Special Considerations

After the use of a chemical becomes widespread, new deleterious effects on human health may be observed. In such situations, the occupational limit values will have to be modified. Usually the OELS tend to decrease when more information on the toxicity of a chemical is obtained.52 Knowledge of the spe­cific features of various chemicals is thus extremely important for planning ventilation of industrial premises. It is important to be especially aware of those chemicals that may cause long-term effects without causing any acute ef­fects. There are also compounds such as isocyanates that are extremely irritat­ing at concentrations as low as 0.5 ppm. However, some workers may become sensitized to isothiocyanates at a concentration of 10 ppb, and therefore this has to be taken into consideration when planning the industrial ventilation. Thus, one has to plan against compounds that can cause serious health effects at concentrations at which their presence cannot be observed by the human senses, i. e., irritation or odor.

Ultimately, the final stage of risk assessment, risk characterization, aims at achieving a synthesis from data gathered in steps 1-3. The goal of such a synthe­sis is, in addition to qualitative risk assessment, quantitative risk assessment. This implies that the outcome of the process should be numerical, e. g., a num­ber or other estimate which indicates how many extra cases of a deleterious health outcome are produced due to exposure to a given exposure level in a given population.49 Decisionmakers demand that toxicologists be able to come up with a reliable estimate of the relative importance in terms of severity of the health outcome or the number of new cases of disease. This would then allow them to prioritize the health hazards, and also carry out the kinds of expense/ benefit analysis usually utilized in these situations. It would then be easier to make decisions on which chemical problems to tackle first, and at which con­centration level the occupational limit value of a given chemical should be set. These measures are important for the preventive measures to be undertaken.

An important issue in the toxicity of chemicals and in assessing their risks is the inherent toxicity of a chemical. This implies the potency, i. e., the magnitude of the dose, at which the chemical can induce a toxic effect, whether cancer, liver damage, or nervous dysfunction. One example of a characteristic of a chemical is its reactivity, which may markedly affect its potential to cause allergic reactions or cancer or to induce irritation of the respiratory tract. Thus, detailed information on the characteristics of a compound is of major significance in understanding the mechanisms of the effects that it can induce in humans and in other living organ­isms and in understanding the effects themselves.87 Important Chemical Carcinogens

Polycyclic aromatic hydrocarbons have been classified as human carcino­gens because they induce cancers in experimental animals and because smok­ing and exposure to mixtures of chemicals containing polycyclic aromatic hydrocarbons in the workplace increase the risk of lung cancer in exposed in­dividuals. In experimental animals, benzo(a)pyrene induces cancer in different organs depending on the route of administration.204 Furthermore, exposure to polycyclic aromatic hydrocarbons commonly occurs in occupations related to traffic (use of diesel engines in transportation and railways).

Tobacco smoke induces a myriad of deleterious health effects in exposed in­dividuals. Carbon monoxide decreases oxygenation of tissues by erythrocytes, nicotine causes vasoconstriction and disturbs circulation especially in the periph­ery, e. g., in the placenta, and tar contains a number of carcinogenic compounds. In addition, tobacco smoke irritates the mucous membranes in the respiratory airways and eyes, depresses cilia in the bronchi, and also has immunosuppressive effects. These effects may also contribute to the increased risk of lung cancer due to smoking. Furthermore, all forms of smoking increase the risk of lung cancer. The association between smoking and lung cancer is no longer open to debate; there is a dose-effect relationship between the number of cigarettes smoked per day and the magnitude of the risk, and an association between the duration of smoking and the lung cancer risk. Also, an increased risk of bladder cancer and kidney-pelvis cancer is associated with smoking. These observations are not sur­prising because tobacco smoke contains many known carcinogens, such as benzo(a)pyrene, at relatively high concentrations.204

Asbestos fibers and arsenic compounds are also clear-cut human carcino­gens.205206 Today, substitutes of asbestos or insulation materials, notably man-made vitreous fibres containing ceramic, glasswool, lockwool, and slog — wool fibres are suspected human carcinogens,222 but further information is re­quired before one can come to a final carcinogenic classification. Other potentially important human carcinogens include reactive agents such as formaldehyde and isocyanates.

IARC has also classified ethyl alcohol as a human carcinogen. The use of ethyl alcohol is associated with increased risk of cancers of the oral cavity, pharynx, larynx, esophagus, and liver. Ethanol is usually considered to be a cocarcinogen which amplifies the effects of other carcinogens. For example, the carcinogenic effects of tobacco smoke are amplified by ethyl alcohol. In addition, ethyl alcohol is also genotoxic, and causes chromosomal aberra­tions, sister chromatid exchanges, and point mutations in test systems where ethyl alcohol can be metabolized. Thus, it seems likely that acetaldehyde, the primary metabolite of ethyl alcohol, is the compound responsible for mutage­nicity of ethyl alcohol.207 Future Perspectives

In the future, the preventive role of toxicology will be emphasized. It will be increasingly important to develop early indicators to monitor long­term subtle exposures that predict deleterious effects that are known to have a causal relationship with occupational exposures. In addition to col­lection of blood and urine samples, also collection of cells from points of

Entry into the body, e. g., by nasal or bronchoalveolar lavage, will provide possibilities to explore functional chemical-induced changes at the cellular and molecular level. Routine measurements of alterations of gene expres­sion in cells so collected may provide valuable information on causality be­tween inhalation exposures and effects in target cells in the nasal cavity or lungs. In many instances, cells collected with nasal or broncho-alveolar la­vage (BAL) methods may be used to demonstrate a causal relationship be­tween inhalational exposure and an effect in the airways. This would then allow protection of exposed workers by assessing the exposure through oc­cupational hygienic measurements.