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














  • Differential effects of olfactory toxicants on olfactory regeneration.

    abstract::The aim was to study the long-term response in the olfactory mucosa of NMRI mice after exposure to the olfactory toxicants dichlobenil (a herbicide) or methimazole (an antithyroid drug). Three and six months after exposure to dichlobenil (2x or 1 x 25 mg/kg i.p.), the dorsomedial part of the olfactory region showed a ...

    journal_title:Archives of toxicology

    pub_type: 杂志文章


    authors: Bergman U,Ostergren A,Gustafson AL,Brittebo B

    更新日期:2002-03-01 00:00:00

  • Study on the mechanism of photosensitive dermatitis caused by ketoprofen in the guinea pig.

    abstract::To investigate the mechanism on photosensitive dermatitis caused by ketoprofen (KP) in humans, the following experiments were performed by topical application on guinea pigs. The phototoxicity study involving treatment with 10% solution of KP, its enantiomers (R-KP and S-KP), loxoprofen, and flurbiprofen revealed no p...

    journal_title:Archives of toxicology

    pub_type: 杂志文章


    authors: Nakazawa T,Shimo T,Chikamatsu N,Igarashi T,Nagata O,Yamamoto M

    更新日期:2006-07-01 00:00:00

  • Scientific analysis of the proposed uses of the T25 dose descriptor in chemical carcinogen regulation.

    abstract::The uncertainties that surround the methods used for risk assessment of exposure to carcinogens have been highlighted by a recent document advocating an approach based on the T25 dose (the dose giving a 25% incidence of cancer in an appropriately designed animal experiment). This method relies on derivation of the T25...

    journal_title:Archives of toxicology



    authors: Roberts RA,Crump KS,Lutz WK,Wiegand HJ,Williams GM,Harrison PT,Purchase IF

    更新日期:2001-11-01 00:00:00

  • Resveratrol protects primary cilia integrity of human mesenchymal stem cells from cigarette smoke to improve osteogenic differentiation in vitro.

    abstract::Several studies have explored the negative effects of cigarette smoke on bone healing; however, the complex pathogenesis still remains unclear. One crucial and primary factor determining effective fracture repair is the recruitment and differentiation of mesenchymal stem cells (MSCs) into bone-forming cells. Recently,...

    journal_title:Archives of toxicology

    pub_type: 杂志文章


    authors: Sreekumar V,Aspera-Werz R,Ehnert S,Strobel J,Tendulkar G,Heid D,Schreiner A,Arnscheidt C,Nussler AK

    更新日期:2018-04-01 00:00:00

  • Distribution and reactivity of inhaled 14C-labeled toluene diisocyanate (TDI) in rats.

    abstract::Inhalation exposure to toluene diisocyanate (TDI) can result in a variety of airway diseases. Concern has been expressed that a putative carcinogenic potential of TDI exists as a result of the formation of toluenediamine (TDA) by hydrolysis of the isocyanate in the body. Results from long-term bioassays (TDI inhalatio...

    journal_title:Archives of toxicology

    pub_type: 杂志文章


    authors: Kennedy AL,Wilson TR,Stock MF,Alarie Y,Brown WE

    更新日期:1994-01-01 00:00:00

  • Exposures to the environmental toxicants pentachlorophenol (PCP) and dichlorodiphenyltrichloroethane (DDT) modify secretion of interleukin 1-beta (IL-1β) from human immune cells.

    abstract::Pentachlorophenol (PCP) and Dichlorodiphenyltrichloroethane (DDT) are environmental contaminants found in human blood. Previous studies have shown that PCP and DDT inhibit the lytic function of highly purified human natural killer (NK) lymphocytes and decrease the expression of several surface proteins on NK cells. In...

    journal_title:Archives of toxicology

    pub_type: 杂志文章


    authors: Martin TJ,Whalen MM

    更新日期:2017-04-01 00:00:00

  • In utero exposure to nicotine and chlorpyrifos alone, and in combination produces persistent sensorimotor deficits and Purkinje neuron loss in the cerebellum of adult offspring rats.

