Comparative biological properties of the four stereoisomers of difethialone, a second-generation anticoagulant rodenticide, in rats: development of a model allowing to choose the appropriate stereoisomeric ratio.


:The current management of rodent pest populations is based on second-generation anticoagulant rodenticides (SGAR). These molecules, of which difethialone is part, are much more efficient than the first generation. Nevertheless, this efficiency comes with a major drawback, SGARs are tissue persistent that increases the exposure of rodent predators to them. According to its chemical structure, difethialone has four stereoisomers, whose specific inhibition potency and pharmacokinetic have never been described and might be useful to design new eco-friendly rodenticides. The study aimed to investigate the ability to inhibit anticoagulant target enzyme (VKORC1) and the pharmacokinetics in rats of the four difethialone stereoisomers in rats. We show that stereoisomers are all highly efficient to inhibit VKORC1 activity, but they have distinct initial half-life with 6.0 h, 25.4 h, 69.3 h, and 82.3 h for, respectively, E4-trans, E2-cis, E1-trans, and E3-cis stereoisomer. These results open the way of the development of eco-friendly and efficient rodenticide by mixing some of these stereoisomers. Preferential incorporation of the E4-trans stereoisomer (high inhibitory VKORC1 potency, relatively shorter liver half-life) into difethialone rodenticides baits might result in a more eco-friendly product than current commercially available difethialone formulations. In addition, we put forward modelling to help design bait according to the circumstance of use (presence of non-target species, food competition, etc.) by modulating the theorical AUC and and the theorical concentration of the product at the death of the rodent pest. Thus, this modeling might allow to diminish the use of laboratory animal in assay.


Arch Toxicol


Archives of toxicology


Lefebvre S,Fourel I,Chatron N,Caruel H,Benoit E,Lattard V




Has Abstract


2020-03-01 00:00:00














  • Role of biological antioxidants in benzanthrone toxicity.

    abstract::Previous studies indicate that benzanthrone, an anthraquinone dye intermediate, caused significant depletion of ascorbic acid (AsA). In this investigation the effect of benzanthrone on the status of different forms of AsA and other bio-antioxidants such as glutathione (GSH) was studied. Oral administration of benzanth...

    journal_title:Archives of toxicology

    pub_type: 杂志文章


    authors: Dwivedi N,Das M,Khanna SK

    更新日期:2001-06-01 00:00:00

  • Atrial thrombosis involving the heart of F-344 rats ingesting quinacrine hydrochloride.

    abstract::Quinacrine hydrochloride is toxic for the heart of F-344 rats. Rats treated with 500 ppm quinacrine hydrochloride in the diet all developed a high incidence of left atrial thrombosis. The lesion was associated with cardiac hypertrophy and dilatation and focal myocardial degeneration. Rats died from cardiac hypertrophy...

    journal_title:Archives of toxicology

    pub_type: 杂志文章


    authors: Reuber MD,Lijinsky W

    更新日期:1984-11-01 00:00:00

  • St. John's wort treatment in women bears risks beyond pharmacokinetic drug interactions.

    abstract::We analyzed adverse events in a clinical phase I trial to assess dose-dependent metabolic effects of St. John's wort co-administered with rifampicin in 12 healthy volunteers. Within 3-6 days after increasing the St. John's wort dose from 300 to 600 mg TID, five of six female participants developed ambient temperature-...

    journal_title:Archives of toxicology

    pub_type: 杂志文章


    authors: Hohmann N,Maus A,Carls A,Haefeli WE,Mikus G

    更新日期:2016-04-01 00:00:00

  • Fate of carbaryl in rat skin.

    abstract::Metabolism of carbaryl by rat liver and skin post-mitochondrial fraction has been measured in the presence and absence of cofactors to promote different metabolic pathways. The metabolic capacity was compared with the metabolism of carbaryl during percutaneous absorption in a static skin diffusion system using a varie...

    journal_title:Archives of toxicology

    pub_type: 杂志文章


    authors: MacPherson SE,Scott RC,Williams FM

    更新日期:1991-01-01 00:00:00

  • Inhibition of mitochondrial respiration in vivo is an early event in acetaminophen-induced hepatotoxicity.

