Towards 'one substance - one assessment': An analysis of EU chemical registration and aquatic risk assessment frameworks.

With the Green Deal the EU aims to achieve a circular economy, restore biodiversity and reduce environmental pollution. As a part of the Green Deal a 'one-substance one-assessment' (OS-OA) approach for chemicals has been proposed. The registration and risk assessment of chemicals on the European market is currently fragmented across different legal frameworks, dependent on the chemical's use. In this review, we analysed the five main European chemical registration frameworks and their risk assessment procedures for the freshwater environment, covering 1) medicines for human use, 2) veterinary medicines, 3) pesticides, 4) biocides and 5) industrial chemicals. Overall, the function of the current frameworks is similar, but important differences exist between the frameworks' environmental protection goals and risk assessment strategies. These differences result in inconsistent assessment outcomes for similar chemicals. Chemicals are also registered under multiple frameworks due to their multiple uses, and chemicals which are not approved under one framework are in some instances allowed on the market under other frameworks. In contrast, an OS-OA will require a uniform hazard assessment between all different frameworks. In addition, we show that across frameworks the industrial chemicals are the least hazardous for the freshwater environment (median PNEC of 2.60E-2 mg/L), whilst biocides are the most toxic following current regulatory assessment schemes (median PNEC of 1.82E-4 mg/L). Finally, in order to facilitate a successful move towards a OS-OA approach we recommend a) harmonisation of environmental protection goals and risk assessment strategies, b) that emission, use and production data should be made publicly available and that data sharing becomes a priority, and c) an alignment of the criteria used to classify problematic substances.

Review: ecotoxicity of organic and organo-metallic antifouling co-biocides and implications for environmental hazard and risk assessments in aquatic ecosystems.

Hazard assessments of Irgarol 1051, diuron, 2-(thiocyanomethylthio)benzothiazole (TCMTB), dichloro-octylisothiazolin (DCOIT), chlorothalonil, dichlofluanid, thiram, zinc pyrithione, copper pyrithione, triphenylborane pyridine (TPBP), capsaicin, nonivamide, tralopyril and medetomidine were performed to establish robust environmental quality standards (EQS), based on predicted no effect concentrations (PNECs). Microalgae, zooplankton, fish and amphibians were the most sensitive ecological groups to all the antifoulants evaluated, especially in the early life stages. No differences were identified between freshwater and seawater species. The use of toxicity tests with non-standard species is encouraged because they increase the datasets, allowing EQS to be derived from probabilistic-based PNECs whilst reducing uncertainties. The global ban of tributyltin (TBT) has been heralded as a major environmental success; however, substitute antifoulants may also pose risks to aquatic ecosystems. Environmental risk assessments (ERAs) have driven decision-makings for regulating antifouling products, but in many countries there is still a lack of regulation of antifouling biocides which should be addressed.

Pancreatic Neuroendocrine Neoplasms: Basic Biology, Current Treatment Strategies and Prospects for the Future.

Pancreatic neuroendocrine neoplasms (pNENs) are rare tumors accounting for only 1%-2% of all pancreatic tumors. pNENs are pathologically heterogeneous and are categorized into three groups (neuroendocrine tumor: NET G1, NET G2; and neuroendocrine carcinoma: NEC) on the basis of the Ki-67 proliferation index and the mitotic count according to the 2010 World Health Organization (WHO) classification of gastroenteropancreatic NENs. NEC in this classification includes both histologically well-differentiated and poorly differentiated subtypes, and modification of the WHO 2010 classification is under discussion based on genetic and clinical data. Genomic analysis has revealed NETs G1/G2 have genetic alterations in chromatin remodeling genes such as MEN1, DAXX and ATRX, whereas NECs have an inactivation of TP53 and RB1, and these data suggest that different treatment approaches would be required for NET G1/G2 and NEC. While there are promising molecular targeted drugs, such as everolimus or sunitinib, for advanced NET G1/G2, treatment stratification based on appropriate predictive and prognostic biomarkers is becoming an important issue. The clinical outcome of NEC is still dismal, and a more detailed understanding of the genetic background together with preclinical studies to develop new agents, including those already under investigation for small cell lung cancer (SCLC), will be needed to improve the prognosis.

