Section 1 - CHEMICAL PRODUCT AND COMPANY IDENTIFICATION

PRODUCT NAME

HYDROFLUMETHIAZIDE

NFPA

PRODUCT USE

Thiazide compounds are diuretics which produce a slight lowering effect on blood pressure
and enhance the effects of other antihypertensive agents. Used in the treatment of oedema
associated with congestive heart failure, renal and hepatic disorders or corticosteroid
therapy. Also used in hypertension, either alone or as an adjunct to other hypertensive
agents. Given by mouth or by intravenous injection.

SYNONYMS

C8-H8-F3-N3-O4-S2, "2H-1, 2, 4-benzothiadiazine-7-sulfonamide, 3, 4-dihydro-6-
(trifluoromethyl)-, 1, 1-dioxide", "2H-1, 2, 4-benzothiadiazine-7-sulfonamide, 3, 4-
dihydro-6-(trifluoromethyl)-, 1, 1-dioxide", "3, 4-dihydro-7-sulfamyl-6-trifluoromethyl-1,
2, 4-benzothiadiazine 1, 1-dioxide", "3, 4-dihydro-7-sulfamyl-6-trifluoromethyl-1, 2, 4-
benzothiadiazine 1, 1-dioxide", "3, 4-dihydro-6-(trifluoromethyl)-2H-1, 2, 4-
benzothiadiazine-7-sulfonamide1, 1-dioxide", "3, 4-dihydro-6-(trifluoromethyl)-2H-1, 2, 4-
benzothiadiazine-7-sulfonamide1, 1-dioxide", "6-trifluoromethyl-3, 4-dihydro-7-sulfamoyl-
2H-1, 2, 4-benzothiadiazine1, 1-dioxide", "6-trifluoromethyl-3, 4-dihydro-7-sulfamoyl-2H-
1, 2, 4-benzothiadiazine1, 1-dioxide", trifluoromethylhydrothiazide, dihydroflumethiazide,
metflorylthiazidine, methflorylthiazidine, Di-Ademil, Diucardin, Enjit, Hydravern,
Hydrenox, Leodrine, NaClex, Rivosil, Robezon, Rontyl, Saluron, Salurona, "thiazide
diuretic/ anti-hypertensive"

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.  Large doses of thiazide diuretics can cause gastrointestinal disturbances with nausea, vomiting and increased bowel movements, and severe mineral imbalance. Potassium deficiency can result in confusion, dizziness and muscle weakness. Low blood pressure when standing can occur and the cardiovascular, respiratory and central nervous systems may be depressed. Coma can occur within hours. Hypersensitivity reactions can occur. Treatment with thiazides can cause decreased blood concentrations of potassium, chloride, sodium, magnesium and phosphate; and increases in calcium, uric acid (sometimes causing gout) and lipids. There is acid-base imbalance, uremia and decreased amounts of iodine bound to the serum, and a reversible drop in the activity of the thyroid gland. Diabetes mellitus may be aggravated. Digestive system effects include dry mouth, unpleasant or bitter taste, obstruction of the saliva ducts, diarrhea, bloating, abdominal pain, constipation, loss of appetite, and weight loss. Inflammation of the gallbladder and liver, hardening of the liver (cirrhosis), and acute inflammation of the pancreas may occur. Central nervous system effects include headache, drowsiness, fatigue, vertigo, restlessness, anxiety, depression, nervousness, fainting, decreased reflexes, yellowing of vision, convulsions, "pins and needles", nerve disorders and psychosis. Cardiovascular effects include low blood pressure, reduced blood volume, coldness of the extremities, chest pain, palpitations, clotting in the veins, heartbeat irregularities, fast heart beat, premature contractions of the ventricles and allergic inflammation of heart muscle. Respiratory effects include cough, sore throat, blocked nose, runny nose, nosebleeds, shortness of breath, respiratory distress, inflammation and swelling of the lungs. Genitourinary system effects include increased frequency of urination, urination at night,  decreased or absent urination, inflammation of kidneys, kidney insufficiency, diabetes insipidus, decreased sex drive and sexual dysfunction. Effects on the blood include loss of white blood cells, platelets, neutrophils, agranulocytosis and anemias (with destruction of red blood cells). Disorders of the bone and muscle include muscle fatigue, pain, cramps, joint pain and swelling. Effects to the skin, which are partially due to hypersensitive reactions, include inflammation with spots, dry skin, itching, hives, sensitivity to light, purple spots due to poor clotting, redness, lupus, and flaking of the skin. Hypersensitivity can cause chills, flushing and temporary blurred vision.  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).  

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.  

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.  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.  

CHRONIC HEALTH EFFECTS

  Principal routes of exposure are usually by skin contact/absorption and inhalation of generated dust.  Crosses the placental barrier and is excreted in milk.  The thiazides are chemically related to the sulfonamides.  Prolonged oral treatment with sulfonamides has caused nausea, vomiting, diarrhea, abdominal pain, loss of appetite, inflammation of the mouth cavity, impaired folic acid absorption, exacerbation of porphyria, acidosis, liver damage with impaired blood clotting, jaundice and inflammation of the pancreas. Effects on the kidney include blood and crystals in the urine, painful and frequent urination or lack of urine with nitrogen retention. Nervous system symptoms include headache, drowsiness, trouble sleeping, dizziness, ringing in the ears, hearing loss, depression, hallucinations, inco-ordination,  paralysis of muscles, numbness in the extremities, spinal cord damage and inflammation, convulsions and unconsciousness. Effects on the blood includes a change in blood cell distribution with loss of white blood cells and platelets, and anemia, which Africans seem to be more prone to developing than Europeans. Cyanosis can occur owing to complexes being formed by hemoglobin. Eye effects include inflamed cornea and conjunctiva with eyelid swelling and in severe cases, fear of the light. Allergies and cross-sensitivity is common, and can cause itches, wheals and sometimes a severe red rash with blisters that is often fatal. This class of drugs can scar the cornea and conjunctiva, swelling around the eyes, painful and inflamed joints, reduced sperm counts, pneumonia, fever, chills, hair loss, inflammation of vessels, lupus, reduced lung function, infertility, hypothyroidism and goiter, and increased urinary output. More seriously, the lungs may become permanently scarred and there may be irreversible damage to the nervous system and muscles. Inflammation of the skin has occurred after the drug is ingested and has traveled through the bloodstream. Skin effects often occur when there has been exposure in conjunction with UV light. Clothed areas are initially less likely to be affected but may be in later stages. Rarely there may be persistence of inflammation on light contact even after the drug has been removed.