Illicit drugs have been identified as emerging aquatic pollutants because of their widespread presence in freshwaters and potential toxicity towards aquatic organisms. Among illicit drug residues, cocaine (COC) and its main metabolites, namely benzoylecgonine (BE) and ecgonine methyl ester (EME), are commonly detected in freshwaters worldwide at concentration that can induce diverse adverse effects to non-target organisms. However, the information of toxicity and mechanisms of action (MoA) of these drugs, mainly of COC metabolites, to aquatic species is still fragmentary and inadequate. Thus, this study was aimed at investigating the toxicity of two concentrations (0.3 and 1.0 μg/L) of COC, BE and EME similar to those found in aquatic ecosystems on zebrafish (Danio rerio) embryos at 96 h post fertilization through a functional proteomics approach. Exposure to COC and both its metabolites significantly altered the protein profile of zebrafish embryos, modulating the expression of diverse proteins belonging to different functional classes, including cytoskeleton, eye constituents, lipid transport, lipid and energy metabolism, and stress response. Expression of vitellogenins and crystallins was modulated by COC and both its main metabolites, while only BE and EME altered proteins related to lipid and energy metabolism, as well as to oxidative stress response. Our data confirmed the potential toxicity of low concentrations of COC, BE and EME, and helped to shed light on their MoA on an aquatic vertebrate during early developmental period.

Assessment of the impact of pharmaceutical residues on living organisms is a very complex subject. Apart from taking into account the toxicity of individual compounds, environmental factors should also be taken into account. In this paper, attempts were made to assess the impact of coexisting inorganic ions and changes in pH on the toxicity of ten selected pharmaceuticals. Two bioassays were used to measure the estrogenic and androgenic effects (XenoScreen YES/YAS – Saccharomyces cerevisiae) and acute toxicity (Microtox® – Vibrio fischeri).The Microtox® test gave the most definitive outputs concerning the determination of interaction type between drugs and chemical species. Synergism was proven for almost all drugs and chemical species, and only two cases of antagonism were found. Significant drug/pH interactions were rare.Regarding the XenoScreen YES/YAS bioassay, when estrogenic and androgenic agonistic effects (YES+ and YAS+, respectively) were studied, many cases of well-expressed synergism for all inorganic ions with limited number of drugs (diazepam, fluoxetine, estrone, chloramphenicol for the YES+ test and diazepam, progesterone, androstenedione, and estrone for the YAS+ test) were found. Antagonism was also proven for the YES+ test, especially for diclofenac and androstenedione interacting with cations. On the other hand, the YES- and YAS- tests (estrogenic and androgenic, respectively, antagonistic effects) did not indicate cases of synergetic interaction except for the couples Br−/diazepam and NH4+/ketoprofen. Antagonistic drug/ion interactions were detected only with diclofenac and fluoxetine. It is interesting that well-expressed (antagonism or synergism) drug/pH interactions were rare.Both tests were found utilizable in performing studies on impact of ions/pH fluctuations on drugs mixtures' toxicity confirming in most cases synergic impact of parameters studied on toxicity. The approach proposed in the paper seems to be proven as a reliable tool in assessing impact of abiotic factors on toxicity and endocrine potential of complex mixtures of pharmaceuticals' mixtures.

Benzotriazole (BT) and 5-methyl-1H-benzotriazole (5-MeBT) are broadly used in industrial applications, such as anti-icing fluids and dishwashing detergent, and act as the primary building blocks for UV absorbers and photostabilizers. This study examined the occurrence of these two compounds in the environment and their unique photochemical behavior affecting photosensitizers and other micro-organic pollutants in aqueous environments. BT and 5-MeBT were detected in all river water samples from the major rivers in Taipei City in the concentration ranges of 147 to 1560 ng/L and 22 to 235 ng/L, respectively, and both compounds persisted through a conventional wastewater treatment plant. The direct photolysis half-lives of BT and 5-MeBT were 56.9 and 14.0 h, respectively. The half-life of photolysis in river water for BT was 44.2 h, whereas the half-life of 5-MeBT was 24.7 h. The long half-lives in real-water matrices resulted in their prevalence in water bodies, and these compounds were also found to minimize the photosensitizing ability of nitrate and dissolved organic matter (DOM) and increase the persistence of other micro-organic pollutant. With BT present, the production of ·OH in nitrate photolysis was reduced, the degradation of DOM under sunlight was hindered, and the photodegradation of pharmaceutical residues in surface water, such as methotrexate, was completely impeded. This study suggests that in cases in which BT and 5-MeBT are highly concentrated, the effectiveness of natural attenuation process, i.e., photodegradation, in the aqueous environment is diminished, which increases the persistence of the pollutants as well as the risk of exposure.

