diphacinone

H300: Fatal if swallowed [Danger Acute toxicity, oral]

H372 **: Causes damage to organs through prolonged or repeated exposure [Danger Specific target organ toxicity, repeated exposure]

P260, P264, P270, P301+P316, P319, P321, P330, P405, and P501 (click each P-code to see the statement)

H300+H310 (100%): Fatal if swallowed or in contact with skin [Danger Acute toxicity, oral; acute toxicity, dermal]

H300 (100%): Fatal if swallowed [Danger Acute toxicity, oral]

H310 (100%): Fatal in contact with skin [Danger Acute toxicity, dermal]

H332 (100%): Harmful if inhaled [Warning Acute toxicity, inhalation]

H372 (100%): Causes damage to organs through prolonged or repeated exposure [Danger Specific target organ toxicity, repeated exposure]

P260, P261, P262, P264, P270, P271, P280, P301+P316, P302+P352, P304+P340, P316, P317, P319, P321, P330, P361+P364, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 39 reports by companies from 2 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Information may vary between notifications depending on impurities, additives, and other factors. The percentage value in parenthesis indicates the notified classification ratio from companies that provide hazard codes. Only hazard codes with percentage values above 10% are shown. For more detailed information, please visit ECHA C&L website.

H310: Fatal in contact with skin [Danger Acute toxicity, dermal]

H330: Fatal if inhaled [Danger Acute toxicity, inhalation]

H371: May cause damage to organs [Warning Specific target organ toxicity, single exposure]

H372: Causes damage to organs through prolonged or repeated exposure [Danger Specific target organ toxicity, repeated exposure]

P260, P262, P264, P270, P271, P280, P284, P301+P316, P302+P352, P304+P340, P308+P316, P316, P319, P320, P321, P330, P361+P364, P403+P233, P405, and P501 (click each P-code to see the statement)

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.

Emergency Life-Support Procedures: Acute exposure to diphacinone may require decontamination and life support for the victims. Emergency personnel should wear protective clothing appropriate to the type and degree of contamination. Air-purifying or supplied-air respiratory equipment should also be worn, as necessary. Rescue vehicles should carry supplies such as plastic sheeting and disposable plastic bags to assist in preventing spread of contamination.

Inhalation Exposure:

1. Move victims to fresh air. Emergency personnel should avoid self-exposure to diphacinone.

2. Evaluate vital signs including pulse and respiratory rate, and note any trauma. If no pulse is detected, provide CPR. If not breathing, provide artificial respiration. If breathing is labored, administer oxygen or other respiratory support.

3. Obtain authorization and/or further instructions from the local hospital for administration of an antidote or performance of other invasive procedures.

4. RUSH to a health care facility.

Dermal/Eye Exposure:

1. Remove victims from exposure. Emergency personnel should avoid self- exposure to diphacinone.

3. Remove contaminated clothing as soon as possible.

4. If eye exposure has occurred, eyes must be flushed with lukewarm water for at least 15 minutes.

5. Wash exposed skin areas twice with soap and water.

6. Obtain authorization and/or further instructions from the local hospital for administration of an antidote or performance of other invasive procedures.

7. RUSH to a health care facility.

Ingestion Exposure:

1. Evaluate vital signs including pulse and respiratory rate, and note any trauma. If no pulse is detected, provide CPR. If not breathing, provide artificial respiration. If breathing is labored, administer oxygen or other respiratory support.

2. Obtain authorization and/or further instructions from the local hospital for administration of an antidote or performance of other invasive procedures.

