Section 1 - CHEMICAL PRODUCT AND COMPANY IDENTIFICATION

PRODUCT NAME

QUETIAPINE FUMARATE

NFPA

PRODUCT USE

Antipsychotic tricyclic drug for the treatment of acute and chronic pyschoses, including
schizophrenia. An antagonist at multiple neurotransmitter receptors in the brain:
serotonin 5HT1A and 5HT2, dopamine D1 and d2, histamine H1 and adrenergic alpha1 and
alpha2 receptors. Has no appreciable affinity at cholinergic, muscarinic and
benzodiazepine receptors and therefore does not possess toxicological properties exhibited
by other tricyclic antidepressants. CAUTION: May modify behaviour and state of alertness;
exposed individuals taking charge of vehicles or machinery should be warned of the
hazards. Regeant

SYNONYMS

C42-H50-N6-O4-S2.C4-H4-O2, "2-[2-(4-dibenzo[b, f](1, 4)thiazepin-11-yl-1-
piperazinyl)ethoxy]ethanol", "2-[2-(4-dibenzo[b, f](1, 4)thiazepin-11-yl-1-
piperazinyl)ethoxy]ethanol", "fumarate (2:1)", "11-[4-(2-(2-hydroxyethoxy)ethyl)-1-
piperazinyl]dibenzo[b, f][1, 4]thiazepine hemifumarate", "11-[4-(2-(2-
hydroxyethoxy)ethyl)-1-piperazinyl]dibenzo[b, f][1, 4]thiazepine hemifumarate", ICI-
204636, Seroquel, "tricyclic dibenzothiazepine", "benzothiazepine antipsychotic"

Section 2 - HAZARDS IDENTIFICATION

CANADIAN WHMIS SYMBOLS

EMERGENCY OVERVIEW

RISK

Irritating to eyes.
May cause long- term adverse effects in the aquatic environment.

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.  A potentially fatal symptom complex sometimes referred to as Neuroleptic Malignant Syndrome (NMS) has been associated with the use of antipsychotic drugs. Clinical manifestations include hyperpyrexia, muscle rigidity, altered mental state, and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis and cardiac dysrhythmia. Additional signs may include elevated creatine phosphokinase, myoglobinuria (rhabdomyolysis) and acute renal failure.Antipsychotic drug therapy may also produce potentially irreversible, involuntary, dyskinetic movements, especially in the elderly and in particular, in elderly women. The development of this syndrome appears to be related to the duration of treatment and the total cumulative dose of antipsychotic drugs administered; the syndrome can, however, develop after relatively brief treatment periods at low doses.Other side-effects of drug therapy may include a disruption to the body's ability to reduce body core temperature and dysphagia (oesophageal dysmotility and aspiration - aspiration pneumonia is a common cause of morbidity or mortality in elderly patients especially those with advanced Alzheimer's dementia).  

EYE

  There is evidence that material may produce eye irritation in some persons and produce eye damage 24 hours or more after instillation. Severe inflammation may be expected with pain. There may be damage to the cornea. Unless treatment is prompt and adequate there may be permanent loss of vision. Conjunctivitis can occur following repeated exposure.  Irritating to eyes.  

SKIN

  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.  Skin contact with the material may damage the health of the individual; systemic effects may result following absorption.  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.  

CHRONIC HEALTH EFFECTS

  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.  Antipsychotic drugs have been shown to chronically elevate prolactin levels in rodents. Increases in mammary neoplasms have been found in rodents after chronic administration of antipsychotic drugs and are considered to be prolactin-mediated.  Increased prolactin levels in serum are a secondary consequence of chronic dopamine antagonism of pituitary lactotrophs.  The relevance of the increased incidence of prolactin-mediated mammary gland tumours in rats, to human risk, is unknown.  Reproductive and developmental toxicity may also result from exposure to dopamine antagonists; these may result from elevation of serum prolactin. Effects may include prolonged oestrus, pre-implantation loss and alterations to the length of the gestational cycle.  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.  Repeated doses produced cataracts and seizures in dogs.  Carcinogenicity studies carried out for two years showed a statistically significant increase in thyroid gland follicular adenomas in male mice given 1.5-4.5 times the human dose, by gavage, and in male rats given 3 times the human dose rate. Mammary gland adenocarcinomas, showed a statistically significant increase in female rats given 0.3 times the maximum recommended human dose on a mg/m2 basis.  Thyroid follicular cell adenomas may result from chronic stimulation of the thyroid gland by thyroid stimulating hormone (TSH) resulting from enhanced metabolism and clearance of thyroxine by rodent liver.  Quetiapine produced a reproducible increase in mutations in one strain of Salmonella in the presence of metabolic activation. No evidence of clastogenic potential was obtained in an in vivo chromosomal aberration assay in cultured human lymphocytes or in the in vivo micronucleus assay  in rats.  Quetiapine decreased mating and fertility in male Sprague-Dawley rats at 0.6 times the maximum human dose on a mg/m2 basis. Drug-related effects included increases in the interval to mate and in the number of matings required for successful impregnation. The drug also affected mating and fertility in female Sprague-Dawley rats at an oral dose equivalent to 0.6 times the maximum human dose on a mg/m2 basis. Drug-related effects included decreases in matings and in matings resulting in pregnancy and an increase in the interval to mate. An increase in irregular oestrus cycles was observed at 0.1 times the maximum human dose.  In teratogenicity studies there was evidence of embryo/ foetal toxicity. Delays in skeletal ossification were detected in rat foetuses at 0.6 times the maximum human dose on a mg/m2 basis. There was an increase in minor soft tissue anomaly (carpal/ tarsal flexure) in rabbit foetuses at a dose rate of 2.4 times the maximum human dos on a mg/m2 basis. Evidence for maternal toxicity was produced in both rats and rabbits.