It is well known that pharmaceuticals are not completely removed by conventional activated sludge wastewater treatment plants. Hospital effluents are of major concern, as they present high concentrations of pharmaceutically active compounds. Despite this, these specific effluents are usually co-treated with domestic wastewaters. Separate treatment has been recommended. However, there is a lack of information concerning the efficiency of separate hospital wastewater treatment by activated sludge, especially on the removal of pharmaceuticals. In this context, this article presents the results of a 2-year monitoring of conventional parameters, surfactants, gadolinium, and 13 pharmaceuticals on the specific study site SIPIBEL. This site allows the characterization of urban and hospital wastewaters and their separate treatment using the same process. Flow proportional sampling, solid-phase extraction, and liquid chromatography coupled with tandem mass spectrometry were used in order to obtain accurate data and limits of quantification consistent with ultra-trace detection. Thanks to these consolidated data, an in-depth characterization of urban and hospital wastewaters was realized, as well as a comparison of treatment efficiency between both effluents. Higher concentrations of organic carbon, AOX, phosphates, gadolinium, paracetamol, ketoprofen, and antibiotics were observed in hospital wastewaters compared to urban wastewaters. Globally higher removals were observed in the hospital wastewater treatment plant, and some parameters were shown to be of high importance regarding removal efficiencies: hydraulic retention time, redox conditions, and ambient temperature. Eleven pharmaceuticals were still quantified at relevant concentrations in hospital and urban wastewaters after treatment (e.g., up to 1 μg/L for sulfamethoxazole). However, as the urban flow was about 37 times higher than the hospital flow, the hospital contribution appeared relatively low compared to domestic discharges. Thanks to the SIPIBEL site, data obtained from this 2-year program are useful to evaluate the relevance of separate hospital wastewater treatment.

A first review on occurrence and distribution of pharmaceuticals and personal care products (PPCPs) is presented. The literature survey conducted here was initiated by the current Assessment of the Arctic Monitoring and Assessment Programme (AMAP). This first review on the occurrence and environmental profile of PPCPs in the Arctic identified the presence of 110 related substances in the Arctic environment based on the reports from scientific publications, national and regional assessments and surveys, as well as academic research studies (i.e., PhD theses). PPCP residues were reported in virtually all environmental compartments from coastal seawater to high trophic level biota. For Arctic environments, domestic and municipal wastes as well as sewage are identified as primary release sources. However, the absence of modern waste water treatment plants (WWTPs), even in larger settlements in the Arctic, is resulting in relatively high release rates for selected PPCPs into the receiving Arctic (mainly) aquatic environment. Pharmaceuticals are designed with specific biochemical functions as a part of an integrated therapeutically procedure. This biochemical effect may cause unwanted environmental toxicological effects on non-target organisms when the compound is released into the environment. In the Arctic environments, pharmaceutical residues are released into low to very low ambient temperatures mainly into aqueous environments. Low biodegradability and, thus, prolonged residence time must be expected for the majority of the pharmaceuticals entering the aquatic system. The environmental toxicological consequence of the continuous PPCP release is, thus, expected to be different in the Arctic compared to the temperate regions of the globe. Exposure risks for Arctic human populations due to consumption of contaminated local fish and invertebrates or through exposure to resistant microbial communities cannot be excluded. However, the scientific results reported and summarized here, published in 23 relevant papers and reports (see Table S1 and following references), must still be considered as indication only. Comprehensive environmental studies on the fate, environmental toxicology, and distribution profiles of pharmaceuticals applied in high volumes and released into the Nordic environment under cold Northern climate conditions should be given high priority by national and international authorities.