3. Vomiting may be induced with syrup of Ipecac. If elapsed time since ingestion of diphacinone is unknown or suspected to be greater than 30 minutes, do not induce vomiting and proceed to Step

4.Ipecac should not be administered to children under 6 months of age.Warning: Ingestion of diphacinone may result in sudden onset of seizures or loss of consciousness. Syrup of Ipecac should be administered only if victims are alert, have an active gag-reflex, and show no signs of impending seizure or coma. If ANY uncertainty exists, proceed to Step

4.The following dosages of Ipecac are recommended: children up to 1 year old, 10 mL (1/3 oz); children 1 to 12 years old, 15 mL (1/2 oz); adults, 30 mL (1 oz). Ambulate (walk) the victims and give large quantities of water. If vomiting has not occurred after 15 minutes, Ipecac may be readministered. Continue to ambulate and give water to the victims. If vomiting has not occurred within 15 minutes after second administration of Ipecac, administer activated charcoal.

4. Activated charcoal may be administered if victims are conscious and alert. Use 15 to 30 g (1/2 to 1 oz) for children, 50 to 100 g (1-3/4 to 3-1/2 oz) for adults, with 125 to 250 mL (1/2 to 1 cup) of water.

5. Promote excretion by administering a saline cathartic or sorbitol to conscious and alert victims. Children require 15 to 30 g (1/2 to 1 oz) of cathartic; 50 to 100 g (1-3/4 to 3-1/2 oz) is recommended for adults.

6. RUSH to a health care facility. (EPA, 1998)

(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.

The material is similar to coumarin and indandione. (Non-Specific -- Coumarin Derivative Pesticide, Solid, n.o.s.) Small fires: dry chemical, carbon dioxide, water spray, or foam. Large fires: water spray, fog, or foam. Move container from fire area if you can do it without risk. Fight fire from maximum distance. Dike fire control water for later disposal; do not scatter the material. (EPA, 1998)

Use water spray, foam, carbon dioxide.

Wear self contained breathing apparatus for fire fighting if necessary.

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

Excerpt from ERG Guide 154 [Substances - Toxic and/or Corrosive (Non-Combustible)]:

IMMEDIATE PRECAUTIONARY MEASURE: Isolate spill or leak area in all directions for at least 50 meters (150 feet) for liquids and at least 25 meters (75 feet) for solids.

SPILL: Increase the immediate precautionary measure distance, in the downwind direction, as necessary.

FIRE: If tank, rail tank car or highway tank is involved in a fire, ISOLATE for 800 meters (1/2 mile) in all directions; also, consider initial evacuation for 800 meters (1/2 mile) in all directions. (ERG, 2024)

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.

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.

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.

(Non-Specific -- Coumarin Derivative Pesticide, Solid, n.o.s.) Do not touch spilled material; stop leak if you can do it without risk. Use water spray to reduce vapors.

Small spills: take up with sand or other noncombustible absorbent material and place into containers for later disposal.

Small dry spills: with clean shovel place material into clean, dry container and cover; move containers from spill area.

Large spills: dike far ahead of spill for later disposal. (EPA, 1998)

Provision to contain effluent from fire extinguishing. Separated from food and feedstuffs. Well closed. Store in an area without drain or sewer access.

0.030 [mg/m3]

0.90 [mg/m3]

88 [mg/m3]

A harmful concentration of airborne particles can be reached quickly when dispersed.

The substance may cause effects on the blood. This may result in bleeding. The effects may be delayed. Medical observation is indicated. Exposure could cause death.

The substance may have effects on the blood. This may result in bleeding.

For emergency situations, wear a positive pressure, pressure-demand, full facepiece self-contained breathing apparatus (SCBA) or pressure- demand supplied air respirator with escape SCBA and a fully-encapsulating, chemical resistant suit. (EPA, 1998)

Where risk assessment shows air-purifying respirators are appropriate use a full-face particle respirator 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 standards such as NIOSH (US) or CEN (EU).

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.

Face shield and safety glasses Use equipment for eye protection tested and approved under appropriate government standards such as NIOSH (US) or EN 166(EU).

Handle with gloves. Gloves must be inspected prior to use. Use proper glove removal technique (without touching glove's outer surface) to avoid skin contact with this product. Dispose of contaminated gloves after use in accordance with applicable laws and good laboratory practices. Wash and dry hands.

