Section 1 - CHEMICAL PRODUCT AND COMPANY IDENTIFICATION

PRODUCT NAME

HYDROCORTISONE 3-O-CARBOXYMETHYLOXIME

NFPA

PRODUCT USE

Hydrocortisone is the main glucocorticoid secreted from the adrenal cortex. Administered
by mouth for replacement therapy in Addison' s disease or chronic adrenocortical
insufficiency secondary to hypopituitarism. When a rapid effect is required such as in
post- adrenalectomy crises, during the acute cases of status asthmaticus and in allergic
crises such as laryngeal oedema and drug sensitivity, hydrocortisone is given by slow
intravenous infusion. Also applied topically in the treatment of various skin disorders.
The acetate is the preferred injectable form and is administered intra- articularly into
joints affected by rheumatoid arthritis, osteoarthritis and similar conditions.

SYNONYMS

C23-H33-N-O7, C23-H33-N-O7, "acetic acid, [(((11beta)-11, 17, 21-trihydroxy-20-oxopregn-
4-en-3-ylidene)-", "acetic acid, [(((11beta)-11, 17, 21-trihydroxy-20-oxopregn-4-en-3-
ylidene)-", amino)oxy], "cortisol 3-(carboxymethyloxime)", "cortisol 3-
(carboxymethyloxime)", "cortisol 3-(O-carboxymethyl)oxime", "cortisol 3-(O-
carboxymethyl)oxime", "4-pregnene-11beta, 17alpha, 21-triol-3, 20-dione 3-(O-
carboxymethyl)oxime", "4-pregnene-11beta, 17alpha, 21-triol-3, 20-dione 3-(O-
carboxymethyl)oxime", "11beta, 17alpha, 21-trihydroxy-4-pregnene-3, 20-dione 3-(O-
carboxymethyl)oxime", "11beta, 17alpha, 21-trihydroxy-4-pregnene-3, 20-dione 3-(O-
carboxymethyl)oxime", corticosteroid, "corticoid anti-inflammatory"

Section 2 - HAZARDS IDENTIFICATION

CANADIAN WHMIS SYMBOLS

EMERGENCY OVERVIEW

RISK

May form explosive peroxides.

POTENTIAL HEALTH EFFECTS

ACUTE HEALTH EFFECTS

SWALLOWED

  Accidental ingestion of the material may be damaging to the health of the individual.  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.  

EYE

  If applied to the eyes, this material causes severe eye damage.  When applied to the eye, corticosteroids may produce ulceration of the cornea, raised eye pressure and reduced vision; internal administration can cause cataracts.  

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.  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 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.  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

  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.  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.  There are generally two types of oximes: ketoximes derived from ketones and aldoximes derived form aldehydes. Several ketoximes (p-quinone dioxime, acetoxime and methyl ethyl ketoxime) have elicited carcinogenic effects on chronic exposure. Few substantive studies have been performed with aldoximes. The fact that aldoximes can be metabolised to cyanide via a pathway not applicable to ketoximes distinguishes the type of response which might be anticipated. Dehydration of aldoximes to produce nitriles has been shown to be catalysed in vitro by cytochrome P450; dehydration of ketoximes produces amides, rather than nitriles, via a Beckmann rearrangement but this apparently has no analogue in biological systems.  The mechanism and toxicity of oximes to erythrocytes is recognised and might be attributed to hydroxylamine, a product of hydrolysis. Hydroxylamine produces haematologic effects such as methaemoglobinaemia and splenomegaly in mice similar to those observed after exposure to oximes such as butanal oxime. Studies demonstrated the formation of haeme-associated free radicals in erythrocytes exposed to hydroxylamine, leading ultimately to peroxidation of membrane lipids. Lipid peroxidation in cellular membranes may produce several morphological alterations resulting, for example, in membrane aggregation, deformation or breakage. This may result in the release of hydrolytic enzymes which in turn may degrade functional macromolecules and cause secondary damage. In addition membrane-bound enzyme systems may be disrupted. Levels of hydroxylamine produced as a result of hydrolysis are thought to be too low to produce another sign of hydroxylamine toxicity, namely the formation of Heinz bodies  Oximes are not easily oxidised at near neutral conditions and hydrolysis by liver microsomes or S9 is hypothesised (however this conclusion was based on the formation of a ketone rather than hydroxylamine). Another possibility is that oximes are oxidatively metabolised to yield a ketone or aldehyde and some yet to be determined nitrogen-  containing species. Cytochrome P450 appears to provide a source of superoxide and hydrogen peroxide which catalyses oxidation in the presence of iron. At least part of the nitrogen in the oxime is converted to nitric oxide which complexes with haeme to give a nitrosylhaemoglobin complex.  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.  Over-exposure may also cause reproductive disorders.