Abstract：
:The development of non-animal methodology to evaluate the potential for a chemical to cause systemic toxicity is one of the grand challenges of modern science. The European research programme SEURAT is active in this field and will conclude its first phase, SEURAT-1, in December 2015. Drawing on the experience gained in SEURAT-1 and appreciating international advancement in both basic and regulatory science, we reflect here on how SEURAT should evolve and propose that further research and development should be directed along two complementary and interconnecting work streams. The first work stream would focus on developing new 'paradigm' approaches for regulatory science. The goal here is the identification of 'critical biological targets' relevant for toxicity and to test their suitability to be used as anchors for predicting toxicity. The second work stream would focus on integration and application of new approach methods for hazard (and risk) assessment within the current regulatory 'paradigm', aiming for acceptance of animal-free testing strategies by regulatory authorities (i.e. translating scientific achievements into regulation). Components for both work streams are discussed and may provide a structure for a future research programme in the field of predictive toxicology.
journal_name
Arch Toxicoljournal_title
Archives of toxicologyauthors
Daston G,Knight DJ,Schwarz M,Gocht T,Thomas RS,Mahony C,Whelan Mdoi
10.1007/s00204-014-1421-5subject
Has Abstractpub_date
2015-01-01 00:00:00pages
15-23issue
1eissn
0340-5761issn
1432-0738journal_volume
89pub_type
杂志文章abstract：:The immunotoxic potential of many classes of environmental contaminants has been well established in laboratory studies, with much attention being focussed on aryl hydrocarbon (Ah)-receptor binding polychlorinated biphenyl (PCB), polychlorinated dibenzo-p-dioxin (PCDD), and polychlorinated dibenzofuran (PCDF) congener...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s002040050326
更新日期：1996-01-01 00:00:00
abstract：:The effects of equimolar doses of the triphenylethylene antiestrogens tamoxifen and toremifene on female Sprague-Dawley rat liver were studied in a 52-week toxicity study which included a 13-week recovery period. Liver tumors were found in four out of five rats at the highest dose level of tamoxifen (45 mg/kg per day)...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/BF02072035
更新日期：1993-01-01 00:00:00
abstract：:To clarify whether oxidative stress is involved in the development of hepatocellular preneoplastic foci induced by fenofibrate (FF), a peroxisome proliferator-activated receptor alpha agonist, male F344/N rats were fed a diet containing 6,000, 3,000, or 0 ppm of FF for 13 weeks after N-diethylnitrosamine initiation. T...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s00204-007-0278-2
更新日期：2008-09-01 00:00:00
abstract：:Previous studies in our laboratory identified retinoid-induced defects that are mediated by RAR-RXR heterodimerization using interaction of synthetic ligands selective for the retinoid receptors RAR and RXR in mice (Elmazar et al. 1997, Toxicol Appl Pharmacol 146:21-28; Elmazar et al. 2001, Toxicol Appl Pharmacol 170:...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s00204-004-0586-8
更新日期：2004-11-01 00:00:00
abstract：:The mechanical properties of the bones of young, adult and old rats administered various concentrations of cadmium were measured to prove the direct effect of cadmium on the bones of young rats. The young rats were divided into three subgroups, which were administered 0 (control), 5 and 10 ppm cadmium, respectively. T...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/BF00278646
更新日期：1989-01-01 00:00:00
abstract：:Retinoids, derivatives of vitamin A, are essential for many vertebrate functions. Furthermore, several drugs of this class of compounds are valuable in the treatment of certain forms of skin disorders and cancer. However, the therapeutic application of retinoids is limited by their teratogenic potency. The limbs are i...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s002040050368
更新日期：1997-01-01 00:00:00
abstract：:Ethylenediaminetetraacetic acid (EDTA) is widely used in food and other industries to sequester metal ions and to prevent their disadvantageous effects. The objective of the current study was to evaluate the protective effect of Panax ginseng extract standardized with ginsenoside Rg3 (ginsenoside Rg3 content was 3.6% ...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s00204-007-0237-y
更新日期：2008-03-01 00:00:00
abstract：:Rhabdomyolysis has been reported in patients who abuse synthetic cannabinoids. However, no studies have yet assessed whether these cases reflect the direct cytotoxicity of synthetic cannabinoids on skeletal muscle, a possibility that the present study sought to address. Specifically, this study investigated the cytoto...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s00204-020-02944-7
更新日期：2020-11-10 00:00:00
abstract：:The ultimate purpose of the present study was to evaluate correlations between acute in vivo and in vitro toxicity and log P (P is n-octanol-water partition coefficient). The in vitro toxicity to cloned cells (neuroblastoma N18TG-2 and glioma C6) in culture (ED50) and the in vivo toxicity to mice (LD50) of ethylene gl...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/BF01973634
更新日期：1992-01-01 00:00:00
abstract：:Glucose is a major energy source for the entire body, while fructose metabolism occurs mainly in the liver. Fructose consumption has increased over the last decade globally and is suspected to contribute to the increased incidence of non-alcoholic fatty liver disease (NAFLD). NAFLD is a manifestation of metabolic synd...