    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


    authors: Abou-Donia MB,Khan WA,Dechkovskaia AM,Goldstein LB,Bullman SL,Abdel-Rahman A

    更新日期:2006-09-01 00:00:00

  • Effects of binge drinking on action cascading processes: an EEG study.

    abstract::High-dosage alcohol intoxication (i.e., binge drinking in humans) is an increasingly prevalent problem. Despite the well-known long-term consequences, the acute effects of high-dosage alcohol intoxication on cognitive control processes have not been investigated with respect to neurophysiological changes in humans. We...

    journal_title:Archives of toxicology

    pub_type: 杂志文章


    authors: Stock AK,Blaszkewicz M,Beste C

    更新日期:2014-02-01 00:00:00

  • Combining in vitro embryotoxicity data with physiologically based kinetic (PBK) modelling to define in vivo dose-response curves for developmental toxicity of phenol in rat and human.

    abstract::In vitro assays are often used for the hazard characterisation of compounds, but their application for quantitative risk assessment purposes is limited. This is because in vitro assays cannot provide a complete in vivo dose-response curve from which a point of departure (PoD) for risk assessment can be derived, like t...

    journal_title:Archives of toxicology

    pub_type: 杂志文章


    authors: Strikwold M,Spenkelink B,Woutersen RA,Rietjens IM,Punt A

    更新日期:2013-09-01 00:00:00

  • AhR-mediated changes in global gene expression in rat liver progenitor cells.

    abstract::Although the tumor-promoting effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), coplanar polychlorinated biphenyls (PCBs), and related compounds in liver tissue are primarily attributed to the activation of the aryl hydrocarbon receptor (AhR), the underlying molecular mechanisms are still unclear. Liver progenitor...

    journal_title:Archives of toxicology

    pub_type: 杂志文章


    authors: Faust D,Vondráček J,Krčmář P,Smerdová L,Procházková J,Hrubá E,Hulinková P,Kaina B,Dietrich C,Machala M

    更新日期:2013-04-01 00:00:00

  • Darbepoetin inhibits proliferation of hepatic cancer cells in the presence of TGF-β.

    abstract::Darbepoetin (DPO), an erythropoietin (EPO) derivative, was licensed in 2002 to treat patients with solid tumors suffering from chemotherapy-dependent anemia, although various tumors express EPO to improve vascularization, thus favoring tumor growth and spreading. Therefore, we wanted to investigate direct effects of D...

    journal_title:Archives of toxicology

    pub_type: 杂志文章


    authors: Ehnert S,Freude T,Eicher C,Burkhardt B,Martínez Sánchez JJ,Neumann J,Mühl-Benninghaus R,Dooley S,Pscherer S,Nussler AK

    更新日期:2014-01-01 00:00:00

  • High perfluorooctanoic acid exposure induces autophagy blockage and disturbs intracellular vesicle fusion in the liver.

    abstract::Perfluorooctanoic acid (PFOA) has been shown to cause hepatotoxicity and other toxicological effects. Though PPARα activation by PFOA in the liver has been well accepted as an important mechanism of PFOA-induced hepatotoxicity, several pieces of evidence have shown that the hepatotoxic effects of PFOA may not be fully...

    journal_title:Archives of toxicology

    pub_type: 杂志文章


    authors: Yan S,Zhang H,Guo X,Wang J,Dai J

    更新日期:2017-01-01 00:00:00

  • Acetaminophen hepatotoxicity: is there a role for prostaglandin synthesis?

    abstract::The hepatotoxicity of acetaminophen (APAP) overdose depends on metabolic activation to a toxic reactive metabolite via hepatic mixed function oxidase. In vitro studies have indicated that APAP may also be cooxidized by prostaglandin H synthetase. The present experiments were designed to assess the possible contributio...

    journal_title:Archives of toxicology

    pub_type: 杂志文章


    authors: Ben-Zvi Z,Weissman-Teitellman B,Katz S,Danon A

    更新日期:1990-01-01 00:00:00

  • Effect of pretreatment with cadmium/cysteine or metallothionein on accumulation of cadmium challenged with either complexes.

    abstract::The effect of pretreatment with cadmium (Cd) complexes on the distribution and accumulation of Cd in the liver and kidneys was examined for the Cd complexes that are reabsorbed site-selectively at the renal proximal tubules of rats. Cd was administered simultaneously with excess cysteine or as metallothionein (MT) and...

    journal_title:Archives of toxicology

    pub_type: 杂志文章


    authors: Suzuki KT,Takahara T,Watanabe H,Nishikawa M,Yamamura M,Murakami M

    更新日期:1986-04-01 00:00:00

  • Acute and subacute oral administration of mycotoxin deoxynivalenol exacerbates the pro-inflammatory and pro-pruritic responses in a mouse model of allergic dermatitis.

    abstract::Deoxynivalenol (DON) contamination in food is a public health concern; however, the effect of DON exposure on immune disorders including allergies remains unclear. The aim of this study is to elucidate the effect of oral exposure to DON on pro-inflammatory and pro-pruritic responses in a mouse model of allergic dermat...

