Abstract：
:About two decades ago in vitro mutagenicity tests were adopted as the first in vitro methods in regulatory toxicology. For reasons of animal welfare and better science, many validation studies of various in vitro methods were performed between 1985 and 1995 for their potential to replace the Draize eye irritation test. Albeit the fact that four in vitro methods (HET-CAM, BCOP, IRE, and ECE) have gained regulatory tolerance in Europe for the classification of severe eye irritants, the lessons learned mainly from these validation studies led to the definition of internationally harmonised OECD validation principles and acceptance criteria (Final Report of the OECD Workshop on Harmonization of Validation and Acceptance Criteria for Alternative Toxicological Tests Methods, 1996. OECD Publication Office, Paris, France). Application of these principles to prevalidation and validation studies, and additional special studies performed in Europe with the support of ECVAM, ended in the scientific validation of new in vitro methods for the prediction of skin corrosivity and phototoxicity. They were accepted for regulatory use in Europe and adopted on 8 June 2000 as test methods B. 40 and B. 41 of Annex V of Directive 67/548/EEC. In quite a different approach, European industry has submitted in-house validation data to support a Draft OECD Test Guideline for in vitro dermal absorption testing, which-after peer review and a long lasting international discussion-will now be adopted by the OECD. The increasing importance of regulatory measures derived from quantitative cytotoxicity tests, and some examples of regulatory accepted in vitro methods, where the specific purpose is restricted to a specific regulation (e.g. testing of medicinal products, or medical devices), are also addressed.
journal_name
Toxicol Lettjournal_title
Toxicology lettersauthors
Liebsch M,Spielmann Hdoi
10.1016/s0378-4274(01)00492-1keywords:
subject
Has Abstractpub_date
2002-02-28 00:00:00pages
127-34issue
1-3eissn
0378-4274issn
1879-3169pii
S0378427401004921journal_volume
127pub_type
杂志文章,评审abstract：:Exercising volunteers exposed in chambers to as little as 80 ppb O3 for several hours exhibit impaired lung function and irritative lower airway symptoms. Comparable changes occur among children and young adults exposed to summer smog containing O3. Intensity of the response is reproducible but varies widely among ind...
journal_title：Toxicology letters
pub_type： 杂志文章,评审
doi：10.1016/0378-4274(95)03565-6
更新日期：1995-12-01 00:00:00
abstract：:The proceedings in this volume suggest several important future research needs. Research is needed to validate modeling in toxicology in order to support the use of the general approach of modeling, either for structure-activity relationships (SAR) or physiologically based pharmacokinetics (PBPK), by regulators. Resea...
journal_title：Toxicology letters
pub_type： 杂志文章,评审
doi：10.1016/0378-4274(95)03382-u
更新日期：1995-09-01 00:00:00
abstract：:Previous studies have suggested that elevated blood homocysteic acid (HCA) levels increased the risk of Alzheimer's disease (AD), but the underlying mechanisms are unclear. Herein, we studied the neuronal toxicity of HCA and the underlying mechanisms in HT-22 cells. Results showed that HCA induced cell death in concen...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2013.08.011
更新日期：2013-10-23 00:00:00
abstract：:The utility of HepaRG cells as an in vitro cell-based assay system for assessing drug-induced liver injury (DILI) risk was investigated. Seventeen DILI-positive and 15 DILI-negative drugs were selected for the assay. HepaRG cells were treated with each drug for 24h at concentrations that were 1.6-, 6.3-, 25-, and 100-...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2015.04.014
更新日期：2015-07-02 00:00:00
abstract：:The aim of this study was to determine the toxicokinetics and some effects of 1,1,1-trifluoroethane (HFC-143a) in humans. Nine male volunteers were experimentally exposed to 500ppm HFC-143a for 2h during light physical exercise (50W) in an exposure chamber. Blood, urine and exhaled air were sampled before, during and ...
journal_title：Toxicology letters
pub_type： 临床试验,杂志文章
doi：10.1016/j.toxlet.2007.05.010
更新日期：2007-08-01 00:00:00
abstract：:Melamine (MA) exposure causes male reproductive toxicity, however, the mechanism remains unclear. In this study, we investigated the roles of the blood-testis barrier (BTB) in MA-induced reproductive toxicity in piglets. Male weaned piglets were exposed to MA concentrations of 0, 100, 300, and 1000 mg/kg in the diet f...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2018.07.019
更新日期：2018-10-15 00:00:00
abstract：:Interactions of chemicals with cerebral neurotransmitters, receptors, and second messenger systems are often accompanied by similar changes involving components in non-neural tissues. On this basis, indirect strategies have been developed to investigate neural cell function parameters by methods using accessible cells...