    abstract::Morphological changes in mitochondria are observed early in the course of acetaminophen (AA)-induced hepatotoxicity, and mitochondrial dysfunction has been observed both in vivo and in vitro following exposure to AA. This study examined the early effects of AA exposure in vivo on mitochondrial respiration and evaluate...

    journal_title:Archives of toxicology

    pub_type: 杂志文章


    authors: Donnelly PJ,Walker RM,Racz WJ

    更新日期:1994-01-01 00:00:00

  • Binding characteristics of ortho-toluidine to rat hemoglobin and albumin.

    abstract::The binding characteristics of [14C]ortho-toluidine (OT), a suspect human carcinogen, were investigated in male Sprague-Dawley rats. Rats were administered [14C]OT i.p. at 10, 20, 40, 50, or 100 mg/kg body weight, then sacrificed at 2, 4, 8, 18, 24, 48, or 72 h, or 7, 14, or 28 days. Hemoglobin (Hb) and albumin (Alb) ...

    journal_title:Archives of toxicology

    pub_type: 杂志文章


    authors: DeBord DG,Swearengin TF,Cheever KL,Booth-Jones AD,Wissinger LA

    更新日期:1992-01-01 00:00:00

  • Toxicological interactions between the mycotoxins deoxynivalenol, nivalenol and their acetylated derivatives in intestinal epithelial cells.

    abstract::In case of mycotoxin contaminations, food and feedstuff are usually contaminated by more than one toxin. However toxicological data concerning the effects of mycotoxin combinations are sparse. The intestinal epithelium is the first barrier against food contaminants and this constantly renewing organ is particularly se...

    journal_title:Archives of toxicology

    pub_type: 杂志文章


    authors: Alassane-Kpembi I,Puel O,Oswald IP

    更新日期:2015-08-01 00:00:00

  • Sensory irritation mechanisms investigated from model compounds: trifluoroethanol, hexafluoroisopropanol and methyl hexafluoroisopropyl ether.

    abstract::Quantitative structure-activity relationships (QSAR) have suggested the importance of hydrogen bonding in relation to activation of the sensory irritant receptor by nonreactive volatile organic chemicals. To investigate this possibility further, three model compounds with different hydrogen bond acidity, trifluoroetha...

    journal_title:Archives of toxicology

    pub_type: 杂志文章


    authors: Nielsen GD,Abraham MH,Hansen LF,Hammer M,Cooksey CJ,Andonian-Haftvan J,Alarie Y

    更新日期:1996-01-01 00:00:00

  • Effect of age on cadmium-induced metallothionein synthesis in the rat.

    abstract::Cadmium-induced metallothionein (MT) synthesis was investigated in male rats of three ages, 3, 12 and 24 months. Physiological levels of MT in kidney, liver and lung measured simultaneously in untreated animals were found to be within the same range in all three age groups. Following 3-day treatment with CdCl2 equival...

    journal_title:Archives of toxicology

    pub_type: 杂志文章


    authors: Wormser U,Nir I

    更新日期:1988-01-01 00:00:00

  • Inhibitory effect of berberine on tert-butyl hydroperoxide-induced oxidative damage in rat liver.

    abstract::Berberine, a main protoberberine component of Coptidis Rhizoma, was studied for the mechanism of its inhibitory effects on the tert-butyl hydroperoxide (t-BHP)-induced cytotoxicity and lipid peroxidation in rat liver. In the preliminary study, berberine expressed an antioxidant property by its capacity for quenching t...

    journal_title:Archives of toxicology

    pub_type: 杂志文章


    authors: Hwang JM,Wang CJ,Chou FP,Tseng TH,Hsieh YS,Lin WL,Chu CY

    更新日期:2002-11-01 00:00:00

  • Prevention by steroids of cerium hepatotoxicity.

    abstract::In female rats, the lethality and hepatotoxicity of cerous chloride (CeCl3) were significantly altered by pretreatment with steroidal and nonsteroidal compounds (pregnenolone-16alpha-carbonitrile "PCN", dexamethasone, spironolactone, phenobarbital) that stimulate hepatic drug-metabolizine enzyme activity and by estrad...

