Setting OELs

The next topic to address is the process of setting OELs. The rationale for set­ting OELs has no basis in absolute information, and the procedure to be fol­lowed may differ from country to country and from substance to substance. Scientific criteria for health protection should be used in combination with considerations of their technical and economic feasibility’ in a dynamic process in which the development of scientific knowledge underlies rapid changes en­tailing the need to periodically review the data.

In general, it requires a multidisciplinary approach that takes data on tox — icological and other relevant properties of chemicals developed in the fields of industrial hygiene, chemistry, toxicology, epidemiology, engineering, occupa­tional medicine, etc., so that interrelated data from all sources combines to give the most rational input upon which to base OELs, even though adequate documentation is not available for the majority of chemical agents.

Scientific information for the process of establishing OELs may come from human or animal data obtained using different methods, from studies of acute, subacute, and chronic toxicity through various routes of entry. Human data, which is usually the best source, is not easily available, and frequently it is incomplete or inadequate due to poor characterization of exposure and clear dose-response relationships. Human data falls into one of the following categories:

• Epidemiological and clinical studies of workers and other long-term case-control studies

• Experimental studies with volunteers, especially for situations involving the acute effects of an identified adverse agent

• Literature from industrial experience, especially individual case reports showing relationship between exposure to a chemical agent and specific adverse effects

Data coming from laboratory studies with animals offer good characteriza­tion of exposure, adequate use of controls, extensive pathological investigations, and the potential to give clear indications of dose-response relationships. How­ever, extrapolating this data to human exposure is not straightforward and may lead to mistakes. Therefore, studies of this type should be used primarily to com­plement other studies, in order to check certain aspects or to guide the study.

The crucial objective is to identify what effects can be produced by ex­posure to chemical agents and to select which effects should be considered adverse to health or well-being in order to quantitatively define exposure levels. The problem arises from the definition of adverse effects to workers’ health. That definition should have a broad scope, including, when possible, effects on the offspring of workers and concepts such as nuisance, irritant, and systemic health effects. In this sense, some scientists define the following categories of effects due to increasing exposure to chemical agents:

• No effects observed

• Compensatory effects or early effects of dubious significance, without adverse health consequences

• Early health impairment with clear adverse effects

• Overt disease w’ith severe consequences

In this scheme, OELs should be a dose somewhere between compensatory ef­fects, in which the organism is able to detoxify, metabolize, or excrete the sub­stance, and early impairment. Although there may be profound differences of opinion as to what constitutes this dose, this approach leads to the conclusion that available scientific data permits identification of a clear threshold dose below’ which exposure to the substance in question is not expected to lead to adverse effects.

However, for some type of adverse effects, such as genotoxicity, carcino­genicity, and respiratory sensitization, it may not be possible from present knowledge to define this threshold of activity, so we may conclude that any level of exposure might carry some finite risk. In this case, OELs should be es­tablished at levels sufficiently low to avoid risks; these are called pragmatic OELs. ‘

Another difficulty comes from the consideration of the route of entry of the contaminant, as chemicals can enter the body by various routes and the human body responds to the action of a toxic agent primarily on the basis of the rate and route of exposure. Without any doubt, the most important route of exposure at the workplace is inhalation, and this should be the route used to set OELs. However, if there is a threat of significant exposure by other routes, such as cutaneously (including mucous membranes and the eyes), ei­ther by contact with vapors or by direct skin contact with the substance, addi­tional recommendations may be necessary.