Time flies over us, but leaves its shadow behind The “shadow” of plastic pollution looms large over environmental and human health research, but time is an overlooked variable as we attempt to understand, assess and mitigate the adverse impacts of synthetic polymer ubiquity. Plastic debris has infiltrated the environment to a level where we find it in air, water, soil, and food; yet, we still have only a rudimentary understanding of how environmental plastics affect human health. Here, we argue that time is the principal but currently underappreciated determinant that is impeding a reliable assessment of human health risks posed by environmental plastics. Time changes plastics, impacting both their physicochemical properties and their role as environmental toxicants, thereby creating a barrier to performing reliable risk assessment (Figure 1). However, the importance of time has yet to be realized and its impact integrated into the life-cycle and risk assessments of present-day plastic polymers. Figure 1. Properties of synthetic mass-produced polymers of daily use are changing as a function of time spent in the environment: well-defined macropolymers considered safe upon production, over time are being transformed into a plurality of microplastics and nanoplastics, which are ill-defined as to their shape, size, transport, persistence, behavior, chemical composition, chemical and biological sorbates, as well as the type and magnitude of corresponding risks they pose. A newly produced consumer product made from conventional plastic will have well-defined characteristics, including a known monomeric and polymeric composition, a known size, geometry and porosity, a known internal chemistry of additives (e.g., phthalate-based plasticizers), and a known external surface chemistry of characteristic coatings (e.g., antimicrobials, flame retardants, etc.).(1)Time spent in the environment changes all of this. The size of the plastic will change from macroplastic (>5 mm diameter) to microplastic (>1 μm to <5 mm) to nanoplastic (<1 μm), but our knowledge on the corresponding rate of change remains limited. Macroscopic meshworks of polymerized monomers break apart and become fragmented,(10) releasing internal additives while becoming ground into small pieces of unpredictable number, size and shape by mechanical stress from human use, from macrobiotic and microbial assault, and from environmental stress caused by soil, sediment, wind, surf, and wave action. Plastic monomers, plasticizers, and uncharacterized degradation products are further released, while fragments scavenge pollutants, nutrients and microbes from the environment and accumulate them on their surfaces. With increasing environmental residence time, environmental chemicals accumulate on the polymeric surfaces and all components are subject to further significant and mostly unpredictable changes. The end result is a shuttling and unloading of plastics-associated chemical and biological agents into new and unexpected locations and hosts,(2) including(9) a broad spectrum of biota and human populations worldwide. By changing the nature of plastic debris over time, this fosters an increasing uncertainty of latent hazards, exposure doses, and associated risks of the ecological and human exposures incurred. As the previously well-defined plastic chemistry becomes ill-defined and more complex, this allows for new risks to arise, including:

(i)	chemical risks from poorly defined, complex mixtures of polar and hydrophobic adsorbing environmental pollutants;
(ii)	biological risks from the colonization of polymeric surfaces with microbial biofilms and biogenic compounds; and
(iii)	physical risks from the geometry and surface characteristics of weathered and fragmented plastic polymers that may range from perfectly smooth spheres to spikes with sharp abrasive edges and needle-like tips that may mimic the appearance of asbestos and the corresponding, potentially devastating health risks posed.

