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This guideline summarizes pertinent information about warfarin for workers and employers as well as for physicians, industrial hygienists, and other occupational safety and health professionals who may need such information to conduct effective occupational safety and health programs. Recommendations may be superseded by new developments in these fields; readers are therefore advised to regard these recommendations as general guidelines and to determine periodically whether new information is available.
(For Structure, see paper copy)* Synonyms
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* Identifiers
1. CAS 81-81-2* Appearance and odor
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.CHEMICAL AND PHYSICAL PROPERTIES
* Physical data
1. Molecular weight: 308.3.* Reactivity
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.* Flammability
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.* Warning properties
Warfarin is odorless. This substance is therefore considered to have inadequate odor warning properties.* Eye irritation properties
No quantitative data are available on the eye irritation threshold for warfarin; this substance is not known to be an eye irritant.EXPOSURE LIMITS
The current Occupational Safety and Health Administration (OSHA) permissible exposure limit (PEL) for warfarin is 0.1 milligram per cubic meter (mg/m(3)) of air as an 8-hour time-weighted average (TWA) concentration [29 CFR 1910.1000, Table Z-1-A]. The National Institute for Occupational Safety and Health (NIOSH) has not issued a recommended exposure limit (REL) for warfarin. The American Conference of Governmental Industrial Hygienists (ACGIH) has assigned warfarin a threshold limit value (TLV) of 0.1 mg/m(3) as a TWA for a normal 8-hour workday and a 40-hour workweek and a short-term exposure limit (STEL) of 0.3 mg/m(3) for periods not to exceed 15 minutes. Exposures at the STEL concentration should not be repeated more than four times a day and should be separated by intervals of at least 60 minutes [ACGIH 1989, p. 42]. The OSHA and ACGIH limits are based on the risk of anticoagulant effects associated with exposure to warfarin.
HEALTH HAZARD INFORMATION
* Routes of Exposure
Exposure to warfarin can occur via inhalation, ingestion, and skin contact.* Summary of toxicology
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].* Signs and symptoms of exposure
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.* Emergency procedures:
In the event of an emergency, remove the victim from further exposure, send for medical assistance, and initiate the following emergency procedures:EXPOSURE SOURCES AND CONTROL METHODS
The following operations may involve warfarin and lead to worker exposures to this substance:
1. ACGIH . Industrial ventilation--a manual of recommended practice. Cincinnati, OH: American Conference of Governmental Industrial Hygienists.
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Workers who may be exposed to chemical hazards should be monitored in a systematic program of medical surveillance that is intended to prevent occupational injury and disease. The program should include education of employers and workers about work-related hazards, placement of workers in jobs that do not jeopardize their safety or health, early detection of adverse health effects, and referral of workers for diagnosis and treatment. The occurrence of disease or other work-related adverse health effects should prompt immediate evaluation of primary preventive measures (e.g., industrial hygiene monitoring, engineering controls, and personal protective equipment). A medical monitoring program is intended to supplement, not replace, such measures. To place workers effectively and to detect and control work-related health effects, medical evaluations should be performed (1) before job placement, (2) periodi-cally during the period of employment, and (3) at the time of job transfer or termination.
* Preplacement medical evaluation
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.* Periodic medical examinations and biological monitoring
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.* Medical examinations recommended at the time of job transfer or termination
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.WORKPLACE MONITORING AND MEASUREMENT PROCEDURES
Determination of a worker's exposure to airborne warfarin is made using a polytetrafluoroethylene filter (1.0 micron). Samples are collected at a maximum flow rate of 2 liters per minute until a maximum air volume of 400 liters is collected. The sample is then treated with methanol to extract the warfarin. Analysis is conducted by high-performance liquid chromatography using an ultraviolet detector. This method has a sampling and analytical error of 0.09 and is included in Method 5002 of the NIOSH Manual of Analytical Methods, 3rd edition, Volume 2 [NIOSH 1984].
PERSONAL HYGIENE PROCEDURES
If warfarin contacts the skin, workers should immediately wash the affected areas twice with soap and water. This substance can cause signs and symptoms of systemic poison-ing if absorbed through the skin.
Clothing contaminated with warfarin should be removed immediately, and provisions should be made for the safe removal of the chemical from the clothing. Persons laundering the clothes should be informed of the hazardous properties of warfarin, particularly its potential to interfere with blood clotting.
A worker who handles warfarin should thoroughly wash hands, forearms, and face with soap and water before eating, using tobacco products, or using toilet facilities.
Workers should not eat, drink, or use tobacco products in areas where warfarin or a solution containing warfarin is handled, processed, or stored.
Warfarin should be stored in a cool, dry, well-ventilated area in tightly sealed containers that are labeled in accordance with OSHA's Hazard Communication Standard [29 CFR 1910.1200]. Containers of warfarin should be protected from physical damage and should be stored separately from feeds and foodstuffs, strong oxidizers, heat, sparks, and open flame. Because empty containers that formerly contained warfarin may still hold product residues, they should be handled appropriately.
SPILLS AND LEAKS
In the event of a spill or leak involving warfarin, persons not wearing protective equipment and clothing should be restricted from contaminated areas until cleanup has been completed. The following steps should be undertaken following a spill or leak:
1. Do not touch the spilled material; stop the leak if it is possible to do so without risk.
2. Notify safety personnel.
3. Remove all sources of heat and ignition.
4. Ventilate potentially explosive atmospheres.
5. Water spray may be used to reduce vapors, but the spray may not prevent ignition in closed spaces.
6. For small dry spills, use a clean shovel and place the material into a clean, dry container; cover and remove the container from the spill area.
7. For small liquid spills, take up with sand or other noncombustible absorbent material and place into containers for later disposal.
8. For large liquid spills, build dikes far ahead of the spill to contain the warfarin for later reclamation or disposal.
EMERGENCY PLANNING, COMMUNITY RIGHT-TO-KNOW, AND HAZARDOUS WASTE MANAGEMENT REQUIREMENTS
The Environmental Protection Agency's (EPA's) regulatory requirements for emergency planning, community right-to-know, and hazardous waste management may vary over time. Users are therefore advised to determine periodically whether new information is available.
* Emergency planning requirements
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.)* Reportable quantity requirements (releases of hazardous substances)
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.* Community right-to-know requirements
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.* Hazardous waste management requirements
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.RESPIRATORY PROTECTION
* Conditions for respirator use
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).* Respiratory protection program
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].PERSONAL PROTECTIVE EQUIPMENT
Protective clothing should be worn to prevent prolonged or repeated skin contact with warfarin. Chemical protective clothing should be selected on the basis of available performance data, manufacturers' recommendations, and evaluation of the clothing under actual conditions of use. No reports have been published on the resistance of various protective clothing materials to warfarin permeation. If permeability data are not readily available, protective clothing manufacturers should be requested to provide information on the best chemical protective clothing for workers to wear when they are exposed to warfarin.
If warfarin is dissolved in an organic solvent, the permeation properties of both the solvent and the mixture must be considered when selecting personal protective equipment and clothing.
Safety glasses, goggles, or faceshields should be worn during operations in which warfarin might contact the eyes (e.g., through dust particles or splashes of solution). Eyewash fountains and emergency showers should be available within the immediate work area whenever the potential exists for eye or skin contact with warfarin. Contact lenses should not be worn if the potential exists for warfarin exposure.
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