Immunophenotypic and prognostic analysis of PAX8 and TTF-1 expressions in neuroendocrine carcinomas of thymic origin: A comparative study with their pulmonary counterparts.

OBJECTIVES: To investigate the immunoreactivity of TTF-1 and PAX8 in neuroendocrine carcinoma of thymic (TNEC) and pulmonary origins (PNEC), and whether their immunophenotyping could be used to distinguish between NEC of the two sites, as well as prognosis of patients with TNEC. METHODS: Twenty-two cases of TNEC and 20 cases of PNEC were selected for immunohistochemical analysis using PAX8 and TTF-1. Clinical data and follow-up information were obtained for survival analyses. RESULTS: TTF-1 immunoreactivity was seen in 19 PNEC cases (95%) and 13 TNEC cases (59.1%). PAX8 was negative in all pulmonary tumors while positive in 19 thymic cases (86.4%). TTF-1 positivity was associated with high sensitivity but low specificity for PNEC, and adding PAX8 negativity significantly increased the specificity. PAX8 positivity alone showed essentially 100% specificity and 86.4% sensitivity for TNEC. Survival analysis showed lung metastasis as a significant prognostic factor in TNEC. CONCLUSION: Our study demonstrated that TTF-1/PAX8 immunophenotyping may be helpful for differential diagnosis of NECs of pulmonary and thymic origins. TTF-1+/PAX8- immunophenotyping showed high specificity for PNECs, while PAX8+ alone showed a good diagnostic accuracy for TNEC. Lung metastasis was a predictive factor that associated with survival of TNEC patients. J. Surg. Oncol. 2016;114:697-702. © 2016 Wiley Periodicals, Inc.

Occurrence and risk assessment of antibiotics in river water in Hong Kong.

The occurrence and distribution of six typical antibiotics in the main rivers of Hong Kong were investigated using high-performance liquid chromatography electrospray ionization tandem mass spectrometry (HPLC-ES-MS/MS). The results revealed that the antibiotics were widely distributed in the area studied. Of the target antibiotics, ofloxacin was the most frequently detected in the rivers, with a detection rate of 69.6% and a median concentration of 0.7ng/L. Sulfadimidine (n.d-580.4ng/L) and doxycycline (n.d-82.2ng/L), with detection frequencies of 65.2% and 30.4%, respectively, were found at the same level as in rivers in North America, Spain, France, Australia, and in the Yangtze and Pearl Rivers of China, while the other target antibiotics were found at lower levels. According to the ratios of the measured environmental concentration to the predicted no-effect concentration, ofloxacin and doxycycline could present a medium to low ecological risk to algae, while sulfonamides posed no obvious ecological risk to the relevant aquatic organisms (algae, Daphnia magna, and fish). A high detection rate of antibiotics occurred in densely populated areas, revealing that population activities might be greatly contributing to the increasing levels of antibiotics in the area. Thus, the residues of antibiotics present in the waters of Hong Kong need to be closely monitored.

Risk screening of pharmaceutical compounds in Romanian aquatic environment.

The aquatic environment is under increased pressure by pharmaceutically active compounds (PhACs) due to anthropogenic activities. In spite of being found at very low concentrations (ng/L to µg/L) in the environment, PhACs represent a real danger to aquatic ecosystems due to their bioaccumulation and long-term effects. In this study, the presence in the aquatic environment of six non-steroidal anti-inflammatory drugs (ibuprofen, diclofenac, acetaminophen, naproxen, indomethacin, and ketoprofen), caffeine, and carbamazepine were monitored. Moreover, their aquatic risk and ecotoxicity by three biological models were evaluated. The monitoring studies performed in Romania showed that all studied PhACs were naturally present at concentrations >0.01 µg/L, pointing out the necessity to perform further toxicity tests for environmental risk assessment. The toxicity studies were carried out on aquatic organisms or bacteria and they indicated, for most of the tested PhACs, an insignificant or low toxicity effects: lethal concentrations (LC50) on fish Cyprinus carpio ranged from 42.60 mg/L to more than 100 mg/L; effective concentrations (EC50) on planktonic crustacean Daphnia magna ranged from 11.02 mg/L to more than 100 mg/L; inhibitory concentrations (IC50)/microbial toxic concentrations (MTC) on Vibrio fischeri and other bacterial strains ranged from 7.02 mg/L to more than 100 mg/L. The PhAC aquatic risk was assessed by using the ratio between measured environmental concentration (MEC) and predicted no effect concentration (PNEC) calculated for each type of organism. The average of quotient risks (RQs) revealed that the presence of these compounds in Romania's aquatic environment induced a lower or moderate aquatic risk.