chemical risks from poorly defined, complex mixtures of polar and hydrophobic adsorbing environmental pollutants; biological risks from the colonization of polymeric surfaces with microbial biofilms and biogenic compounds; and physical risks from the geometry and surface characteristics of weathered and fragmented plastic polymers that may range from perfectly smooth spheres to spikes with sharp abrasive edges and needle-like tips that may mimic the appearance of asbestos and the corresponding, potentially devastating health risks posed. The range of uncertainties time introduces then impedes the process of risk assessment adopted by the United States and many other countries globally, that consists of (i) hazard identification, (ii) dose–response assessment, (iii) exposure assessment, and (iv) risk characterization. Over time, information fades from known to diffuse to unknown, presenting unique challenges in the context of toxicity assessment, exposure calculations and risk assessment. The time of macroplastic fragmentation and degradation is particularly critical, ultimately resulting in the formation of microplastics at first and then of nanoplastics, with the latter not being properly captured by current sampling and detection techniques,(3) yet having the highest propensity for uptake into the human body through the gut, the airways and the skin, and the subsequent distribution of these exposure agents by the circulatory system into human organs and tissues.(4) How abundant are environmental nanoplastics and to what extent have they progressed their voyage into the human body? Although we do not yet know precisely, exposure is occurring from sources ranging from plastic-laden ambient air to drinking water to sea salt and seafood that all have been confirmed to show detectable microplastic contamination.(5,6) And studies of biomedical products (e.g., contact lenses, bite guards, artificial joints) have demonstrated that larger plastics can give rise to microplastics and nanoplastics, and that uptake and distribution within the human body of such materials is not only possible but known to occur.(7) So how should we deal with time, the driver of uncertainty and, ultimately, a key determinant of the risk posed by environmental plastics? Time needs to enter into plastic design and life cycle considerations. With the annual plastic production volume now exceeding 368 million metric tons worldwide,(8) conventional single-use consumer plastics have not only outlasted their useful lifespan but they also have overstayed their initial, enthusiastic welcome on planet Earth. As the principles of green chemistry are internalized as essential design criteria in modern high-volume manufacturing, nonrenewable energy (fossil fuel), carcinogenic monomers (vinyl chloride), and endocrine disrupting components and modifiers (such as bisphenol A and various alkyl phthalates) will have to be confined to the past at last. Successes in this area include the replacement of plastic microbeads with natural alternatives within personal care products(12) and the experimental use of biodegradable polymers in a variety of products, including biomedical applications.(13) Currently, these cases remain notable outliers. But it is time to find a more sustainable and safer alternative to present-day polymers, whose design criteria and composition—which were informed by yesterday’s science—today are recognized as not being protective anymore of human health and ecosystem viability.(14) Moving forward, the polymeric material itself must have environmentally benign properties, such as those exhibited by biobased plastics or natural polymers (e.g., chitin or lignin), materials whose eventual fate, degradation and associated impacts upon the environment are deemed sufficiently understood and acceptable.(15) Use of nonfossil fuel-based polymers has potential but scalability remains a challenge. However, a transition to polymers of improved resource renewability, biodegradability, and recyclability is imperative.(16) Once accomplished, this long overdue shift finally will bring relief for human populations, aquatic life and the world’s ecosystems that have been burdened with layers upon layers of first-generation, nonbiodegradable, nonrecyclable (i.e., only downcyclable) plastics. However, when the time of safe, sustainable plastics finally arrives, the environmental pollution from existing plastics will continue to increase and reach peak concentrations further into the future as nanoplastics—a prognosis that previously has been reached when considering the inventory of environmental microplastics.(17) This regrettable future scenario stems from the fact that the disintegration of previously released macro- and microplastics will continue to produce nanoplastics for some time. An estimated 8 million metric tons of anthropogenic (macro-) plastics enters the oceans each year(18) to then become fragmented and converted into environmental nanoplastics(11) prior to their ultimate, much delayed complete destruction into monomers and their elemental components upon mineralization. Much of this polymeric mass is deemed unrecoverable, constituting an inevitable precursor of the toxic, yet inevitable nanoplastics of the future. Time thus is critical to consider, not only in the context of exposure and hazard, but also with respect to sources of plastics and their steadily increasing environmental inventories. Do we have a sufficient level of knowledge to (counter)act and take action now? When it comes to mass-produced, short-lived consumer products made from plastics, the answer is yes, it is time for a change. It is time to let go of first-generation polymers and to instead manufacture smart plastics that are benign by design,(14,19−21) synthetic polymers that are safe irrespective of time. This work was made possible in part by funding from the National Institutes of Health (U01DA053976), the National Science Foundation (2038087; 2028564; 2038372), the Kaplan Foundation (30009070), the Catena Foundation (00103668), and Plastic Oceans International. Rolf Halden, PhD, PE, is a Professor at Arizona State University and Founding Director of the Biodesign Center for Environmental Health Engineering, the Human Health Observatory, the nonprofit OneWaterOneHealth, and the ASU startup company, AquaVitas LLC. Halden has authored over 250 research papers, patents, monographs, technical reports, book chapters, and the 2020 popular science book, Environment, published on the occasion of Earth Day 50. Halden is an expert in tracking harmful chemicals and infectious disease agents like SARS-CoV-2 by using wastewater treatment plants as chemical and biological observatories. His research team pioneered methods for detecting and quantifying threat agents in wastewater and sewage sludge and for estimating associated human exposures through the analysis of characteristic fecal and urinary human metabolites. Halden serves on the Expert Team of the U.S. American Chemical Society (ACS) and has been invited repeatedly to brief the Environmental Protection Agency, the Food and Drug Administration, the National Academies, the Centers for Disease Control and Prevention, and members of U.S. Congress on environmental health and sustainability challenges. We thank Dr. Chelsea Rochman (University of Toronto) for her critical reading of earlier drafts of this viewpoint. This article references 21 other publications.

