Difenacoum

Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide.

Wear self contained breathing apparatus for fire fighting if necessary.

Heating of containers will cause a pressure rise, with the risk of bursting and subsequent ignition. Fire-exposed containers should be kept cool by spraying with water.

The use of carbon dioxide or dry powder is recommended for extinguishing small fires, and foam or water fog for larger fires. A water jet should not be used. Run-off water from the fire should be prevented from entering surface-water drains or water sources.

Keep away from food or water supplies, children, domestic animals, and wildlife. Keep container closed for freshness; do not re-use empty container.

Technical difenacoum and formulations should be stored in sealed containers in locked, well-ventilated, dry areas away from frost, direct sunlight, and sources of heat and ignition. Keep products out of reach of children and unauthorized personnel. Do not store near food or animal feed.

Wear respiratory protection. Avoid dust formation. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Evacuate personnel to safe areas. Avoid breathing dust.

Prevent further leakage or spillage if safe to do so. Do not let product enter drains. Discharge into the environment must be avoided.

Dry spillages should be collected at once, by suction, and disposed of as toxic waste, according to local legislation.

SRP: The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational harm/injury/toxicity or environmental contamination. Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in soil or water; effects on animal and plant life; and conformance with environmental and public health regulations.

Avoid all contact by mouth. Wash hands after handling bait.

After skin exposure, all areas should be thoroughly washed with soap and water. For respiratory exposure, removal from the source of the exposure is sufficient.

Complete suit protecting against chemicals. The type of protective equipment must be selected according to the concentration and amount of the dangerous substance at the specific workplace.

Where risk assessment shows air-purifying respirators are appropriate use a full-face particle repirator type N100 (US) or type P3 (EN 143) respirator cartridges as a backup to engineering controls. If the respirator is the sole means of protection, use a full-face supplied air respirator. Use respirators and components tested and approved under appropriate government standars such as NIOSH (US) or CEN (EU).

Face shield and safety glasses. Use equipment for eye protection tested and approved under appropriate government standards such as NIOSH. ...

The primary antidote to difenacoum poisoning is immediate administration of vitamin K1 (initially slow intravenous injections of 10-25 mg repeated all 3-6 hours until normalisation of the prothrombin time; then 10 mg orally four times daily as a "maintenance dose"). It is an extremely effective antidote, provided the poisoning is caught before too much damage has been done to the victim's circulatory system. At high doses difenacoum can affect the body for many months, and the antidote must be administered regularly for a long period of time. (L1257)

The pharmacological response to vitamin K1 (Konakion) /phytonadione/ in anticoagulated (prothrombin complex activity <30%) New Zealand white rabbits was determined by measuring prothrombin complex activity (P.C.A.) in peripheral plasma. In animals pretreated with ... difenacoum (0.85 mg/kg or 8.5 mg/kg) P.C.A. reached a max 4 hr after admin of vitamin K1 (0.5 mg/kg) and declined at a rate indicating complete inhibition of clotting factor synthesis. ... The duration of action of ... difenacoum was much longer than that of warfarin. ... Difenacoum /is a/ ... more potent and persistent antagonist of vitamin K1 than warfarin in vivo. ...

The following drugs ... may increase ... response to coumarin or indandione derivatives: alcohol (acute intoxication), allopurinol, aminosalicylic acid, amiodarone, anabolic steroids, chloral hydrate, chloramphenicol, cimetidine, clofibrate, co-trimoxazole, danazol, dextrothyroxine sodium, diazoxide, diflunisal, disulfiram, erythromycin, ethacrynic acid, fenoprofen calcium, glucagon, ibuprofen, indomethacin, influenza virus vaccine, isoniazid, meclofenamate, mefenamic acid, methylthiouracil, metronidazole, miconazole, nalidixic acid, neomycin (oral), pentoxifylline, phenylbutazone, propoxyphene, propylthiouracil, quinidine, quinine, salicylates, streptokinase, sulfinpyrazone, sulfonamides, sulindac, tetracyclines, thiazides, thyroid drugs, tricyclic antidepressants, urokinase, vitamin E. /Coumarin and indandione derivatives/