    journal_title:Archives of toxicology

    pub_type: 杂志文章


    authors: Salas M,Tuchweber B

    更新日期:1976-03-11 00:00:00

  • Spectral evidence for 2,2,3-trichloro-oxirane formation during microsomal trichloroethylene oxidation.

    abstract::During aerobic incubation of trichloroethylene with rabbit liver microsomes and NADPH a difference absorption peak appears at 451-452 nm. Trichloroethylene does not form a ligand absorption spectrum with hepatic microsomes reduced by dithionite, or in anaerobic incubates in the presence of NADPH. Addition of trichloro...

    journal_title:Archives of toxicology

    pub_type: 杂志文章


    authors: Uehleke H,Tabarelli-Poplawski S,Bonse G,Henschler D

    更新日期:1977-06-18 00:00:00

  • Assessment of the teratogenicity of di(2-ethylhexyl)phthalate and mono(2-ethylhexyl)phthalate in mice.

    abstract::Di(2-ethylhexyl)phthalate (DEHP) and mono-(2-ethylhexyl)phthalate (MEHP) were administered PO or IP to pregnant ICR mice at varying doses on days 7, 8, and 9 of gestation. In groups given DEHP orally, resorptions and malformed fetuses increased significantly at 1,000 mg/kg. Fetal weights were also significantly suppre...

    journal_title:Archives of toxicology

    pub_type: 杂志文章


    authors: Shiota K,Mima S

    更新日期:1985-02-01 00:00:00

  • Investigations on the liver toxicity of a blend of HCFC-123 (2,2-dichloro-1,1,1-trifluoroethane) and HCFC-124 (2-chloro-1,1,1,2-tetrafluoroethane) in guinea-pigs.

    abstract::2,2-Dichloro-1,1,1-trifluoroethane (HCFC-123) has been developed as a substitute for ozone-depleting chlorofluorocarbons (CFCs). It is a structural analogue of halothane and similarities in the metabolic pathways and liver toxicity of both compounds have been described. The present study was initiated after an acciden...

    journal_title:Archives of toxicology

    pub_type: 杂志文章


    authors: Hoet P,Buchet JP,Sempoux C,Nomiyama T,Rahier J,Lison D

    更新日期:2001-07-01 00:00:00

  • Effect of acrylamide on neurotransmitter metabolism and neuropeptide levels in several brain regions and upon circulating hormones.

    abstract::The effect of acute and subchronic acrylamide treatment on levels of dopamine, serotonin, and their metabolites was determined in several brain regions of the rat. Concentrations of several neuropeptides and circulating hormones were also measured. Both a single and repeated doses of acrylamide resulted in elevated le...

    journal_title:Archives of toxicology

    pub_type: 杂志文章


    authors: Ali SF,Hong JS,Wilson WE,Uphouse LL,Bondy SC

    更新日期:1983-01-01 00:00:00

  • Effect of osmotic diuresis on gentamicin-induced nephrotoxicity in rats.

    abstract::The effect of isosorbide diuresis on gentamicin excretion and tissue accumulation as well as gentamicin-induced histopathologic changes in renal tissue were examine in rats. Gentamicin (30, 60, 120, 160 mg/kg) was administered s.c. for 10 consecutive days with or without isosorbide pretreatment. Osmotic diuresis with ...

    journal_title:Archives of toxicology

    pub_type: 杂志文章


    authors: Newman RA,Weinstock LB,Gump DW,Hacker MP,Yates JW

    更新日期:1980-09-01 00:00:00

  • Hydrogen peroxide production in mouse tissues after acute d-amphetamine administration. Influence of monoamine oxidase inhibition.

    abstract::The toxicity of amphetamines is conditioned by a complex array of mechanisms, involving the increase of neurotransmission (e.g. leading to hyperthermia) and enzymatic and non-enzymatic oxidation of amphetamines and biogenic amines. Considering that all these processes may increase the generation of hydrogen peroxide (...

