Linearity, low-dose

Howci cr, this linear equation is valid only at low risk levels (i.e., below estimated risks of 0.01). For situations where chemical intakes might be liigh (i.e., risk above 0.01), an altcrmilc equation should be used. The one-liit equation, which is consistent with the linear low-dose model given above and described below, should be used instead. 

Hill, C.K., Han, A., and Elkind, M.M. (1984). Fission-spectrum neutrons at a low dose rate enhance neoplastic transformation in the linear, low dose region (0-10 cGy), Int. J. Radiat. BioL 46 11. 

A 1977 National Academy of Sciences report (NAS 1977) was highly influential in the decision by regulatory agencies such as the ERA to adopt a default of linear low-dose (or no threshold) extrapolation for carcinogens. This report presented three key lines of reasoning ... 

Moreover, several scientists unequivocally reject a linear low-dose extrapolation because it ignores the impact of dose-related differences in toxicokinetics and toxicodynamics, as mentioned above, as well as other biological principles as stated in other chapters in this book. For example, Rozman et al. (1996) argue that rather than use an arithmetic scale for dose, which compresses the dose scale in the... 

Finally, the linear low-dose extrapolation obviates de facto the concept of a threshold in the dose-response curve. The threshold concept is universally accepted for most other, noncancer toxicity and for many other biological phenomena (e.g., taste thresholds), and many scientists would argue that such thresholds (or practical thresholds ) should apply to the cancer or mutation response due to the undo-lying complexities in toxicokinetics and in the dynamics of DNA damage and repair, immune surveillance, and the variation in the progression of clinical diseases. ... 

Linear low-dose extrapolation has been chosen by many regulatory agencies as a health-protective approach to cancer risk assessment. While this is a conservative approach, research in recent years has found many exceptions to this approach. 

Rhomberg, L. R. (2009). Linear low-dose extrapolation for noncancer responses is not generally appropriate (Letter). Environ Health Perspect 117(4), A141—A142. 

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