    journal_title:Archives of toxicology

    pub_type: 杂志文章


    authors: Aihara R,Ookawara T,Morimoto A,Iwashita N,Takagi Y,Miyasaka A,Kushiro M,Miyake S,Fukuyama T

    更新日期:2020-12-01 00:00:00

  • Critical assessment and integration of separate lines of evidence for risk assessment of chemical mixtures.

    abstract::Humans are exposed to multiple chemicals on a daily basis instead of to just a single chemical, yet the majority of existing toxicity data comes from single-chemical exposure. Multiple factors must be considered such as the route, concentration, duration, and the timing of exposure when determining toxicity to the org...

    journal_title:Archives of toxicology

    pub_type: 杂志文章


    authors: Hernandez AF,Buha A,Constantin C,Wallace DR,Sarigiannis D,Neagu M,Antonijevic B,Hayes AW,Wilks MF,Tsatsakis A

    更新日期:2019-10-01 00:00:00

  • Effect of phenobarbital pretreatment on in vitro enzyme kinetics and in vivo biotransformation of benzene in the rat.

    abstract::Phenobarbital pretreatment (50 mg/kg/day for 3 days orally) of male Wistar rats increased Vmax of benzene in vitro hepatic microsomal biotransformation about 6-fold without changing Km. However, benzene blood levels after oral, intraperitoneal, or subcutaneous benzene administration (3-3.5 mmoles/kg) were not influenc...

    journal_title:Archives of toxicology

    pub_type: 杂志文章


    authors: Gut I

    更新日期:1976-06-08 00:00:00

  • Exposure to multi-walled carbon nanotubes results in aggravation of airway inflammation and remodeling and in increased production of epithelium-derived innate cytokines in a mouse model of asthma.

    abstract::With the development of nanotechnologies, the potential adverse effects of nanomaterials such as multi-walled carbon nanotubes (MWCNT) on the respiratory tract of asthmatics are questioned. Furthermore, investigations are necessary to understand how these effects might arise. In the present study, we hypothesized that...

    journal_title:Archives of toxicology

    pub_type: 杂志文章


    authors: Ronzani C,Casset A,Pons F

    更新日期:2014-02-01 00:00:00

  • The mycotoxin patulin reacts with DNA bases with and without previous conjugation to GSH: implication for related α,β-unsaturated carbonyl compounds?

    abstract::The α,β-unsaturated carbonyl group is recognized as alert for mutagenicity, attributed to (1) its direct reaction with DNA, counteractable by glutathione (GSH), and (2) oxidative stress caused indirectly by GSH depletion. Accordingly, the α,β,γ,δ-unsaturated lactone patulin (PAT), a mycotoxin detected in fruits and pr...

    journal_title:Archives of toxicology

    pub_type: 杂志文章


    authors: Pfenning C,Esch HL,Fliege R,Lehmann L

    更新日期:2016-02-01 00:00:00

  • Effect of cadmium or magnesium on calcium-dependent central function that reduces blood pressure.

    abstract::The effect of intracerebroventricular (i.c.v.) administration of cadmium or magnesium on central calcium-dependent blood pressure regulation was investigated. The systolic blood pressure of spontaneously hypertensive rats (SHR; male, 13 weeks of age) decreased following i.c.v. administration of cadmium chloride (20 nm...

    journal_title:Archives of toxicology

    pub_type: 杂志文章


    authors: Sutoo D,Akiyama K

    更新日期:2000-03-01 00:00:00

  • Long-term simulation of lead concentrations in agricultural soils in relation to human adverse health effects.

    abstract::Lead (Pb) exposure of consumers and the environment has been reduced over the past decades. Despite all measures taken, immission of Pb onto agricultural soils still occurs, with fertilizer application, lead shot from hunting activities, and Pb from air deposition representing major sources. Little is known about the ...

    journal_title:Archives of toxicology

    pub_type: 杂志文章


    authors: Schupp T,Damm G,Foth H,Freyberger A,Gebel T,Gundert-Remy U,Hengstler JG,Mangerich A,Partosch F,Röhl C,Wollin KM

    更新日期:2020-07-01 00:00:00

  • Lack of direct immunosuppressive effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on human peripheral blood lymphocyte subsets in vitro.

    abstract::A wide variety of immunosuppressive effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in experimental animals has been documented. In contrast, the impact of dioxin on the human immune system remains controversial, although adverse health effects have been reported in humans after occupational or accidental exposu...

