Abstract:
:Clinical trials with antidotes are difficult to perform for a variety of practical, ethical, and financial reasons. As acute poisoning is a rare event, the commercial interest in basic and clinical research is low. Poisoned patients are usually not available for normal clinical trial procedures and, if they are, they cannot give informed consent. This situation results in a dilemma: antidotes are essential drugs. A resolution of the Council of Europe requests to guarantee the optimal availability of antidotes and the improvement of their use. As comprehensive data on the efficacy of antidotes are often missing, a marketing authorisation under exceptional circumstances according to Article 14(8) of Regulation (EC) No. 276/2004, will often be the only way to get an approval, as: (1) the indications for which the product in question is intended are encountered so rarely that the applicant cannot reasonably be expected to provide comprehensive evidence ("orphan drug"), (2) in the present state of scientific knowledge, comprehensive information cannot be provided, or (3) it would be contrary to generally accepted principles of medical ethics to collect such data. Typically, data on antidotes are obtained from a patchwork of studies with animals, human tissue and a few observations from human poisoning corroborated with data from clinical observations and biochemistry. Generalisations from chemical and mechanistic similarities between groups of poisons are usual, but often lack scientific evidence. Current standards of good clinical practice can rarely be observed. Therefore, public funding and other financial support are necessary incentives to initiate trials in this important area.
journal_name
Toxicologyjournal_title
Toxicologyauthors
Steffen Cdoi
10.1016/j.tox.2006.11.065subject
Has Abstractpub_date
2007-04-20 00:00:00pages
13-9issue
1-3eissn
0300-483Xissn
1879-3185pii
S0300-483X(06)00712-8journal_volume
233pub_type
杂志文章相关文献
TOXICOLOGY文献大全abstract::Dioxins, including the most toxic congener, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), exert diverse biological effects in humans and animals. Host resistance, especially to virus infections, is considered one of the most sensitive targets of TCDD-toxicity, while a recent study showed that the vulnerability to TCDD o...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/s0300-483x(01)00535-2
更新日期:2002-01-15 00:00:00
abstract::Epidemiological studies in humans and experimental work in rodents suggest that exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a persistent environmental toxicant, is associated with incidence of heart disease. Although TCDD toxicity depends by and large on the aryl hydrocarbon receptor (AHR), the role of the...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/j.tox.2016.05.006
更新日期:2016-04-29 00:00:00
abstract::Drug-induced hypersensitivity syndrome (DIHS) is a severe multi-organ system reaction caused by specific drugs. Many reports have revealed that human herpesvirus 6 (HHV-6) reactivation contributes to the development of DIHS. In addition, recent articles have shown that reactivation of other herpesviruses such as human...
journal_title:Toxicology
pub_type: 杂志文章,评审
doi:10.1016/j.tox.2004.12.013
更新日期:2005-04-15 00:00:00
abstract::The mean concentrations of polybrominated diphenyl ethers (PBDEs) (sum tetra- to octaBDEs) were determined in samples of foodstuffs widely consumed by the population of Catalonia, Northeast Spain. The following six tetra-through heptabrominated congeners were also individually analyzed: PBDEs 47, 99, 100, 153, 154 and...
journal_title:Toxicology
pub_type: 杂志文章,评审
doi:10.1016/j.tox.2008.03.006
更新日期:2008-06-03 00:00:00
abstract::Polycyclic aromatic hydrocarbons (PAHs) including benzo[a]pyrene (B[a]P) and 7,12-dimethylbenz[a]anthracene (DMBA) are environmental pollutants, which undergo metabolic activation to exert their carcinogenic effects. Our earlier studies showed that naturally occurring plant phenols, protocatechuic, chlorogenic, tannic...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/j.tox.2008.07.047
更新日期:2008-09-29 00:00:00
abstract::A clonal cell line, R40F, was selected from a heterogenous population of Cd2+ and Zn2+-resistant CHO-K1 cells. These R40F cells demonstrated resistance to 120- and 4-fold higher concentrations of Cd2+ and Zn2+, respectively, than did wild type CHO-K1 cells. When cultured in the presence of low concentrations of Cd2+ (...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/0300-483x(83)90088-4
更新日期:1983-03-01 00:00:00
abstract::Mycotoxins (frequently referred to as secondary metabolites of toxigenic fungi) are commonly found in foodstuffs and are important because of their association with disease. The mycotoxin diacetoxyscirpenol, or 3-hydroxy-4,15-diacetoxy-12,13-epoxytrichothec-9-ene (DAS), is produced by numerous species of Fusarium and ...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/0300-483x(87)90016-3
更新日期:1987-09-01 00:00:00
abstract::The concept that the highly reactive hydroxyl radical (HO) could be generated from an interaction between superoxide (O(2)(-)) and hydrogen peroxide (H(2)O(2)) was proposed (with Joseph Weiss) in Professor Haber's final paper published in 1934. Until it was recognized that free radicals are produced in biological syst...
