Fundamental aspects of dose--response relationships and their extrapolation for noncarcinogenic effects of metals.

Fundamental differences in dose--response relationships between "stochastic" and "nonstochastic" effects of chemicals are identified and discussed. The difficulties in extrapolating into the low-dose region of dose--response curves are pointed out. In some instances of nonstochastic effects, observations concerning interindividual variability in biological half-time and threshold body burden for symptoms may be used for such extrapolation. An example based on data from the literature concerning effects of methyl-mercury on the nervous system is given. The confidence intervals of the extrapolated risk-values are computed and discussed in relation to assumptions concerning the mathematical model to be used in the extrapolation process.