Environmental life-cycle of pharmacologically active compounds: new (bio)analytical approaches and environmental risk assessment

药理活性化合物（PAC）是不受管制的环境微污染物。它们主要通过（未）处理的污水、径流和污泥进入环境。它们具有生物活性、普遍存在和持久性，具有协同作用。一些最常用的PAC仅在英国就以数百吨/年的速度销售。令人惊讶的是，评估PAC的环境风险时没有考虑其对映异构体形式（这是尽管存在关于PAC对人体的对映异构体依赖性毒性的知识，以沙利度胺为突出实例）。这种方法可能导致对活性炭毒性的低估或高估、不正确的环境风险评估以及对环境和人类健康的直接风险，因为活性炭可能以非外消旋形式存在于环境中。由于西方国家人口老龄化和发展中国家消费水平的提高，PAC的使用量将在未来增加。城市用水及其用户受到这些环境压力的风险最高。随着人口的增长和气候的变化，这将影响清洁水的可获得性，并迫使基于水回用的新解决方案，了解PAC的生命周期对于为后代提供安全的可持续水资源管理解决方案至关重要。本项目将解决上述问题，目标如下：1。开发研究PAC生命周期所需的新分析方法这将涉及对映体特异性和基于质谱的化学分析，结合不同营养级毒性测试的生物测定以及暴露和效应驱动的ERA方法。了解PAC在城市水中的生命周期重点将放在确定城市水中（手性）PAC带来的新问题和威胁，包括废水，洗澡沃茨和河流集水区。将特别强调研究不足的问题：（一）可能导致手性PAC风险变化的PAC的手性和可能的立体选择性命运;（二）PAC对固体（如沉积物、污泥）的吸附;（三）风险的整体评估。将研究几组PAC：抗菌剂（高使用率，抗生素耐药性的发展），抗抑郁药（高使用率，高效力），抗真菌塑料（高效力，高生态毒性），镇痛药和抗炎药（高使用率，经历手性转化，高环境影响）和激素。3.为了进行PAC的环境风险评估，ERA将联合收割机结合确定性驱动和效应驱动的研究方法（在对映体水平上）。该方法将利用化学分析来确定PAC的转化动力学以及潜在有毒代谢物和转化副产物的形成。效应驱动方法将利用不同营养水平的毒性测试来验证PAC（或PAC和代谢物的混合物）的毒性发展。该项目将加强水研究，并有可能产生突破性成果，使广大用户群体受益，并提高生活质量和健康水平。科学界将受益于城市水中PAC知识的进步。政策制定者和政府机构将能够更好地判断限制PAC的必要性。该项目将为水工业和更广泛的商业/私营环境部门的工作人员提供关于关键水处理和环境过程的宝贵见解。它将评估PAC在城市用水中造成的潜在风险，并将表明是否有必要开发新技术。该项目将有利于整个社会，因为它将有助于加强供水安全。

Pharmacologically active compounds (PACs) are unregulated environmental micropollutants. They enter the environment mainly through (un)treated sewage, runoff and sludge. They are bioactive, ubiquitous and persistent with synergistic properties. Some of the most commonly used PACs are sold in hundreds of tonnes/year in the UK alone. Surprisingly, the environmental risks of PACs are assessed without taking into consideration their enantiomeric forms (this is despite existing knowledge on enantiomer dependant toxicity of PACs to humans, taking thalidomide as a prominent example). Such an approach could lead to an under- or over-estimation of toxicity of PACs, incorrect environmental risk assessment (ERA), and direct risk to the environment and human health, as PACs are likely to be present in the environment in their non-racemic forms. Usage of PACs will increase in the future due to an ageing population in western countries and an increase in consumption levels in the developing world. Urban water and its users are at the highest risk of exposure to these environmental stressors. With a growing population and changing climate, which will influence the accessibility of clean water and force new solutions based on water reuse, an understanding of the life-cycle of PACs is vital to provide safe sustainable water resource management solutions for future generations.Stricter regulation of PACs in water is envisaged. This project will address the above concerns with the following objectives: 1. To develop new analytical approaches required to study life-cycle of PACs This will involve enantiomer specific and mass spectrometry based chemical analysis combined with bioassays for toxicity testing at different trophic levels and both exposure and effect driven ERA methods.2. To understand life-cycle of PACs in urban water The emphasis will be put on identifying emerging concerns and threats posed by (chiral)PACs in urban water including wastewater, bathing waters and river catchments. A particular emphasis will be put on underinvestigated: (i) chirality and possible stereoselective fate of PACs which might lead to changes in risks posed by chiral PACs (ii) sorption of PACs to solids (e.g. sediments, sludge) and (iii) holistic evaluation of risks. Several groups of PACs will be studied: antimicrobials (high usage, development of antibiotic resistance), antidepressants (high usage, high potency), antineoplastics (high potency, high ecotoxicity), analgesics & anti-inflammatory drugs (high usage, undergo chiral inversion, high environmental impact) and hormones. 3. To undertake environmental risk assessment of PACs ERA will combine both exposure-driven and effect-driven research methods (at enantiomeric level). The exposure-driven approach will utilise chemical analysis to determine transformation kinetics of PACs and the formation of potentially toxic metabolites and transformation by-products. The effect-driven approach will utilise toxicity testing at different trophic levels to verify the development of toxicity of PACs (or a mixture of PACs and metabolites). The project will strengthen water research and has the potential to result in ground-breaking outcomes benefiting a wide range of user groups and to enhance the quality of life and health. The scientific community will benefit from advancements in knowledge of PACs in urban water. Policy makers and government agencies will be in a better position to make judgments regarding the necessity of restriction of PACs. The project will provide a valuable insight into key water treatment and environmental processes of interest to those working in the water industry and in the wider commercial/private environmental sector. It will evaluate the potential risks posed by PACs in urban water and will indicate if there is a necessity for new technological development. The project will be beneficial to society in general as it will contribute to the increase of security of water supply.