Page 320 - Industrial Ventilation Design Guidebook

276 CHAPTER 5 PHYSIOLOGICAL AND TOX1COLOGICAL CONSIDERATIONS

main difficulty in using these models is that in most cases not enough informa-
68 85
tion is currently available about the compound under study. '

5.3.4 Toxic Effects of Chemical Compounds
5.3.4.1 The Nature of Toxic Reactions
A toxic reaction may take place during or soon after exposure, or it may
only appear after a latency period. Chronic toxicity requires exposure of sev-
eral years for a toxic effect to occur in humans. With respect to experimental
animals, the animals are usually exposed for most or all of their life time to as-
certain the occurrence of chronic toxicity. Acute toxic reactions that occur im-
mediately are easy to associate with the exposure and the exposure-effect
relationship can readily be demonstrated. The longer the time interval be-
tween exposure and effect, the more difficult it is to delineate the relationship
between exposure and effect.
Toxic effects often disappear after the cessation of the exposure, but they
can also be permanent. The tissue's ability to regenerate is one of the most im-
portant factors that determines the nature of toxic effects. For example, liver
tissue has a remarkable capacity to regenerate, and therefore liver injury is of-
ten reversible. On the other hand, neuronal cells do not regenerate at all, thus
neuronal injury is irreversible. It is true that neuronal cells can compensate for
possible losses, but only to a minor degree. In particular, chronic effects tend
to be irreversible. 64
There are some basic differences between toxic and allergic reactions. The
most important differences are: (1) an allergic reaction always requires a prior ex-
posure to the compound, and this reaction only occurs in sensitized individuals;
and (2) a dose-response relationship is characteristic to a toxic reaction, whereas
such a relationship is much less clear for an allergic reaction. Even minute doses
can elicit an allergic reaction in a sensitized individual (see Fig. 5.42). 64

5.3.4.2 Antagonism and Synergism
Industrial workers are almost always exposed to several agents simulta-
neously. The possible interactions of these multiple exposures are and will re-
main (because the possible combinations are almost infinite) an area of great
uncertainty. The situation is further complicated by the simultaneous presence
of many lifestyle factors, especially smoking and the use of alcohol and drugs.
Other exposures may enhance the toxic effect of an agent. The increased com-
bined effect may be additive (1 + 1 = 2) or synergistic (1 + 1 > 2). The neu-
rotoxic effects of most organic solvents are usually considered to be additive;
therefore, industrial hygienists use the combined exposure level to assess the
conditions. It is obtained by dividing the concentration of each solvent by its
OEL and by adding the quotients. If the sum exceeds one, the exposure is
considered excessive. There are cases of synergism, where the toxic effects of
individual exposures become greatly potentiated. A well known example is
the combination of asbestos exposure and smoking. The various constituents
may have no mutual interactions. In such a case, the effects of different agents
can be considered individually. Since in most cases we are ignorant of these