journal_title:Toxicology
pub_type: 杂志文章,评审
doi:10.1016/s0300-483x(00)00231-6
更新日期:2000-08-14 00:00:00
abstract::We have reported that excessive nitric oxide (NO), like other reactive oxygen species (ROS), causes a decrease in cytochrome c oxidase (CCO) activity and ATP levels (mitochondrial damage) resulting in lens opacity. In addition, previous reports have shown that oxidative stress caused by ROS enhances amyloid β (Aβ) pro...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/j.tox.2017.02.014
更新日期:2017-04-15 00:00:00
abstract::The presence of inclusion bodies in renal proximal tubules was studied in rats exposed to lead and/or disulfiram (tetraethylthiuram disulfide). Pregnant rats were treated with only lead acetate (0.25% Pb in the drinking water), only disulfiram (0.1 mmol/kg p.o. twice a week) or with both lead acetate and disulfiram fr...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/0300-483x(87)90046-1
更新日期:1987-04-01 00:00:00
abstract::No clinical data are available on the acute cutaneous toxicity of spin traps which are frequently used in combination with the electron paramagnetic resonance (EPR) technique for detection of free radicals and reactive oxygen/nitrogen species. The purpose of this study was to evaluate the acute dermatotoxicity of the ...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/s0300-483x(00)00284-5
更新日期:2000-10-26 00:00:00
abstract::Repeated intraperitoneal administration of benzene (1.0 ml/kg body wt) for 3 days produced leucopenia, lymphocytopenia and an increased number of nucleated cells in the bone marrow and significantly decreased organ weights of thymus (P less than 0.001) and spleen (P less than 0.001) in female albino rats. Iron content...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/0300-483x(86)90029-6
更新日期:1986-06-01 00:00:00
abstract::There is a close relationship between the central nervous system activity and bone metabolism. Therefore, methamphetamine (METH), which stimulates the central nervous system, is expected to affect bone turnover. The aim of this study was to investigate the role of METH in bone metabolism. Mice were divided into 3 grou...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/j.tox.2014.01.014
更新日期:2014-05-07 00:00:00
abstract::This article traces the evolution of risk assessment as an essential analytical tool in the federal government. In many programs and agencies, decisions cannot be made without the benefit of information from risk assessment. Although this analytical tool influences important public health and economic decisions, there...
journal_title:Toxicology
pub_type: 历史文章,杂志文章,评审
doi:10.1016/0300-483x(95)03035-e
更新日期:1995-09-01 00:00:00
abstract::The effects of triethyl lead chloride (TEL) on the expression of two detoxication enzyme families, glutathione S-transferases (GSTs) and NAD(P)H:quinone oxidoreductase (QR) were determined in rat liver and kidney. Fischer 344 rats were given one intraperitoneal (i.p.) injection of TEL. GST activity, GST isoenzyme leve...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/s0300-483x(96)03555-x
更新日期:1997-02-14 00:00:00
abstract::Fifteen Chinchilla rabbits were treated by seven daily i.v. injections of two doses (25 or 50 mg/kg body wt.) of sodium borocaptate (Na2B12H11SH), an agent now widely investigated for potential use in Boron Neutron Capture Therapy (BNCT) of malignant brain tumors. Definite nephrotoxic lesions hyperemic and dilated glo...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/0300-483x(93)90123-a
更新日期:1993-04-30 00:00:00
abstract::Although several specific micronutrient deficiencies are associated with disease progression and increased mortality risk in HIV/AIDS, and even a simple multivitamin/mineral supplement can prolong survival, this is typically viewed merely as nutritional support of the immune system, and only necessary if there are def...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/j.tox.2009.10.018
更新日期:2010-11-28 00:00:00
abstract::Ketamine, an anaesthetic agent used in newborns and toddlers, has been shown to induce neurodegeneration and alter adult behavior in mice, when administered during the neonatal period. Mammals have a marked period of rapid brain growth and development (BGS), which is postnatal in mice and rats, spanning the first 3-4 ...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/j.tox.2008.04.019
更新日期:2008-07-30 00:00:00
abstract::Calf thymus DNA was reacted with 1,2-epoxybutene (BDO) in phosphate buffered saline at 37 degrees C for 12 h. DNA was ethanol precipitated and hydrolyzed with 1 M HCl to release DNA bases. Adenine (A)-BDO and guanine (Gua)-BDO adducts were analyzed in the ethanol supernatant and DNA hydrolysate using LC/ESI MS/MS. Rea...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/0300-483x(96)03468-3
