Section 1 - CHEMICAL PRODUCT AND COMPANY IDENTIFICATION

PRODUCT NAME

WARFARIN-DEANOL

NFPA

PRODUCT USE

Oral anticoagulant. Medicine

SYNONYMS

C19-H16-O4.C4-H11-N-O, C19-H16-O4.C4-H11-N-O, "coumarin, 3-(alpha-acetonylbenzyl)-4-
hydroxy-, compd. with", "coumarin, 3-(alpha-acetonylbenzyl)-4-hydroxy-, compd. with",
"2-(dimethylamino)ethanol (1:1)", "2-(dimethylamino)ethanol (1:1)", "3-(alpha-
acetonylbenzyl)-4-hydroxycoumarin compd. with", "3-(alpha-acetonylbenzyl)-4-
hydroxycoumarin compd. with", "3-alpha-acetonyl-benzyl-4-hydroxycoumarine
dimethylaminoethanol", "3-alpha-acetonyl-benzyl-4-hydroxycoumarine dimethylaminoethanol",
WDMA, anticoagulant

Section 2 - HAZARDS IDENTIFICATION

CANADIAN WHMIS SYMBOLS

EMERGENCY OVERVIEW

RISK

May cause harm to the unborn child.
Harmful: danger of serious damage to health by prolonged exposure through
inhalation.
Harmful to aquatic organisms, may cause long- term adverse effects in the
aquatic environment.

POTENTIAL HEALTH EFFECTS

ACUTE HEALTH EFFECTS

SWALLOWED

  Accidental ingestion of the material may be seriously damaging to the health of the individual; animal experiments indicate that ingestion of less than 40 gram may be fatal.  Heparin, coumarin and indan-1,3-dione derivatives are used to kill rodents and to prevent blood clotting. They block the synthesis of prothrombin by antagonizing vitamin K. They are safe in normal use but with high does or prolonged use, they can cause bleeding accidents, especially in sensitive persons. Symptoms of poisoning include nausea and vomiting; effects may be delayed for days. Other symptoms include bleeding gums, easy bruising, blood in the urine and excessive bleeding from minor wounds. Severe poisonings can cause shock, coma and death.  

EYE

  Although the material is not thought to be an irritant, direct contact with the eye may cause transient discomfort characterized by tearing or conjunctival redness (as with windburn). Slight abrasive damage may also result. The material may produce foreign body irritation in certain individuals.  

SKIN

  The material is not thought to be a skin irritant (as classified using animal models). Abrasive damage however, may result from prolonged exposures. Good hygiene practice requires that exposure be kept to a minimum and that suitable gloves be used in an occupational setting.  Skin contact with the material may damage the health of the individual; systemic effects may result following absorption.  Coumarin and its derivatives may act as slight allergens in contact withskin.  Open cuts, abraded or irritated skin should not be exposed to this material.  Entry into the blood-stream, through, for example, cuts, abrasions or lesions, may produce systemic injury with harmful effects. Examine the skin prior to the use of the material and ensure that any external damage is suitably protected.  

INHALED

  Inhalation may produce serious health damage*.  The material is not thought to produce respiratory irritation (as classified using animal models). Nevertheless inhalation of dusts, or fume, especially for prolonged periods, may produce respiratory discomfort and occasionally, distress.  Inhalation of dusts, generated by the material during the course of normal handling, may produce serious damage to the health of the individual.  Persons with impaired respiratory function, airway diseases and conditions such as emphysema or chronic bronchitis, may incur further disability if excessive concentrations of particulate are inhaled.  Coumarin and its derivatives may act as slight allergens in contact withmucous membranes. Absorption by the lungs is not considered to be asignificant route of entry.  

