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S.3 TOXICITY AND RISKS INDUCED BY OCCUPATIONAL EXPOSURE TO CHEMICAL COMPOUNDS 253

fossil fuels. There are major risks in mining or oil drilling, during the trans
portation of the fuel, and due to the extensive emissions emanating from the
combustion of the fuel. In Europe, annual loss of life due to energy produc-
tion utilizing fossil fuels, and due to traffic exhaust, is close to 100 000, The
verifiable health hazards due to nuclear energy are only a small fraction of
the losses due to the use of fossil fuels. However, the potential risk due to a
nuclear accident raises alarm in individuals, because the true risk due to nu-
clear energy cannot be calculated. Even if the accident probability is small,
the losses due to even one incident may be catastrophic. This is well illus-
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trated by the accident in Chernobyl in 1986. '
If one is to estimate the potential hazards of some chemicals prior to their
release to the market, the chemicals must be tested for their toxicity in experi-
mental animals. Animals are exposed to high doses of chemicals to avoid the
use of large numbers of animals. When the results of animal experiments are
applied to humans, several assumptions have to be made, including (1) that
animals are a good model to predict human hazards caused by chemicals, and
(2) that large doses of chemicals used in studies utilizing small groups of ex-
perimental animals cause similar effects to what would be seen in humans
though at a lower frequency or with a milder change in functions of target or-
gans. Toxic effects of chemicals may, however, be quite different in rodents
than in humans. For example, guinea pigs tolerate the effects of strychnine
rather well, in contrast to humans. For organ toxicity (neurotoxicity, liver tox-
icity, kidney toxicity) endpoints, safety factors can be used for assessing safe
levels for humans (see below). Dose-responses are regularly used to delineate
the toxicological characteristics of chemical compounds, and to make com-
1 47
parisons of effects between species. '
In most cases, experimental animal studies are used to define the so-called
no-observable-adverse-effect level (NOAEL), i.e., the lowest dose that does
not cause an adverse effect in experimental animals. This dose is then divided
by a safety factor of 100, ten for interspecies differences between rodents and
humans and ten for intraspecies differences between humans, to calculate the
dose (rng/kg) which is considered to be safe for humans. This approach con-
tains the assumption that there is a safe dose below which a chemical does not
cause harmful effects on humans (for the safety factor of 100, see Fig. 5.31).
This assumption of a safe threshold dose is used for most endpoints of deter-
ministic toxicology, i.e., organ toxicology. However, whether in fact there can
be any safe dose for carcinogens, especially for genotoxic carcinogens, has
been challenged, and the linear extrapolation models widely used in carcino-
genic risk assessment do not utilize safety factors. However, this approach has
also been recently challenged because throughout biology, one does not find
effects without any threshold, and because it neglects biological defence mech-
anisms present within cells. The thresholds may, however, be so low in some
instances that the arguments are purely theoretical. However, they have im-
47 49
portant implications for risk assessment. ' Furthermore, one can argue that
none of the toxicological endpoints, whether deterministic (organ toxicity) or
stochastic (cancer) in nature, have a threshold. This may be true conceptually,
and it is especially true experimentally because in most cases determination of
a true threshold is beyond the limit of detection of the experimental approach.