Approach on environmental risk assessment of nanosilver released from textiles.

Based on the increased utilization of nanosilver (silver nanomaterials=AgNM) as antibacterial agent, there is the strong need to assess the potential environmental implication associated with its new application areas. In this study an exemplary environmental risk assessment (ERA) of AgNM applied in textiles was performed. Environmental exposure scenarios (via municipal sewage treatment plant (STP)) with wastewater supply from domestic homes) were developed for three different types of textiles equipped with AgNM. Based on these scenarios predicted environmental concentrations (PECs) were deduced for STPs and for the environmental compartments surface water, sediment as well as soil. These PECs were related to PNECs (predicted no effect concentrations). PNECs were deduced from results of ecotoxicity tests of a selected AgNM (NM-300K). Data on ecotoxicology were derived from various tests with activated sludge, cyanobacteria, algae, daphnids, fish, duckweed, macrophytes, chironomids, earthworms, terrestrial plants as well as soil microorganisms. Emission data for the AgNM NM-300K from textiles were derived from washing experiments. The performed ERA was based on the specifications defined in the ECHA Guidances on information requirements and chemical safety assessment. Based on the chosen scenarios and preconditions, no environmental risk of the AgNM NM-300K released from textiles was detected. Under conservative assumptions a risk quotient for surface water close to 1 indicated that the aquatic compartment may be affected by an increased emission of AgNM to the environment due to the high sensitivity of aquatic organisms to silver. Based on the successful retention of AgNM in the sewage sludge and the still ongoing continual application of sewage sludge on farmland it is recommended to introduce a threshold for total silver content in sewage sludge into the respective regulations. Regarding potential risk mitigation measures, it is emphasized to preferably directly introduce AgNM into the textile fiber since this will strongly minimize the release of AgNM during washing. If this is not possible due to technical limitations or other reasons, the introduction of a threshold level controlling the release of AgNM from textiles is suggested. It has to be noted that this study is a case study which is only valid for the investigated NM-300K and its potential application in textiles.

Thymic stromal lymphopoietin activity is increased in nasal polyps of patients with chronic rhinosinusitis.

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is associated with TH2-dominant inflammation. Thymic stromal lymphopoietin (TSLP) is a cytokine that triggers dendritic cell-mediated TH2 inflammatory responses and that enhances IL-1-dependent TH2 cytokine production in mast cells. Although increased TSLP mRNA levels have been found in nasal polyps (NPs), expression of TSLP protein and its function in patients with chronic rhinosinusitis (CRS) have not been fully explored. OBJECTIVES: The objective of this study was to investigate the role of TSLP in patients with CRS. METHODS: We investigated the presence and stability of TSLP protein in NPs using ELISA and Western blotting and investigated the function of TSLP in nasal tissue extracts with a bioassay based on activation of human mast cells. RESULTS: Although TSLP mRNA levels were significantly increased in NP tissue from patients with CRSwNP compared with uncinate tissue from patients with CRS or control subjects, TSLP protein was significantly decreased in NP tissue, as detected by using the commercial ELISA kit. We found that recombinant TSLP was time-dependently degraded by NP extracts, and this degradation was completely inhibited by a protease inhibitor cocktail, suggesting that TSLP is sensitive to tissue proteases. Interestingly, NP extract-treated TSLP had higher activity in mast cells, although the amount of full-length TSLP was reduced up to 85%. NP extracts significantly enhanced IL-1ß-dependent IL-5 production in mast cells compared with uncinate tissue homogenates, and responses were significantly inhibited by anti-TSLP, suggesting that NPs contain biologically relevant levels of TSLP activity. CONCLUSION: TSLP and its metabolic products might play an important role in the inflammation seen in patients with CRSwNP.

