Department of Biology, McMaster University, Hamilton, Ontario, Canada.
School of Earth, Environment and Society, McMaster University, Hamilton, Ontario, Canada.
Environ Toxicol Chem. 2024 Mar;43(3):549-558. doi: 10.1002/etc.5726. Epub 2023 Aug 18.
Pharmaceuticals and personal care products (PPCPs) occur as variable mixtures in surface waters receiving discharges of human and animal wastes. A key question identified a decade ago is how to assess the effects of long-term exposures of these PPCP mixtures on nontarget organisms. We review the recent progress made on assessing the aquatic ecotoxicity of PPCP mixtures-with a focus on active pharmaceutical ingredients-and the challenges and research needs that remain. New knowledge has arisen from the use of whole-mixture testing combined with component-based approaches, and these studies show that mixtures often result in responses that meet the concentration addition model. However, such studies have mainly been done on individual species over shorter time periods, and longer-term, multispecies assessments remain limited. The recent use of targeted and nontargeted gene analyses has improved our understanding of the diverse pathways that are impacted, and there are promising new "read-across" methods that use mammalian data to predict toxicity in wildlife. Risk assessments remain challenging given the paucity of ecotoxicological and exposure data on PPCP mixtures. As such, the assessment of PPCP mixtures in aquatic environments should remain a priority given the potential for additive-as well as nontarget-effects in nontarget organisms. In addition, we need to improve our understanding of which species, life stages, and relevant endpoints are most sensitive to which types of PPCP mixtures and to expand our knowledge of environmental PPCP levels in regions of the globe that have been poorly studied to date. We recommend an increased use of new approach methodologies, in particular "omics," to advance our understanding of the molecular mechanics of mixture effects. Finally, we call for systematic research on the role of PPCP mixtures in the development of antimicrobial resistance. Environ Toxicol Chem 2024;43:549-558. © 2023 SETAC.
药品和个人护理产品（PPCPs）作为人类和动物废物排放的可变混合物存在于地表水中。十年前提出的一个关键问题是如何评估这些 PPCP 混合物对非目标生物的长期暴露的影响。我们综述了最近在评估 PPCP 混合物（重点是活性药物成分）的水生生态毒性方面取得的进展，以及仍然存在的挑战和研究需求。使用全混合物测试与基于成分的方法相结合产生了新的知识，这些研究表明，混合物通常会导致符合浓度加和模型的反应。然而，这些研究主要是在较短的时间内对单个物种进行的，而对多物种的长期评估仍然有限。最近使用靶向和非靶向基因分析提高了我们对受影响的不同途径的理解，并且有很有前途的新的“外推”方法利用哺乳动物数据来预测野生动物的毒性。鉴于 PPCP 混合物的生态毒理学和暴露数据匮乏，风险评估仍然具有挑战性。因此，鉴于非目标生物中存在的加性和非目标效应的可能性，应对水生环境中的 PPCP 混合物进行评估仍然是一个优先事项。此外，我们需要提高对哪些物种、生命阶段和相关终点对哪些类型的 PPCP 混合物最敏感的认识，并扩大我们对迄今为止研究较少的全球各地区环境 PPCP 水平的认识。我们建议更多地使用新方法，特别是“组学”，以推进我们对混合物效应的分子机制的理解。最后，我们呼吁对 PPCP 混合物在抗微生物药物耐药性发展中的作用进行系统研究。环境毒理化学 2024；43:549-558. © 2023 SETAC.
