Section 1 - CHEMICAL PRODUCT AND COMPANY IDENTIFICATION

PRODUCT NAME

RALTITREXED

NFPA

PRODUCT USE

Antineoplastic which acts as an antimetabolite; used in the treatment of colorectal
cancer. Also used in the treatment of breast cancer, gastroesophageal cancer and
mesothelioma. Given by intravenous injection or infusion. A quinazoline folate antagonist
that selectively inhibits thymidylate synthases (TS). TS is a key enzyme in the de novo
synthesis of thymidine triphosphate (TTP), a nucleotide required exclusively for DNA
synthesis. Inhibition of TS leads to DNA fragmentation and cell death. Intracellular
retention of polyglutamated forms of raltitrexed leads to prolonged inhibitory effects.
Raltitrexed is a radiation sensitising agent. It is cell cycle phase- specific (S- phase).
Transported into cells via a reduced folate carrier and then extensively metabolised to
polyglutamate forms with metabolic degradation.

SYNONYMS

C21-H22-N4-O6-S, "L-glutamic acid, N-[(5-(((1, 4-dihydro-2-methyl-4-oxo-6-quinazolinyl)-
", "L-glutamic acid, N-[(5-(((1, 4-dihydro-2-methyl-4-oxo-6-quinazolinyl)-",
methyl)methylamino)-2-thienyl)carbonyl]-, methyl)methylamino)-2-thienyl)carbonyl]-, D-
1694, D-1694, "ICI-D 1694", Tomudex, ZD-1694, "antineolastic/ cytotoxic/ antimetabolite",
"quinazoline folate antifolate antagonist", "thymidylate synthase inhibitor",
"antineoplastic/ cytotoxic"

Section 2 - HAZARDS IDENTIFICATION

CANADIAN WHMIS SYMBOLS

EMERGENCY OVERVIEW

RISK

Limited evidence of a carcinogenic effect.
Possible risk of impaired fertility.
Possible risk of harm to the unborn child.

POTENTIAL HEALTH EFFECTS

ACUTE HEALTH EFFECTS

SWALLOWED

  Accidental ingestion of the material may be damaging to the health of the individual.  The killing action of antineoplastic drugs used for cancer chemotherapy is not selective for cancerous cells alone but affect all dividing cells. Acute side effects include loss of appetite, nausea and vomiting, allergic reaction (skin rash, itch, redness, low blood pressure, unwellness and anaphylactic shock) and local irritation. Gout and renal failure can occur.  At sufficiently high doses the material may be nephrotoxic(i.e. poisonous to the kidney).  

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.  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

  The material is not thought to produce either adverse health effects or irritation of the respiratory tract following inhalation (as classified using animal models). Nevertheless, adverse effects have been produced following exposure of animals by at least one other route and 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

  There has been concern that this material can cause cancer or mutations, but there is not enough data to make an assessment.  Ample evidence from experiments exists that there is a suspicionthis material directly reduces fertility.  Results in experiments suggest that this material may cause disorders in the development of the embryo or fetus, even when no signs of poisoning show in the mother.  Anti-cancer drugs used for chemotherapy can depress the bone marrow with reduction in the number of white blood cells and platelets and bleeding. Susceptibility to infections and bleeding is increased, which can be life- threatening. Digestive system effects may include inflammation of the mouth cavity, mouth ulcers, esophagus inflammation, abdominal pain and bleeds, diarrhea, bowel ulcers and perforation. Reversible hair loss can result and wound healing may be delayed. Long-term effects on the gonads may cause periods to stop and inhibit sperm production. Most anti-cancer drugs can potentially cause mutations and birth defects, and coupled with the effects of the suppression of the immune system, may also cause cancer.  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.  Animal studies showed impairment of male fertility; fertility returned to normal three months after dosing ceased. In pregnant rats, raltitrexed caused embryolethality and foetal abnormalities.  Animal studies indicate that repeated doses produce teratogenic effects. Studies in animals have shown that repeated doses produce cytotoxic effects on the gastrointestinal tract, bone marrow, kidney, liver, thymus, glands and testes. The no-effect level was 0.005 mg/kg/day (dog). Symptoms  of long-term exposure may include nausea, vomiting and malaise.