Section 1 - CHEMICAL PRODUCT AND COMPANY IDENTIFICATION

PRODUCT NAME

IDARUBICIN HYDROCHLORIDE

NFPA

PRODUCT USE

Antineoplastic/ cytotoxic Medicine

SYNONYMS

C26-H27-N-O9.HCl, C26-H27-N-O9.HCl, "daunomycin, 4-demethoxy-, hydrochloride",
"daunomycin, 4-demethoxy-, hydrochloride", "4-demethoxydaunorubicin hydrochloride", "4-
demethoxydaunorubicin hydrochloride", "5, 12-naphthacenedione, 9-acetyl-7-[(3-amino-2, 3,
6-trideoxy-alpha-", "5, 12-naphthacenedione, 9-acetyl-7-[(3-amino-2, 3, 6-trideoxy-alpha-
", "L-lyxo-hexapyranosyl)oxy]-7, 8, 9, 10-tetrahydro", "L-lyxo-hexapyranosyl)oxy]-7, 8, 9,
10-tetrahydro", "6.9.11-trihydroxyhydrochloride, (7S-cis)", "anthracycline
antineoplastic/ cytotoxic"

Section 2 - HAZARDS IDENTIFICATION

CANADIAN WHMIS SYMBOLS

EMERGENCY OVERVIEW

RISK

May cause CANCER.
May cause heritable genetic damage.
Very toxic by inhalation, in contact with skin and if swallowed.

POTENTIAL HEALTH EFFECTS

ACUTE HEALTH EFFECTS

SWALLOWED

  Severely toxic effects may result from the accidental ingestion of the material; animal experiments indicate that ingestion of less than 5 gram may be fatal or may produce serious damage 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.  

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

  Skin contact with the material may produce severely toxic effects; systemic effects may result following absorption and these may be fatal.  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.  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 of dusts, generated by the material, during the course of normal handling, may produce severely toxic effects; these may be fatal.  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 be damaging to the health of the individual.  Anthracyclines, which are used in chemotherapy, has been shown to cause nausea and vomiting, suppression of bone marrow, inflammation of the oral cavity, hair loss and leukemia. It is also toxic to the heart, causing changes in the ECG and heart failure can result later, after months of treatment.  

CHRONIC HEALTH EFFECTS

  There is ample evidence that this material can be regarded as being able to cause cancer in humans based on experiments and other information.  Based on experiments and other information, there is ample evidence to presume that exposure to this material can cause genetic defects that can be inherited.  Limited evidence suggests that repeated or long-term occupational exposure may produce cumulative health effects involving organs or biochemical systems.  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.  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.  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.  Exposure to the material for prolonged periods may cause physical defects in the developing embryo (teratogenesis).  The inhibitory effects of the aminoglycoside antibiotics on calcium ion homeostasis in peripheral neurones, vascular smooth muscle and the myocardium are thought to be the cause of disruption to haemodynamic control mechanisms. Therefore the adverse effect of aminoglycosides on blood circulation does not seem to be due to cytotoxic damage of cardiovascular tissues but is related to a reversible interaction with calcium ion binding sites of excitable membranes. Many of the biological actions of aminoglycosides in mammals, including cellular damage of the kidney an inner ear tissues, are also associated with disturbance of membrane phospholipids where calcium ion is normally distributed. Kerzee, J. Kevin et al: Cardiovascular Toxicology, Part 7, Third Edition; Edited Daniel Acosta Jr.; Published Taylor and Francis 2001.  Anthracycline therapies may produce a range of long-term effects.  Allergic reactions to mitoxantrone have been reported (rarely); these include vasculitis, facial oedema, skin rashes, breathlessness, tachypnoea, cyanosis, unrecordable pulse and blood pressure. Two patients developed selective alopecia of white but not dark hair. Transient blue-green discoloration of the urine, and occasionally the sclerae, may occur with mitoxantrone; daunorubicin therapies may produce a transient red discolouration of the urine.  Daunorubicin and doxorubicin therapies produce alopecia, impaired wound healing, and enhanced toxic effects of radiotherapy. Both also produce a unique chronic effect on the heart. Cardiotoxicity is characterised by a clinically insignificant arrhythmia and late reversible cardiomyopathy. Most patients show cardiac damage though the incidence of congestive heart failure is low if treatment is stopped after a cumulative dose of 450 mg/m2 (doxorubicin) to 550 mg/m2 body-surface (daunorubicin).  Evidence suggest that the semiquinoline metabolite of doxorubicin (and other anthracyclines) produces a superoxide anion and superhydroxide free radicals with iron as a cofactor. The heart muscle has only a low concentration of protective enzymes, so the free radicals cause lipid peroxidation, destroying the mitochondria in myocardial cells.  Intravesical instillation of doxorubicin into 4-week female rats induced an increase in DNA synthesis associated with abnormal cell division in the bladder (epithelial hyperplasia characterised by elevated nuclear cytoplasmic ratios, cytomegaly and pleomorphism).  This indicates that chemotherapy may itself play a role in the promotion of bladder carcinogenicity. Doxorubicin produces mammary tumours, in rats, after a single intravenous injection and local sarcomas after single or repeated subcutaneous injections.  Intravenous injection of a single dose of daunorubicin, in rats, produced mammary and kidney tumours; repeated subcutaneous injections in mice produce local sarcomas.