Linear low-dose extrapolation for non-cancer responses: Burke et al. respond

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From: Environmental Health Perspectives(Vol. 117, Issue 4)
Publisher: National Institute of Environmental Health Sciences
Document Type: Article
Length: 1,112 words

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doi: 10. 1289lehp.0800329R

In his letter, Rhomberg raises several issues concerning recommendations in our report of the workshop "Issues and Approaches to Low Dose-Response Extrapolation for Environmental Health Risk Assessment" (White et al. 2009). One recommendation of the workshop was to set aside the generally held presumption that dose-response functions should follow a threshold model when extrapolating from higher dose studies of non-carcinogenic responses to lower dose levels typical for environmental exposures to chemicals. Workshop participants generally concluded that the selection of population-level low-dose extrapolation models should be informed by population factors such as interindividual variability in susceptibility and coexposures, as well as by categorization of mechanisms of toxicity. As indicated in the meeting report (White et al. 2009), most workshop participants preferred a linear, no-threshold approach to low-dose extrapolation modeling, combined with modeled estimates of the low range of observed data, for noncancer, as well as cancer, outcomes in the absence of convincing evidence to indicate that an alternative model is more appropriate. We recognize that this recommendation represents a departure from current generally accepted practice.

On a nonsubstantive point, Rhomberg's comment that we did not include additional information regarding "fuller discussions" at the workshop on this and other issues reflects the constraints imposed by EHP's article length limits and changes made to accommodate reviewer comments encouraging emphasis on workshop findings and recommendations rather than on workshop discussions.

We disagree with Rhomberg's assertion that the finding of a linear, no-threshold exposure-response relationship in many epidemiologic studies of the effect of environmental pollutants, such as particulate matter and ozone air pollution, can be attributed entirely to a small range of exposures and measurement error. Although these factors need...

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Gale Document Number: GALE|A199122309