中文翻译：

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时间：评估环境塑料对人类健康风险时不确定性的关键驱动因素


时间在我们身边飞逝，但留下了阴影塑料污染的“阴影”笼罩在环境和人类健康研究中，但当我们试图理解、评估和减轻普遍存在的合成聚合物的不利影响时，时间是一个被忽视的变量。塑料碎片已经渗透到环境中，我们在空气、水、土壤和食物中都可以找到它；然而，我们对环境塑料如何影响人类健康仍然只有初步的了解。在这里，我们认为时间是主要但目前被低估的决定因素，阻碍了对环境塑料造成的人类健康风险的可靠评估。时间会改变塑料，影响其物理化学性质及其作为环境毒物的作用，从而为进行可靠的风险评估造成障碍（图 1）。然而，时间的重要性尚未认识到，其影响也尚未纳入当今塑​​料聚合物的生命周期和风险评估中。图 1. 日常使用的大规模生产的合成聚合物的特性随着在环境中度过的时间的变化而变化：在生产时被认为是安全的明确的大分子聚合物，随着时间的推移，正在转变为多种微塑料和纳米塑料，这些塑料是有害的- 定义其形状、大小、运输、持久性、行为、化学成分、化学和生物山梨酸盐，以及它们造成的相应风险的类型和程度。由传统塑料制成的新生产的消费品将具有明确的特性，包括已知的单体和聚合物成分、已知的尺寸、几何形状和孔隙率、已知的添加剂内部化学性质（例如，化学成分）。（例如，基于邻苯二甲酸酯的增塑剂），以及已知的特征涂层的外表面化学（例如，抗菌剂、阻燃剂等）。（1）在环境中度过的时间会改变这一切。塑料的尺寸将从大塑料（>5 mm直径）变化到微塑料（>1 μm到<5 mm）再到纳米塑料（<1 μm），但我们对相应变化率的了解仍然有限。聚合单体的宏观网络破裂并变得支离破碎，(10) 释放出内部添加剂，同时由于人类使用、长寿和微生物攻击以及土壤引起的环境压力而被磨成数量、大小和形状不可预测的小块。 、沉积物、风、海浪和波浪作用。塑料单体、增塑剂和未表征的降解产物进一步释放，而碎片则从环境中清除污染物、营养物和微生物，并将其积聚在其表面。随着环境停留时间的增加，环境化学物质会积聚在聚合物表面，所有成分都会发生进一步显着且大多数不可预测的变化。最终结果是将与塑料相关的化学和生物制剂穿梭和卸载到新的和意想不到的地点和宿主，（2）包括（9）全世界范围广泛的生物群和人类群体。随着时间的推移，塑料碎片的性质发生变化，这导致潜在危害、暴露剂量以及生态和人类暴露相关风险的不确定性不断增加。随着以前明确定义的塑料化学变得不明确且更加复杂，这会出现新的风险，包括：

（我）	极性和疏水性吸附环境污染物的定义不明确、复杂的混合物带来的化学风险；
(二)	微生物生物膜和生物化合物在聚合物表面定植带来的生物风险；和
(三)	风化和碎片塑料聚合物的几何形状和表面特征带来的物理风险，其范围可能从完全光滑的球体到具有锋利磨料边缘和针状尖端的尖峰，这些尖峰可能模仿石棉的外观以及相应的潜在破坏性健康风险。

