Page 375 - Industrial Ventilation Design Guidebook

330 CHAPTER 5 PHYSIOLOGICAL AND TOX1COLOGICAL CONSIDERATIONS

49
FIGURE 5.56 The "threshold region" for chronic dose-response curves. [Reprinted with per-
mission from Tardiff, R.G., and Rodricks, J.V. (1987). (Eds.), Toxic Substances and Human Risks: Principles
of Data Interpretation. New York: Plenum Press.]

certainly factor is added, and then the dose is divided by a factor of 1000. A similar
approach is also used when one deals with an exceptionally serious toxicological end
point, such as epigenetic carcinogenesis or malformations, which has a threshold
dose. This kind of approach is utilized when one deals with deterministic toxicologi-
cal effects, e.g., target organ toxicity (neurotoxicity, kidney toxicity). This approach
also requires the assumption of a threshold for the effect, i.e., that there is a safe dose
below which no harmful effects occur. Typically, this approach assumes that a chem-
ical compound expresses a typical sigmoidal dose-effect curve in its toxic effects (see
Fig. 5.56). 49
When one has to assess risks of compounds with carcinogenic or allergic
properties, risk assessment becomes much more difficult. This applies espe-
cially to genotoxic carcinogens, which have been assumed not to have a safe
level; the only safe level would be zero. In this circumstance, linear extrapola-
tion (straight line from LOAEL to zero) or various mathematical models that
assume the absence of a safe dose have been utilized in human risk assessment.
In these instances, the acceptable risk level has been set to 1/1000000. It has
to be kept in mind that linear extrapolation or mathematical models are being
used because the true mechanisms of chemical carcinogenesis are not known.
Therefore, risk regulators, when carrying out risk assessment, are conservative
in their risk assessment to guarantee safety of exposed populations. This does
49 180 201 202
not mean, however, that the approach is correct. ' ' ' Figure 5.57 indi-
cates the differences in risk estimates that can be obtained from the same set of
data utilizing different mathematical models. 49
Recently it has been argued that genotoxic carcinogens may also have a
threshold in their carcinogenic effect. If this assumption were to be accepted
by the regulators, it would have a tremendous impact on risk assessment
throughout the world. It would mean that safety factors would also be used
when determining safe dose levels for genotoxic carcinogens, and this would
affect most of the regulatory limits set for chemicals.
5.3.6.2 The Significance of Health Risks Caused by Chemical
Compounds
Assessing health risks induced by exposure to chemical compounds is differ-
ent in different societies. Typically, in industrialized societies, traffic exhausts, ex-