Doseresponse Relationship

When toxicological evaluation indicates that a chemical may cause an adverse effect, the next step is to determine the potency of the chemical. The dose-response analysis determines the relationship between the degree of chemical exposure (or dose) and the magnitude of the effect (response) in the exposed organism. Scientists use this analysis to determine the amount of a chemical that causes tumor development in skin irritation, animals, or death in animals.

Dose-response curves are generated from various acute and chronic toxicity tests. Depending on chemical action, the curve may rise with or without a threshold. As Figure 11.8.4 shows, the TD50 and TD 100 points indicate the doses associated with 50% and 100% occurrence of the measured toxic effect; also shown are the No Observable Adverse Effect Level (NOAEL) and Lowest Observable Adverse Effect Level (LOAEL). The NOAEL is assumed to be the basis for the Acceptable Daily Intake (ADI).

Figure 11.8.5 illustrates the threshold and no-threshold dose-response curve. In both cases, the response normally reaches a maximum, after which the dose-response curve becomes flat.

To estimate the effects of low doses, scientists extrapolate from the observed dose-response curve. Extrapolation models extend laboratory results into ranges where observations are not yet available or possible. Most current models are not based exclusively upon known biol-

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