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326 CHAPTER 5 PHYSIOLOGICAL AND TOXICOLOGICAL CONSIDERATIONS

observed with compounds that require metabolic activation (e.g., polycyclic aro-
matic compounds). Even though the formation of the adducts is an expression of an
interaction of a carcinogen with DNA, the significance of these adducts in chemical
carcinogenesis is not yet known. DNA repair and cell proliferation mechanisms re-
move damage caused by adducts. Peripheral white blood cells are often used in
DNA adduct studies; T cells are especially popular because they are long-lived (half-
life is about three years) and therefore they do not solely reflect current exposure.
Peripheral white blood cells have also been frequently used for studies of chromo-
somal changes. Individuals who have high enzyme activity for formation of reactive
metabolites and/or abnormally low metabolic activity of detoxifying enzymes are
197 199
probably especially susceptible to toxicity. ~ The use of biomarkers in biomoni-
toring is likely to provide a valuable tool for this purpose in the future. This technol-
ogy can also be used for molecular dosimetry, or target dose monitoring, in exposed
individuals. The goal is to assess the dose at a critical organ or site, such as DNA or
a protein. 187 198 200 Figure 5.55 depicts some essential features and prerequisites of
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biomonitoring. Table 5.23 indicates the main purposes of biological monitoring of
exposure to chemical compounds in the workplace.
5.3.6 Toxicity, Risks, and Risk Assessment
Earlier in this chapter, a short introduction to risk assessment and the concept of
risk was given (see section 5.3.1.5). In this context, the same issues will not be re-
peated. However, the risk assessment concepts and methodologies will be dis-
cussed in more depth after the reader has received more insight into the role of
toxicology in risk assessment, and after many of the principles of risk assessment,
such as dose-effect and dose-response relationship, have been clarified. It is still
worth emphasizing that the concept of risk is utilized to indicate hazards in the
traffic, sports, health care, and even in the monetary markets, not to mention in
relation to alternatives of energy production, e.g., nuclear power and its utiliza-
tion. Toxicology has taken advantage of the concept of risk because it so neatly
crystallizes the key issues of toxicology, prevention of chemical and other health
49 129 180
hazards, and guaranteeing safety to humans. ' '
The term risk implies the probability that a certain deleterious health effect
will take place under defined circumstances. Likewise, the term security implies
the probability that no such deleterious incident will take place under defined
circumstances. This kind of definition of risk or security has its foundation in an
experimental setting. However, humans or wild animals do not live under de-
fined conditions, but rather face a variety of challenges each day. Therefore, reli-
able risk assessment is an extremely difficult and tedious undertaking. One of
the most challenging issues of toxicology has been assessment of carcinogenic
risks induced by chemicals. In the first phase, we shall assess, on the basis of
weight of evidence, whether a chemical is a carcinogen or not. This estimation is
followed by another, even more demanding task with the goal of estimating the
magnitude of the risk of humans exposed to a given chemical in an occupational
setting or in their general environment. The outcome of such an assessment
should be an estimate of the actual number of additional cases of cancer among
exposed persons. This risk assessment utilizes data from experimental animal
studies, epidemiological human studies, and all available information on human
exposure under different occupational and other living conditions. 49