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

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.