更新日期:1996-10-28 00:00:00
abstract::Pilinskaya showed that the fungicide ziram induced chrocosome aberrations in the lymphocytes of exposed industrial workers and also in lymphocyte cultures treated in vitro. Ziram is chemically similar to the drug Antabuse (disulfirm) which is used in the treatment of alcoholics. To establish whether disulfirm can also...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/0300-483x(75)90055-4
更新日期:1975-07-01 00:00:00
abstract::The present study was undertaken to investigate the involvement of oxidative damage in lead-induced toxicity in humans and to enlighten whether oxidative stress indicators are correlated with the known indices of lead toxicity. For these purposes, selected oxidative stress parameters along with some clinical indices o...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/j.tox.2003.09.009
更新日期:2004-02-15 00:00:00
abstract::Our previous study revealed that exposure to 0.4 ppm ozone (O(3)) enhanced nasal allergy-like reactions in guinea pigs. In the present study, we investigated the concentration-dependency of the effects of exposure to O(3) on the aggravation of nasal allergy-like reactions induced by repeated nasal administration of an...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/j.tox.2004.01.008
更新日期:2004-06-01 00:00:00
abstract::Female mice were given nutrient-sufficient, purified diets containing cadmium at either 0.25, 5, or 50 ppm, as described in the accompanying publication. One-half of the females were bred for 6 consecutive 42-day rounds of pregnancy/lactation (PL mice); remaining females were non-pregnant controls (NP mice). PL mice a...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/0300-483x(88)90092-3
更新日期:1988-07-01 00:00:00
abstract::National and international law is an essential component of the array of measures serving to protect against the hostile release of biological or chemical agents, and to help to mitigate the consequences should such a release nevertheless take place. These includes the Geneva Protocol of 1925, the Chemical Weapons Con...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/j.tox.2005.06.017
更新日期:2005-10-30 00:00:00
abstract::CI-959 is an orally effective inhibitor of cellular activation in both in vitro and animal models. To assess the effects of CI-959 on immune function, male Fischer 344 rats were evaluated for splenic T- and B-lymphocyte populations, antibody-forming cell response to sheep red blood cells (sRBC), concanavalin A and pok...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/0300-483x(94)02985-4
更新日期:1995-04-12 00:00:00
abstract::We provide an overview of the functional interrelationship between genes and proteins related to DNA repair by homologous recombination and cell cycle regulation in relation to the progression and therapy resistance of human tumours. To ensure the high-fidelity transmission of genetic information from one generation t...
journal_title:Toxicology
pub_type: 杂志文章,评审
doi:10.1016/s0300-483x(03)00291-9
更新日期:2003-11-15 00:00:00
abstract::Fusarenon-X (FX), a trichothecene mycotoxin, is well known to be cytotoxic to mammalian cells. Our previous study revealed that FX induced apoptosis in mouse thymocytes both in vivo and in vitro. We investigated the mode of apoptosis induced by FX using HL-60 cell culture. When FX at a final concentration of 0.5 micro...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/s0300-483x(01)00586-8
更新日期:2002-03-20 00:00:00
abstract::Exposure of rats to 0.1 and 0.5 mg Cd/kg subcutaneously (s.c.) thrice weekly for 5 weeks resulted in an accumulation of cadmium in the liver in concentrations of 40 and 95 micrograms/g tissue, respectively, and a microsomal burden of Cd amounting to approx. 2-3% of the retained cadmium. The cytoplasm contained about 8...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/0300-483x(84)90079-9
更新日期:1984-09-14 00:00:00
abstract::The two major mammalian metabolites of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), namely 2-hydroxy-3,7,8-trichlorodibenzo-p-dioxin and 2-hydroxy-1,3,7,8-tetrachlorodibenzo-p-dioxin, have been synthesized. The compounds were individually administered to immature male Wistar rats and their effects on body weight loss, ...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/0300-483x(86)90196-4
更新日期:1986-10-01 00:00:00
abstract::Studies on the pulmonary retention of benzo[a]pyrene after inhalation have shown that clearance is biphasic, with one component clearing with a half-time greater than 1 day and another with a half-time less than 1 day. In the work reported here we demonstrated that the amount of benzo[a]pyrene instilled in the lungs c...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/0300-483x(85)90066-6
更新日期:1985-06-28 00:00:00