NO open flames.

AVOID ALL CONTACT! PREVENT DISPERSION OF DUST! IN ALL CASES CONSULT A DOCTOR! FIRST AID: USE PERSONAL PROTECTION.

Use closed system.

Protective gloves. Protective clothing.

Wear face shield or eye protection in combination with breathing protection if powder.

Do not eat, drink, or smoke during work. Wash hands before eating.

Diphacinone appears as odorless pale yellow crystals. Used as a rodenticide and anticoagulant medication. (EPA, 1998)

Odorless, pale yellow powder formulated as meal, pellet, wax block, and liquid bait; [EXTOXNET]

YELLOW-TO-WHITE CRYSTALS.

Yellow crystals

Crystalline powder

White powder at room temperature

Odorless

295 to 297 °F (EPA, 1998)

141-145 °C

In water, 0.3 mg/L, temp not specified

Soluble in methyl cyanide, cyclohexane

SOL IN ETHER, GLACIAL ACETIC ACID

Soluble in acetic acid

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

Solubility in water: very poor

Bulk density: 1.87 g/mL

1.3 g/cm³

1.281 @25 °C

VP: 1.2X10-8 mm Hg

1.03X10-10 mm Hg at 25 °C

Vapor pressure, Pa at 25 °C: (negligible)

log Kow = 4.27

Henry's Law constant = 1.55X10-5 Pa-cu m/mol /1.54X10-10 atm-cu m/mol/ at 25 °C (calc)

Sensitive to light

Stable for 14 days (pH 6-9); hydrolyzed in <24 hr (pH 4). /Technical diphenadione/

Tomcat shelflife is 3 yr. Keep dry.

Stable in weakly acidic and weakly alkaline media at room temperature.

When heated to decomposition it emits acrid smoke and fumes.

Diphacinone is rapidly decomposed in water by sunlight.

Decomposes at 338 °C (without boiling).

NON-CORROSIVE

Index of refraction: 1.670 C/D

Acidic, forming water soluble alkali metal salts

Yellow powder; mp: 145-147 °C; density: 1.281; vapor pressure: 1.37X10-5 mPa (25 °C) /Technical diphacinone/

Pharmaceuticals

Rodenticides

Active substance -> EU Pesticides database: Not approved

Pesticides -> Rodenticides, Anticoagulant

Practically insoluble in water (17mg/L). Hydrolyzed by strong acid.

Acids, Weak

DIPHACINONE is a ketone, and behaves as a weak acid. Forms water soluble alkali metal salts. Ketones are reactive with many acids and bases liberating heat and flammable gases (e.g., H2). The amount of heat may be sufficient to start a fire in the unreacted portion of the ketone. Ketones react with reducing agents such as hydrides, alkali metals, and nitrides to produce flammable gas (H2) and heat. Ketones are incompatible with isocyanates, aldehydes, cyanides, peroxides, and anhydrides. They react violently with aldehydes, HNO3, HNO3 + H2O2, and HClO4.

The substance can be absorbed into the body by inhalation of its aerosol, through the skin and by ingestion.

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

EASILY ABSORBED! See Inhalation.

Abdominal pain. Further see Inhalation.

Diphacinone

Children

Human Health Benchmarks for Pesticides - 2021 Update

LC50 (rat) = 2000 mg/m3/4H

LD50 Rat oral 0.3 to 2.3 mg/kg

LD50 Mouse oral 340 mg/kg

LD50 Rabbit oral 35 mg/kg

LD50 Rat percutaneous <200 mg/kg

For more Non-Human Toxicity Values (Complete) data for Diphacinone (16 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.

