We thank Dr. Adenuga for his interest in our recent ES&T study (1) and note the continued interest in toxicological evaluations of diisononyl phthalate by his colleagues at ExxonMobil. (2,3) The comment suggested that the prioritization of diisononyl phthalate (DINP) was inaccurate and that DINP does not pose an environmental hazard. We would like to take this opportunity to respond to this comment. Our original work primarily focused on using high-resolution mass spectrometry and nontargeted methods to evaluate the occurrence of anthropogenic contaminants in an urbanizing estuary while providing a screening-level evaluation of the potential for the many detected chemicals to cause biological harm. The approach, based on a risk quotient (RQ) (4) calculated from environmental concentrations and published predicted no-effect concentrations (PNECs), has been widely applied, and our screening methodologies used in this study align with global guidelines for environmental risk assessment (5−8) for potentially harmful chemicals. Such RQ calculations are clearly not meant to be a final characterization of risk, and a full, chemical-by-chemical, risk-based evaluation is well beyond the scope of the original study. We note that the detection of diisononyl phthalate (DINP) in Puget Sound marine water was unambiguous, based on the comparison of mass spectra and retention time with those of a DINP reference standard. We also detected other similar high-molecular weight phthalate homologues (isononyl decyl phthalate and isononyl undecyl phthalate). These analogues were not quantified because standards were not available (we suggest plasticizer manufacturers like ExxonMobil make available to the research community pure standards of all chemical products they produce commercially), but their abundance may be similar to or even higher than that of DINP based on peak areas. Detecting multiple phthalates at concentrations of >100 ng/L, in addition to other plasticizers, demonstrates clear contamination of this marine water and suggests that an evaluation of the combined toxicity of complex mixtures, including the contributions from phthalates, is an appropriate approach for screening the potential risks of chemical exposures to aquatic species. Considering Dr. Adenuga’s concerns about the accuracy of the PNEC values communicated in the NORMAN Ecotoxicology Database, we encourage Dr. Adenuga to discuss the reliability and/or accuracy of NORMAN PNEC values with the publishers of this well-used prioritization database. Beyond the NORMAN estimates, we note that DINP, a plasticizer added to various plastic products, has been listed as a reproductive and developmental toxicant by National Toxicology Program (9) and as a carcinogen by the State of California (California’s Proposition 65 list.3). (10) Multiple studies suggest that DINP is an endocrine disruptor and carcinogen to mammals, (11−16) and recent studies have demonstrated its endocrine disrupting activity on aquatic species at an environmentally relevant concentration (420 ng/L). (17−19) These studies would seem to contradict, across numerous end points and organisms, Dr. Adenuga’s suggestion that DINP “does not pose a hazard to the environment” or that DINP is “not toxic to aquatic species”. We fully agree that a more thorough and data-driven investigation of DINP and similar is warranted and certainly support the development of complete, comprehensive, and unambiguous ecotoxicological data to ensure accurate risk assessment as demonstrated in the commentary by Dr. Adenuga. We also encourage the toxicological communities, including both regulators and chemical manufacturers, to carefully consider the use of new information as it becomes available. Finally, we would suggest that major manufacturers of the many chemicals and products subject to widespread environmental dispersal bear a special responsibility to aid our societal efforts to generate reliable and independent ecotoxicological information that informs the management of these residual chemical contaminants. We appreciate their contributions to this effort. This article references 19 other publications. This article has not yet been cited by other publications. This article references 19 other publications.

中文翻译：

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反驳关于“城市河口新兴关注污染物的可疑和非目标筛查”的信件

我们感谢 Adenuga 博士对我们最近的ES&T感兴趣研究 (1) 并注意到他在埃克森美孚的同事对邻苯二甲酸二异壬酯的毒理学评估持续感兴趣。(2,3) 该意见表明，邻苯二甲酸二异壬酯 (DINP) 的优先排序是不准确的，而且 DINP 不会造成环境危害。我们想借此机会回应这一评论。我们最初的工作主要集中在使用高分辨率质谱法和非靶向方法来评估城市化河口中人为污染物的发生，同时对许多检测到的化学物质造成生物危害的可能性进行筛选级评估。该方法基于根据环境浓度和公布的预测无影响浓度 (PNEC) 计算的风险商数 (RQ) (4)，已得到广泛应用，我们在本研究中使用的筛选方法符合潜在有害化学品的全球环境风险评估指南 (5-8)。这样的 RQ 计算显然不是风险的最终表征，并且完整的、逐个化学品的、基于风险的评估远远超出了原始研究的范围。我们注意到，根据质谱和保留时间与 DINP 参考标准的比较，普吉湾海水中邻苯二甲酸二异壬酯 (DINP) 的检测是明确的。我们还检测到其他类似的高分子量邻苯二甲酸酯同系物（邻苯二甲酸异壬基癸酯和邻苯二甲酸异壬基十一烷基酯）。这些类似物没有量化，因为没有标准（我们建议像埃克森美孚这样的增塑剂制造商向研究界提供他们商业生产的所有化学产品的纯标准），但它们的丰度可能与 DINP 相似甚至更高，基于峰区。除了其他增塑剂外，还检测到浓度 >100 ng/L 的多种邻苯二甲酸酯，表明该海水受到明显污染，并表明评估复杂混合物的综合毒性（包括邻苯二甲酸酯的贡献）是一种合适的筛选方法化学品接触水生物种的潜在风险。考虑到 Adenuga 博士对 NORMAN 生态毒理学数据库中传达的 PNEC 值的准确性的担忧，我们鼓励 Dr. Adenuga 与该常用优先级数据库的发布者讨论 NORMAN PNEC 值的可靠性和/或准确性。除了 NORMAN 的估计之外，我们注意到 DINP 是一种添加到各种塑料产品中的增塑剂，已被国家毒理学计划 (9) 列为生殖和发育毒物，并被加利福尼亚州列为致癌物（加利福尼亚州第 65 号提案清单。 3 ). (10) 多项研究表明，DINP 是哺乳动物的内分泌干扰物和致癌物，(11-16)，最近的研究表明其在环境相关浓度 (420 ng/L) 下对水生物种的内分泌干扰活性。(17-19) 这些研究似乎在许多终点和生物体上相互矛盾，博士。Adenuga 建议 DINP“不会对环境造成危害”或 DINP“对水生物种无毒”。我们完全同意，有必要对 DINP 和类似物进行更彻底和数据驱动的调查，并且当然支持开发完整、全面和明确的生态毒理学数据，以确保准确的风险评估，如 Adenuga 博士的评论所示。我们还鼓励毒理学界，包括监管机构和化学品制造商，在新信息可用时仔细考虑使用。最后，我们建议许多化学品和产品的主要制造商承担特殊责任，以帮助我们的社会努力生成可靠和独立的生态毒理学信息，为这些残留化学污染物的管理提供信息。我们感谢他们对这项工作的贡献。本文引用了 19 篇其他出版物。这篇文章尚未被其他出版物引用。本文引用了 19 篇其他出版物。