Common use of Dose-Response Evaluation Clause in Contracts

Dose-Response Evaluation. Dose-response assessment is the process of characterizing the relationship between the dose of an agent and the anticipated incidence of an adverse health effect in an exposed population. The bulk of our knowledge about the dose-response relationship is based on data collected from animal studies (usually rodents) and theoretical precepts about what might occur in humans. Mathematical models are used to estimate the possible response at levels far below those tested in animals. These models contain several limitations which should be considered when the results (e.g., risk estimates) are evaluated. Primary among these limitations is the uncertainty in extrapolating results obtained in animal research to humans and the shortcomings of extrapolating responses obtained from high-dose studies to estimate responses at very low doses. For example, humans are typically exposed to environmental contaminants at levels that are less than a thousandth of the lowest dose tested in animals. Such doses may be easily handled by the myriad of biological protective mechanisms that are present in humans (Ames, ▇▇87). Consequently, at best, we have a limited ability to use the results of standard rodent bioassays, which are usually the basis for regulatory limits or guidelines, to understand the human biological hazard or cancer risk posed by typical levels of exposure (Crum▇ ▇▇ al., 1976; Sielken, 1985). An independent evaluation of the dose-response literature for each of the chemicals of concern was not considered necessary for the purposes of this risk assessment. Instead, a number of regulatory limits and guidelines have been identified that are based on extrapolations from the literature and identify what are widely viewed as acceptable measures of risk, or levels of exposure or dose. Exposure being defined as the concentration of a compound at a particular point of contact, e.g. concentration in inspired air or ingested water; and dose being the amount of the compound that actually enters the body through all routes. Non-carcinogenic and carcinogenic health effects have been addressed separately as described in the following sections.