The following drugs ... may ... decrease ... response to coumarin or indandione derivatives: alcohol (chronic alcoholism), barbiturates, carbamazepine, corticosteroids, corticotropin, ethchlorvynol, glutethimide, griseofulvin, mercaptopurine, methaqualone, oral contraceptives containing estrogen, rifampin, spironolactone, vitamin K. /Coumarin and indandione derivatives/

The binding constants (K) of a series of anticoagulant rodenticides with the main soil organic component, humic acid (HA), were determined using frontal analysis approach. The order of the binding constants was identical as the one obtained in a previous paper, i.e. bromadiolone>brodifacoum>difenacoum>chlorophacinone>diphacinone, confirming the power of this frontal analysis approach for the determination of binding constants. Moreover, and for the first time, the concentration of unbound rodenticide to HAs could be determined. Thanks this approach, /researchers/ could clearly demonstrate that HA acid protected the human hepatoma cell line HepG2 against the cytotoxicity of all the rodenticides tested and that the toxicity of rodenticides was directly linked to the free rodenticide fraction in the medium (i.e. unbound rodenticide to HA).

LC50; Species: /Oncorhynchus mykiss/ (Rainbow trout); Concentration: 0.10 mg/L for 96 hr /Conditions of bioassay not specified/

LC50; Species: Anas platyrhynchos (Mallard Duck) age 12 days; chemical incorporated into food >15.5 ppm for 40 days (95% confidence interval: 7.6-96.8 ppm)

LC50; Species: Colinus virginianus (Northern Bobwhite Quail) age 31 weeks; chemical incorporated into food 989 ppm for 19 days

LC50; Species: Phasianus colchicus (Ring-Necked Pheasant) age 28 weeks; chemical incorporated into food 57.3 ppm for 19 days (95% confidence interval: 30.0-121.9 ppm)

For more Ecotoxicity Values (Complete) data for DIFENACOUM (6 total), please visit the HSDB record page.

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 4.8X10+6(SRC), determined from a structure estimation method(2), indicates that difenacoum is expected to be immobile in soil(SRC). The pKa of difenacoum is 4.84(3), indicating that this compound will exist partially in the anion form in the environment and anions generally do not adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4). While ionized difenacoum may adsorb less strongly to soil than the neutral form, the low mobility of difenacoum in soil is supported by results of soil column leaching studies(3). Volatilization of difenacoum from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 1.4X10-12 atm-cu m/mole(SRC), using a fragment constant estimation method(2). Difenacoum is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 5.0X10-11 mm Hg at 25 °C(3). Difenacoum is susceptible to direct photolysis(3); therefore, photodegradation on soil surfaces exposed to sunlight may occur(SRC). Difenacoum is not readily or inherently biodegradable(3). In the ready biodegradability tests according to OECD 301B, OECD 301D, and OECD 301F guidelines, the level of degradation reached only 0-31%(3). In the inherent biodegradation test according to OECD 302D draft guideline, the degradation was only 3%(3). Difenacoum degrades slowly in soil with a half-life of 439 days(3).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 4.8X10+6(SRC), determined from a structure estimation method(2), indicates that difenacoum is expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surface is not expected(3) based upon an estimated Henry's Law constant of 1.4X10-12 atm-cu m/mole(SRC), developed using a fragment constant estimation method(2). According to a classification scheme(4), an estimated BCF of 6580(SRC), from an estimated log Kow of 7.62(2) and a regression-derived equation(2), suggests the potential for bioconcentration in aquatic organisms is very high, provided the compound is not metabolized by the organism(SRC). Using the OECD 111 test method, difenacoum was determined to be stable to hydrolysis at pH 5, pH 7 and pH 9 with half-lives greater than 1 year at 25 °C(5). Difenacoum undergoes rapid phototransformation in water with half-lives on the order of about 8 hours or less(5). Aqueous photolysis half-lives at pH 5, pH 7 and pH 9 are reported to be 0.14, 0.34 and 0.30 days respectively(6). Difenacoum is not readily or inherently biodegradable(5). In the ready biodegradability tests according to OECD 301B, OECD 301D, and OECD 301F guidelines, the level of degradation reached only 0-31%(5). In the inherent biodegradation test according to OECD 302D draft guideline, the degradation was only 3%(5). Difenacoum was stable to anaerobic biodegradation in an aquatic test after 49 days of incubation(6).

