High Dose to Low Dose Extrapolation:
An important step in the estimation of chemical toxicity is
generating a dose response curve. This is a graphic representation
of the data showing adverse effects at particular dose levels
as depicted by the red line. The data in the red line area are
generated by giving relatively high doses to a fairly small number
of test animals.
If low doses are given to the animals, no adverse effects
may show up in a small sample of test animals. Sometimes risk
effects which should be regulated need to be observed at a level
of one case in a million cases. Since this is not possible with
small samples of test animals, the high doses are used. The high
doses themselves may cause problems in interpreting the data.
Linear Extrapolation Theory: Once the high dose data
is obtained and plotted as in the red line, an extrapolation
to low does is made. A straight line, linear extrapolation may
be used, which then assumes that even a very tiny dose may cause
some adverse effect.
Threshold Theory: According to the threshold theory
of toxicity, a toxic substance must be present in an organism
at some threshold concentration before any adverse effects are
evident. Below this concentration, no such adverse effects are
observed. By using this theory it is assumed that tiny doses
of a toxic substance will not cause any adverse effects.
Scientists do not agree which theory provides the correct
answer concerning low dose effects of toxic substances. A further
complication is the fact that animal data is then extrapolated
to human effects, which may not provide the correct answer either,
a human is not a "giant rat".