Section 1 - CHEMICAL PRODUCT AND COMPANY IDENTIFICATION

PRODUCT NAME

RALOXIFENE HYDROCHLORIDE

NFPA

PRODUCT USE

In the treatment of osteoporosis. A non- steroidal oestrogen receptor mixed agonist/
antagonist. One of the class of so- called SERMs (Selective Estrogen Receptor Modulators)
- is also effective in reducing the risk of breast cancer. Medicine

SYNONYMS

C28-H27-N-O4-S.HCl, C28-H27-N-O4-S.HCl, "methanone, ", "[6-hydroxy-2-(4-
hydroxyphenyl)benzo[b]thien-3-yl][4-(2-(1-piperidenyl)ethoxy]phenyl]-, ", "[6-hydroxy-2-
(4-hydroxyphenyl)benzo[b]thien-3-yl][4-(2-(1-piperidenyl)ethoxy]phenyl]-, ",
hydrochloride, keoxifene, Evista, "LY 156758", "antiosteoporotic anti-osteoporotic/
osteoporosis treatment", antineoplastic, SERM

Section 2 - HAZARDS IDENTIFICATION

CANADIAN WHMIS SYMBOLS

EMERGENCY OVERVIEW

RISK

May impair fertility.
May cause harm to the unborn child.
Harmful to aquatic organisms.

POTENTIAL HEALTH EFFECTS

ACUTE HEALTH EFFECTS

SWALLOWED

  Although ingestion is not thought to produce harmful effects, the material may still be damaging to the health of the individual following ingestion, especially where pre-  existing organ (e.g. liver, kidney) damage is evident. Present definitions of harmful or toxic substances are generally based on doses producing mortality (death) rather than those producing morbidity (disease, ill-health). Gastrointestinal tract discomfort may produce nausea and vomiting. In an occupational setting however, ingestion of insignificant quantities is not thought to be cause for concern.  

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 produce adverse health effects or skin irritation following contact (as classified using animal models). Nevertheless, good hygiene practice requires that exposure be kept to a minimum and that suitable gloves be used in an occupational setting.  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

  The material is not thought to produce adverse health effects or irritation of the respiratory tract (as classified using animal models). Nevertheless, good hygiene practice requires that exposure be kept to a minimum and that suitable control measures be used in an occupational setting.  

CHRONIC HEALTH EFFECTS

  Ample evidence exists from experimentation that reduced human fertility is directly caused by exposure to the material.  Ample evidence exists, from results in experimentation, that developmental disorders are directly caused by human exposure to the material.  

  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.  This material can be regarded as being able to cause cancer in humans based on experiments and other information.  There is some evidence to provide a presumption that human exposure to the material may result in impaired fertility on the basis of: some evidence in animal studies of impaired fertility in the absence of toxic effects, or evidence of impaired fertility occurring at around the same dose levels as other toxic effects but which is not a secondary non-  specific consequence of other toxic effects.  There is some evidence that human exposure to the material may result in developmental toxicity. This evidence is based on animal studies where effects have been observed in the absence of marked maternal toxicity, or at around the same dose levels as other toxic effects but which are not secondary non-specific consequences of the other toxic effects.  Reproductive effects:  No pregnancies occurred when male and female rats were given daily doses of 5  mg/kg prior to and during mating. In female rats, disrupted oestrus cycles and  inhibited ovulation (all reversible) and delayed and disrupted embryo  implantation resulting in prolonged gestation and reduced litter size were  reported. Developmental effects reported included decreased foetal weight and  delayed skeletal development, growth retardation, malformations of the heart,  oedema, and hydrocephaly in offspring. In male rats, daily doses up to 100 mg/kg  for at least two weeks did not effect sperm production/ quality or reproductive  performance. Decreased prostate weights and a single case of aspermatogenesis  were observed in dogs given 30 mg/kg for 6-months. No significant observations  in sperm count/ motility and morphology were observed in humans during a 3 month  clinical trial when given daily doses of 120 mg.  The substance is contraindicated in women who are or may become pregnant. It may  cause fetal harm when administered to a pregnant woman. In rabbit studies,  abortion and a low rate of fetal heart anomalies (ventricular septal defects)  occurred in rabbits at doses  0.1 mg/kg (0.04 times the human dose based on  surface area, mg/m2), and hydrocephaly was observed in fetuses at doses 10  mg/kg (4 times the human dose based on surface area, mg/m2). In rat studies,  retardation of fetal development and developmental abnormalities (wavy ribs,  kidney cavitation) occurred at doses 1mg/kg (0.2 times the human dose based  on surface area, mg/m2). Treatment of rats at doses of 0.1 to 10 mg/kg (0.02 to  1.6 times the human dose based on surface area, mg/m2) during gestation and  lactation produced effects that included delayed and disrupted parturition;  decreased neonatal survival and altered physical development; sex-and  age-specific reductions in growth and changes in pituitary hormone content; and  decreased lymphoid compartment size in offspring. At 10 mg/kg, raloxifene  disrupted parturition which resulted in maternal and progeny death and  morbidity. Effects in adult offspring (4 months of age) included uterine  hypoplasia and reduced fertility; however, no ovarian or vaginal pathology was  observed.  The substance is contraindicated in women with active or past history of venous  thromboembolic events, including deep vein thrombosis, pulmonary embolism, and  retinal vein thrombosis. It is also contraindicated in women known to be  hypersensitive to raloxifene.