CHRONIC HEALTH EFFECTS

  Harmful: danger of serious damage to health by prolonged exposure through inhalation.  This material can cause serious damage if one is exposed to it for long periods. It can be assumed that it contains a substance which can produce severe defects. This has been demonstrated via both short- and long-term experimentation.  Ample evidence exists, from results in experimentation, that developmental disorders are directly caused by human exposure to the material.  Limited evidence suggests that repeated or long-term occupational exposure may produce cumulative health effects involving organs or biochemical systems.  There is some evidence that inhaling this product is more likely to cause a sensitization reaction in some persons compared to the general population.  There is limited evidence that, skin contact with this product is more likely to cause a sensitization reaction in some persons compared to the general population.  Long term exposure to high dust concentrations may cause changes in lung function i.e. pneumoconiosis; caused by particles less than 0.5 micron penetrating and remaining in the lung. Prime symptom is breathlessness; lung shadows show on X-ray.  Repeated exposure to some coumarin derivatives may cause nosebleed, bleeding gut and pharynx, dark red bleeding spots, widespread bruising, blood swelling, blood in the phlegm, vomitus, urine or stools. Bleeding into the organs, digestive tract, joints, abdomen can cause localized pain. Exposure at work can cause anemia with weakness, pallor and shock. Many coumarins cause mutations and cancer. Coumarins also inhibit tumor production by carcinogens and inhibit metastasis.  Coumarin and its derivatives may act as slight allergens in contact withmucous membranes. Absorption by the lungs is not considered to be asignificant route of entry.  Prolonged or chronic exposure to alkanolamines may result in liver, kidney or nervous system injury. Repeated inhalation may aggravate asthma and inflammatory or fibrotic pulmonary disease.Results of repeated exposure tests with diethanolamine (DEA) in laboratory animals include anaemia (rats) and effects on the kidneys (rats and mice) and liver (mice). DEA produces nervous system injury in dogs and rats. Heart and salivary gland lesions have also been seen in mice treated cutaneously with DEA and in mice receiving DEA in drinking water. Rats given high doses of DEA developed anaemia and testicular lesions.Exaggerated doses of DEA produced heart and nervous system effects in other animals. Changes in other organs were judged to be secondary due to the poor health of animals subjected to extremely high doses of DEA. Rats, rabbits and guinea pigs exposed to high vapour concentrations of volatile monoethanolamine (MEA) (up to 1250 ppm) for periods of up to 5 weeks developed pulmonary, hepatic and renal lesions. Dogs, rats and guinea pigs exposed to 100 ppm MEA for 30 days, became apathetic and developed poor appetites. Animal tests also indicate that inhalation exposure to MEA may result in nervous system injury. All species exposed to airborne MEA experienced dermal effects, varying from ulceration to hair loss probably resulting from contact with the cage.An increased incidence of skeletal variations, suggestive of a slight developmental delay was seen in the foetuses of rats given 1500 mg/kg/day DEA cutaneously; this also produced significant maternal toxicity. No foetal malformations, however, were seen in rats nor in rabbits receiving identical treatment. The foetus of rats given high doses of MEA by gavage, showed an increased rate of embryofoetal death, growth retardation, and some malformations including hydronephrosis and hydroureter. The high doses required to produce these effects bring into question the relevance of this finding to humans. There is some evidence that embryofoetotoxicity and teratogenicity does not occur in rats when MEA is administered by dermal application to the mother.The National Toxicology Program (NTP) concluded that there is clear evidence of liver tumours and some evidence of kidney tumours in mice exposed dermally to DEA over their lifetime. Chronic skin painting studies in mice of both sexes produced liver tumours and an increased incidence of kidney tumours in male mice. The significance of these findings to humans is unclear as DEA is neither genotoxic, mutagenic nor clastogenic, and did not induce tumours in rats or transgenic mice similarly treated. Alkanolamines (especially those containing a secondary amine moiety) may react with nitrites or other nitrosating agents to form carcinogenic N-  nitrosamines. Alkanolamines are metabolised by biosynthetic routes to ethanolamine and choline and incorporated into phospholipids. They are excreted predominantly unchanged with a half-life of approximately one week. In the absence of sodium nitrite, no conversion to carcinogenic N-nitrosamines was observed.Diethanolamine competitively inhibits the cellular uptake of choline, in vitro, and hepatic changes in choline homeostasis, consistent with choline deficiency, are observed in vivo.Many amines are potent skin and respiratory sensitisers and certain individuals especially those described as "atopic" (i.e. those predisposed to asthma and other allergic responses) may show allergic reactions when chronically exposed to alkanolamines.In a study with coconut diethanolamide, the National Toxicology Program (Technical Report Series 479), showed clear evidence of carcinogenic activity in male B6C3F1 mice based on increased incidences of hepatic and renal tubule neoplasms and in female B6C3F1 mice based on increased incidences of hepatic neoplasms. There was equivocal evidence of carcinogenic activity in female F344/N rats based on a marginal increase in the incidence of renal tube neoplasms. These increases were associated with the concentration of free diethanolamine present as a contaminant in the diethanolamine condensate. Exposure to rats to coconut oil diethanolamine condensate by dermal application in ethanol for 2 years resulted in epidermal hyperplasia, sebaceous gland hyperplasia, hyperkeratosis and parakeratosis in males and females and ulcer in females at the site of application. There were increases in the incidences of chronic inflammation, epithelial hyperplasia, and epithelial ulcer in the forestomach of female rats. The severity of nephropathy in dosed female rats were increased. Exposure of mice to coconut oil diethanolamine condensate by dermal application for 2 years resulted in increased incidences of eosinophilic foci of the liver in males. Increased incidences of epidermal hyperplasia, sebaceous gland hyperplasia, and hyperkeratosis in males and females, ulcer in males, and parakeratosis and inflammation in females at the site of application and of follicular cell hyperplasia in the thyroid gland of males and females, were chemical related.  Congenital malformations have occurred following maternal exposure to warfarin. Effects are primarily seen in the craniofacial region of the foetus and include nasal hypoplasia, bone stippling and mental retardation. Central nervous system abnormalities have occurred during second or third trimester exposures. Exposure during early pregnancy may also produce dysmorphia.