다이파시논(디파시논)

(Non-Specific -- Coumarin Derivative Pesticide, Solid, n.o.s.) Keep unnecessary people away; isolate hazard area and deny entry. Stay upwind; keep out of low areas. Ventilate closed spaces before entering them. Wear positive pressure breathing apparatus and special protective clothing. Remove and isolate contaminated clothing at the site.

Use water spray, foam, carbon dioxide.

Refer immediately for medical attention.

Wear protective gloves when administering first aid. Remove contaminated clothes. Rinse and then wash skin with water and soap. Refer immediately for medical attention.

Rinse with plenty of water (remove contact lenses if easily possible).

Rinse mouth. Give a slurry of activated charcoal in water to drink. Refer immediately for medical attention.

Signs and Symptoms of Acute Diphacinone Exposure: Diphacinone is an anticoagulant. Hemorrhage is the most common effect and may be manifested by nose bleeding, gum bleeding, bloody stools and urine, ecchymoses (extravasations of blood into skin), and hemoptysis (coughing up of blood). Bruising is heightened. Abdominal and flank pain are also common. Other signs and symptoms include flushing, dizziness, hypotension (low blood pressure), dyspnea (shortness of breath), cyanosis (blue tint to the skin and mucous membranes), fever, and diarrhea.

Wear self contained breathing apparatus for fire fighting if necessary.

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

Pick up and arrange disposal without creating dust. Sweep up and shovel. Keep in suitable, closed containers for disposal.

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

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

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.

Personal protection: chemical protection suit including self-contained breathing apparatus. Do NOT let this chemical enter the environment. Sweep spilled substance into containers. If appropriate, moisten first to prevent dusting. Carefully collect remainder. Store and dispose of according to local regulations.

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.

Avoid contact with skin, eyes and clothing. Wash hands before breaks and immediately after handling the product.

Fatal if swallowed or in contact with skin.

Wherever possible, toxic chemicals, concentrates and bait preparations should be handled in a fume cupboard. When bait mixing has been done in the field, operators should take care to remain sheltered from the wind. /Rodenticides/

For more Preventive Measures (Complete) data for Diphacinone (9 total), please visit the HSDB record page.

Frequently cited interactions that enhance the risk of hemorrhage in patients taking oral anticoagulants incl decrease metabolism due to CYP2C9 inhibition by amiodarone, azole antifungals, cimetidine, clopidogrel, cotrimoxazole, disulfiram, flouxetine, isoniazid, metronidazole, sulfinpyrazone, tolcapone, or zafirlukast, and displacement from protein binding sites caused by loop diuretics or valproate. ...Consequently, antibiotics can cause excessive PT prolongation in patients adequately controlled on /oral anticoagulants/.

Increased responsiveness to oral anticoagulants occurs with other hypolipidemic drugs, such as d-thyroxine, and also with anabolic steroids. ... Drugs that decrease the response to oral anticoagulants: induction of hepatic microsomal enzymes by barbiturates increases the clearance of oral anticoagulants, which correlates with a decrease in the degree of hypoprothrombinemia. Glutethimide has similar effects. ... Rifampin markedly reduces both the concentrations of drug in the blood and the hypoprothrombinemia produced by oral anticoagulants. Diuretics either have no effect or decrease the response to oral anticoagulants. The latter effect may be due to concentration of clotting factors in plasma subsequent to diuresis, as reported for chlorthalidone and spironolactone. Cholestyramine reduces the hypoprothrombinemia and enhances the plasma clearance of oral anticoagulants by increasing the elimination of unchanged drug in the stool. ... Vitamin C in massive doses reduces the hypoprothrombinemic response of some patients on long-term therapy with oral anticoagulants. /oral anticoagulants/

Diphenadione decreased the binding of the sulfonylureas acetohexamide, chlorpropamide, and tolbutamide to human serum albumin in vitro.

The anticoagulant effect of phenindione in rats was influenced by the monoamine oxidase inhibitors phenylcyclopropylamine-hydrochloride, isocarboxazide, iproniazid, nialamide, 1-p-chlorobenzoyl-2-(alpha-methyl-beta-n-isopropylcarbamyl ethylisopropyl)hydrazine, and amitriptyline.

For more Interactions (Complete) data for Diphacinone (6 total), please visit the HSDB record page.

