Deficiencies in Dose-Response Assessment

2 Deficiencies in dose-response assessment. In addition to the sources of uncertainty in dose-response assessment described above, there are several important deficiencies in the way that the 

Although some investigators have claimed that models lacking low-dose linearity are not appropriate for substances that cause 

A difficulty with epidemiologic studies at low doses is the inability to adequately control for potentially confounding factors to the extent necessary to exclude spurious observations, either positive or negative. Epidemiologic studies are not capable of detecting increased responses unless the excess relative risk is on the order of 30 to 40 percent or higher. 

As an alternative to relying on simple scaling factors, PB-PK models described in Section 3.2.1.3.4 can be used to more accurately predict responses in humans based on rodent data (Corley et al., 1990 Reitz et al., 1988 1996). The benefits of this approach have been so impressive that a special symposium was held by the National Academy of Sciences to encourage its use (Krewski et al., 1987). 

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Uncertainties and Deficiencies in Dose-Response Assessment. Any approach to determining the dose-response relationship for hazardous chemicals involves many attendant uncertainties that limit its accuracy. In addition, many dose-response assessments suffer from deficiencies in the way they are conducted, which further decreases accuracy. These two aspects of dose-response assessment, which in some ways have led to adoption of such conservative approaches as large safety factors and UCLs in applying the results to health protection of the public, are discussed in the following two sections. 

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