Toxic Mixtures in Time-The Sequence Makes the Poison
Toxic Mixtures in Time-The Sequence Makes the Poison
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DOI：
10.1021/acs.est.6b06163
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发表时间：
2017-03-07
影响因子：
11.4
通讯作者：
Escher, Beate I.
中科院分区：
文献类型：
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作者：
Ashauer, Roman;O'Connor, Isabel;Escher, Beate I.
“剂量产生毒药”。该原理假设，一旦化学物质从生物体中清除（毒代动力学恢复），它就不再具有任何作用。然而，它忽略了重建体内平衡的另一个过程，即毒效动力学恢复，该过程可能快也可能慢，具体取决于化学物质。因此，当生物体依次暴露于两种毒物时，如果顺序颠倒，毒性可能会有所不同。我们用淡水甲壳动物 Gammarus pulex 和作用于不同目标的四种毒物（二嗪农、丙环唑、4,6-二硝基邻甲酚、4-硝基苄基氯）来检验这一假设。当两种毒物的暴露顺序颠倒，同时保持相同剂量时，我们发现明显不同的毒性。缓慢的毒效动力学恢复会导致后续暴露中的残留毒性，从而导致序列效应，但仅当毒效动力学恢复相对于暴露之间的间隔较慢时。这表明残留毒性是生物体适应性的有用指标，并且应修订风险评估方法，因为它们目前可能低估风险。我们提供第一个。有证据表明，作用于不同目标的化学品之间以及当接触时间相隔数天时，会发生残留毒性。因此，造成中毒的不仅是剂量，还有暴露的顺序。
"The dose makes the poison". This principle assumes that once a chemical is cleared out of the organism (toxicokinetic recovery), it no longer has any effect. However, it overlooks the other process of reestablishing homeostasis, toxicodynamic recovery, which can be fast or slow depending on the chemical. Therefore, when organisms are exposed to two toxicants in sequence, the toxicity can differ if their order is reversed. We test this hypothesis with the freshwater crustacean Gammarus pulex and four toxicants that act on different targets (diazinon, propiconazole, 4,6-dinitro-o-cresol, 4-nitrobenzyl chloride). We found clearly different toxicity when the exposure order of two toxicants was reversed, while maintaining the same dose. Slow toxicodynamic recovery caused carry-over toxicity in subsequent exposures, thereby resulting in a sequence effect but only when toxicodynamic recovery was slow relative to the interval between exposures. This suggests that carry-over toxicity is a useful proxy for organism fitness and that risk assessment methods should be revised as they currently could underestimate risk. We provide the first. evidence that carry-over toxicity occurs among chemicals acting on different targets and when exposure is several days apart. It is therefore not only the dose that makes the poison but also the exposure sequence.