LC50; Species: /Lepomis macrochirus/ (Bluegill sunfish); Concentration: 7.6 mg/L for 96 hr /Conditions of bioassay not specified/

LC50; Species: /Oncorhynchus mykiss/ (Rainbow trout); Concentration: 2.8 mg/L for 96 hr /Conditions of bioassay not specified/

LC50; Species: Channel catfish; Concentration: 2.1 mg/L for 96 hr /Conditions of bioassay not specified/

LC50; Species: Daphnia; Concentration: 1.8 mg/L for 48 hr /Conditions of bioassay not specified in source examined/

For more Ecotoxicity Values (Complete) data for Diphacinone (23 total), please visit the HSDB record page.

TERRESTRIAL FATE: Based on a soil column study where diphacinone was not detected in any of the leachates collected(1), diphacinone is expected to be immobile in soil(SRC). Volatilization of diphacinone from moist soil surfaces is not expected to be an important fate process(SRC) given a Henry's Law constant of 1.5X10-10 atm-cu m/mole(2). Diphacinone is not expected to volatilize from dry soil surfaces(SRC) based upon a vapor pressure of 1.03X10-10 mm Hg at 25 °C(2). A biodegradation half-life of 28.3 to 31.7 days when incubated aerobically in sandy loam soils for 3.5 months(1), suggests that biodegradation may be an important environmental fate process in soil(SRC). The major degradate was identified as diphenylglycolic acid and was present at a maximum of 24.5% of the applied one month after application(1).

AQUATIC FATE: Based on a soil column study where diphacinone was not detected in any of the leachates collected(1), diphacinone is expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(2) based upon a Henry's Law constant of 1.5X10-10 atm-cu m/mole at 25 °C(3). According to a classification scheme(4), an estimated BCF of 79(SRC), from a log Kow of 4.27(1) and a regression-derived equation(5), suggests the potential for bioconcentration in aquatic organisms is moderate(SRC). Diphacinone is rapidly decomposed in water by sunlight(1). A biodegradation half-life of 28.3 to 31.7 days when incubated aerobically in sandy loam soils for 3.5 months(1), suggests that biodegradation may be an important environmental fate process in water(SRC).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), diphacinone , which has a vapor pressure of 1.03X10-10 mm Hg at 25 °C(2)is expected to exist solely in the particulate phase in the ambient atmosphere. Particulate-phase diphacinone may be removed from the air by wet and dry deposition(SRC). Diphacinone is rapidly decomposed in water by sunlight(2) and, therefore, may be susceptible to photolysis by direct sunlight(SRC).

/BIRDS and MAMMALS/ Diphacinone was studied by acute oral toxicity tests with captive and free-ranging coyotes. The LD50 with 95% confidence limits in captive coyotes was 0.6 (0.3-1.2) mg/kg. Time to death did not differ for the two groups. There is a secondary hazard to susceptible animals that feed repeatedly on tissue containing at least 0.5 ppm diphenadione. Seven golden eagles and rats were fed sheep meat containing 2.7 ppm diphenadione as the sole source of food for 5 and 10 days. All eagles survived, but various degrees of toxicity were noted, and some rats died.

/BIRDS and MAMMALS/ The anticoagulant rodenticide diphacinone was slightly toxic (acute oral LD50 2014 mg/kg) to Northern bobwhite (Colinus virginianus) in a 14-day acute toxicity trial. Precise and sensitive assays of blood clotting (prothrombin time, Russell's Viper venom time, and thrombin clotting time) were adapted for use in quail, and this combination of assays is recommended to measure the effects of anticoagulant rodenticides. A single oral sublethal dose of diphacinone (434 mg/kg body weight) prolonged clotting time at 48 hr post-dose compared to controls. At 783 mg/kg (approximate LD02), clotting time was prolonged at both 24 and 48 hr post-dose. Prolongation of in vitro clotting time reflects impaired coagulation complex activity, and was detected before overt signs of toxicity were apparent at the greatest dosages (2868 and 3666 mg/kg) in the acute toxicity trial. These clotting time assays and toxicity data will assist in the development of a pharmacodynamic model to predict toxicity, and also facilitate rodenticide hazard and risk assessments in avian species.