Administration of vitamin K1, SC, to anticoagulant-poisoned (diphenadione) dogs provided diagnostic information within 4 hours, when vitamin K1 and its epoxide were measured in canine sera. Twelve dogs (2 groups of 6) were given 2.5 mg of diphenadione/kg of body weight for 3 days. Dogs were treated with vitamin K1, 2.5 (n = 6) or 5 mg/kg/day (n = 6) SC for 21 days, and their responses were compared. Four nonexposed control dogs were given 5 mg of vitamin K1/kg/day. Serum concentration of vitamin K epoxide was significantly (P less than 0.02) higher in diphenadione-exposed dogs than in control dogs 1 to 4 hours after the initial vitamin K1 treatment on day 4. Vitamin K epoxide/vitamin K1 ratios were similarly higher and became more distinct. Cessation of vitamin K1 therapy on day 24 resulted in prolongation of one-stage prothrombin times in diphenadione-exposed dogs, becoming clearly evident on day 27. Serum vitamin K1 concentrations were not detectable on day 27 in diphenadione-exposed dogs, whereas serum vitamin K1 concentrations were readily detectable in control dogs. One-stage prothrombin time changes, during days 24 to 32, indicated 5 mg of vitamin K1/kg provided better protection than did 2.5 mg of vitamin K1/kg. Coagulopathy in the dogs was resolved by day 32.

Hypoprothrombinemia may be treated with vitamin K1 or parenteral injections of aquamephyton or similar products 20-40 mg, repeatable every four hours until the prothrombin time returns to normal.

Vitamin K1. ... For suicidal ingestions with large amounts taken, if there is uncertainty about the amount of bait ingested or the general health of the patient, phytonadione (vitamin K1) given orally protects against the anticoagulant effect of these rodenticides, with essentially no risk to the patient. In accidental ingestions with healthy children involving only a taste or single swallow, no medical treatment is required, but children should be observed for bleeding and bruising. If a larger amount may have been ingested, prothrombin time (PT) should be monitored at 24 and 48 hours, with phytonadione therapy initiated for elevated PT or clinical signs of bleeding. CAUTION: Phytonadione, specificaly, is required. Neither vitamin K3 (menadione, Hykinone) nor vitamin K4 (menadiol) is an antidote for these anticoagulants. /Coumarins and Indandiones/

Gastrointestinal decontamination. If large amounts of anticoagulant have been ingested within several hours prior to treatment, consider gastric decontamination procedures ... . /Coumarins and Indandiones/

For more Antidote and Emergency Treatment (Complete) data for Diphacinone (13 total), please visit the HSDB record page.

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.

/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.

/LABORATORY ANIMALS: Acute Exposure/ Multiple dose toxicity ... /of diphenadione/ involves same hemorrhagic phenomenas with hydroxycoumarins. Massive single oral doses /100-200 mg/kg/ ... killed rats and rabbits within 2-12 hr. In ... acute exposures hemorrhages were not usually found on postmortem exam, and prothrombin levels were not invariably depressed.

/LABORATORY ANIMALS: Acute Exposure/ Animals receiving ... Single lethal doses of substituted indandiones /diphenadione/ (100-200 mg/kg) exhibited labored breathing, progressive muscular weakness, hyperexcitability, pulmonary congestion, venous engorgement, and cardiac standstill in systole.

/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ In a dermal sensitization study with Hartley albino male guinea pigs with diphacinone technical (96.57%), the test material was administered as a topical application at various dose concns. The test article was kept in contact with the skin surface for a 6 hr period. After the initial exposure, the test article was administered on alternate days 3 days/wk such that each animal received 10 sensitizing treatments. Following the tenth treatment, animals were rested for 2 weeks, and then given an 11th (challenge) dose. The major problem in this dermal sensitization study was on determining a non-lethal dose level. In the initial assay application of 500 mg caused death and/or severe hemorrhage from the external nares in some animals and evident discomfort in others, with the result that all surviving animals were euthanized. Further testing at doses of 5, 10, 20, 40 or 80 mg with two male guinea pigs/dose resulted in all animals either dying or being euthanized on or about the 7th day after the initial dose. Additional dosing at 0.1, 0.5, 1.0 or 2.5 mg with two animals/dose resulted in the death of one animal in the 0.5 mg group. As a result, the final dose selected was 2.5 mg in 10 guinea pigs (one of these animals died 13 days after the initial dose). Signs of dermal irritation were not observed in any of the guinea pigs at any dose level during the study, and there were no indications of any sensitization reaction in the survivors of the final assay (dose level: 2.5 mg/animal). There were 3 guinea pigs in a positive control group (each received 2.5 mg/application). One of these positive control animals died before the challenge application, but positive responses were elicited in the remaining 2 guinea pigs. The findings of this study adequately demonstrate that technical diphacinone at a non-lethal exposure level is neither a dermal irritant nor a sensitizer. /Technical diphacinone (96.57%)/