Difenacoum inhibits the enzyme Vitamin K epoxide reductase. This enzyme is needed for the reconstitution of the vitamin K in its cycle from vitamin K-epoxide, and so difenacoum steadily decreases the level of active vitamin K in the blood. Vitamin K is required for the synthesis of important substances including prothrombin, which is involved in blood clotting. This disruption becomes increasingly severe until the blood effectively loses any ability to clot. In addition, difenacoum increases permeability of blood capillaries. The blood plasma and blood itself begins to leak from the blood vessels, causing internal bleeding leading to shock, loss of consciousness, and eventually death. (L1257)

/BIRDS and MAMMALS/ Mice (weighing 35 g) were fed for 1 day (no choice) on a mixture containing either 0.005% difenacoum or 0.002% brodifacoum. The mean mass of residue on the day of death in a whole mouse was estimated to be 10.17 g for difenacoum and 15.36 g for brodifacoum. Difenacoum- and brodifacoum poisoned mice were fed to captive barn owls for successive periods of 1, 3 and 6 days. All of the owls fed on difenacoum-poisoned mice survived the treatments and none showed external bleeding.

/BIRDS and MAMMALS/ Despite the documented risk of secondary poisoning to non-target species by anticoagulant rodenticides there is no statutory post-approval monitoring of their use in the UK. This paper presents results from two Scottish monitoring schemes for the period 2000-2010; recording rodenticide use on arable farms and the presence of residues in raptor carcasses. More than three quarters of arable farms used anticoagulant rodenticides; predominately the second generation compounds difenacoum and bromadiolone. There was widespread exposure to anticoagulant rodenticides in liver tissues of the raptor species tested and the residues encountered generally reflected agricultural use patterns. As found in other studies, Red Kites (Milvus milvus) appeared to be particularly vulnerable to rodenticide exposure, 70% of those sampled (n = 114) contained residues and 10% died as a result of rodenticide ingestion. More unexpectedly, sparrowhawks (Accipiter nisus), which prey almost exclusively on birds, had similar exposure rates to species which prey on rodents. Although, with the exception of kites, confirmed mortality from rodenticides was low, the widespread exposure recorded is concerning, particularly when coupled with a lack of data about the sub-lethal effects of these compounds. This raises questions regarding whether statutory monitoring of use is needed; both to address whether there are deficiencies in compliance with approval conditions or whether the recommended risk management procedures are themselves adequate to protect non-target wildlife.

/BIRDS and MAMMALS/ Rock hyraxes (Procavia capensis) were individually caged and were given 2 second-generation anticoagulants, difenacoum and difethialone, in fresh sliced apple bait. Mortality caused by 0.1-0.2 g/kg difenacoum bait was rather low: 0/6, 1/4 and 2/4 only.

/BIRDS and MAMMALS/ Residues of difenacoum were detected in dead barn owls in the United Kingdom at levels of 0.005-0.106 mg/kg.

For more Ecotoxicity Excerpts (Complete) data for DIFENACOUM (10 total), please visit the HSDB record page.