journal_title：Toxicology letters
pub_type： 杂志文章,评审
doi：10.1016/0378-4274(95)03273-8
更新日期：1995-05-01 00:00:00
abstract：:Betulinic acid (BA) is known to induce apoptosis in melanoma neuroectodermal and malignant brain cancer cell lines. Present report describes the role of antioxidants on the BA-induced toxicity to human cell line SK-N-MC. Hydrophilic antioxidants viz., L-ascorbic acid (VitC) and N-acetyl-L-cysteine (l-NAC) had no prote...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2004.03.027
更新日期：2004-11-02 00:00:00
abstract：:The study aimed to investigate the effects of egg white hydrolysate (EWH) on vascular disorders induced by mercury (Hg). For this, male Wistar rats were treated for 60days: Untreated (saline, i.m.); Mercury (HgCl2, i.m., 1st dose 4.6μg/kg, subsequent doses 0.07μg/kg/day); Hydrolysate (EWH, gavage, 1g/kg/day); Hydrolys...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2017.10.001
更新日期：2017-11-05 00:00:00
abstract：:Environmental toxicants such as methylmercury play a critical role in the pathogenesis of many neurodevelopmental disorders. Environmental exposure to methylmercury frequently occurs at low doses, most frequently through fish consumption. Although the general population is at risk for exposure, pregnant women and youn...
journal_title：Toxicology letters
pub_type： 杂志文章,评审
doi：10.1016/j.toxlet.2013.08.002
更新日期：2013-10-09 00:00:00
abstract：:Phosgene Oxime (CX, Cl2CNOH), a halogenated oxime, is a potent chemical weapon that causes immediate acute injury and systemic effects. CX, grouped together with vesicating agents, is an urticant or nettle agent with highly volatile, reactive, corrosive, and irritating vapor, and has considerably different chemical pr...
journal_title：Toxicology letters
pub_type： 杂志文章,评审
doi：10.1016/j.toxlet.2017.11.011
更新日期：2018-09-01 00:00:00
abstract：:Tetramethylenedisulfotetramine (TMDT) is a synthetic neurotoxic rodenticide and potential chemical threat agent. Signs of TMDT poisoning include convulsions which can progress into status epilepticus and death. Although clinical reports clearly show that poisoning via food and drink is the main route of exposure, expe...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2019.03.014
更新日期：2019-06-15 00:00:00
abstract：:Many xenobiotics and carcinogens are oxidized in vitro by prostaglandin-H synthase (PHS) in the presence of arachidonic acid or lipid peroxides. PHS has been suggested to serve as an alternative metabolic activation enzyme to the cytochrome P-450 isoenzymes, particularly in tissues low in monooxygenase activity. This ...
journal_title：Toxicology letters
pub_type： 杂志文章,评审
doi：10.1016/0378-4274(93)90055-3
更新日期：1993-04-01 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：:Acetylcholinesterase (AChE)-induced chewing movements, tremors, convulsions and hind limb abduction at doses of 50-85% LD50 in rats were monitored in order to determine whether the severity of these different signs would correlate with brain AChE levels and the time course of such a relationship. 30 min after subcutan...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/0378-4274(86)90094-9
更新日期：1986-02-01 00:00:00
abstract：:A diversity of chemicals cause discrete lesions in the kidney by a number of different mechanisms, and similar types of chemicals may give rise to more than one target cell injury. Screening for these lesions in vivo may be unreliable if a single noninvasive or invasive criterion is used. Instead, evidence of nephroto...
