Module 3: Toxicology - Section 1: Introduction to Occupational Toxicology
TOX 1.6: Assessment of Toxic Hazards

ASSESSMENT OF TOXIC HAZARDS BY CLINICAL OR EPIDEMIOLOGIC METHODS:

Health problems, particularly chronic diseases, associated with environmental contaminants usually have multiple causes, including social and cultural behaviour such as diet and smoking, family history and socio-economic status generally. These characteristics interacting with biological factors of age, sex, genotype and physiologic and biochemical traits result in inter-individual differences in toxicity for a given exposure to a toxic substance.

The differentiation between a disease induced by chemical toxicity and the same disease caused by other causes is a difficult problem for the practitioner or researcher. Many diseases are of poorly understood or unknown aetiology, as in the case of many cancers, whereupon chemicals or pesticides may become suspect by default.

Clinical scenarios more often than not have scant exposure information and require additional investigation. Clinical presentation are either acute or chronic and may occur in all degrees of severity. While acute illnesses induced by most chemicals are relatively easily recognized, much remains to be learned about chronic illnesses that may have chemical aetiologies. Most chronic diseases are non-specific, i.e. multiple causes can result in the same injury or disease. Very few diseases are pathognomonic, (highly specific) for environmental exposures. The one example always quoted is mesothelioma in which a very high proportion are thought to be associated with past asbestos exposure.

In the individual case, exposure information must be sought by takin a detailed occupational and environmental history, either from the individual or close associates.

After documenting exposure to a toxic agent one must characterize the probable extent of exposure and expected toxic effects. For expected toxic effects, one needs to have recourse to databases or textbooks of toxicology or occupational medicine.

In assessing exposure, you should make some attempt to infer the concentration of the agent as well as the route, duration and frequency of exposure. Occupational hygiene data are seldom available and one typically settles for the approximation of an occupational and residential history. It is important to know the length of time from exposure to onset of symptoms. Acute illness may result from a single high dose exposure to onset of symptoms. In many instances acute illness may result from a single exposure to a toxicant, whereas the appearance of either acute or chronic effects may result from multiple lower doses exposure to a toxic agent.

Laboratory tests may be available. Occasionally, some estimation of dosage for contaminants that are retained in the body can be made by measuring the concentration of the toxicant in tissues or by measuring the response of a target site, such as cholinesterase activity in response to the presence of an organophosphate insecticide.

Clinical case studies or descriptive case series can provide useful information about acute effects, or identify previously unrecognised hazards, but for chronic effects epidemiological studies are needed. It is this information that is usually lacking in the toxicological database, e.g. on material safety data sheets.

Epidemiologic studies may examine the prevalence or incidence of a certain disease across a variety of industries or sectors, with multiple chemical exposures, e.g. bladder cancer. This is an example of a disease in search of a cause. Other studies examine multiple diseases in a specific exposure setting, e.g. a variety of cancers in asbestos workers -a cause in search of a disease.

In occupational epidemiology one aims to compare the incidence or prevalence of a health outcome in comparable exposed and unexposed populations. The sample size needs to be adequate. Latency effects, i.e. the effect of the time elapsed between exposure and effect need to be understood. Health effects need to be measured with some degree of specificity - e.g. a specific cancer rather than "any" cancer. Confounding by age, smoking, alcohol, education, and other exposures are usually a problem.

However, the major limitation of epidemiologic studies is usually poor estimates of exposure, particularly as most studies are retrospective.

Given these limitations, the implication is that for many substances, lack of proof of a harmful effect is NOT equivalent to proof of no harmful effect. The data are simply lacking.

Question: Consider the statement that one sometimes hears from managers (or even workers): " I have worked in the industry for many years and we have never had a problem with this substance." What questions would you ask to try to establish the usefulness of such an observation?

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Answer: What records are kept of illnesses among workers and if there were a recurring problem in a particular exposed group how would this become known to management? Do the medical practitioners who attend to workers in the company take occupational histories? What is known about the health status of workers who have been exposed but have left the company? If there is a high staff turnover, could exposure effects be contributing to this? (Back to main text.)



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Postgraduate Diploma in Occupational Health (DOH) - Modules 3: Occupational Medicine & Toxicology (Basic) by Profs Mohamed Jeebhay and Rodney Ehrlich, Health Sciences UCT is licensed under a Creative Commons Attribution-Noncommercial-Share Alike 2.5 South Africa License. Major contributors: Mohamed Jeebhay, Rodney Ehrlich, Jonny Myers, Leslie London, Sophie Kisting, Rajen Naidoo, Saloshni Naidoo. Source available from here. For any updates to the material, or more permissions beyond the scope of this license, please email healthoer@uct.ac.za or visit www.healthedu.uct.ac.za. Last updated Jan 2007.
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