Difethialone

539.48200

539.48

600-594-7

DTXSID4032374

White, slightly yellowish powder

65.54000

8.25850

1.3614 g/cm³ @ Temp: 25 °C

233-236 °C

659.6ºC at 760mmHg

352.7ºC

1.707

Solubility in ethanol 0.7, methanol 0.47, hexane 0.2, chloroform 40.8, dimethylformamide 332.7, acetone 4.3 (g/l at 25 °C)|In water, 0.39 g/l @ 25 °C

0mmHg at 25°C

Ratios of the racemates (1RS,3RS) to (1RS,3SR) lie in the range 0-15 to 85-100.

SRP: Contaminated protective clothing should be segregated in such a manner so that there is no direct personal contact by personnel who handle, dispose, or clean the clothing. Quality assurance to ascertain the completeness of the cleaning procedures should be implemented before the decontaminated protective clothing is returned for reuse by the workers. Contaminated clothing should not be taken home at end of shift, but should remain at employee's place of work for cleaning.

|Danger|H300: Fatal if swallowed [Danger Acute toxicity, oral]|P201, P202, P260, P262, P264, P270, P271, P273, P280, P281, P284, P301+P310, P302+P350, P304+P340, P308+P313, P310, P314, P320, P321, P322, P330, P361, P363, P391, P403+P233, P405, and P501|H300 (100%): Fatal if swallowed [Danger Acute toxicity, oral]|Aggregated GHS information provided by 2 companies from 2 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

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 & 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 & indandione derivatives/

LD50 Rat oral 0.56 mg/kg|LD50 Mouse oral 1.29 mg/kg|LD50 Dog oral 4 mg/kg|LD50 Rabbit percutaneous 5.3 mg/kg|For more Non-Human Toxicity Values (Complete) data for DIFETHIALONE (10 total), please visit the HSDB record page.

/BIRDS and MAMMALS/ Rock hyraxes were individually caged and were given two second-generation anticoagulants, difenacoum and difethialone, in fresh sliced apple bait. ...Mortality caused by 0.05 g/kg difethialone bait was 5/6, and by 0.065 g/kg 6/6.|/ACCIDENTAL POISONINGS/ /In domestic animals,/ signs of poisoning occur after a latent period of 12 hr to several days and may include: bruising easily with occasional nose or gum bleeds; blood in stools or urine; excessive bleeding from minor cuts or abrasions; laboured breathing; pale mouth and cold gums; anorexia and general weakness. A reliable indication of an anticoagulant effect is the determination of prothrombin time. /Anticoagulant rodenticides/

SRP: Persons with bleeding disorders or who are taking anticoagulants should be protected from exposure.

Difethialone's production may result in its release to the environment through various waste streams; its use as a rodenticide(1) will result in its direct release to the environment(SRC).

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 9.7X10+6(SRC), determined from a structure estimation method(2), indicates that difethialone is expected to be immobile in soil(SRC). Volatilization of difethialone from moist soil surfaces may be slow(SRC), given a Henry's Law constant of 1.0X10-6 atm-cu m/mole(SRC), derived from its vapor pressure 5.55X10-7 mm Hg(3) and water solubility 0.39 mg/l(3). However, adsorption to soil is expected to attenuate volatilization. Difethialone is not expected to volatilize from dry soil surfaces(SRC), based upon a vapor pressure of 5.55X10-7 mm Hg(3).|AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 9.7X10+6(SRC), determined from a structure estimation method(2), indicates that difethialone is expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces may be expected(3) based upon a Henry's Law constant of 1.0X10-6 atm-cu m/mole(SRC), derived from its vapor pressure 5.55X10-7 mm Hg(4) and water solubility 0.39 mg/l(4). This Henry's Law constant indicates that difethialone may very slowly volatilize from water surfaces(2). Using this Henry's Law constant and an estimation method(3), volatilization half-lives for a model river and model lake are 85 and 630 days, respectively(SRC). However, volatilization from water surfaces is expected to be attenuated by adsorption to suspended solids and sediment in the water column(SRC). The volatilization half-life from a model pond is about 8.3X10+4 years when adsorption is considered(8). Estimated BCF values of 9 and 1900(SRC) were obtained using an estimated log Kow of 9.8(6) and a reported log Kow (whether estimated or measured was not specified) of 5.17(4), respectively, and a regression-derived equation(7). According to a classification scheme(5), BCF values of <30 suggest that potential for bioconcentration is low and values >1000 suggest the potential for bioconcentration is very high. Difethialone may be expected to undergo hydrolysis in the environment since it has a hydrolyzable functional group(9).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), difethialone, which has a vapor pressure of 5.55X10-7 mm Hg at 25 °C(2), is expected to exist in both the vapor and particulate phases in the ambient atmosphere. Vapor-phase difethialone is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals(SRC); the half-life for this reaction in air is estimated to be 6.6 hours(SRC), calculated from its rate constant of 5.9X10-11 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). Particulate-phase difethialone may be removed from the air by wet and dry deposition(SRC). Difethialone may absorb light with wavelengths >290 and may be susceptible to direct photolysis in sunlight(SRC). The rate constant for the vapor-phase reaction of difethialone with ozone has been estimated as 1.4X10-16 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). This corresponds to an atmospheric half-life of about 2 hours at an atmospheric concentration of 7X10+11 ozone molecules per cu cm(4).