极性和疏水性吸附环境污染物的定义不明确、复杂的混合物带来的化学风险；微生物生物膜和生物化合物在聚合物表面定植带来的生物风险；风化和碎片塑料聚合物的几何形状和表面特征带来的物理风险，其范围可能从完全光滑的球体到具有锋利磨料边缘和针状尖端的尖峰，可能模仿石棉的外观以及相应的潜在破坏性健康风险。时间引入的不确定性范围阻碍了美国和全球许多其他国家采用的风险评估过程，该过程包括（i）危害识别，（ii）剂量反应评估，（iii）暴露评估，以及（iv） ) 风险描述。随着时间的推移，信息从已知逐渐扩散到未知，在毒性评估、暴露计算和风险评估方面提出了独特的挑战。大塑料碎片和降解的时间尤为关键，最终导致首先形成微塑料，然后形成纳米塑料，而后者无法被当前的采样和检测技术正确捕获，(3) 但其被吸收的可能性最高。通过肠道、气道和皮肤进入人体，以及这些接触剂随后通过循环系统分布到人体器官和组织中。(4) 环境纳米塑料的丰富程度以及它们进入海洋的程度如何？人体？ 尽管我们尚不清楚确切的情况，但暴露的来源包括充满塑料的环境空气、饮用水、海盐和海鲜，所有这些都已被证实显示出可检测到的微塑料污染。(5,6) 以及生物医学产品的研究 (例如，隐形眼镜、护牙套、人工关节）已经证明，较大的塑料可以产生微塑料和纳米塑料，并且此类材料在人体内的吸收和分布不仅是可能的，而且已知会发生。(7) 那么如何我们是否应该处理时间这个不确定性的驱动因素，并最终成为环境塑料带来的风险的关键决定因素？需要时间考虑塑料设计和生命周期。目前，全球塑料年产量已超过 3.68 亿吨，(8) 传统的一次性消费塑料不仅已经超过了其使用寿命，而且也已经过了地球最初受到热烈欢迎的时期。随着绿色化学原理被内化为现代大批量制造的基本设计标准，不可再生能源（化石燃料）、致癌单体（氯乙烯）以及内分泌干扰成分和改性剂（例如双酚 A 和各种邻苯二甲酸烷基酯）将最后不得不局限于过去。该领域的成功包括在个人护理产品中用天然替代品取代塑料微珠(12)，以及在各种产品中实验性使用可生物降解聚合物，包括生物医学应用。(13) 目前，这些案例仍然是值得注意的异常值。 但现在是时候寻找一种更可持续、更安全的替代品来替代当今的聚合物了，其设计标准和成分（基于昨天的科学）如今被认为不再能保护人类健康和生态系统的生存能力。(14)展望未来，聚合物材料本身必须具有环境友好的特性，例如生物基塑料或天然聚合物（例如甲壳素或木质素）所表现出的特性，这些材料的最终命运、降解和对环境的相关影响被认为是充分理解和可接受的。 15) 使用非化石燃料聚合物具有潜力，但可扩展性仍然是一个挑战。然而，向具有更高资源可再生性、可生物降解性和可回收性的聚合物转型势在必行。(16) 一旦实现，这一姗姗来迟的转变最终将为承受层层负担的人类、水生生物和世界生态系统带来缓解。第一代不可生物降解、不可回收（即只能向下回收）的塑料。然而，当安全、可持续塑料的时代最终到来时，现有塑料对环境的污染将继续增加，并在未来以纳米塑料的形式进一步达到峰值浓度——这是之前在考虑环境微塑料库存时得出的预测。（ 17) 这种令人遗憾的未来情景源于这样一个事实：先前释放的宏观塑料和微观塑料的分解将在一段时间内继续产生纳米塑料。 据估计，每年有 800 万吨人类（宏观）塑料进入海洋(18)，然后破碎并转化为环境纳米塑料(11)，然后在矿化时最终、延迟得多的完全破坏为单体及其元素成分。这些聚合物大部分被认为是不可回收的，构成了未来不可避免的有毒纳米塑料的前体。因此，时间至关重要，不仅在暴露和危害方面，而且在塑料来源及其稳步增加的环境库存方面。我们现在是否有足够的知识来（对抗）行动并采取行动？当谈到由塑料制成的批量生产、寿命较短的消费品时，答案是肯定的，是时候做出改变了。现在是时候放弃第一代聚合物，转而制造设计上无害的智能塑料，（14,19−21）无论时间如何都是安全的合成聚合物。这项工作的部分资助来自美国国立卫生研究院 (U01DA053976)、国家科学基金会 (2038087; 2028564; 2038372)、卡普兰基金会 (30009070)、卡泰纳基金会 (00103668) 和塑料海洋国际组织。 Rolf Halden 博士、PE 是亚利桑那州立大学教授，也是环境健康工程生物设计中心、人类健康观察站、非营利组织 OneWaterOneHealth 和亚利桑那州立大学初创公司 AquaVitas LLC 的创始主任。 哈尔登撰写了 250 多篇研究论文、专利、专着、技术报告、书籍章节，以及在第 50 届地球日之际出版的 2020 年科普书籍《环境》 。哈尔登是追踪有害化学物质和 SARS 等传染病病原体的专家-利用废水处理厂作为化学和生物观测站来检测 CoV-2。他的研究团队开创了检测和量化废水和污水污泥中威胁物质的方法，并通过分析特征性粪便和尿液人体代谢物来估计相关的人体暴露量。 Halden 是美国化学会 (ACS) 专家团队成员，多次受邀向环境保护局、食品和药物管理局、国家科学院、疾病控制和预防中心以及美国国会议员通报情况环境健康和可持续发展挑战。我们感谢 Chelsea Rochman 博士（多伦多大学）对这一观点的早期草稿的批判性阅读。本文引用了其他 21 篇出版物。