Development of an integrative approach to assess the toxic risk of complex mixture of pharmaceuticals and personal care products in aquatic environment

Abstract

Excessive use of chemicals has escalated concerns about aquatic contamination and its detrimental effects on health and ecosystems. Micropollutants, also known as emerging contaminants (ECs), have become significant water pollutants due to advancements in analytical techniques. Among ECs, pharmaceuticals and personal care products (PPCPs) have raised global concerns due to their presence in aquatic environments and potential adverse effects on organisms. Despite removal efforts, the complex structures and physicochemical properties of PPCPs make their complete removal challenging. Previous studies have mainly focused on acute toxic effects, but these PPCPs tend to exert chronic adverse effects on aquatic organisms. Moreover, PPCPs are continuously and simultaneously present in the environment as complex mixtures, and the ecotoxicity of such mixtures typically exceeds the toxic effects of individual components. Traditional toxicity evaluation methods are inadequate for assessing the environmental risk of PPCPs, and a universally accepted prioritization method is yet to be established. Therefore, this study aims to develop optimized approaches for prioritizing individual PPCPs and their mixtures. This thesis presents a comprehensive investigation into the occurrence, prioritization, and risk assessment of individual and mixed PPCPs in the aquatic environment of Korea. Firstly, a year-long monitoring campaign was conducted from April 2020 to March 2021, during which 137 targeted PPCPs were analyzed in four major Korean rivers using LC-HRMS. This process focused on detecting a wide range of physicochemicals of PPCPs. Consequently, 120 PPCPs were detected in these rivers, with the most prevalent being metformin, cetirizine, dimethyl phthalate, caffeine, and carbamazepine. These chemicals exhibited high concentrations and detection frequencies, reflecting their widespread usage and pseudo-persistence in the environment. The prioritization of the detected 120 PPCPs was based on scores calculated using the 95 percent upper confidence limits (UCL95) of the mean measured environmental concentration (MEC) and detection frequency. The study also investigated spatial trends and seasonal variability in PPCP contamination across these major rivers. Notably, the Yeongsan River had the highest mean summed concentrations of PPCPs, while the Han River showed the highest absolute value when considering the total load based on the monthly flow rate. The findings underline the importance of considering both spatial and temporal variations when assessing the impact of PPCP pollution in aquatic environments. Next, a risk-based prioritization was conducted on the 120 detected PPCPs, which exhibited spatial variation. The MEC was computed using exposure data from the monitoring study, while the Predicted No-Effect Concentration (PNEC) was derived from a database using a tiered approach. The highest Risk Quotient (RQ) for the PPCPs was observed for clotrimazole, indicating a significant risk to aquatic organisms. After considering the frequency of PNEC exceedance, RQ values for most compounds were found to be lower than their original values. However, clotrimazole still exhibited the highest RQ value, and several other compounds exceeded the RQ threshold. A comparison between risk-based and exposure-based prioritization revealed a significant difference in the priority lists. Lastly, a predictive tiered approach was used to conduct a risk assessment of the 120 PPCP mixtures detected during the monitoring campaign. Out of 120 target PPCPs, metformin was detected in the highest concentration. However, concentration alone did not reflect ecological risk; dichlorvos, an insecticide, exhibited high toxicity to aquatic organisms with a low PNEC despite being present in lower concentrations. HI were calculated using the lowest PNECs derived from all available aquatic organisms and the PNEC derived from three trophic levels and HI values were 24.02 and 11.37, respectively. Focusing on three trophic levels may underestimate the ecological risk of PPCPs by excluding highly sensitive species like insects, which can be particularly vulnerable due to shared functionalities between PPCPs and pesticides. The comparison between MCR, HI, and RQmax indicates that the risk in the mixture is primarily due to individual PPCPs, especially clotrimazole. This led to the subsequent calculation of RQSTU, and with an RQSTU value of 6.45 for PPCP mixtures in three trophic levels, fish emerged as the most sensitive group in assessing ecological risks. The study further implements a Tier 2 assessment by incorporating the concept of IA and classification based on MOA to refine the ecological risk assessment. Inconsistencies in traditional MOA classification tools highlighted the need for an alternative approach, and the study suggests using the Fish Plasma Model assumption for a more accurate representation. The study provides crucial insights into the risks posed by PPCPs to aquatic ecosystems. The results emphasize the need for robust risk assessment methods and more focused studies for the development of effective risk management strategies.