Identifying Greener and Safer Plasticizers: A 4-Step Approach
Identifying Greener and Safer Plasticizers: A 4-Step Approach
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DOI：
10.1093/toxsci/kfx156
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发表时间：
2018-02-01
影响因子：
3.8
通讯作者：
Robaire, Bernard
中科院分区：
文献类型：
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作者：
Albert, Oceane;Nardelli, Thomas C.;Robaire, Bernard
增塑剂邻苯二甲酸二（2-乙基己基）酯（DEHP）等内分泌干扰化学品的健康和经济负担促使工业界开发替代品。然而，由于没有要求制造商确保这些替代品的安全性，导致产生了可能具有与原始化学品相似或更差影响的替代品。因此，科学家、监管机构和工业界越来越认识到，需要采取积极主动的方法来开发安全的化学替代品。我们提出了一个4步法，用于设计、表征和毒理学测试负责任的替代化学品，我们正在进行的DEHP替代品研究说明了这一点。我们的方法包括：（1）根据创新的化学结构和环境考虑因素设计替代化学品并确定其特性;（2）进行大规模的体外细胞高通量和选择性的体外研究，以预选最无害的替代品;（3）进行体内急性毒性研究，以排除所选候选物的明显毒性;和（4）子宫内和哺乳期暴露研究，比较所选候选药物与目前使用的药物的效果，强调暴露于后者后通常描述的表型。使用这4步方法，我们已经确定了2种替代化学品，它们具有良好的塑化性能、更好的生物降解性，并且比DEHP的沥滤更少，在体内没有任何明显的毒性。迄今为止，该过程已被证明在主动识别DEHP的可靠化学替代品方面是有用的。
The health and economic burden of endocrine disrupting chemicals, such as the plasticizer di(2-ethylhexyl) phthalate (DEHP), is prompting industry to develop alternatives. However, the absence of requirements for manufacturers to ensure the safety of these alternatives has led to the generation of replacements that may have similar or worse effects than the original chemicals. Consequently, there is increasing recognition by scientists, regulators and industry that proactive approaches are needed to develop safe chemical substitutes. We propose a 4-step approach for the design, characterization and toxicological testing of responsible alternative chemicals that we illustrate with our ongoing studies on DEHP replacements. Our approach is comprised of: (1) the design and characterization of alternative chemicals based on innovative chemical structures and environmental considerations; (2) large-scale in vitro cell-based high throughput and selective ex vivo studies to preselect the most innocuous alternatives; (3) an acute toxicity in vivo study to rule out overt toxicity of the selected candidates; and (4) an in utero and lactational exposure study comparing the effects of selected candidates to those currently in use, emphasizing commonly described phenotypes after exposure to the latter. Using this 4-step approach, we have identified 2 alternative chemicals displaying good plasticizing properties, better biodegradability, and less leaching than DEHP without any apparent toxicity in vivo. This process has thus far proven useful in the proactive identification of responsible chemical replacements for DEHP.