CHM 110 - CHEMISTRY AND ISSUES IN THE ENVIRONMENT
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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 no provide the correct answer either, a human are not a "giant rat".