The rate constant for the vapor-phase reaction of difethialone with photochemically-produced hydroxyl radicals has been estimated as 5.9X10-11 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 6.6 hours at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). Difethialone may be expected to undergo hydrolysis in the environment since it has a hydrolyzable functional group(2). Difethialone may absorb light with wavelengths >290, and may be susceptible to direct photolysis in sunlight(SRC). The rate constant for the vapor-phase reaction of difethialone with ozone has been estimated as 1.4X10-16 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(1). This corresponds to an atmospheric half-life of about 2 hours at an atmospheric concentration of 7X10+11 ozone molecules per cu cm(3).

Estimated BCF values of 9 and 1900(SRC) were obtained using an estimated log Kow of 9.8(1) and a reported log Kow (whether estimated or measured was not specified) of 5.17(4), respectively, and a regression-derived equation(2). According to a classification scheme(3), BCF values of <30 suggest that potential for bioconcentration is low and values >1000 suggest the potential for bioconcentration is very high.

Using a structure estimation method based on molecular connectivity indices(1), the Koc for difethialone can be estimated to be 9.7X10+6(SRC). According to a classification scheme(2), this estimated Koc value suggests that difethialone is expected to be immobile in soil.

The Henry's Law constant for difethialone is 1.0X10-6 atm-cu m/mole(SRC) derived from its vapor pressure, 5.55X10-7 mm Hg(1), and water solubility, 0.39 mg/l(1). This Henry's Law constant indicates that difethialone may slowly volatilize from water surfaces(2). Based on this Henry's Law constant, the volatilization half-life from a model river (1 m deep, flowing 1 m/sec, wind velocity of 3 m/sec)(2) is estimated as 85 days(SRC). The volatilization half-life from a model lake (1 m deep, flowing 0.05 m/sec, wind velocity of 0.5 m/sec)(2) is estimated as 630 days(SRC). The volatilization half-life from a model pond is about 8.3X10+4 years when adsorption is considered(4). Difethialone's Henry's Law constant indicates that volatilization from moist soil surfaces may occur(SRC); however, adsorption to soil is expected to attenuate volatilization. Difethialone is not expected to volatilize from dry soil surfaces(SRC), based upon a vapor pressure of 5.55X10-7 mm Hg(1).

Occupational exposure to difethialone may occur through inhalation and dermal contact with this compound at workplaces where difethialone is produced or used. The general population may be exposed to difethialone via dermal contact with products containing difethialone. (SRC)

In rats, following oral admin, difethialone is characterised by a short half-life in blood, a longer half-life in liver, and an essentially fecal elimination with almost complete absence of metabolism.