Impact of Prophylactic Antibiotic Use in Ornamental Fish Tanks on Microbial Communities and Pathogen Selection in Carriage Water in Hong Kong Retail Shops.

Antibiotics are routinely added to ornamental fish tanks for treating bacterial infection or as a prophylactic measure. However, the overuse or subtherapeutical application of antibiotics could potentially facilitate the selection of antibiotic resistance in bacteria, yet no studies have investigated antibiotic use in the retail ornamental fish sector and its impact on microbial communities. The present study analyzed the concentrations of twenty antibiotics in the carriage water (which also originates from fish tanks in retail shops) collected monthly from ten local ornamental fish shops over a duration of three months. The antibiotic concentrations were correlated with the sequenced microbial community composition, and the risk of resistance selection in bacteria was assessed. Results revealed that the detected concentrations of tetracyclines were the highest among samples, followed by fluoroquinolones and macrolides. The concentrations of oxytetracycline (44.3 to 2,262,064.2 ng L-1) detected across three months demonstrated a high risk for resistance selection at most of the sampled shops. Zoonotic pathogens (species of Rhodococcus, Legionella, and Citrobacter) were positively correlated with the concentrations of oxytetracycline, tetracycline, chlortetracycline, and enrofloxacin. This suggests that antibiotic use in retail shops may increase the likelihood of selecting for zoonotic pathogens. These findings shed light on the potential for ornamental fish retail shops to create a favorable environment for the selection of pathogens with antibiotics, thereby highlighting the urgent need for enhanced antibiotic stewardship within the industry.

Ecotoxicological, ecological, and human health risks of total carbohydrates and some inorganic pollutants on the Nile Delta region along the Egyptian Mediterranean Coast.

This is one of few studies dealing with the potential impact of total carbohydrates (TCHO), and some inorganic pollutants (F, B, As, V, Se) on human health. Additionally, the latter pollutants toxicological and ecological effects on the Egyptian Mediterranean Coast, especially, the Nile Delta region, were investigated. Both F (0.18 ± 0.09 mg/g) and As (2.47 ± 5.39 µg/g) were of lower concentrations compared to previous reports. Values of all ecological and ecotoxicity indices, particularly, the risk quotient (RQ), showed that arsenic had the most adverse biological effects on three trophic levels (algae, invertebrates, and fish). Children and adults non-carcinogenic hazard index (HI) values were <1, revealing that sediments in the studied area would pose no risk to humans. However, arsenic carcinogenic risk (CR) values exceeded the maximum permissible limits, implying risk to children and adults. These findings could anticipate toxic impacts of polluted effluents on the Nile Delta region.

A Review on Fluoroquinolones' Toxicity to Freshwater Organisms and a Risk Assessment.

Fluoroquinolones (FQs) have achieved significant success in both human and veterinary medicine. However, regulatory authorities have recommended limiting their use, firstly because they can have disabling side effects; secondly, because of the need to limit the spread of antibiotic resistance. This review addresses another concerning consequence of the excessive use of FQs: the freshwater environments contamination and the impact on non-target organisms. Here, an overview of the highest concentrations found in Europe, Asia, and the USA is provided, the sensitivity of various taxa is presented through a comparison of the lowest EC50s from about a hundred acute toxicity tests, and primary mechanisms of FQ toxicity are described. A risk assessment is conducted based on the estimation of the Predicted No Effect Concentration (PNEC). This is calculated traditionally and, in a more contemporary manner, by constructing a normalized Species Sensitivity Distribution curve. The lowest individual HC5 (6.52 µg L-1) was obtained for levofloxacin, followed by ciprofloxacin (7.51 µg L-1), sarafloxacin and clinafloxacin (12.23 µg L-1), and ofloxacin (17.12 µg L-1). By comparing the calculated PNEC with detected concentrations, it is evident that the risk cannot be denied: the potential impact of FQs on freshwater ecosystems is a further reason to minimize their use.

