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Bogen's Critique of Linear-No-Threshold Default Assumptions

机译：Bogen对线性无阈值默认假设的批评

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In an article recently published in this journal, Bogen((1)) concluded that an NRC committee's recommendations that default linear, nonthreshold (LNT) assumptions be applied to dose- response assessment for noncarcinogens and nonlinear mode of action carcinogens are not justified. Bogen criticized two arguments used by the committee for LNT: when any new dose adds to a background dose that explains background levels of risk (additivity to background or AB), or when there is substantial interindividual heterogeneity in susceptibility (SIH) in the exposed human population. Bogen showed by examples that SIH can be false. Herein is outlined a general proof that confirms Bogen's claim. However, it is also noted that SIH leads to a nonthreshold population distribution even if individual distributions all have thresholds, and that small changes to SIH assumptions can result in LNT. Bogen criticizes AB because it only applies when there is additivity to background, but offers no help in deciding when or how often AB holds. Bogen does not contradict the fact that AB can lead to LNT but notes that, even if low-dose linearity results, the response at higher doses may not be useful in predicting the amount of low-dose linearity. Although this is theoretically true, it seems reasonable to assume that generally there is some quantitative relationship between the low-dose slope and the slope suggested at higher doses. Several incorrect or misleading statements by Bogen are noted.
机译：在最近在该杂志上发表的一篇文章中，Bogen（（1））得出结论，NRC委员会的建议是将默认线性，非阈值（LNT）假设应用于非致癌物的剂量反应评估，而非线性作用致癌物的建议不成立。 Bogen批评了委员会针对LNT的两种论点：当任何新剂量加到可以解释背景风险水平（对背景或AB的可加性）的背景剂量时，或当暴露的人群中个体之间的易感性（SIH）存在实质性异质性时人口。 Bogen通过实例表明SIH可能是错误的。本文概述了确认Bogen主张的一般证明。但是，还要注意的是，即使个别分布都具有阈值，SIH仍会导致非阈值人口分布，并且对SIH假设的微小更改可能会导致LNT。 Bogen批评AB，因为它仅在背景具有可加性时才适用，但对确定AB的持有时间或频率没有帮助。 Bogen并没有与AB会导致LNT的事实相矛盾，但是指出，即使导致了低剂量线性，较高剂量下的反应可能也无法用于预测低剂量线性量。尽管从理论上讲这是正确的，但可以合理地假设低剂量斜率与较高剂量时建议的斜率之间存在一定的定量关系。注意到Bogen的一些错误或误导性陈述。

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