Both 4-hydroxycoumarin derivatives and indandiones (also known as oral anticoagulants) are antagonists of vitamin K. Their use as rodenticides is based on the inhibition of the vitamin K-dependent step in the synthesis of a number of blood coagulation factors. The vitamin K-dependent proteins involved in the coagulation cascade (Fig. 1) are the procoagulant factors II (prothrombin), VII (proconvertin), IX (Christmas factor) and X (Stuart-Prower factor), and the coagulation-inhibiting proteins C and S. All these proteins are synthesized in the liver. Before they are released into the circulation the various precursor proteins undergo substantial (intracellular) post-translational modification. Vitamin K functions as a co-enzyme in one of these modifications, namely the carboxylation at well-defined positions of 10-12 glutamate residues into gamma-carboxyglutamate (Gla). The presence of these Gla residues is essential for the procoagulant activity of the various coagulations factors. Vitamin K hydroquinone (KH2) is the active co-enzyme, and its oxidation to vitamin K 2,3-epoxide (KO) provides the energy required for the carboxylation reaction. The epoxide is than recycled in two reduction steps mediated by the enzyme KO reductase (Fig. 2). The latter enzyme is the target enzyme for coumarin anticoagulants. Their blocking of the KO reductase leads to a rapid exhaustion of the supply of KH2, and thus to an effective prevention of the formation of Gla residues. This leads to an accumulation of non-carboxylated coagulation factor precursors in the liver. In some cases these precursors are processed further without being carboxylated, and (depending on the species) may appear in the circulation. At that stage the under-carboxylated proteins are designated as descarboxy coagulation factors. Normal coagulation factors circulate in the form of zymogens, which can only participate in the coagulation cascade after being activated by limited proteolytic degradation. Descarboxy coagulation factors have no procoagulant activity (i.e. they cannot be activated) and neither they can be converted into the active zymogens by vitamin K action. Whereas in anticoagulated humans high levels of circulating descarboxy coagulation factors are detectable, these levels are negligible in warfarin-treated rats and mice. /Anticoagulant rodenticides/

Human exposure to second-generation and indandione anticoagulants produces symptoms consistent with anticoagulation effects (e.g., hematomas, hematemesis, hematuria, easy bruisability). Treatment of cases of exposure, particularly of substantial and repeated exposure, may require vitamin K1 therapy and monitoring of prothrombin times for periods of many months.|We report a 22 years old male, admitted to the emergency room due to a life threatening coagulation disorder, with prothrombin times fluctuation between 5 and 37% and very low activity of factors II, VII, IX and X. In the month prior to the admission, the patient had used the rodenticide difethialone, without any precaution to avoid accidental exposure. The patient was maintained with fresh frozen plasma until oral vitamin K1 was obtained. This medication corrected the coagulation disorder.|The occurrence, the diagnosis, and the treatment of anticoagulant rodenticide poisoning in dogs in the Netherlands was evaluated by a survey among Dutch veterinarians carried out by the National Poisons Control Center (NPCC). The survey included information on 54 dogs, 32 being treated by veterinarians who consulted the NPCC and 22 that were admitted to the Utrecht University Clinic for Companion Animals (UUCCA). The poisons that were suspected were brodifacoum (n = 19), bromadiolone (n = 14), difenacoum (n = 8), difethialone (n = 6) and chlorophacinone (n = 1). In 6 dogs the identity of the poison was unknown. Of 31 dogs with hemorrhages, 2 died shortly after presentation to practitioners and 2 died shortly after admission to the UUCCA. Signs of bleeding occurred especially in poisoning by brodifacoum (n = 16). In all but one of the dogs without hemorrhages, the intake of poison had taken place within 24 hours before presentation. The method of treatment varied, with the induction of vomiting and the use of vitamin K mentioned most. The choice of therapy was determined by the length of time after intake of the poison, the clinical signs and whether or not an anticoagulant toxicosis was suspected at the time of the initial examination.

/HUMAN EXPOSURE STUDIES/ Typical features of poisoning result from increased bleeding tendency and include: minor poisoning: coagulation disturbance detected only by laboratory analyses; moderate poisoning: coagulation disturbance resulting in hematomata, hematuria, blood in feces or excessive bleeding from minor cuts or abrasions, gum bleeding; severe poisoning: retroperitoneal hemorrhage, severe GI bleeding, cerebrovascular accidents, massive hemorrhage (internal bleeding) resulting in shock. If anaemia or liver disease is present then the above features may be more severe and persistent and the poisoning may be more difficult to control. The onset of the signs of poisoning may not be evident until a few days after ingestion. /Anticoagulant rodenticides/

difethialone

Trade/other Names: Baraki, Frap, Quell.|/Difethialone/ is formulated as ready-to-use whole grain cereals and husked oat grain baits contaning 0.0025% active substance.|Trade Names: LM-2219.

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

Agrochemicals -> Rodenticides