A comparative study of surfactant distribution and fate (western and eastern) Egyptian Mediterranean coasts focusing on its environmental toxicity.

One of the most difficult-to-manage new contaminants constantly released into the environment is linear alkylbenzene sulphonate (LAS), an anionic surfactant. Significant volumes of LAS are received by the Mediterranean coast of Egypt. The current study is a comprehensive assessment of the environmental fate of the LAS 1505 km off the Mediterranean coast of Egypt in the fall of 2023 in order to track its geographic spread and eventual demise in the water column. Critical analysis of LAS revealed that it is vertically distributed in various ways according to sources, uses, production amounts, and salinity levels. The vertical variation of LAS can be explained by its amphiphilic structure. A significant increase in surfactant concentration (>300 µg/L) was recorded in 66% and 43% of the total samples, ranging from 301.128 to 455.36 and from 304.556 to 486.135 for the western and eastern sides along the Egyptian Mediterranean coast, respectively. Evaluation of the average acute and chronic risk quotient (RQ) along the investigated locations revealed that fish were the most susceptible to LAS in both long and short exposure periods. The presented results also indicated significant LAS toxicity to three trophic levels (RQ values > 1). LAS toxicity to marine organisms was greater in the western than in eastern coastal regions according to acute and chronic mixture risk characterization ratios (RCRmix). The three trophic levels in the study area had the following order of acute relative contribution (RC) to LAS toxicity: fish > invertebrates > algae. The ANOVA test results showed that in both the western and eastern regions, LAS varied significantly (p < 0.05) with salinity (1.04E-60 and 5.44E-42) and depth (6.02E-65 and 1.59E-47), respectively. In addition, a significant difference was observed using the ANOVA test between the eastern and western regions of the Egyptian Mediterranean coast.

Impact of land development along the western Mediterranean coast of Egypt regarding surfactant sources, interfering elements and ecotoxicity.

The effect of recent land development of the western side of the Egyptian Mediterranean coast on the fates, behaviors, interactions, and ecotoxicology of surfactant (LAS), F, Br, B, Ca, Mg, and P was studied. Samples of seawater and sediments were collected from 15 stations at different depths representing, 5 perpendicular sectors. Elevated levels of LAS were identified in seawater columns in the El-Hamam (467.3 ± 220.8 µg/L) and El-Dabaa (480.0 ± 314.1 µg/L) stations. LAS homologue in sediment was in the range of 0.013-0.024, 0.042-0.184, 0.086-0.402, and 0.025-0.058 µg/g for C10, C11, C12, and C13, respectively. Studied parameters showed mixture risk characterization ratios RCRmix > 1 for algae, invertebrates, and fish in seawater and sediments, except for P, which showed low risk (RCRmix ≤ 1) in sediment. Acute relative contribution (RC) of LAS reflected that fish were the most sensitive species (RCFish = 48.5), followed by algae (RCAlgae = 44.4) and invertebrates (RCInvert = 7.1).

Toxicity threshold and ecological risk of nitrate in rivers based on endocrine-disrupting effects: A case study in the Luan River basin, China.

Nitrate, as a crucial nutrient, is consistently targeted for controlling water eutrophication globally. However, there is considerable evidence suggesting that nitrate has endocrine-disrupting potential on aquatic organisms. In this study, the sensitivity of various adverse effects to nitrate nitrogen (nitrate-N) was compared, and a toxicity threshold based on endocrine-disrupting effects was derived. The spatiotemporal variations of nitrate-N concentrations in the Luan River basin were investigated, and the associated aquatic ecological risks were evaluated using a comprehensive approach. The results showed that reproduction and development were the most sensitive endpoints to nitrate, and their distribution exhibited significant differences compared to behavior. The derived threshold based on endocrine-disrupting effects was 0.65 mgL-1, providing adequate protection for the aquatic ecosystem. In the Luan River basin, the mean nitrate-N concentrations during winter (4.4 mgL-1) were significantly higher than those observed in spring (0.7 mgL-1) and summer (1.2 mgL-1). Tributary inputs had an important influence on the spatial characteristics of nitrate-N in the mainstream, primarily due to agricultural and population-related contamination. The risk quotients (RQ) during winter, summer, and spring were evaluated as 6.7, 1.8, and 1.1, respectively, and the frequency of exposure concentrations exceeding the threshold was 100 %, 64.3 %, and 42.5 %, respectively. At the ecosystem level, nitrate posed intermediate risks to aquatic organisms during winter and summer in the Luan River basin and at the national scale in China. We suggest that nitrate pollution control should not solely focus on water eutrophication but also consider the endocrine disruptive effect on aquatic animals.