journal_title：Archives of toxicology
pub_type： 杂志文章,评审
doi：10.1007/s00204-016-1892-7
更新日期：2017-04-01 00:00:00
abstract：:The reduction of 20 microM hexavalent chromium [chromium(VI)] by L-ascorbic acid (AsA) (0.06-2 mM) and/or glutathione (GSH) (2-15 mM) in buffer solutions, cell-free bronchoalveolar lavage fluids or soluble fractions of rat lungs was investigated at physiological pH (37 degrees C). The reduction in AsA solution was pse...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/BF02010721
更新日期：1990-01-01 00:00:00
abstract：:Cyclohexylmethylphosphonofluoridate (cyclosarin) is a highly toxic organophosphate, which was shown to be rather resistant to conventional oxime therapy. To give more insight into the inhibition, reactivation and aging kinetics, human acetyl-(AChE) and butyrylcholinesterase (BChE) were inhibited by cyclosarin (k2 of 7...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s002040050546
更新日期：1998-09-01 00:00:00
abstract：:The effects of a single dose of ethanol on the metabolism and toxicity of chloroform administered to rats per os (p.o.), intraperitoneally (i.p.), or by inhalation (inh) at different doses were investigated. Rats that had been given either ethanol (2 g/kg) or vehicle (water) alone at 4 p.m. on the previous day were ch...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s002040050131
更新日期：1994-01-01 00:00:00
abstract：:The mycotoxin ochratoxin A (OTA) and its metabolite ochratoxin alpha (OT-alpha) were investigated, to examine their potency to induce sister chromatid exchanges (SCE) in cultured porcine urinary bladder epithelial cells (PUBEC) (primary culture). Serum-free cultured PUBEC were incubated for 5 h with either OTA or OT-a...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s002040050171
更新日期：1995-01-01 00:00:00
abstract：:Heat shock proteins (HSPs) are a group of proteins that are rapidly induced in response to physiological stress, including hyperthermia and exposure to toxicants. Thus they may provide a useful index of toxicity in in vitro systems for screening for toxicity. We have recently developed a rat nasal explant system for i...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s00204-004-0541-8
更新日期：2004-06-01 00:00:00
abstract：:Cadmium (Cd), a highly toxic heavy metal, is distributed widely in the general environment of today. The characteristic clinical manifestations of chronic Cd intoxication include renal proximal tubular dysfunction, general osteomalacia with severe pains, and anemia. We have recently reported that the serum level of er...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s002040050352
更新日期：1996-01-01 00:00:00
abstract：:Chronic arsenite exposure induces immunosuppression, but the precise mechanisms remain elusive. Our previous studies demonstrated that arsenite exposure for 24 h induces G0/G1 arrest in mouse B lymphoma A20 cells and the arrest is caused through induction of cyclin-dependent kinase inhibitor p16(INK4a) followed by acc...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s00204-015-1500-2
更新日期：2016-04-01 00:00:00
abstract：:Exposure to toxic metals is a well-known problem in industrialized countries. Metals interfere with a number of physiological processes, including central nervous system (CNS), haematopoietic, hepatic and renal functions. In the evaluation of the toxicity of a particular metal it is crucial to consider many parameters...
