Hazard Assessment and Contaminated Sites - Dealing with Contaminated Sites: From Theory Towards Practical Application - page 547

• therapeutic indices; and

• models to interpolate high dose experimental data to the low doses likely to be

experienced in the environment (Klaassen 1996 ).

There are often limited human exposure data and animal bio-assay data are
most often used for dose response assessment. The use of these data requires
extrapolations from animals to humans and from high doses to low doses (ibid).
Where data is derived from animal studies, the doses are nearly always higher
(often considerably higher) than the experimental range. The shape of the dose
response curve below the experimental range will be unknown and can have a vari-
ety of shapes depending on the mathematical model used for fitting the curve. The
choice of the model should be based on mechanistic information about how the
contaminant exerts its effects if such information is available.
The dose response curves for different effects will have different shapes and will
occur at different doses (see Fig. 12.3 ). The shape of the dose response curve will
be different again when dealing with, for example, an essential trace element such
as copper where at low doses there will be a dose response curve for the effects of
deficiency and at higher doses another dose response curve describing the effects
of excess.
The Internation Programme on Chemical Safety has reviewed many of the issues
relating to dose-response in a recent publication (WHO 2009 ).

Fig. 12.3 Different dose-response curves for different effects from a hypothetical contaminant

12.5.2 Methodologies

All methodologies make the distinction between neoplastic and non-neoplastic end-
points in Risk Assessment. The impetus for this distinction was the concept of a lack
of threshold in the dose-response for carcinogens based on the initial premise that
all carcinogens are mutagens (Ames et al. 1973 ). One mutation or one DNA damage