/BIRDS and MAMMALS/ The acute oral toxicity of the anticoagulant rodenticide diphacinone was found to be over 20 times greater in American kestrels (Falco sparverius; median lethal dose 96.8 mg/kg body weight) compared with Northern bobwhite (Colinus virginianus) and mallards (Anas platyrhynchos). Modest evidence of internal bleeding was observed at necropsy, although histological examination of heart, liver, kidney, lung, intestine, and skeletal muscle revealed hemorrhage over a wide range of doses (35.1-675 mg/kg). Residue analysis suggests that the half-life of diphacinone in the liver of kestrels that survived was relatively short, with the majority of the dose cleared within 7 days of exposure. Several precise and sensitive clotting assays (prothrombin time, Russell's viper venom time, thrombin clotting time) were adapted for use in this species, and oral administration of diphacinone at 50 mg/kg increased prothrombin time and Russell's viper venom time at 48 and 96 hr postdose compared with controls. Prolongation of in vitro clotting time reflects impaired coagulation complex activity, and generally corresponded with the onset of overt signs of toxicity and lethality. In view of the toxicity and risk evaluation data derived from American kestrels, the involvement of diphacinone in some raptor mortality events, and the paucity of threshold effects data following short-term dietary exposure for birds of prey, additional feeding trials with captive raptors are warranted to characterize more fully the risk of secondary poisoning.

Fifty one incidences of poisoning by anticoagulant rodenticides were documented in wildlife submitted for diagnosis by the public between 1971 and 1997 in New York and two adjoining states. Diphacinone was identified in the livers of 1 snowy owl (Nyctea scandiaca), 2 white-tailed deer (Odocoileus virginianus), and 1 gray squirrel (Sciurus carolinensis) at concentrations ranging from 0.2 - 0.93 ppm (1). Diphacinone was detected at a concentration range of 0.008 - 0.02 ppm (wet-wt) in livers from 8 of 164 barn owls (Tyto alba), barred owls (Strix varia), and great horned owls (Bubo virginianus) collected in the province of British Columbia and the Yukon Territory, Canada from 1988 to 2003(2).

Coughing up blood. Blood in the urine. Bleeding under the skin. Symptoms may be delayed.

EASILY ABSORBED! See Inhalation.

Abdominal pain. Further see Inhalation.

Determine prothrombin time. If anticoagulant has been ingested any time in the preceding 15 days, determination of the prothrombin time (PT) provides a basis for judging the severity of poisoning. Patients who ingest large amounts, particularly of the superwarfarin compounds, will likely have a very prolonged period of decreased prothrombin activity. Patients may need to be treated for as long as 3 or 4 months. ... /Coumarins and Indandiones/

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. /Superwarfarin/

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.

Kd values of 5.4-1000 have been measured for diphacinone(1). The compound was immobile in columns (60 cm in length) packed with sandy loam, silt loam, sand, and loamy sand soils to a depth of 30 cm. Diphacinone was detected in the 0-6 cm layer in the columns with sandy loam and silt loam soils. In the sand soil, diphacinone was detected in the 0-6 cm layer (at 117.1% of the applied) and in the 6-12 cm layer (at <3% of the applied). Diphacinone was present in the 0-6 cm layer of the loamy sand soil at 76.1% of the applied, and was also present in the 6-12 cm, 12-18 cm, and 18-24 cm layers at 3.4%, 4.8%, and 4.4% of the applied, respectively. Diphacinone was not detected in any of the leachates collected from the four soil columns(2).

/HUMAN EXPOSURE STUDIES/ No permanent or life-threatening effects occurred in humans on recommended dose regimes of an initial 20 mg dose (ca. 0.29 mg/kg in a 70 kg human), followed by successive 2 to 4 mg daily doses (ca. 0.03 to 0.06 mg/kg/day in a 70 kg person) for several days to weeks /Former use/.

/SIGNS AND SYMPTOMS/ Diphacinone is highly toxic to humans and other mammals by inhalation, dermal absorption, and ingestion. It causes internal hemorrhaging that can lead to death. It acts by inhibiting enzymes involved in blood clotting.

/SIGNS AND SYMPTOMS/ Bleeding is the major toxicity of ... /anticoagulant/.

/SIGNS AND SYMPTOMS/ The only side effects /of diphenadione/ reported in man are mild GI disorders.

For more Human Toxicity Excerpts (Complete) data for Diphacinone (11 total), please visit the HSDB record page.