journal_title：Archives of toxicology
pub_type： 杂志文章,评审
doi：10.1007/s00204-010-0544-6
更新日期：2010-07-01 00:00:00
abstract：:Chlorpyrifos (CPF) is a widely used organophosphorus pesticide. Earlier work from our laboratory and others has demonstrated that the sensitivity to CPF exposure changes markedly during maturation. A number of studies suggest that in addition to inhibiting acetylcholinesterase (AChE), CPF oxon may also interact direct...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s00204-001-0309-3
更新日期：2002-01-01 00:00:00
abstract：:Free radical processes are proposed to play a crucial role in the development of procainamide adverse effects. Therefore, selenium, as a potent antioxidant, may modified procainamide toxicity. To test this hypothesis plasma and liver thiobarbituric acid-reacting substances (TBARS), plasma antioxidant activity (AOA), e...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/BF01973693
更新日期：1993-01-01 00:00:00
abstract：:Treatment of cats with acrylamide, either 7.5 or 15 mg/kg IM, once a day for 10 days, resulted in increases of 31 and 47% in the phospholipid content of sciatic nerve, respectively, from a control level of 41.1 +/- 2.7 mg/kg wet weight. Determination of the distribution of individual phospholipids indicated no signifi...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/BF00316124
更新日期：1984-09-01 00:00:00
abstract：:The tetrahydroxylated biphenyl-ketone 2,2',4,4'-tetrahydroxybenzophenone (BP2), one of twelve benzophenone-derived UV-filters, is used in cosmetic products and in packaging materials to protect these products from light induced damage. Recently published studies showed that BP2 exerts estrogenic activity; thus, it is ...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s00204-006-0085-1
更新日期：2006-10-01 00:00:00
abstract：:Vitamin E acetate (VEA) has come under significant scrutiny due to its association with e-cigarette, or vaping, product use-associated lung injury (EVALI). In 1965, Sir Austin Bradford Hill proposed a set of criteria used to critically assess an association for causality. In this article, we apply the Bradford Hill ca...
journal_title：Archives of toxicology
pub_type： 杂志文章,评审
doi：10.1007/s00204-020-02770-x
更新日期：2020-06-01 00:00:00
abstract：:A method is outlined to estimate from hemodialysis or hemoperfusion data, respectively, the rate constants, the distribution volume in the beta-phase, and other pharmacokinetic parameters of toxic substances. All calculations are based on the assumption that the usual linear open two-compartment system is also the app...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/BF01459998
更新日期：1983-05-01 00:00:00
abstract：:Iron (Fe) plays essential roles in biological processes, whereas cadmium (Cd) is a toxic and non-essential metal. Two metal transporters, divalent metal transporter 1 (DMT1) and metal transporter protein 1 (MTP1), are responsible for Fe transport in mammals. Here, we studied the effect of dietary Fe on the expression ...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s00204-006-0160-7
更新日期：2007-05-01 00:00:00
abstract：:Exposure to alkylanilines found in tobacco smoke and indoor air is associated with risk of bladder cancer. Genetic factors significantly influence the metabolism of arylamine carcinogens and the toxicological outcomes that result from exposure. We utilized nucleotide excision repair (NER)-deficient immortalized human ...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s00204-020-02901-4
更新日期：2021-01-01 00:00:00
abstract：:There is considerable epidemiological evidence that workers exposed to carbon disulfide (CS2) develop premature atherosclerosis leading to increased rates of coronary heart disease (CHD), but mechanisms underlying this association remain obscure. The present study documents that occupational exposure to CS2 modifies t...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s00204-001-0311-9
更新日期：2002-04-01 00:00:00
abstract：:This study was carried out to investigate the effect of in utero exposure to the cholinotoxicants, nicotine and chlorpyrifos, alone or in combination on neurobehavioral alterations and neuronal morphology latter in adult age. In the present study, 90 days old (corresponding to a human adult age) male and female offspr...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s00204-006-0077-1
更新日期：2006-09-01 00:00:00
abstract：:The highly directional maternal-to-fetal transfer of essential fatty acids (EFAs) across the placenta plays a critical role in guiding proper fetal development. Exposure to xenobiotics that may alter the fetal supply of EFAs/lipids could lead to fetal toxicity. Since the placenta is the first fetal arising organ that ...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s00204-005-0047-z
更新日期：2006-05-01 00:00:00
abstract：:To investigate possible persistent nephrotoxic effects of trichloroethylene (TRI), a retrospective study was carried out on 39 workers exposed to high levels of TRI from 1956 to 1975. Total protein levels in urine, as well as serum and urine creatinine and serum urea were unchanged in comparison with the control. Sodi...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s002040050613
更新日期：1999-06-01 00:00:00
