drawback of this approach is that the existing guidelines were designed to protect different populations (e.g., the general population, workers) and were intended for different settings (e.g., ambient exposures, workplace, accidental releases), which made it necessary for USACHPPM to adjust the values to make them relevant to the military population in the deployment setting. Problems with using pre-existing guidelines and adjusting them for deployment purposes are described below.
The following procedures typically are used by regulatory and other agencies to establish health-protective exposure guidelines and therefore form bases of the MEGs.
Most noncancer assessments begin by selecting a no-observed-adverse-effect level (NOAEL) from experimental data and adjusting and extrapolating that value by applying factors to account for uncertainties related to exposure duration, varying levels of susceptibility among humans or between species when animal data are being used, and other facets of the data. Typically, the adverse effect having the lowest NOAEL in the most sensitive species for which data are available is chosen as the critical toxicity end point for derivation of the guideline. The assumption is that if the population is protected from that adverse effect, it will also be protected from the other adverse effects observed at higher concentrations. NOAELs can be determined by identifying the lowest NOAEL from a single critical study or by doing a benchmark dose analysis and selecting the mathematical result to use as a surrogate NOAEL. Data from the selected study or studies of interest are typically transformed to a product of concentration and time (i.e., C × t) to account for differences between the exposure duration used in the study or studies and the duration for which the health-protective guideline is being established.
The NOAEL is adjusted by the use of uncertainty factors (UFs). These factors are applied to account for uncertainties in extrapolating experimental animal data to humans (interspecies differences) or variable susceptibilities in the human population (intraspecies differences); to represent the expected ratio of the lowest-observed-adverse-effect level (LOAEL) to NOAEL