Section 1 - CHEMICAL PRODUCT AND COMPANY IDENTIFICATION

PRODUCT NAME

ZK-91587

NFPA

PRODUCT USE

Spironolactone analogue. Steroid with a structure similar to the natural adrenocortical
hormone, aldosterone. Spironolactone acts on the distal portion of the renal tubule as a
competitive inhibitor of aldosterone, increasing sodium and water excretion and decreases
potassium excretion. Acts both as a diuretic and antihypertensive agent. Spiroolactone is
used in the treatment of refractory oedema associated with congestive heart failure,
cirrhosis of the liver or nephrotic syndrome. Usually given by mouth.

SYNONYMS

C25-H32-O5, "3'H-cyclopropa(15, 16)pregna-4, 15-diene-7, 21-dicarboxylic acid, 15, 16-
dihydro-17-hydroxy-3-oxo-, gamma-lactone, methyl ester, (7alpha, 15alpha, 16alpha,
17alpha)-", "3'H-cyclopropa(15, 16)pregna-4, 15-diene-7, 21-dicarboxylic acid, 15, 16-
dihydro-17-hydroxy-3-oxo-, gamma-lactone, methyl ester, (7alpha, 15alpha, 16alpha,
17alpha)-", "7alpha-methoxycarbonyl-15beta, 16beta-methylen-3-oxo-17alpha-pregn-4-ene-21,
27-carbolactone", "7alpha-methoxycarbonyl-15beta, 16beta-methylen-3-oxo-17alpha-pregn-4-
ene-21, 27-carbolactone", "SH-D 515", ZK91587, "ZK 91587", diuretic, "aldosterone
antagonist"

Section 2 - HAZARDS IDENTIFICATION

CANADIAN WHMIS SYMBOLS

EMERGENCY OVERVIEW

RISK

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.  Considered an unlikely route of entry in commercial/industrial environments.  The corticosteroids cause alterations in metabolism of fats, proteins and carbohydrates, and affect a range of organs in the body including the heart, muscle and kidneys. Blood chemistry may change and there is decreased activity and shrinkage of the thymus gland, adrenal glands, spleen and lymph nodes. The liver becomes enlarged, thyroid activity decreases, and mineral is drawn away from bone. Muscle wasting occurs, and the immune system is adversely affected causing the person to be more susceptible to infections, especially of the eye. Allergies can occur. Wound healing is slowed. In large doses, corticosteroids cause a severe chemical imbalance in the body's minerals, leading to salt and water being retained in the body, causing swelling and high blood pressure. This is more severe when natural rather than synthetic drugs are used. Blood glucose is raised, and in extreme cases the heart may fail. The characteristic "moon-face" appearance may be seen, with weakness of the muscles and bones, high blood pressure, cessation of periods, profuse sweating, mental disturbance, flushing, a humped back, hairiness, and obesity of the trunk with wasting of the arms and limbs ("lemon with matchsticks" shape). These generally improve when treatment is stopped. High pressure in the head, an inflamed pancreas and mental disturbance become more common, and bone tissue may die. The blood also condenses more easily leading to an increased risk of clots. Psychiatric changes include mood swings, personality changes, severe depression and psychosis (hallucinations and delusions). One should be beware of an increased susceptibility to a wide range of infections which may be masked by the ability of corticosteroids to reduce pain, inflammation and fever. Those with ulcers, gastrointestinal disease, kidney impairment, hypothyroidism, high blood pressure, liver damage and osteoporosis may be especially susceptible to the adverse effects of corticosteroids. Prolonged exposure can cause cataracts and eye nerve damage, leading to blindness.  Large doses or frequent use of diuretics may produce fluid and electrolyte imbalance.  This, in turn, may produce increased urination, dry mouth, increased thirst, irregular heartbeat, mood or mental changes, muscle cramps or pain, nausea or vomiting, unusual tiredness or weakness, weak pulse, blurred vision, diarrhoea, headache, dizziness, loss of appetite,skin rash, pruritus, and stomach cramps or pain. Orthostatic hypotension may also result from excessive use.  Concern has been raised about the potential for diuretic-induced hypokalaemia, even when chronic or mild, to play a part in the development of ventricular arrhythmias, and sudden death. A trend towards increased mortality due coronary heart disease, in patients with pre-existing ECG abnormalities, has also been suggested in some studies.  

EYE

  Although the material is not thought to be an irritant, direct contact with the eye may produce transient discomfort characterized by tearing or conjunctival redness (as with windburn).  When applied to the eye, corticosteroids may produce ulceration of the cornea, raised eye pressure and reduced vision; internal administration can cause cataracts.  

SKIN

  Skin contact with the material may damage the health of the individual; systemic effects may result following absorption.  The material is not thought to be a skin irritant (as classified using animal models). Temporary discomfort, however, may result from prolonged dermal exposures. Good hygiene practice requires that exposure be kept to a minimum and that suitable gloves be used in an occupational setting.  Topically applied corticosteroids may be absorbed in sufficient quantity to produce systemic effects. Application to the skin may result in collagen loss and subcutaneous atrophy and local bleaching of deeply pigmented skin. Systemic absorption may produce adrenal suppression and collapse.  

INHALED

  Inhalation may produce health damage*.  The material is not thought to produce respiratory irritation (as classified using animal models). Nevertheless inhalation of the material, especially for prolonged periods, may produce respiratory discomfort and occasionally, distress.  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.  Systemic absorption of aerosols containing corticosteroids may produceadrenal insufficiency and collapse.  

CHRONIC HEALTH EFFECTS

  Principal routes of exposure are usually by skin contact/absorption and inhalation of generated dust.  Spironolactone produces thyroid and testicular tumours in rats.  Potassium canrenoate, a metabolite of spironolactone in humans, caused  resorption in the offspring of mice administered 80 mg/kg during 7-13 days  of pregnancy.  Spironolactone was found to block testosterone secretion and increase  progesterone concentration without inducing cell mortality in a primary  culture of immature pig Leydig cells.  Chronic exposure to glucocorticoids can lead to changes in hormone production, a characteristic "moon face" appearance and a "lemon with matchsticks" fat distribution (central obesity with wasting of limbs), susceptibility to infections, osteoporosis, cataracts, glaucoma, mental disturbance, high blood sugar and sugar in the urine. There may be muscular weakness and fatigue, acne, period disturbances in women and peptic ulcers. Growth retardation can occur in children and birth defects are possible. Corticosteroids appear in human milk and ' may stunt the growth of infants.