    journal_title:Archives of toxicology

    pub_type: 杂志文章


    authors: Carvalho F,Duarte JA,Neuparth MJ,Carmo H,Fernandes E,Remião F,Bastos ML

    更新日期:2001-10-01 00:00:00

  • Changes in the excretion of endogenous glycine conjugate as a possible artifact in toxicological experiments.

    abstract::Changes in the urinary excretion of hippuric acid (HIA) and phenaceturic acid (PUA) as well as their metabolic precursors, i.e. benzoic (BA) and phenylacetic acid (PAA), in rats housed in glass metabolic cages for 4 days were monitored using gas-liquid chromatography. The amount of HIA excreted was 128 +/- 63 mumol/kg...

    journal_title:Archives of toxicology

    pub_type: 杂志文章


    authors: Linhart I,Smejkal J

    更新日期:1987-01-01 00:00:00

  • Determination of urinary thymidine glycol using affinity chromatography, HPLC and post-column reaction detection: a biomarker of oxidative DNA damage upon kidney transplantation.

    abstract::Reactive oxygen species are generated during ischaemia-reperfusion of tissue. Oxidation of thymidine by hydroxyl radicals (HO) leads to the formation of 5,6-dihydroxy-5,6-dihydrothymidine (thymidine glycol). Thymidine glycol is excreted in urine and can be used as biomarker of oxidative DNA damage. Time dependent chan...

    journal_title:Archives of toxicology

    pub_type: 杂志文章


    authors: Thier R,Brüning T,Kocher K,Blaszkewicz M,Makropoulos V,Sundberg A,Bolt HM

    更新日期:1999-11-01 00:00:00

  • Effects of four nucleoside analogues used as antiviral agents on rat Sertoli cells (SerW3) in vitro.

    abstract::Some nucleoside analogues are used to treat herpes simplex and other viral infections. They are known to impair spermatogenesis, but published data are scarce. We studied the effects of four nucleosides on SerW3 cells, a rat Sertoli cell line. Cells were cultured for 3 days in DMEM supplemented with four different con...

    journal_title:Archives of toxicology

    pub_type: 杂志文章


    authors: Qiu R,Horvath A,Stahlmann R

    更新日期:2016-08-01 00:00:00

  • 5-Aza-2'-deoxycytidine inhibited PDGF-induced rat airway smooth muscle cell phenotypic switching.

    abstract::Airway smooth muscle (ASM) cell phenotypic switching played an important role in airway remodeling in asthma. In vitro platelet-derived growth factor (PDGF) induced ASM cell phenotypic switching from a mature to pro-remodeling phenotype, but the mechanism remained incompletely understood. This study was to explore the...

    journal_title:Archives of toxicology

    pub_type: 杂志文章


    authors: Ning Y,Huang H,Dong Y,Sun Q,Zhang W,Xu W,Li Q

    更新日期:2013-05-01 00:00:00

  • Dual-label time-resolved fluoroimmunoassay for simultaneous detection of aflatoxin B1 and ochratoxin A.

    abstract::A dual-label time-resolved fluoroimmunoassay (TRFIA) for simultaneous quantification of aflatoxin B1 (AFB1) and ochratoxin A (OTA) is described. For this, microtitration wells were coated with AFB1-horse radish peroxidase (HRP) and OTA-bovine serum albumin. The standards and samples were loaded on the coated plates, a...

    journal_title:Archives of toxicology

    pub_type: 杂志文章


    authors: Huang B,Xiao H,Zhang J,Zhang L,Yang H,Zhang Y,Jin J

    更新日期:2009-06-01 00:00:00

  • Urinary trehalase as an early indicator of cadmium-induced renal tubular damage in rabbit.

    abstract::The significance of urinary trehalase as a possible early indicator of renal disorder was examined using Cd-treated rabbits, which received 1 mg/kg Cd thrice weekly for 3 months subcutaneously. The results showed that urinary trehalase increased significantly from 1 week after treatment, earlier than LAP, ALP, protein...

