C(19)H(16)O(4)

(For Structure, see paper copy)

3-(alpha-Acetonylbenzyl)-4-hydroxycoumarin; Arab Rat Deth; Athrombine-K; Brumolin; Co-Rax; Coumadin; Cov-R-Tox;d-CON; Dethmor; Fasco Fascrat Powder; Liqua-Tox; Mar-Frin; Mouse-Pak; Prothromadin; Rat-A-Way; Rat-B-Gon; Rat & Mice Bait; Rax; Rodex; Solfarin; Tox-Hid; WARF compound 42

1. CAS 81-81-2

2. RTECS GN4550000

3. Specific DOT UN: None

4. Specific DOT label: None

Warfarin is an odorless, colorless or white, crystalline powder. It is available commercially as a dust or liquid concentrate and in various formulations with other pesticides.

1. Molecular weight: 308.3.

2. Boiling point (760 torr): Decomposes.

3. Specific gravity (water = 1): Greater than 1 at 20 degrees C (68 degrees F).

4. Vapor density: Not applicable.

5. Melting point: 161 degrees C (322 degrees F).

6. Vapor pressure at 21 degrees C (70.7 degrees F): 0.09 millibar.

7. Solubility: Insoluble in water and benzene; slightly soluble in methanol and ethanol; soluble in acetone and dioxane.

8. Evaporation rate: Not applicable.

1. Conditions contributing to instability: In liquid form, warfarin rodenticides may be flammable and explosive and should be kept away from heat, sparks, and flames. In solid form, warfarin rodenticides are not combustible.

2. Incompatibilities: Contact of warfarin rodenticides with strong oxidizers may cause fires and explosions.

3. Hazardous decomposition products: Toxic gases (such as carbon monoxide) and fumes may be released in a fire involving warfarin.

4. Special precautions: None.

There is no National Fire Protection Association fire hazard rating for warfarin; when mixed with flammable liquids, warfarin-containing rodenticides may be flammable. In solid form, however, warfarin-containing rodenticides are not combustible.

1. Flash point (for the pure substance): Not applicable.

2. Autoignition temperature (for the pure substance): Not applicable.

3. Flammable limits in air: Not applicable.

4. Extinguishant: Use an extinguishant that is suitable for the materials involved in the surrounding fire.

Firefighters should wear a full set of protective clothing, including a self-contained breathing apparatus, when fighting fires involving warfarin.

Warfarin is odorless. This substance is therefore considered to have inadequate odor warning properties.

No quantitative data are available on the eye irritation threshold for warfarin; this substance is not known to be an eye irritant.

Exposure to warfarin can occur via inhalation, ingestion, and skin contact.

1. Effects on Animals: Warfarin acts on the liver to inhibit prothrombin formation, which interferes with blood clotting; it also damages the blood vessels directly. The lowest reported oral LD(50) in rats is 1600 ug/kg, and the LC(50) in the same species is 320 mg/m(3) [RTECS 1989]. The dermal LD(50) in rats is 1400 mg/kg [RTECS 1989]. Although a large single dose of warfarin can cause poisoning, this substance is most toxic when ingested daily in small amounts over a 5- to 7-day period. Rats and mice die after ingesting 1 mg/kg/day for 6 days [HSDB 1987]. The clinical signs of lethal warfarin poisoning include massive hemorrhages, visible hematomas under the skin and around the joints, and bloody discharges from body orifices. Shock, weakness, and labored breathing may also occur [HSDB 1987]. Intramuscular exposure to 10 mg/kg on days 8 through 28 of pregnancy caused stillbirths and developmental abnormalities in the offspring of dosed rabbits [RTECS 1989].

2. Effects on Humans: Warfarin acts on the liver to inhibit prothrombin formation, which interferes with blood clotting; it also damages the blood vessels directly. Several days of warfarin administration are required to deplete the body's stores of clotting factors and produce an anticoagulant effect [Gosselin, Smith, and Hodge 1984, p. III-395]. Toxic doses of warfarin also produce dilation and engorgement of blood vessels and increased capillary fragility, which may further increase the risk of hemorrhage [Proctor, Hughes, and Fischman 1988, p. 510]. Except for abnormal bleeding, warfarin has few toxic effects, although anorexia, nausea, vomiting, diarrhea, and skin lesions may occur [HSDB 1987]. The lowest reported lethal dose in humans is 6667 ug/kg [RTECS 1989]. As in animals, warfarin is most toxic when ingested in small doses over a period of 5 to 6 days; 1-2 mg/kg/day for 6 days is estimated to be lethal [Klaassen, Amdur, and Doull 1986, p. 564]. Two deaths occurred among 14 members of a Korean family ingesting an estimated 1-2 mg/kg dose of warfarin per day for 15 days in contaminated cornmeal [Gosselin, Smith, and Hodge 1984, p. III-395]. Another death occurred in an adult who consumed an estimated 1000 mg warfarin over a 13-day period [Baselt 1980, p. 282]. A 23-year-old farmer was exposed to a 0.5 percent warfarin sodium salt by skin contact for several hours on 10 occasions during a 24-day period. On day 26, he developed gross hematuria. On day 27, hematomas appeared on his arms and legs and he complained of dull pain in both sides of the groin area. On day 30, the hematuria resolved and he developed nosebleeds. Laboratory analysis revealed prolongation of prothrombin, bleeding, and clotting times as well as severe anemia. The patient subsequently responded to the administration of vitamin-K and recovered fully [Proctor, Hughes, and Fischman 1988, p. 510]. Warfarin causes fetotoxic and teratogenic effects in the offspring of women taking this substance as an anticoagulant during pregnancy; many cases of stillbirths and deformities have been attributed to the therapeutic use of warfarin [Hayes 1982, p. 511].