/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ Rats were fed diets containing 0.0313-0.5 ppm diphacinone for 90 days or 0.125-4.0 ppm for 21 days. In the 90 day test, only 2 of 72 rats died, and survivors showed little change in prothrombin clotting time and blood chemistry values. The fibrinogen levels were decreased in rats fed 0.5 ppm. In 21day study, all rats fed 2 and 4 ppm died. In survivors fed lower doses, prothrombin times were not affected.

For more Non-Human Toxicity Excerpts (Complete) data for Diphacinone (15 total), please visit the HSDB record page.

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

The available studies also suggest that some individuals in any population may be much more succeptible to effects than others. These individuals may include those with poor nutritional status and/or Vitamin K deficiency, liver or kidney disorders, or infectious diseases.

If anemia or liver disease is present then the above features may be more severe and persistent and the poisoning may be more difficult to control. /Anticoagulant rodenticides/

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

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.

/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.

/BIRDS and MAMMALS/ In the United States, new regulatory restrictions have been placed on the use of some second-generation anticoagulant rodenticides. This action may be offset by expanded use of first-generation compounds (e.g., diphacinone; DPN). Single-day acute oral exposure of adult Eastern screech-owls (Megascops asio) to DPN evoked overt signs of intoxication, coagulopathy, histopathological lesions (e.g., hemorrhage, hepatocellular vacuolation), and/or lethality at doses as low as 130 mg/kg body weight, although there was no dose-response relation. However, this single-day exposure protocol does not mimic the multiple-day field exposures required to cause mortality in rodent pest species and non-target birds and mammals. In 7-day feeding trials, similar toxic effects were observed in owls fed diets containing 2.15, 9.55 or 22.6 ppm DPN, but at a small fraction (<5%) of the acute oral dose. In the dietary trial, the average lowest-observed-adverse-effect-level for prolonged clotting time was 1.68 mg DPN/kg owl/week (0.24 mg/kg owl/day; 0.049 mg/owl/day) and the lowest lethal dose was 5.75 mg DPN/kg owl/week (0.82 mg/kg owl/day). In this feeding trial, DPN concentration in liver ranged from 0.473 to 2.21 ug/g wet weight, and was directly related to the daily and cumulative dose consumed by each owl. A probabilistic risk assessment indicated that daily exposure to as little as 3-5 g of liver from DPN-poisoned rodents for 7 days could result in prolonged clotting time in the endangered Hawaiian short-eared owl (Asio flammeus sandwichensis) and Hawaiian hawk (Buteo solitarius), and daily exposure to greater quantities (9-13 g of liver) could result in low-level mortality. ...

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

The substance is toxic to aquatic organisms. This substance does enter the environment under normal use. Great care, however, should be taken to avoid any additional release, for example through inappropriate disposal.

