Abstract:
:To cope with the rapid onset of the life-threatening cholinergic crisis after poisoning with organophosphorus compounds, atropine-oxime preparations should be available in autoinjectors allowing i.m. administration also in the absence of a physician. Such a scenario is conceivable in the battlefield, when nerve agents are disseminated, and can no longer be excluded in civilian areas, as demonstrated most recently in Tokyo. In addition, autoinjectors may be of value in agriculture when medical care is remote. The use of second generation oximes with broad antidotal spectrum, e.g., HI 6 (1-(((4-(aminocarbonyl)pyridinio)methoxy)methyl)-2-((hydr oxyimino)methyl) pyridinium dichloride monohydrate; CAS 34433-31-3) and HLö 7 (1-(((4-(aminocarbonyl)pyridinio)methoxy)methyl) 2,4-bis((hydroxyimino)methyl) pyridinium dimethanesulfonate; CAS 145613-73-6) is only possible in dry/wet autoinjectors because their stability is limited in concentrated solution. To detect a possible delay in atropine absorption by the two oximes, the pharmacokinetics of atropine after "autoinjection" in beagle dogs were determined. Commercially available autoinjectors from two manufacturers [STI International Ltd (BJ) and Astra Tech (AT)] were filled with atropine sulfate, either alone (2 mg) or in combination with HI 6 (500 mg) and HLö 7 (200 mg), respectively, and injected according to a complete cross-over design. Atropine concentration was determined as l-hyoscyamine equivalents in a radioreceptor assay (RRA). In the range of 0.1-6.9 ng/ml, atropine sulfate displaced [N-methyl-3H]-scopolamine methyl chloride ([3H]NMS) competitively from rat cerebral cortex membranes. At 200 pmol/l [3H]NMS, IC50 was 1.4 +/- 0.1 x 10(-9) M atropine (CV = 8.1%). The intra-assay deviation was about 6%; day-to-day deviation in determination of 1 nM (0.695 ng/ml) atropine was 2.6% (CV = 5.2%). AT autoinjectors containing HI 6 delivered only 1.81 mg atropine sulfate while 2.14 mg was released by the other injectors. According to the manufacturer, the reduced delivery was caused by a defective Teflon-coated O-ring as detected later on in the batch used. To allow comparison of the bioavailability of atropine from various autoinjectors, the AUCs were normalized to a constant dose. The atropine absorption half-time (7 min) was not affected either by the autoinjector type or by the combination with oximes. The other pharmacokinetic data likewise did not reveal any differences between the groups. Maximal plasma concentration was 33 ng ml-1, elimination half-life 52 min, Vapp 3.2 l kg-1 and Clpl 44 ml min-1 kg-1. The relatively high clearance of l-hyoscyamine is discussed.
journal_name
Arch Toxicoljournal_title
Archives of toxicologyauthors
Thiermann H,Radtke M,Spöhrer U,Klimmek R,Eyer Pdoi
10.1007/s002040050276subject
Has Abstractpub_date
1996-01-01 00:00:00pages
293-9issue
5eissn
0340-5761issn
1432-0738journal_volume
70pub_type
杂志文章abstract::As part of a study on cadmium nephrotoxicity, we studied the effect of cadmium chloride (CdCl2) in isolated human renal proximal tubules metabolizing the physiological substrate lactate. Dose-effect experiments showed that 10-500 μM CdCl2 reduced lactate removal, glucose production and the cellular levels of ATP, coen...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/s00204-010-0633-6
更新日期:2011-09-01 00:00:00
abstract::Millions of tons of all kind of munitions, including mines, bombs and torpedoes have been dumped after World War II in the marine environment and do now pose a new threat to the seas worldwide. Beside the acute risk of unwanted detonation, there is a chronic risk of contamination, because the metal vessels corrode and...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/s00204-020-02931-y
更新日期:2020-12-01 00:00:00
abstract::The use of new psychoactive substances (NPSs) as a substitute for illegal drugs is increasing rapidly and is a serious threat to public health. 25C-NBF is a newly synthesized phenethylamine-type NPS that acts as a 5-hydroxyindoleacetic acid (5-HT) receptor agonist, but little is known about its pharmacological effects...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/s00204-020-02740-3
更新日期:2020-07-01 00:00:00
abstract::In vivo screening methods for detection of thyroid function modulators are now under development in many research laboratories. We assessed the applicability of the Hershberger assay protocol to screen for thyroid function modulators. In experiment 1, castrated male BrlHan WIST@Jcl (GALAS) rats were administered a pot...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/s00204-005-0677-1
更新日期:2005-11-01 00:00:00
abstract::Dibromoacetonitrile (DBAN) is a disinfection byproduct of chlorination of drinking water. Epidemiological studies indicate that it might present a potential hazard to human health. The present work provides evidence for DBAN activation to cyanide (CN(-)) by the hypoxanthine (HX)/xanthine oxidase (XO)/iron (Fe) system ...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/s00204-002-0418-7
