adult male, Sprague-Dawley rats received nicotine via a time-release pellet, at a rate of 1.65 micrograms/min for 3 weeks. At the end of the experimental period, it was observed that although nicotine did not affect final...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/0041-008x(88)90255-4
更新日期：1988-10-01 00:00:00
abstract：:Arsenic is an environmental toxicant and carcinogen. Exposure to arsenic is associated with development of liver fibrosis and portal hypertension through ill defined mechanisms. We evaluated hepatic fibrogenesis after long term arsenic exposure in a murine model. BALB/c mice were exposed to arsenic by daily gavages of...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2010.11.016
更新日期：2011-02-15 00:00:00
abstract：:Calcium uptake in cells occurs through specific membrane channels. Since cadmium and mercury inhibit calcium uptake, this study examined whether the calcium channels may also be involved in the uptake of these metals. Primary cultures of rat hepatocytes were incubated with 3 microM CdCl2 or HgCl2 in the absence or pre...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/s0041-008x(05)80018-3
更新日期：1991-09-01 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：:Dendritic cells (DC) are known to play a major role during contact allergy induced by contact sensitizers (CS). Our previous studies showed that Nrf2 was induced in DC and controlled allergic skin inflammation in mice in response to chemicals. In this work, we raised the question of the role of Nrf2 in response to a s...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2017.02.014
更新日期：2017-05-01 00:00:00
abstract：:Although insulin and atorvastatin have been shown to exert glycemic control and could improve brain function, the effects of atorvastatin or insulin as well as the combination of atorvastatin plus insulin on brain pathology in diabetes mellitus type 1 (T1DM) are unclear. Therefore, this study investigated the effect o...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2018.01.021
更新日期：2018-03-01 00:00:00
abstract：:Triple-negative breast cancers (TNBCs) are highly invasive and have a higher rate of distant metastasis. Matrix metalloproteinase-9 (MMP-9) plays a crucial role in EGF/EGFR-mediated malignant progression and metastasis of TNBCs. Various studies have revealed that treatment with gallic acid down-regulates MMP-9 express...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2016.09.007
更新日期：2016-11-01 00:00:00
abstract：:Gap junctional intercellular communication appears to be important in the regulation of cellular homeostasis, differentiated cell functions, and growth control in adult tissues. Interruption of intercellular communication by chemical compounds has been shown to be a sublethal response to a number of tumor promoters. T...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/0041-008x(90)90050-5
更新日期：1990-03-01 00:00:00