1. Acute exposure: The signs and symptoms of acute exposure (i.e., for a period of one week or less) to warfarin include bloody nose; bleeding gums; muscle and joint pain; hematomas of the arms, legs, buttocks, and/or joints; frank blood in the urine and feces; anorexia, nausea, vomiting, diarrhea or abdominal pain; pallor and fatigue caused by anemia; paralysis caused by intracranial hemorrhage; blurry vision, eye pain, and blindness; and/or skin lesions and petechiae. These symptoms generally do not develop until small doses have been ingested over a period of several days.

2. Chronic exposure: The signs and symptoms of chronic low-level exposure to warfarin are the same as those listed above.

In the event of an emergency, remove the victim from further exposure, send for medical assistance, and initiate the following emergency procedures:

1. Eye exposure: If warfarin or a solution containing warfarin gets into the eyes, immediately flush the eyes with large amounts of water for a minimum of 15 minutes, lifting the lower and upper lids occasionally. If irritation persists, get medical attention as soon as possible.

2. Skin exposure: This substance can cause poisoning by the dermal route of exposure. Therefore, if warfarin or a solution containing warfarin contacts the skin, the contaminated skin should be washed twice with soap and water. If irritation persists or symptoms develop, get medical attention immediately.

3. Inhalation: If the vapors or dust of warfarin-containing compounds are inhaled, move the victim at once to fresh air and get medical care as soon as possible. If the victim is not breathing, perform cardiopulmonary resuscitation; if breathing is difficult, give oxygen. Keep the victim warm and quiet until medical help arrives.

4. Ingestion: If warfarin or a solution containing warfarin is ingested, give the victim several glasses of water to drink and then induce vomiting by having the victim touch the back of the throat with the finger or by giving syrup of ipecac as directed on the package. Do not force an unconscious or convulsing person to drink liquids or to vomit. Get medical help immediately. Keep the victim warm and quiet until medical help arrives.

5. Rescue: Remove an incapacitated worker from further exposure and implement appropriate emergency procedures (e.g., those listed on the Material Safety Data Sheet required by OSHA's Hazard Communication Standard, 29 CFR 1910.1200). All workers should be familiar with emergency procedures and the location and proper use of emergency equipment.

Before a worker is placed in a job with a potential for exposure to warfarin, the examining physician should evaluate and document the worker's baseline health status with thorough medical, environmental, and occupational histories, a physical examination, and physiologic and laboratory tests appropriate for the anticipated occupational risks. These should concentrate on the function and integrity of the blood, cardiovascular system, and kidneys.

A preplacement medical evaluation is recommended to assess an individual's suitability for employment at a specific job and to detect and assess medical conditions that may be aggravated or may result in increased risk when a worker is exposed to warfarin at or below the prescribed exposure limit. The examining physician should consider the probable frequency, intensity, and duration of exposure as well as the nature and degree of any applicable medical condition. Such conditions (which should not be regarded as absolute contraindications to job placement) include a history and other findings consistent with diseases of the blood, cardiovascular system, or kidneys.

Occupational health interviews and physical examinations should be performed at regular intervals during the employment period, as mandated by any applicable Federal, State, or local standard. Where no standard exists and the hazard is minimal, evaluations should be conducted every 3 to 5 years or as frequently as recommended by an experienced occupational health physician. Additional examinations may be necessary if a worker develops symptoms attributable to warfarin exposure. The interviews, examinations, and medical screening tests should focus on identifying the adverse effects of warfarin on the blood, cardiovascular system, or kidneys. Current health status should be compared with the baseline health status of the individual worker or with expected values for a suitable reference population.