更新日期:2003-02-01 00:00:00
abstract::3-monochloropropane-1,2-diol (3-MCPD), a rat renal and testicular carcinogen, has been reported to occur in various foods and food ingredients as free or esterified forms. Since reports about toxicity of 3-MCPD esters are limited, we conducted a 13-week rat subchronic toxicity study of 3-MCPD esters (palmitate diester...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/s00204-013-1190-6
更新日期:2014-04-01 00:00:00
abstract::Sodium diethyldithiocarbamate (DETC) is the main metabolite of disulfiram. Recently, we reported that mechanism of disulfiram cytotoxicity in V79 cells might be partially connected with thiol redox-state imbalance. Here, we examined the effect of DETC on the level of intracellular glutathione (GSH), protein oxidation ...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/s00204-012-0909-0
更新日期:2012-12-01 00:00:00
abstract::Primary human hepatocytes (hHeps) are still gold standard to perform human drug metabolism studies, but their availability is limited by donor organ scarcity. Therefore, hepatoma cell lines are widely used as alternatives, although their phases I and II drug-metabolizing activities are substantially lower compared wit...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/s00204-011-0733-y
更新日期:2012-01-01 00:00:00
abstract::Neurotoxic properties of acrylamide and seven related compounds in rats were studied with regard to the effects on rotarod performance, morphology of nerves and neurotubulin. Compounds used in the present study were acrylamide, N-hydroxymethylacrylamide, N-isopropylacrylamide, methacrylamide, N-methylacrylamide, croto...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/BF01239204
更新日期:1983-11-01 00:00:00
abstract::Gene expression analysis has been established as a tool for the characterization of genotoxic mechanisms of chemical mutagens. It has been suggested that expression analysis is capable of distinguishing compounds that cause DNA damage from those that interfere with mitotic spindle function. Formaldehyde (FA) is known ...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/s00204-013-1060-2
更新日期:2013-11-01 00:00:00
abstract::Perfluoroalkyl acids are widely used in numerous industrial and commercial applications due to their unique physical and chemical characteristics. Although perfluorooctanoic acid (PFOA) is associated with hepatomegaly through peroxisome proliferator-activated receptor α (PPARα) activation, liver fat accumulation and c...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/s00204-014-1322-7
更新日期:2015-09-01 00:00:00
abstract::Many in the welding industry suffer from bronchitis, lung function changes, metal fume fever, and diseases related to respiratory damage. These phenomena are associated with welding fumes; however, the mechanism behind these findings remains to be elucidated. In this study, the lungs of cynomolgus monkeys were exposed...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/s00204-009-0486-z
更新日期:2010-03-01 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::HCB was detected in all preparations of human placenta, maternal blood, milk, and cord blood. It was confirmed that HCB transferred from mother to fetus through the placenta. A significant linear correlation exists between the HCB concentration in placenta and that in cord blood. Therefore, the placental concentration...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/BF00333426
更新日期:1985-01-01 00:00:00
abstract::Second order rate constants for the initial reaction of 12 mammalian oxyhemoglobins (Hb) with equimolar phenylhydrazine (PHZ), a compound inducing Heinz body hemolytic anemia, were determined by recording continuous changes in absorbance with time at 577 nm. The rate constants were varied in a range from 43 m-1.s-1 wi...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/s002040050161
更新日期:1995-01-01 00:00:00
abstract::Prudhoe Bay crude oil (PBCO) and its aliphatic, aromatic and heterocyclic fractions were tested on the developing chick embryo for (i) embryotoxicity (ii) their ability to induce hepatic and renal cytochrome P450 levels as well as hepatic, renal and pulmonary aryl hydrocarbon hydroxylase activities. On the basis of it...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/BF00302389
更新日期:1987-08-01 00:00:00
abstract::Mercury exists in the environment in various forms, all of which pose a risk to human health. Despite guidelines regulating the industrial release of mercury into the environment, humans continue to be exposed regularly to various forms of this metal via inhalation or ingestion. Following exposure, mercuric ions are t...