    journal_title:Archives of toxicology

    pub_type: 杂志文章


    authors: Lang DS,Becker S,Clark GC,Devlin RB,Koren HS

    更新日期:1994-01-01 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

  • Interlaboratory comparison of total cytochrome P-450 and protein determinations in rat liver microsomes. Reinvestigation of assay conditions.

    abstract::Assay conditions in determining total cytochrome P-450 in four laboratories were compared. Although the determination was derived from the original Omura and Sato method in each laboratory, the four standard protocols differed slightly, resulting in considerable differences in the results. Since the cytochrome P-450 c...

    journal_title:Archives of toxicology

    pub_type: 杂志文章


    authors: Rutten AA,Falke HE,Catsburg JF,Topp R,Blaauboer BJ,van Holsteijn I,Doorn L,van Leeuwen FX

    更新日期:1987-01-01 00:00:00

  • Tamoxifen induces hepatocellular carcinoma in rat liver: a 1-year study with two antiestrogens.

    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


    authors: Hirsimäki P,Hirsimäki Y,Nieminen L,Payne BJ

    更新日期:1993-01-01 00:00:00

  • In vitro toxicological evaluation of a dinuclear platinum(II) complex with acetate ligands.

    abstract::In the present study the toxicological potential of a tumor-inhibiting dinuclear platinum(II) complex (bis(acetato)diammine-bis-micro-acetato diplatinum(II) dihydrate (BAP)) was evaluated, utilizing in vitro models of nephrotoxicity, myelosuppression and neurotoxicity. Regarding the discrepancies between the hallmark ...

    journal_title:Archives of toxicology

    pub_type: 杂志文章


    authors: Momekov G,Ferdinandov D,Bakalova A,Zaharieva M,Konstantinov S,Karaivanova M

    更新日期:2006-09-01 00:00:00

  • Production of liver preneoplasia and gallbladder agenesis in turkey fetuses administered diethylnitrosamine.

    abstract::The in ovo carcinogenicity assessing (IOCA) assay was used to examine the morphological changes in fetal turkey livers caused by the DNA-reactive carcinogen diethylnitrosamine (DEN). Fertilized turkey eggs were allocated into 3 groups: nondosed control (NDC), vehicle (water) control (VC) and DEN-dosed. At day 0, the f...

    journal_title:Archives of toxicology

    pub_type: 杂志文章


    authors: Williams GM,Brunnemann KD,Iatropoulos MJ,Smart DJ,Enzmann HG

    更新日期:2011-06-01 00:00:00

  • Toxic effects of A2E in human ARPE-19 cells were prevented by resveratrol: a potential nutritional bioactive for age-related macular degeneration treatment.

    abstract::Age-related macular degeneration (AMD) is a late-onset retinal disease and the leading cause of central vision loss in the elderly. Degeneration of retinal pigment epithelial cells (RPE) is a crucial contributing factor responsible for the onset and progression of AMD. The toxic fluorophore N-retinyl-N-retinylidene et...

    journal_title:Archives of toxicology

    pub_type: 杂志文章


    authors: Alaimo A,Di Santo MC,Domínguez Rubio AP,Chaufan G,García Liñares G,Pérez OE

    更新日期:2020-02-01 00:00:00

  • Modulation of serum concentrations and hepatic metabolism of 17beta-estradiol and testosterone by amitraz in rats.

    abstract::The present study has investigated the ability of amitraz, a widely used formamidine pesticide, to modulate serum concentrations and liver microsomal metabolism of 17beta-estradiol (E2) and testosterone in rats. Amitraz was administered intraperitoneally to male rats for 4 days and to intact female rats or ovariectomi...

    journal_title:Archives of toxicology

    pub_type: 杂志文章


    authors: Chou CP,Lu SY,Ueng TH

    更新日期:2008-10-01 00:00:00

  • Acrylonitrile biotransformation in rats, mice, and chinese hamsters as influenced by the route of administration and by phenobarbital, SKF 525-A, cysteine, dimercaprol, or thiosulfate.

    abstract::Female wistar rats, conventional albino mice, and Chinese hamsters were given a single dose of acrylonitrile, 0.5 or 0.75 mM/kg body weight. The elimination in the urine of thiocyanate, which is the main metabolite of acrylonitrile, indicated a decreasing proportion of biotransformation after oral (over 20%), intraper...

    journal_title:Archives of toxicology

    pub_type: 杂志文章


    authors: Gut I,Nerudová J,Kopecký J,Holecek V

    更新日期:1975-02-14 00:00:00