Ecological impact of pharmaceutical pollutants and options of river health improvements - A risk analysis-based approach.

Pharmaceuticals are one of the emerging pollutants (EPs) in river waters across the world. Due to their toxic effects on aquatic organisms, they have drawn the global attention of the scientific community concerned with river ecosystems. This paper reviews the existing occurrence data for various pharmaceutical pollutants (PPs) reported in river waters in some part of the world and their ecological impacts. Using algae, macroinvertebrates (MI), and fish as biotic indicator groups in water to reflect river health conditions, an attempt has been made to assess the ecological risk due to the presence of PPs in the water environment. After ascertaining the predicted no-effect concentration (PNEC) of PPs for selected groups of aquatic organisms, the risk quotient (RQ) is estimated based on their measured environmental concentration (MEC). When MEC > PNEC and RQ > 1 for any of the biotic indicator, ecologically it is 'high risk' condition. The determination of PNEC uses a minimum assessment factor (AF) of 10 due to uncertainty in data over the no observed effect level (NOEL) or lowest observed effect level (LOEL). Accordingly, MEC 10 times higher than PNEC, (RQ = 10) represents a threshold risk concentration (RCT) beyond which adverse effects may start showing observable manifestations. In the present study, a new classification system of 'high risk' conditions for RQ = 1-10 has been proposed, starting from 'moderately high' to 'severely high'. For RQ > 10, the ecological condition of the river is considered 'impaired'. For river health assessment, in the present study, the whole range of physico-chemical characteristics of river water quality has been divided into three groups based on their ease of measurement and frequency of monitoring. Dissolved oxygen related parameters (DORPs), nutrients (NTs), and EPs. PPs represent EPs in this study. A framework for calculating separate indicator group score (IGS) and the overall river health index (RHI) has been developed to predict indicator group condition (IGC) and river health condition (RHC), respectively. Color-coded hexagonal pictorial forms representing IGC and RHC provide a direct visible perception of the existing aquatic environment and a scientific basis for prioritization of corrective measures in terms of treatment technology selection for river health improvements. The analyses indicate that many rivers across the world are under 'high risk' conditions due to PPs having MEC > PNEC and RQ > 1. Up to RCT, (where RQ = 10), the 'high risk' condition varies from 'moderately high' to 'severely high'. In many instances, RQ is found much more higher than 10, indicating that the ecological condition of river may be considered as 'impaired'. Algae is the most frequently affected group of biotic indicators, followed by MI and fish. A review of treatment methods for selection of appropriate technology to reduce the pollution load, especially PPs from the wastewater streams has been summarized. It appears that constructed wetlands (CWs) are at present the most suitable nature-based solutions, particularly for the developing economies of the world, to reduce the concentrations of PPs within limits to minimize the ecological impacts of pharmaceutical compounds on biotic indicators and restore the river health condition. Some suggestive design guidelines for the CWs have also been presented to initiate the process.

Ecological risks of polycyclic musk in soils irrigated with reclaimed municipal wastewater.

HHCB (1,3,4,6,7,8-hexahydro-4,6,6,7,8-hexamethylcyclopenta-c-2-benzopyrane) and AHTN (7-acetyl-1,1,3,4,4,6-hexamethyl-1,2,3,4-tetrahydronaphthalene) are found in reclaimed municipal wastewater. They may accumulate in soils receiving long-term application of reclaimed water thus adversely impact the soil biota. We evaluated the extent of their accumulation in receiving soils using HYDRUS-1D based on reclaimed municipal wastewater irrigation data at a public park in Beijing. The potential for ecological harms were assessed according to tested and reported outcomes of acute toxicity tests using wheat (Triticum aetivum L), earthworm (Eisenia fetida) and springtail (Bourletiella hortensis) as target organisms. Results of comparison among EC50 values from wheat, earthworm and springtail showed the EC50 value for root elongation inhibition of wheat germination was the least. Based on the least EC50, predicted no effect concentration in soils were 290 and 320ng /g for HHCB and ATHN, respectively. Comparable results from simulation to experimental and field investigating date validated the using of HYDRUS-1D in the work. Results of risk prediction showed it would take 243 and 666 years for HHCB and AHTN accumulated in soils at current irrigation practice to reach the levels for the resulting risk characterization ratios (RCRs) to cause potential ecosystem harms.