    journal_title:Archives of toxicology

    pub_type: 杂志文章


    authors: Nishimura N,Oshima H,Nakano M

    更新日期:1986-12-01 00:00:00

  • Protective effect of topical iodine containing anti-inflammatory drugs against sulfur mustard-induced skin lesions.

    abstract::Previous studies have shown the antidotal efficacy of topical iodine at 15 and 30 min post-exposure to sulfur mustard (SM). Here we demonstrate efficacy at longer intervals (20, 30, 45, and 60 min, respectively, for data) using an improved topical povidone-iodine preparation termed N66, which contains steroidal and no...

    journal_title:Archives of toxicology

    pub_type: 杂志文章


    authors: Wormser U,Sintov A,Brodsky B,Casillas RP,Nyska A

    更新日期:2004-03-01 00:00:00

  • Regional alterations of brain catecholamines by styrene exposure in rabbits.

    abstract::The regional distribution of dopamine, norepinephrine and homovanillic acid was assessed in adult male rabbits exposed to styrene vapours. The turnover of dopamine and norepinephrine was also measured in several brain regions by the decay in endogenous catecholamines after inhibition of tyrosine hydroxylase by alpha-m...

    journal_title:Archives of toxicology

    pub_type: 杂志文章


    authors: Mutti A,Falzoi M,Romanelli A,Franchini I

    更新日期:1984-09-01 00:00:00

  • The pharmacokinetics of amygdalin.

    abstract::Amygdalin (D-mandelonitrile-beta-D-gentiobioside) is a cyanogenic glycoside claimed to show anti-cancer activity, sold under the incorrect name "Laetrile". For a sensible discussion of its alleged activity and its established toxicity it is necessary that its fate in the organism is known. The pharmacokinetics of amyg...

    journal_title:Archives of toxicology

    pub_type: 杂志文章


    authors: Rauws AG,Olling M,Timmerman A

    更新日期:1982-03-01 00:00:00

  • Long-term cadmium exposure induces anemia in rats through hypoinduction of erythropoietin in the kidneys.

    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


    authors: Horiguchi H,Sato M,Konno N,Fukushima M

    更新日期:1996-01-01 00:00:00

  • miR-138-1* regulates aflatoxin B1-induced malignant transformation of BEAS-2B cells by targeting PDK1.

    abstract::Environmental carcinogens-induced lung cancer and potential mechanisms have attracted widespread attention. Currently, microRNAs (miRNAs) have been recognized as key players in development of cancer, among which guide strand of miRNA has been well documented rather than its passenger strand (miRNA*). Our previous stud...

    journal_title:Archives of toxicology

    pub_type: 杂志文章


    authors: Wang Y,Zhang Z,Wang H,Zhang Y,Ji M,Xu H,Wang C,Sun Z,Gao W,Wang SL

    更新日期:2016-05-01 00:00:00

  • Teratogenic effects of nitroimidazopyridazine on the CNS in fetal Wistar (WU) rats.

    abstract::Teratogenic effects caused by a new nitroimidazopyridazine were examined in Wistar (WU) rats after repeated oral administration of 0, 2.5, 10, and 40 mg/kg, given on days 6-17 post coitum (p.c.) (Day of mating = Day 0) in a regular study on embryo-fetal development according to ICH S5A. At day 20 p.c., fetuses were re...

    journal_title:Archives of toxicology

    pub_type: 杂志文章


    authors: Woehrmann T,Volland J,Tuch K,Bode G,Hübel U

    更新日期:2006-07-01 00:00:00

  • Protective effects of vitamin E and C on cisplatin nephrotoxicity in developing rats.

    abstract::The kinetics of vitamin E was followed in serum, liver and kidney of 10- and 55-day-old rats after the administration of a single i.m. dose of 100 mg alpha-tocopherol acetate/100 g body wt. The basal levels without vitamin E administration were significantly higher in serum and liver of 10- than 55-day-old rats. The e...

    journal_title:Archives of toxicology

    pub_type: 杂志文章


    authors: Appenroth D,Fröb S,Kersten L,Splinter FK,Winnefeld K

    更新日期:1997-01-01 00:00:00