Section 1 - CHEMICAL PRODUCT AND COMPANY IDENTIFICATION

PRODUCT NAME

HYDROCHLOROTHIAZIDE

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. Carbonic anhydrase inhibitor.

SYNONYMS

C7-H8-Cl-N3-O4-S2, "2H-1, 2, 4-benzothiadiazine-7-sulfonamide, 6-chloro-3, 4-dihydro-,
1, 1-dioxide", "2H-1, 2, 4-benzothiadiazine-7-sulfonamide, 6-chloro-3, 4-dihydro-, 1, 1-
dioxide", "6-chloro-3, 4-dihydro-2H-1, 2, 4-benzothiadiazine-7-sulfonamide 1, 1-dioxide",
"6-chloro-3, 4-dihydro-2H-1, 2, 4-benzothiadiazine-7-sulfonamide 1, 1-dioxide",
dihydrochlorothiazide, "3, 4-dihydrochlorothiazide", "3, 4-dihydrochlorothiazide",
hypothiazide, Aquarius, Bremil, Diclotride, Disalunil, Esidrex, HCTZ, Hydril, Hydro-Aquil,
Hydro-Diuril, "thiazide diuretic/ anti-hypertensive"

Section 2 - HAZARDS IDENTIFICATION

CANADIAN WHMIS SYMBOLS

EMERGENCY OVERVIEW

RISK

Toxic to soil organisms.

POTENTIAL HEALTH EFFECTS

ACUTE HEALTH EFFECTS

SWALLOWED

  Accidental ingestion of the material may be damaging to the health of the individual.  Limited evidence exists that the substance may cause irreversible but non-lethal mutagenic effects following a single exposure.  Sulfonamides and their derivatives can cause extensive kidney damage, and destroy red blood cells. Overdose may cause an accumulation of acid in the blood or a diminished blood sugar level with confusion and coma resulting. Predisposed persons can develop hypersensitivity reactions, including for topical application. Deaths have occurred due to hypersensitivity, anemia, imbalances in blood cell distribution and kidney and liver damage. 2-5 grams can be fatal. Sulfonamides cross the placental barrier, are excreted in the breast milk and may produce adverse effects in the fetus/ embryo and newborn, including loss of certain white blood cells causing immune function deficiency, anemia, jaundice and kernicterus.  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.  

EYE

  There is some evidence to suggest that this material can causeeye irritation and damage in some persons.  Eye drops with sulfonamides can cause local irritation, sensations of burning and stinging, blurred vision and loss of depth perception. The conjunctiva and cornea may become inflamed, and the cornea and lens may become clouded.  

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.  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.  Limited evidence exists that the substance may cause irreversible but non-lethal mutagenic effects following a single exposure.  

CHRONIC HEALTH EFFECTS

  There has been some concern that this material can cause cancer or mutations but there is not enough data to make an assessment.  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.  Based on experience with animal studies, there is a possibility that exposure to the material may result in toxic effects to the development of the fetus, at levels which do not cause significant toxic effects to the mother.  Exposure to the material may result in a possible risk of irreversible effects. The material may produce mutagenic effects in man. This concern is raised, generally, on the basis ofappropriate studies with similar materials using mammalian somatic cells in vivo. Such findings are often supported by positive results from in vitro mutagenicity studies.  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.  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.  Animals exposed to 3-50000 ppm for up to 2 years exhibited chronic renal disease with parathyroid hyperplasia, mineralisation in multiple organs and fibrous osteodystrophy. Proliferative lesions in the haematopoietic system were reported in female rats. Other animals sttudies have described cardiac thrombosis, polyarteritis, osteitis fibrosa and calcification of the aorta, other arteries, mucosa of the glandular stomach, muscles of the forestomach, heart and pulmonary alveoli.  Some evidence of carcinogenic activity was reported in male mice with an increased incidence of hepatocellular neoplasms.  Equivocal evidence of carcinogenic evidence was reported in male rats with a marginal increase in the incidence of neoplasms of the Zymbal gland. No evidence of carcinogenic activity was found in female rats or mice. NTP TR-357  Hydrochlorothiazide crosses the placental barrier and may cause foetal or neonatal jaundice, thrombocytopenia, haemolytic anaemia, electrolyte imbalances and hypoglycaemia. It is excreted in milk. The thiazides are chemically related to the sulfonamides.