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

药理活性化合物的环境生命周期：新的（生物）分析方法和环境风险评估

• 批准号: NE/L009579/1
• 金额: $ 10.64万
• 依托单位: University of Bath
• 依托单位国家: 英国
• 项目类别: Training Grant
• 财政年份: 2014
• 资助国家: 英国
• 起止时间: 2014 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=NE%2FL009579%2F1
• 关键词: Environmental; life; cycle; pharmacologically; active

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.

药物活性化合物（PACs）是一种不受管制的环境微污染物。它们主要通过（未经）处理的污水、径流和污泥进入环境。它们具有生物活性、普遍存在性和持久性，并具有协同作用。仅在英国，一些最常用的pac每年就销售数百吨。令人惊讶的是，PACs的环境风险评估没有考虑其对映体形式（尽管已有关于PACs对人体的对映体依赖性毒性的知识，以沙利度胺为一个突出的例子）。这种方法可能导致对聚氯环己烷毒性的低估或高估、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，因为聚氯环己烷很可能以非外消旋形式存在于环境中。由于西方国家的人口老龄化和发展中国家消费水平的提高，未来pac的使用将会增加。城市用水及其使用者暴露于这些环境压力源的风险最高。随着人口的增长和气候的变化，这将影响清洁水的可及性，并迫使以水再利用为基础的新解决办法，了解pac的生命周期对于为子孙后代提供安全、可持续的水资源管理解决办法至关重要。设想对水中的pac进行更严格的管制。本项目将通过以下目标解决上述问题：开发新的分析方法来研究PACs的生命周期，这将包括基于对映体特异性和质谱的化学分析，结合不同营养水平的毒性测试的生物测定，以及暴露和效应驱动的ERA方法。为了了解城市水中pac的生命周期，重点将放在确定城市水中（手性）pac所带来的新问题和威胁，包括废水、洗澡水和河流集水区。将特别强调未充分研究的：(i)手性和可能的立体选择命运，这可能导致手性pac所带来的风险的变化；（ii） pac对固体（例如沉积物，污泥）的吸附；（iii）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，高效能），抗肿瘤药（高效能，高生态毒性），镇痛药和抗炎药（高使用率，发生手性反转，高环境影响）和激素。3. 对PACs进行环境风险评估将结合暴露驱动和效果驱动两种研究方法（在对映体水平）。暴露驱动的方法将利用化学分析来确定pac的转化动力学以及潜在毒性代谢物和转化副产物的形成。效应驱动的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）毒性的发展。该项目将加强水的研究，并有可能产生有利于广大用户群体的突破性成果，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。政策制定者和政府部门将能够更好地判断限制政治行动委员会的必要性。该项目将为在水工业和更广泛的商业/私营环境部门工作的人提供有关关键水处理和环境过程的宝贵见解。它将评估pac在城市水中所构成的潜在风险，并将指出是否有必要开发新技术。该项目将有利于整个社会，因为它将有助于提高供水的安全性。