Section 1 - CHEMICAL PRODUCT AND COMPANY IDENTIFICATION

PRODUCT NAME

UROCANIC ACID

NFPA

PRODUCT USE

Occurs in the outer layer of the skin. The substance has been removed, under legislative
pressure from cosmetic preparations, where it was previously thought to have moisturising
and sun- screen activity.

SYNONYMS

C6-H6-N2-O2, "imadazoleacrylic acid", "5-imadazoleacrylic acid", "5-imadazoleacrylic
acid", "3-(1H-imadazol-4-yl)-2-propenoic acid", "3-(1H-imadazol-4-yl)-2-propenoic acid",
"urocaninic acid", "urocanoic acid (sic)"

Section 2 - HAZARDS IDENTIFICATION

CANADIAN WHMIS SYMBOLS

EMERGENCY OVERVIEW

RISK

Irritating to eyes, respiratory system and skin.

POTENTIAL HEALTH EFFECTS

ACUTE HEALTH EFFECTS

SWALLOWED

  The material has NOT been classified as "harmful by ingestion". This is because of the lack of corroborating animal or human evidence. 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, unintentional ingestion is not thought to be cause for concern.  

EYE

  This material can cause eye irritation and damage in some persons.  

SKIN

  This material can cause inflammation of the skin oncontact in some persons.  The material may accentuate any pre-existing dermatitis condition.  Skin contact is not thought to have harmful health effects, however the material may still produce health damage following entry through wounds, lesions or abrasions.  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 can cause respiratory irritation in some persons. The body's response to such irritation can cause further lung damage.  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

  Long-term exposure to respiratory irritants may result in disease of the airways involving difficult breathing and related systemic problems.  There has been some concern that this material can cause cancer or mutations but there is not enough data to make an assessment.  Limited evidence suggests that repeated or long-term occupational exposure may produce cumulative health effects involving organs or biochemical systems.  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.  Imidazole is structurally related to histamine and has been used as an antagonist to counteract the effects of excess histamine found in certain induced physiological conditions (it therefore acts as an antihistamine).  Imidazoles have been reported to disrupt male fertility through disruption of testicular function.  2-Methylimidazole decreased luteinising hormone secretion and tissue interstitial fluid testosterone concentration two hours after injection into Sprague Dawley rats.  Imidazoles bind to cytochrome P450 haeme, resulting in inhibition of catalysis. However, 2-substituted imidazoles are considered to be poor inhibitors. Imidazole is probably an inducer of cytochrome P4502E1. In general, inducers of this isozyme stabilise the enzyme by preventing phosporylation of a serine which leads to haeme loss.  Several drugs containing an imidazole moiety were retained and bound in connective tissue when administered to laboratory animals. The bound material was primarily recovered from elastin (70%) and the collagen. It is postulated that reaction with aldehydes gives an aldol condensation product.  · CAUTION: May produce immunosuppression in individuals occupationally exposed to the material.  Exposure to immunosuppressives may aggravate infectious diseases.  Chronic exposure to therapeutic doses of compounds which produce immunosuppression has been associated with development of lymphomas (occasionally malignant) and mammary tumours. These may be secondary effects induced by activation of endogenous retroviruses.  Increased incidences of neoplasms, in mice and humans, have been reported after long-term immunosuppression by azathioprine and cyclosporin. Cyclosporin has been classified as a human carcinogen, by IARC, based on development of lymphomas after repeated and prolonged exposures to therapeutic doses.  Urocanic acid is the most abundant substance found in the outer layer of the skin. It has been implicated as an agent promoting the immune suppression by UVB, a component of sun-  light. Under the influence of this wave-length of light, urocanic acid switches from trans to cis geometry and becomes immunogically active. Mice treated by painting cis-  urocanic acid on the skin, exhibit both local and systemic immune deficiency. Most important of all they produce suppressor T cells in profusion.  Many people have experienced an exacerbation of herpes labialis after extensive exposure to sunlight - the systemic immunosuppressive effect of UV light is established. In addition to susceptibility to (mostly viral) infections, experimental contact hypersensitivity of the skin (e.g. against dinitrochlorobenzene) is dose-dependently inhibited by UVB in humans. This UV susceptibility appears to be genetically-linked. It may also be a risk factor for skin cancer and seems to involve urocanic acid (or urocanates).  Speculative discussion surrounds the use of sunscreens and a possible rise in the incidence of melanoma. One mechanism proposed involves the development of free radicals following UVB absorption by the chemical agent; free radicals are potentially damaging to DNA. A further mechanism involves the inhibition of Vitamin D production; low levels of Vitamin D have been associated with an increased risk of the development of breast and colon cancer and may also accelerate the growth of melanoma.