Benchmark dose concept

The concept of the Benchmark Dose (BMD), a benchmark is a point of reference for a measurement, in health risk assessment of chemicals was first mentioned by Crump (1984) as an alternative to the NOAEL and LOAEL for noncancer health effects in the derivation of the ADI/TDI these terms are addressed in detail in Chapter 5. The BMD approach provides a more quantitative alternative to the dose-response assessment than the NOAEL/LOAEL approach. The goal of the BMD approach is to define a starting point of depariure (POD) for the establishment of a tolerable exposure level (e.g., ADI/TDI) that is more independent of the study design. In this respect, the BMD approach is not... 

Although dose-response assessments for deterministic and stochastic effects are discussed separately in this Report, it should be appreciated that many of the concepts discussed in Section 3.2.1.2 for substances that cause deterministic effects apply to substances that cause stochastic effects as well. The processes of hazard identification, including identification of the critical response, and development of data on dose-response based on studies in humans or animals are common to both types of substances. Based on the dose-response data, a NOAEL or a LOAEL can be established based on the limited ability of any study to detect statistically significant increases in responses in exposed populations compared with controls, even though the dose-response relationship is assumed not to have a threshold. Because of the assumed form of the dose-response relationship, however, NOAEL or LOAEL is not normally used as a point of departure to establish safe levels of exposure to substances causing stochastic effects. This is in contrast to the common practice for substances causing deterministic effects of establishing safe levels of exposure, such as RfDs, based on NOAEL or LOAEL (or the benchmark dose) and the use of safety and uncertainty factors. 

One outcome of the dependence of the NOEL/ NOAEL on the statistical significance test is that it tends to penalize chemicals for which there is more or better data. To remedy this problem, the benchmark dose (BMD) concept was introduced as an alternative approach. The BMD depends on the specification of a low level effect that would typically be unobservable. The endpoint may be the specified percentage (5 or 10%) above background of a population for an endpoint deemed to be adverse. Since the endpoint is defined, determinations for different chemicals and different data sets tend to be more comparable. 

Notice that the estimated BMD simply corresponds to a constant divided by the dose-response slope from the regression model. That concept is important, because it provides some theoretical justification for some analyses (presented later) that are based on the inverse of the estimated benchmark doses from several MeHg studies. 

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