Section 1 - CHEMICAL PRODUCT AND COMPANY IDENTIFICATION

PRODUCT NAME

OESTRIOL 6-(O-CARBOXYMETHYL)OXIME

NFPA

PRODUCT USE

Oestriol is used in replacement therapies in deficiency states, for the treatment of
conditions such as primary amenorrhoea, delayed onset of puberty, and the management of
menopausal syndrome. Other uses include the treatment of malignant neoplasms of the
prostate and of the breast of menopausal women. Normally administered by mouth. Oestriol
is a naturally occurring oestrogenic hormone claimed to have a selective action on the
cervix and vagina and to have little effect on the endometrium. The hormone controls the
development and maintenance of female sex organs, secondary sex characteristics, the
mammary glands, functions of the uterus and accessory organs and cyclic changes in the
cervix and vagina. Obtained from human placental tissue and urine of pregnant women. A
metabolite of 17beta- oestradiol with a much lower activity, it is the primary oestrogen
found in the urine. Large quantities of oestriol and oestrone are produced by the placenta
during pregnancy. These are also the primary oestrogens produced by the adipose tissue in
men and in post- menopausal women.

SYNONYMS

C20-H25-N-O6, C20-H25-N-O6, "6-ketoestriol 6-(O-carboxymethyl)oxime", "6-ketoestriol 6-(O-
carboxymethyl)oxime", "6-ketooestriol 6-(O-carboxymethyl)oxime", "6-ketooestriol 6-(O-
carboxymethyl)oxime", "6-(O-carboxymethyl)oxime of:", "6-(O-carboxymethyl)oxime of:", "1,
3, 5(10)-estratrien-3, 16alpha, 17beta-triol", "estra-1, 3, 5(10)-triene-3, 16-alpha, 17-
beta-triol", "estra-1, 3, 5(10)-triene-3, 16-alpha, 17-beta-triol", "1, 3, 5-estratriene-
3-beta, 16-alpha, 17-beta-triol", "1, 3, 5-estratriene-3-beta, 16-alpha, 17-beta-triol",
"(16alpha, 17beta)-estra-1, 3, 5(10)-triene-3, 16, 17-triol", "(16alpha, 17beta)-estra-
1, 3, 5(10)-triene-3, 16, 17-triol", estriol, estratriol, "3, 16-alpha, 17beta-
estratriol", "3, 16-alpha, 17beta-estratriol", "16alpha, 17beta-estratriol", "follicular
hormone hydrate", 16alpha-hydroxyestradiol, 16alpha-hydroxyoestradiol, "oestra-1, 3,
5(10)-triene-3, 16alpha, 17beta-triol", "oestratriene-3beta, 16alpha, 17beta-triol",
"(16alpha, 17beta)oestra-1, 3, 5(10)-triene-3, 16, 17-triol", "(16alpha, 17beta)oestra-1,
3, 5(10)-triene-3, 16, 17-triol", oestratriol, "3, 16-alpha, 17beta-oestriol", "3, 16-
alpha, 17beta-oestriol", "16alpha, 17beta-oestriol", "3, 16alpha, 17beta-trihydroxy-delta-
1, 3, 5-oestratriene", "3, 16alpha, 17beta-trihydroxy-delta-1, 3, 5-oestratriene", "3,
16alpha, 17beta-trihydroxyestra-1, 3, 5(10)-triene", trihydroxyestrin, trihydroxyoestrin,
"sex hormone/ oestrogen/ estrogen steroid"

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 estrogens may produce dose-related nausea and vomiting, undesirable uterine growth, proliferation and withdrawal bleeding or loss of periods. It causes enlargement of the breasts in males. Other side effects include weight gain, swelling, breast tenderness, liver dysfunction, jaundice, depression, headache, and dizziness. Growth may be stunted due to premature closing of the growth plates. Skin reactions can include excess pigmentation of the face, rashes, and hives. Redness, itching and blistering has also been reported.  

EYE

  Although the material is not thought to be an irritant, direct contact with the eye may cause transient discomfort characterized by tearing or conjunctival redness (as with windburn). Slight abrasive damage may also result. The material may produce foreign body irritation in certain individuals.  

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

  Limited evidence suggests that repeated or long-term occupational exposure may produce cumulative health effects involving organs or biochemical systems.  There is some evidence that human exposure to the material may result in developmental toxicity. This evidence is based on animal studies where effects have been observed in the absence of marked maternal toxicity, or at around the same dose levels as other toxic effects but which are not secondary non-specific consequences of the other toxic effects.  Exposure to the material may cause concerns for human fertility, on the basis that similar materials provide some evidence 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 are not a secondary non-specific consequence of other toxic effects..  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.  Exposure to the material for prolonged periods may cause physical defects in the developing embryo (teratogenesis).