Based on the reviews of the generic data for the active ingredients .. diphacinone and its sodium salt, the Agency has sufficient information on the health effects of these chemicals and on their potential for causing adverse effects in fish, wildlife, and the environment. The Agency has determined that these chemicals, labeled and used as specified in this Reregistration Eligibility Decision document, will not pose unreasonable risks or adverse effects to humans or the environment. Therefore, the Agency concludes that products containing ... diphacinone and its sodium salt, are eligible for reregistration. ... The Agency has determined that all uses of ... diphacinone and its sodium salt are eligible for reregistration, with the exception of certain field bait uses. The Agency has determined that field-bait uses containing 0.005% ... diphacinone and its sodium salt are eligible for reregistration. ... The Agency has determined that field-bait uses containing more than 0.005% ... diphacinone and its sodium salt are ineligible for reregistration. Field tests have adequately demonstrated that products with lower-concentrations of /this/ ... active ingredient ... /is/ sufficiently efficacious for target pest species, and that the uses with higher concentrations have the potential to cause unnecessary secondary poisonings to avian and mammalian consumers.

As the federal pesticide law FIFRA directs, EPA is conducting a comprehensive review of older pesticides to consider their health and environmental effects and make decisions about their continued use. Under this pesticide reregistration program, EPA examines newer health and safety data for pesticide active ingredients initially registered before November 1, 1984, and determines whether the use of the pesticide does not pose unreasonable risk in accordance to newer saftey standards, such as those described in the Food Quality Protection Act of 1996. Pesticides for which EPA had not issued Registration Standards prior to the effective date of FIFRA '88 were divided into three lists based upon their potential for human exposure and other factors, with List B containing pesticides of greater concern than those on List C, and with List C containing pesticides of greater concern than those on List D. 2-Diphacinone, and salts is found on List B. Case No: 2205; Pesticide type: Rodenticide; Case Status: RED Approved 09/97; OPP has made a decision that some/all uses of the pesticide are eligible for reregistration, as reflected in a Reregistration Eligibility Decision (RED) document.; Active ingredient (AI): 2-Diphacinone, and salts; Data Call-in (DCI) Date(s): 06/06/91, 10/13/95; AI Status: OPP has completed a Reregistration Eligibility Decision (RED) document for the case/AI.

Releases of CERCLA hazardous substances are subject to the release reporting requirement of CERCLA section 103, codified at 40 CFR part 302, in addition to the requirements of 40 CFR part 355. Diphacinone is an extremely hazardous substance (EHS) subject to reporting requirements when stored in amounts in excess of its threshold planning quantity (TPQ) of 10 or 10,000 lbs. Extremely hazardous substances that are solids are subject to either of two threshold planning quantities ... The lower quantity applies only if the solid exists in powdered form and has a particle size less than 100 microns; or is handled in solution or in molten form; or meets the criteria for a National Fire Protection Association (NFPA) rating of 2, 3 or 4 for reactivity. If the solid does not meet any of these criteria, it is subject to the upper ... threshold planning quantity ... .

Used as a medication, rodenticide, and baticide; [HSDB]

Farming (Pesticides) [Category: Industry]

For diphacinone (USEPA/OPP Pesticide Code: 067701) ACTIVE products with label matches. /SRP: Registered for use in the U.S. but approved pesticide uses may change periodically and so federal, state and local authorities must be consulted for currently approved uses./

... Control of mammal pest, particularly commensal rats and mice but also a variety of field rodents (note: commensal rodents are Norway rat, roof rat, and house mouse).

Control of ... prairie dogs (Cynomys spp.), ground squirrels, and other rodents

Baticide

Preparation: D.G. Thomas, United States of America patent 2672483 (1954 to Upjohn).

... By the condensation of dimethyl phthalate with diphenylacetone in an inert solvent in the presence of sodium methoxide.

Diphacinone and salt 2-(diphenylacetyl)-1,3-Indandione products are formulated predominantly as 0.005% a.i. food baits (loose bait, feeder boxes, place packs, or paraffinized bait blocks).

Baits, pellets, concentrates.

Trade Names: Ditrac, Kill-Ko Rat Killer; P.C.Q., Promar, Ramik, Rodent Cake.

Bait Block Rodenticide with Peanut Butter Flavorizer (J.T. Eaton & Co., Inc.): Active ingredient: Diphacinone 0.005%.

For more Formulations/Preparations (Complete) data for Diphacinone (58 total), please visit the HSDB record page.

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

The compound is not widely used except for rat control in the United States and, as the sodium salt, for rodent control in China.

... Diphacinone ... induced development of resistant population of Norway rat on farm in Western Scotland.

This is most toxic of anticoagulants in use at present /in rodent control/. While other chem in this class are usually used, in bait, at concn of 0.025%, diphacinone is effective in 0.005% concn.

For more General Manufacturing Information (Complete) data for Diphacinone (10 total), please visit the HSDB record page.