journal_title:Archives of toxicology
pub_type: 杂志文章,评审
doi:10.1007/s00204-016-1803-y
更新日期:2017-01-01 00:00:00
abstract::The influence of pivalic acid (PIV), a compound often used to make pro-drugs, and of the structurally related trichloroacetic acid (TCA), on several hepatic and renal enzymes was investigated in Sprague-Dawley rats, following a 4-day treatment period. The PIV and TCA treatments resulted in a similar and selective indu...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/s002040050253
更新日期:1996-01-01 00:00:00
abstract::Acetaminophen (APAP) is a widely-used analgesic and a known hepatotoxic agent. Vascular endothelial growth factor (VEGF) is a growth factor with multiple functional roles. VEGF plays an important role in angiogenesis and hepatic regeneration. The aim of this study was to determine the expression of VEGF isoforms and i...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/s00204-007-0201-x
更新日期:2007-10-01 00:00:00
abstract::The effect of methantheline, a quaternary ammonium compound, on the reactivation by HI 6 of soman-inhibited human erythrocyte acetylcholinesterase (AChE) was investigated in vitro using purified human erythrocyte AChE or washed human erythrocytes. Methantheline itself was found to be a mixed competitive/non-competitiv...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/s002040050243
更新日期:1995-01-01 00:00:00
abstract::Mouse liver CYP2A5 is induced by several structurally unrelated compounds. In intact mouse liver, pyrazole (PYR) and 4-hydroxypyrazole (4-OH) induce selectively the expression of CYP2A5 while expression of other CYPs is decreased. In this study we exposed mouse primary hepatocytes to PYR, 4-OH, 4-methylpyrazole (4Me; ...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/s002040050511
更新日期:1998-05-01 00:00:00
abstract::The International Agency for Research on Cancer considers the carcinogenicity of welding fume of priority for re-evaluation. Genotoxic effects in experimental animals are still inconclusive. Here, we investigated the association of personal exposure to metals in respirable welding fumes during a working shift with oxi...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/s00204-014-1319-2
更新日期:2015-08-01 00:00:00
abstract::The toxicity of 60 micrograms/kg 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) given IP in corn oil/5% acetone was examined in male Sprague-Dawley rats adapted to 25 degrees C or 4 degrees C ambient temperature. Cold exposure significantly reduced mean time to death and tended to increase mortality. Body weight at the ti...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/BF00290540
更新日期:1986-12-01 00:00:00
abstract::The increasing number of man-made chemicals in the environment that may pose a carcinogenic risk emphasizes the need to develop reliable time- and cost-effective approaches for carcinogen detection. To address this issue, we have investigated the utility of human hepatocytes for the in vitro identification of genotoxi...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/s00204-019-02569-5
更新日期:2019-11-01 00:00:00
abstract::Quercetin (QC), a polyphenolic compound widely distributed in fruits and vegetables has recently gained interest due to its cisplatin (CP) sensitizing properties in cancer cells. It is currently unknown, whether quercetin also increases the susceptibility of the kidneys to cisplatin toxicity. We studied the effects of...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/s002040050539
更新日期:1998-07-01 00:00:00
abstract::Nanoparticles (NP) have a tendency to agglomerate after dispersion in physiological media, which can be prevented by the addition of serum. This may however result in modification of the toxic potential of particles due to the formation of protein corona. Our study aimed to analyze the role of serum that is added to i...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/s00204-016-1673-3
更新日期:2017-01-01 00:00:00
abstract::This study was conducted to determine the functional role of phospholipase D (PLD) involved in testicular Leydig cell damage caused by di (2-ethylhexyl) phthalate (DEHP) in Sprague-Dawley rats. DEHP (500 mg/kg/day) was administered orally to prepubertal rats for 1, 7, 14, 21 or 28 days. After 7 days of exposure, DEHP ...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/s00204-010-0618-5
更新日期:2011-08-01 00:00:00
abstract::The involvement of oxidative stress has been suggested as a mechanism for neurotoxicity caused by methylmercury (MeHg), but the mechanism for MeHg selective toxicity in the central nervous system is still unclear. In this research, to clarify the mechanism of selective neurotoxicity caused by MeHg, the oxygen consumpt...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/s00204-007-0209-2
更新日期:2007-11-01 00:00:00
abstract::A histochemical technique for detection of the in vivo induced cellular aldehydes based on the direct Schiff's reaction is reported in this paper. CCl4-intoxicated rat liver was used as an experimental model. Fresh and non-pretreated rat liver cryostat sections fixed in 10% formol calcium solution and washed in distil...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/BF00334622
更新日期:1988-04-01 00:00:00
abstract::4-Nonylphenol (para-nonylphenol, 4-NP), metabolites including linear and branched isoforms of nonylphenol (n-NP and t-NP, respectively), has been considered an endocrine disrupting substance resulting in reproductive dysfunction and increasing reactive oxygen species production in testis, liver, kidney, and brain. How...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/s00204-009-0447-6
更新日期:2009-10-01 00:00:00