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Of Reductionism and The Pendulum Swing: Connecting Toxicology and Human Health

机译:还原论与钟摆:将毒理学与人类健康联系起来

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In this contribution we will show that research in the field of toxicology, pharmacology and physiology is by and large characterised by a pendulum swing of which the amplitudes represent risks and benefits of exposure. As toxicology usually tests at higher levels than the populace routinely is exposed to, it reverts to mostly linear extrapolative models that express the risks of exposure, irrespective of dosages, only. However, as we will explicate in two examples, depending on dosages, it is less easy to separate risks and benefits than current toxicological research and regulatory efforts suggest. The same chemical compound, in the final analysis, is represented within the boundaries of both amplitudes, that is, show a biphasic, hormetic, dose-response. This is notable, as low-level exposures from the food-matrix are progressively more under scrutiny as a result of increasing analytical capabilities. Presence of low-level concentrations of a chemical in food is a regulatory proxy for human health, but in light of this hormetic dose-response objectionable. Moreover, given that an ecological threshold probably holds for most, if not all, man-made (bio)organic chemicals, these will be found to be naturally present in the food matrix. Both aspects require toxicology to close the gap between reductionist models and its extrapolative deficiencies and real-life scenarios.
机译:在这项贡献中,我们将显示毒理学,药理学和生理学领域的研究大体上以摆幅为特征,其振幅代表暴露的风险和益处。由于毒理学测试的水平通常高于普通民众所承受的水平,因此毒理学可以恢复为主要线性的外推模型,该模型仅表示暴露的风险,而与剂量无关。但是,正如我们将在两个示例中说明的那样,根据剂量,与目前的毒理学研究和监管工作所建议的相比,将风险和益处区分开来并不容易。在最终分析中,相同的化合物表示在两个幅度的边界内,即显示出双相,钟形,剂量响应。这是值得注意的,因为随着分析能力的提高,食品基质的低水平暴露越来越受到严格审查。食物中低浓度化学物质的存在是人类健康的监管代表,但鉴于这种令人讨厌的剂量反应令人反感。此外,考虑到大多数(如果不是全部)人造(生物)有机化学品的生态阈值可能适用,则将发现这些天然存在于食品基质中。这两个方面都需要毒理学来弥合还原论模型及其外推缺陷和现实情况之间的鸿沟。

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