Biological monitoring involves sampling and analyzing body tissues or fluids to provide an index of exposure to a toxic substance or metabolite. Warfarin can be detected in the plasma of exposed individuals, and plasma levels are believed to correlate well with airborne concentrations of warfarin. However, the levels of warfarin in the plasma that correspond to 8-hour TWA exposures to a 0.1-mg/m(3) airborne concentration of warfarin have not been established. Therefore, no biological monitoring test acceptable for routine use has yet been developed for warfarin.

The medical, environmental, and occupational history interviews, the physical examination, and selected physiologic or laboratory tests that were conducted at the time of placement should be repeated at the time of job transfer or termination to determine the worker's medical status at the end of his or her employment. Any changes in the worker's health status should be compared with those expected for a suitable reference population.

Employers owning or operating a facility at which there are 10,000 pounds or more of warfarin must comply with EPA's emergency planning requirements [40 CFR Part 355.30]. (If warfarin is in the form of a finely divided powder or is handled in solution or in molten form, the employer must comply with these requirements if 500 pounds or more of warfarin are present at the facility.)

A hazardous substance release is defined by EPA as any spilling, pumping, pouring, emitting, emptying, discharging, injecting, escaping, leaching, dumping, or disposing into the environment (including the abandonment or discarding of containers) of hazardous substances. In the event of a release that is above the reportable quantity for that chemical, employers are required by the Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA) to notify the proper Federal, State, and local authorities.

The reportable quantity for warfarin is 100 pounds. If an amount equal to or greater than this quantity is released within a 24-hour period, CERCLA [40 CFR Part 302.6] requires employers to notify the National Response Center IMMEDIATELY at (800) 424-8802 (in Washington, D.C. at (202) 426-2675), and 40 CFR Part 355.40 requires employers to notify (1) the State emergency response commission of any State likely to be affected by the release, and (2) the community emergency coordinator of the local emergency planning committee (or relevant local emergency response personnel) and to identify any area likely to be affected by the release.

Employers are not required by Section 313 of the Superfund Amendments and Reauthorization Act (SARA) to submit a Toxic Chemical Release Inventory form (Form R) to EPA reporting the amount of warfarin emitted or released from their facility annually.

EPA considers a waste to be hazardous if it exhibits any of the following characteristics: ignitability, corrosivity, reactivity, or toxicity, as defined in 40 CFR 261.21-261.24. Under the Resource Conservation and Recovery Act (RCRA), EPA has specifically listed many chemical wastes as hazardous. Warfarin is listed as a hazardous waste under RCRA and has been assigned EPA Hazardous Waste No. P001. This substance has been banned from land disposal and may be treated by fuel substitution or incineration. Warfarin also may be disposed of in an organometallic or organic lab pack that meets the requirements of 40 CFR 264.316 or 265.316.

Providing more information about the removal and disposal of specific chemicals is beyond the scope of this guideline. EPA, U.S. Department of Transportation, and State and local regulations should be followed to ensure that removal, transport, and disposal of this substance are conducted in accordance with existing regulations. To be certain that chemical waste disposal meets EPA regulatory requirements, employers should address any questions to the RCRA hotline at (202) 382-3000 (in Washington, D.C.) or toll-free at (800) 424-9346 (outside Washington, D.C.). In addition, relevant State and local authorities should be contacted for information on any requirements they may have for the waste removal and disposal of this substance.

Good industrial hygiene practice requires that engineering controls be used where feasible to reduce workplace concentrations of hazardous materials to the prescribed exposure limit. However, some situations may require the use of respirators to control exposure. Respirators must be worn if the ambient concentration of warfarin exceeds prescribed exposure limits. Respirators may be used (1) before engineering controls have been installed, (2) during work operations such as maintenance or repair activities that involve unknown exposures, (3) during operations that require entry into tanks or closed vessels, and (4) during emergency situations. If the use of respirators is necessary, the only respirators permitted are those that have been approved by NIOSH and the Mine Safety and Health Administration (MSHA).

Employers should institute a complete respiratory protection program that, at a minimum, complies with the requirements of OSHA's Respiratory Protection Standard [29 CFR 1910.134]. Such a program must include respirator selection (see Table 1), an evaluation of the worker's ability to perform the work while wearing a respirator, the regular training of personnel, fit testing, periodic workplace monitoring, and regular respirator maintenance, inspection, and cleaning. The implementation of an adequate respiratory protection program (including selection of the correct respirator) requires that a knowledgeable person be in charge of the program and that the program be evaluated regularly. For additional information on the selection and use of respirators and on the medical screening of respirator users, consult the NIOSH Respirator Decision Logic [NIOSH 1987c] and the NIOSH Guide to Industrial Respiratory Protection [NIOSH 1987a].

Table 1 lists the respiratory protection that NIOSH recommends for workers exposed to warfarin. The recommended protection may vary over time because of changes in the exposure limit for warfarin or in respirator certification requirements. Users are therefore advised to determine periodically whether new information is available.