Difenacoum was not detected in tissue samples of the Eurasian otter (Lutra lutra) collected from the upper Loire River (France) region between 2004-2008(1). Difenacoum was detected, at concentrations of 0.08 ug/g or higher, in liver tissue from bird species (common buzzard, barn owl) collected from Loire Atlantique France in 2003(2). Difenacoum was detected in a liver sample from one great horn owl (Bubo virginianus) collected during a monitoring study between June 2008 and Feb 2010 in the New Jersey area(3). Difenacoum, brodifacoum, bromadiolone and flocoumafen were detected in golden eagle (Aquila chrysaetos) and eagle owl (Bubo bubo) livers at a total concentration of between 11 and 255 ng/g in approximately 70% of the golden eagles and 50% of the eagle owls examined in a Norwegian study between 2009 and 2011(4). Difenacoum was detected in British tawny owl (Strix aluco) livers at a geometric mean concentration of 0.03 ug/g(5). In British polecat (Mustela putorius) livers, difenacoum was detected at concentrations of 0.1-0.35 ug/g(6). Liver tissue from eagle owls collected in Sweden contained difenacoum levels of 15 ng/g while muscle tissue contained levels ranging from <1 ng/g (the detection limit) to 1.8 ng/g(7).

A PT (Prothrombin Time) 24 to 48 hr after exposure in asymptomatic children with accidental ingestions of large or unknown amounts should be obtained. In adults with deliberate ingestions and children with clinical evidence of bleeding, an initial PT and PTT (Partial Thromboplastin Time) should be obtained and then repeated at 24 and 48 hr.

A serum vitamin K 2,3-epoxide level may provide a more sensitive biomarker of industrial coumarin (brodifiacoum, difenacoum, and warfarin) exposure or acccumulation than the PT (Prothrombin Time). ... In patients chronically exposed to coumarin anticoagulants, serum vitamin K 2,3-epoxide levels are significantly elevated, whereas the clotting factor activities and antigen levels remain in the normal range. This apparant dissociation between the coumarin anticoagulant effects on vitamin K metabolism and clotting factor activity may persist for years after termination of the occupational exposure.

Used as second generation anticoagulant rodenticide; [Merck Index] Registered in 2007 for use in the US in and around buildings and in transport vehicles; Has been registered in European countries since the 1970's; [Reference #1]

Farming (Pesticides) [Category: Industry]

For difenacoum (USEPA/OPP Pesticide Code: 119901) ACTIVE products with label matches. /SRP: Registered for use in the USA but approved pesticide uses may change periodically and so federal, state and local authorities must be consulted for currently approved uses./

Rodenticide

... Control commensal rodents (Norway rat, roof rat, and house mice) in and around buildings and inside of transport vehicles.

Difenacoum is a rodenticide. (L1252)

Preparation: M.R. Hadler, R..S. Shadbolt, German patent 2424806; idem, United States of America patent 3957824 (1975, 1976 both to Ward Blenkinsop).

... Synthesized by the condensation of 4-hydroxycoumarin and 3-biphenyl-4-yl-1,2,3,4-tetrahydro-1-naphthol.

Ready-to-use cereal based bait in pellets, whole and broken grains, water proof wax blocks, loose, or bait packets.

Premix Partners: Calciferol.

Mixtures: difenacoum + calciferol.

Trade Names: Neosorexa PP580, WBA 8107, Ratak, PP 580.

For more Formulations/Preparations (Complete) data for DIFENACOUM (10 total), please visit the HSDB record page.

The WHO Recommended Classification of Pesticides by Hazard identifies difenacoum (technical grade) as Class IA: extremely hazardous; Main Use: rodenticide.

Appearing in 1974, difenacoum was the first of the new generation of anticoagulants to be commercialized for the control of rodents resistant to warfarin and related compounds.

Chemical warfare agents may be manufactured from a wide range of commercially manufactured household industrial products such as bleach, antifreeze, fertilizers containing anhydrous ammonia, pesticides, or anticoagulant rodenticides particularly superwarfarins, to name a few. ... Superwarfarins may be used to harm or terrorize people through the ingestion of contaminated food or water. /Superwarfarins/

Rodenticide anticoagulants are used in the control of rodent populations. In addition to accidental ingestions in humans, such agents have also been used for homicidal and suicidal purposes. There are two major groups of rodenticide anticoagulants - hydroxycoumarins and indanediones. /Rodenticide anticoagulants/