journal_title：Toxicology letters
pub_type： 杂志文章,评审
doi：10.1016/0378-4274(89)90132-x
更新日期：1989-03-01 00:00:00
abstract：:Alternaria spp. are ubiquitous molds that are able to produce toxic secondary metabolites which may contaminate food globally. One of those is the mycotoxin altertoxin II (ATX-II), a genotoxic and mutagenic compound. In recent years, different flavonoids that may co-occur with mycotoxins in food were demonstrated to t...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2017.12.002
更新日期：2018-03-01 00:00:00
abstract：:To reduce the production of pollutants in motor vehicle exhaust, methyl tert-butyl ether (MTBE) and other ethers such as ethyl tert-butyl ether (ETBE) and tert-amyl methyl ether (TAME) are added to gasoline as oxygenates for more complete combustion. Metabolism of these gasoline ethers is catalyzed by cytochrome P450 ...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/s0378-4274(98)00389-0
更新日期：1999-03-08 00:00:00
abstract：:Administration of the chemical carcinogen 2-acetylaminofluorene (2-AAF) has previously been shown to lower hepatic epidermal growth factor (EGF) binding levels during chemically induced hepatocarcinogenesis. To further characterize the specificity of this response, EGF binding levels for liver microsomes were determin...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/s0378-4274(96)03866-0
更新日期：1997-03-14 00:00:00
abstract：:The present study investigated the effects of in vitro methylmercury (MeHg) exposure on endogenous dopamine (DA) efflux from mouse striatal slices. MeHg produced a concentration-dependent increase in the spontaneous efflux of DA which was independent of the availability of Ca2+ in the superfusion medium. The Ca(2+)-de...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/s0378-4274(96)03787-3
更新日期：1996-12-01 00:00:00
abstract：:Dioxins are persistent environmental contaminants that cause multiple disorders in laboratory animals, including teratogenesis. In mice, the most important teratogenic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) are hydronephrosis and cleft palate. Aryl hydrocarbon receptor (AHR) mediates most of the TCDD-in...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2004.02.009
更新日期：2004-05-02 00:00:00
abstract：:Behavioral endpoints offer special challenges to toxicology. One arises from the sometimes conflicting ways in which adverse effects may be expressed. For example, both increases and decreases in response rates of schedule-controlled performance may be produced by a specific agent, depending on the specific schedule. ...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/0378-4274(88)90034-3
更新日期：1988-10-01 00:00:00
abstract：:A major public health concern is the degree to which environmental or occupational exposures to exogenous chemicals result in adverse health effects. Biological markers have the potential for helping to answer this important question by providing links between markers of exposures and markers of early stages of the de...
journal_title：Toxicology letters
pub_type： 杂志文章,评审
doi：10.1016/0378-4274(95)03569-9
更新日期：1995-12-01 00:00:00
abstract：:The NLRP3 inflammasome, composed of caspase-1, NLRP3 and ASC, plays a critical role in the clearance of microbial pathogens. Here, we found that the treatment of mouse macrophages with the zinc-containing dithiocarbamate ziram, a widely used fungicide in agriculture, caused a decrease in pro-caspase-1 and NLRP3 levels...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2015.04.012
更新日期：2015-06-15 00:00:00
abstract：:E-64d (a calpain and autophagy inhibitor) has previously been shown safe for the treatment of Alzheimer's disease in humans. In the present study, the potential protective mechanism of E-64d on hippocampal aberrant mossy fiber sprouting was examined in a developmental rat model of penicillin-induced recurrent epilepti...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2012.12.010
更新日期：2013-02-27 00:00:00
abstract：:Poly(ADP-ribose) polymerases (PARPs) are a group of protein-modifying and nucleotide-polymerizing enzymes able to catalyze the transfer of multiple ADP-ribose units from NAD to substrate proteins. In the human genome, 16 different genes encoding for members of this emerging family of enzymes have been identified. Know...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/s0378-4274(02)00429-0
更新日期：2003-04-04 00:00:00
abstract：:Mitochondrial enzymes are targets of newly synthesized drugs being tested for the treatment of neurodegenerative disorders, such as Alzheimer's disease (AD). The enzyme 17β-hydroxysteroid dehydrogenase type 10 (HSD10) is a multifunctional mitochondrial protein that is thought to play a role in the pathophysiology of A...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2020.12.012
更新日期：2021-03-15 00:00:00
abstract：:In order to evaluate the possibility that the metabolism of pyridine may be important for its toxic actions, pyridine was compared with pyridine N-oxide, 2-hydroxypyridine, 3-hydroxypyridine, 4-hydroxypyridine and pyridinium methyliodide in rats given equal molar doses of the chemicals i.p. Hepatoxicity was assessed b...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/0378-4274(96)03660-0
更新日期：1996-06-01 00:00:00
abstract：:Toxicity of an aqueous extract prepared from Echinodorus macrophyllus dried leaves, a plant used in folk medicine to treat inflammation and kidney malfunctions, was estimated by different bioassays. Mutagenicity of the aqueous extract was evaluated in the Salmonella/microsome assay (TA97a, TA98, TA100 and TA102 strain...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/s0378-4274(00)00220-4
更新日期：2000-08-16 00:00:00
abstract：:Male rats are the most frequently used experimental animals in drug toxicity tests. However, there are clear sex-related differences in toxicity of various drugs and chemicals in rats. These differences, in most cases, are closely connected with the sex-related differences in hepatic drug metabolisms. Recent studies i...
journal_title：Toxicology letters
pub_type： 杂志文章,评审
doi：10.1016/0378-4274(92)90245-f
更新日期：1992-12-01 00:00:00
