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Basic Course: Supplemental Topics

Updated Approach: Overview

As greater insight has been obtained about the mechanism(s) of toxicity for a wide variety of toxicants, it is becoming more and more obvious that separating carcinogenic and noncarcinogenic chemicals into nonthreshold and threshold modes of action was a naive approach to risk assessment. 

Updated focus graphic: Illustration of updated thinking that some carcinogens appear to act through an indirect threshold mechanism and do not show a linear response to dose as the dose approaches zero. Further illustrates that linearity in the response to dose may also apply to some noncancer endpoints.In particular, it appears that some carcinogens act through an indirect threshold mechanism and do not show a linear response to dose as the dose approaches zero. Under the updated methodology for deriving ambient water quality criteria (AWQC) for human health (i.e., the 2000 Human Health Methodology), these are characterized by a nonlinear Point of Departure divided by Uncertainty Factors.

Further, linearity in the response to dose may also apply to some noncancer endpoints. Lead is the contaminant that is most frequently characterized in this way. Thus far, it has not been possible to define a dose for lead that has no effect.

Key Point. Accordingly, we are seeing a shift from the traditional approach of viewing quantitative risk assessment for carcinogens as a linear process and noncancer assessments as nonlinear. Increasingly, the determination of whether to use a linear or a nonlinear approach for deriving human health AWQC is based on the mode of action for an effect more than whether the effect of interest is cancer or not.

Disclaimer:
For informational purposes only–Not official statements of EPA policy.

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