Module 3: Toxicology - Section 1: Introduction to Occupational Toxicology

TOX 1.2: Introduction and Uses of Toxicology

WHY STUDY TOXICOLOGY?

Toxicology has been defined as: "the study of the adverse effects of chemicals on living organisms, and the assessment of the probability of their occurrence".

(See the page on Definitions in Toxicology)

The field has evolved to include adverse effects to humans and the environment. There are several sub-disciplines in toxicology and these include environmental, industrial, forensic and regulatory toxicology among others.

Toxicology has an interesting biographic history.

Toxicology as a discipline has produced a large body of knowledge much of it from laboratory, including, animal work. The detail is impossible to remember, and much of it does not have day to day application to occupational medicine. Nevertheless, a skilled occupational medicine practitioner should understand the principles of toxicology as applied to workplaces and know something about the toxicology of some important industrial substances.

For context, consider what we call the basic causal model in occupational medicine:

There must be exposure, i.e. the substance must enter the body, to produce an effect. If there is enough exposure, this may lead to ill health. This exposure effect association is modified by host susceptibility, so that only a minority of exposed workers are usually affected. See Axioms of toxicology.

WHERE DOES THE INFORMATION THAT WE USE TO FILL IN THE CAUSAL MODEL COME FROM?

1. Occupational hygiene - measures exposures.
2. Clinical observation - often the first identification of a hazard. In some cases still the only source of information about the effect of chemical compounds on workers.
3. Epidemiological studies.
4. Toxicological investigation. This is the focus of this session.

TOXICOLOGY HAS A NUMBER OF USES IN OCCUPATIONAL HEALTH:

1. Determining whether a substance is toxic, through laboratory investigation.
2. Predicting hazard (risk) of a substance which has not been studied, or which has not been studied in working populations, e.g. through extrapolation, or on the basis of a class effect or structural similarity to known substances.
3. As a basis of biological monitoring. You need to understand how substances move through the body in order to interpret the meaning of biological sampling results and to determine the correct timing of sampling.
4. Understanding clinical effects. Toxicology provides a model for the mechanisms by which the substance affects an organ system. This mechanism could be physical (e.g. solvents "dissolving" fatty protection of skin), biochemical (e.g. carbon monoxide binding to haemoglobin, or lead interfering with certain enzymes in producing red blood cells), or immunological (flour causing asthma, cement causing allergic contact dermatitis), etc.
5. As a basis for worker education. Questions may be asked about how the chemical gets into and out of the body, how long it affects them, whether it affects reproduction, whether milk is protective, etc.

As toxicology plays an important part in occupational risk assessment, you need to understand the four stages of epidemiologic and toxicologic risk assessment:

1. Hazard identification: This may come from clinical observation, epidemiological studies or toxicological screening, e.g. of new compounds for carcinogenicity.
   
2. Dose-response assessment: This attempts to give a more precise form to the nature of the hazard and may be toxicological or epidemiological.
   
3. Exposure assessment: Estimation of exposure levels of worker population at risk - this is the province of occupational hygiene. This may be retrospective.
   
4. Risk characterisation: Estimation of incidence of adverse health effects expected in the worker population at the estimated exposures.
   

Our ignorance is legion. It is said that of the 65000 chemicals used in industry in the USA, human toxicity information is available on only about 1000. Less than are 100 fully characterized

REFERENCES:

1. Ladou J. (ed.) Textbook of Occupational and Environmental Medicine. Chapter 13. pp. 171-179.
2. Rees D and Cantrell A. No need for milk in the prevention of occupational illness. Occup. Health Southern Afr. 1995; 1(4): 25.
3. There is an excellent Toxicology Tutorial available at the National Institutes of Health, National Library of Medicine website at http://www.sis.nlm.nih.gov/Tox/ToxTutor.html

Answer to Question 1: Usually applied to cancer, it has no meaning, as one would have to observe an infinitely large number of subjects to show an effect at such a low dose. It is also biologically extremely unlikely that one fibre could induce a carcinogenic response. (Back to main text.)

Answer to Question 2: Everyone has a different susceptibility to disease depending on their inborn constitution and life experience. We do not understand much about these susceptibilities and thus which individuals will get disease and who will not. (However, we can predict that a group of exposed workers will have a higher percentage of individuals with disease than a group of unexposed workers.) (Back to main text.)

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, Gail Todd, Neil White. 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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