Ranking of concern, based on environmental indexes, for pharmaceutical and personal care products: an application to the Spanish case.

A wide range of Pharmaceuticals and Personal Care Products (PPCPs) are present in the environment, and many of their adverse effects are unknown. The emergence of new compounds or changes in regulations have led to dynamical studies of occurrence, impact and treatment, which consider geographical areas and trends in consumption and innovation in the pharmaceutical industry. A Quantitative study of Structure-Activity Relationship ((Q)SAR) was performed to assess the possible adverse effects of ninety six PPCPs and metabolites with negligible experimental data and establish a ranking of concern, which was supported by the EPA EPI Suite™ interface. The environmental and toxicological indexes, the persistence (P), the bioaccumulation (B), the toxicity (T) (extensive) and the occurrence in Spanish aquatic environments (O) (intensive) were evaluated. The most hazardous characteristics in the largest number of compounds were generated by the P index, followed by the T and B indexes. A high number of metabolites has a concern score equal to or greater than their parent compounds. Three PBT and OPBT rankings of concern were proposed using the total and partial ranking method (supported by a Hasse diagram) by the Decision Analysis by Ranking Techniques (DART) tool, which was recently recommended by the European Commission. An analysis of the sensibility of the relative weights of these indexes has been conducted. Hormones, antidepressants (and their metabolites), blood lipid regulators and all of the personal care products considered in this study were at the highest levels of risk according to the PBT and OPBT total rankings. Furthermore, when the OPBT partial ranking was performed, X-ray contrast media, H2 blockers and some antibiotics were included at the highest level of concern. It is important to improve and incorporate useful indexes for the predicted environmental impact of PPCPs and metabolites and thus focus experimental analysis on the compounds that require urgent attention.

Spatial and temporal trends of 64 pesticides and their removal from Australian wastewater.

Pesticides are necessary for the control of pest plant, fungi and insect species. After application, they may find their way into waste streams, such as municipal sewage, where their spatio-temporal distribution has not been well characterised. To further understand the spatio-temporal distribution and to evaluate potential sources and fate after treatment, 64 pesticides were analysed in matched influents and effluents of 22 wastewater treatment plants (WWTPs) from across Australia. The pesticides consisted of 30 herbicides and 8 herbicide metabolites or transformation products, 16 insecticides and 10 fungicides. The samples were 1084 24-hr composite samples pooled into 113 samples. Pools represented two influent and one effluent pools at each of 22 sites in 2019, as well as two pools per year from 2009 to 2021 for an 11-year long-term temporal trend at a subset of two locations. The total population served by the 22 sites was equivalent to ~41 % of the Australian population. Of the 64 pesticides, 25 were detected in influent, with highest influent concentrations up to 100 µg/L and effluent concentrations up to 16 µg/L for the herbicide 2,4-D. The total mass of pesticides was extrapolated to Australia, suggesting ~33 t of the targeted pesticides entered WWTP influent annually nation-wide, with 14 t emitted into effluents annually. Long-term trends varied by analyte and for carbendazim decreases over time, may be related to restrictions in use. Risk quotients (RQs) were calculated for 14 analytes in the effluent. 35 % had an RQ above one, indicating a potential environmental risk. Fipronil had the highest RQ (49) at Site 6. The population-normalized mass loads of pesticides were site-specific, and in some cases correlated with land use attributes suggestive of point sources. This reflects a need to better characterise sources to enable prevention, or possible pre-treatment of pesticide-containing wastewater entering municipal sewage streams.