Diphacinone's production may result in its release to the environment through various waste streams; its use as a rodenticide will result in its direct release to the environment. If released to air, a vapor pressure of 1.03X10-10 mm Hg at 25 °C indicates diphacinone will exist solely in the particulate phase in the atmosphere. Particulate-phase diphacinone will be removed from the atmosphere by wet and dry deposition. Diphacinone is rapidly decomposed in water by sunlight and, therefore, may be susceptible to direct photolysis by sunlight. If released to soil, diphacinone is reported to be immobile based upon a column study. A laboratory study indicated most of the chemical would remain in the top 0-6 cm soil layer of packed columns. Volatilization from moist soil surfaces is not expected to be an important fate process based upon a Henry's Law constant of 1.5X10-10 atm-cu m/mole at 25 °C. Diphacinone is not expected to volatilize from dry soil surfaces based upon its vapor pressure. A biodegradation half-life of 28.3 to 31.7 days when incubated aerobically in sandy loam soils for 3.5 months, suggests that biodegradation may be an important environmental fate process in soil and water. If released into water, diphacinone is expected to adsorb to suspended solids and sediment based upon a column study. Volatilization from water surfaces is not expected to be an important fate process based upon this compound's Henry's Law constant of 1.5X10-10 atm-cu m/mole at 25 °C. An estimated BCF of 76 suggests the potential for bioconcentration in aquatic organisms is moderate. Diphacinone is stable at pH 7 and 9; a half-life of 44 days was observed at pH 5. Occupational exposure to diphacinone may occur through inhalation and dermal contact with this compound at workplaces where diphacinone is produced or used. Use data indicate that the general population may be exposed to diphacinone via dermal contact with consumer products containing diphacinone. Wildlife monitoring studies suggest that nontarget species may be exposed to diphacinone and other anticoagulant rodenticides through primary consumption of bait and secondary consumption of poisoned target species. (SRC)

Diphacinone's production may result in its release to the environment through various waste streams; it's use as a rodenticide in the control of commensal rats and house mice(1) will result in its direct release to the environment(SRC).

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).

AEROBIC: Radio-labeled (benzyl ring or both phenyl rings)[14C]diphacinone was metabolized with a half-life of 28.3 to 31.7 days, respectively, in sandy loam soils incubated aerobically in the dark at 25 °C for 3.5 months. The major degradate (defined as >10% of the applied) detected in the phenyl ring labeled study was identified as diphenylglycolic acid and was present at a maximum of 24.5% of the applied at one month after application. Diphenylglycolic acid was also detected in the benzyl ring labeled study at a very low concentration (<10% of the applied). By 3.5 months post-treatment, 42.5% of the applied radioactivity was accounted for as 14CO2 in benzyl ring labeled [14C]diphacinone, and 37.3% of the applied radioactivity was accounted for as 14CO2 in the phenyl ring labeled [14C]diphacinone(1).

Diphacinone is stable to hydrolysis at pH 7 and pH 9, but degraded at pH 5 (half-life of 44 days)(1). Diphacinone is rapidly decomposed in water by sunlight(2) and, therefore, may be susceptible to direct photolysis by sunlight(SRC).

An estimated BCF of 79 was calculated in fish for diphacinone(SRC), using a log Kow of 4.27(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is moderate(SRC).

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).

The Henry's Law constant for diphacinone is 1.54X10-10 at 25 °C(1). This Henry's Law constant indicates that diphacinone is expected to be essentially nonvolatile from water surfaces and moist soil(2). Diphacinone is not expected to volatilize from dry soil surfaces(SRC) based upon its vapor pressure of 1.03X10-10 at 25 °C(1).

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).

NIOSH (NOES Survey 1981-1983) has statistically estimated that 8,704 workers (561 of these are female) are potentially exposed to diphacinone in the US(1). The NOES Survey does not include farm workers. Occupational exposure to diphacinone may occur through inhalation and dermal contact with this compound at workplaces where diphacinone is produced or used. Use data indicate that the general population may be exposed to diphacinone via dermal contact with this compound and other consumer products containing diphacinone(SRC).

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.

Do not transport with food and feedstuffs.

Symbol: T+; R: 28-48/23/24/25; S: (1/2)-36/37-44

UN Hazard Class: 6.1; UN Pack Group: I