Ecotoxicity Of Pharmaceuticals Research Articles

Micro(nano)plastics as a vector of pharmaceuticals in aquatic ecosystem: Historical review and future trends

Pharmaceuticals can be adsorbed by microplastics (MPs) and nanoplastics (NPs) in the aquatic environment. The interaction between these emerging pollutants can induce several effects on environmental and human health. Thus, the current study aimed to summarize and discuss the literature on the interactions and ecotoxicity of MP/NPs with pharmaceuticals in the aquatic environment. A scientometric and systematic review was conducted, and the data were summarized and discussed. The historical analysis indicated that the first article on the interactive effects between MP/NPs and pharmaceuticals was published in 2016. Scientific production is emerging in fourteen countries. Several types of MP/NPs (n = 13) and pharmaceuticals (n = 65) were studied, while the toxicity was evaluated in 30 articles (37.04 %). The interaction of MP/NPs with several pharmaceutical groups was confirmed, mainly antibiotics. In general, results confirmed the Trojan horse effects and indicated that MP/NPs changed the bioaccumulation and ecotoxicity of pharmaceuticals. The data reviewed demonstrated that future studies under environmentally relevant conditions are necessary for a better understanding of the mechanisms of action and toxicity of pharmaceuticals adsorbed to MP/NPs, especially mixtures with NPs. This study confirms that MP/NPs can alter the bioaccumulation and ecotoxicity of pharmaceuticals in aquatic organisms, indicating their potential toxicological risk.

Performance Comparison between the Specific and Baseline Prediction Models of Ecotoxicity for Pharmaceuticals: Is a Specific QSAR Model Inevitable?

Assessing the ecotoxicity of pharmaceuticals is of urgent need due to the recognition of their possible adverse effects on nontarget organisms in the aquatic environment. The reality of ecotoxicity data scarcity promotes the development and application of quantitative structure activity relationship (QSAR) models. In the present study, we aimed to clarify whether a QSAR model of ecotoxicity specifically for pharmaceuticals is needed considering that pharmaceuticals are a class of chemicals with complex structures, multiple functional groups, and reactive properties. To this end, we conducted a performance comparison of two previously developed and validated QSAR models specifically for pharmaceuticals with the commonly used narcosis toxicity prediction model, i.e., Ecological Structure Activity Relationship (ECOSAR), using a subset of pharmaceuticals produced in China that had not been included in the training datasets of QSAR models under consideration. A variety of statistical measures demonstrated that the pharmaceutical specific model outperformed ECOSAR, indicating the necessity of developing a specific QSAR model of ecotoxicity for the active pharmaceutical contaminants. ECOSAR, which was generally used to predict the baseline or the minimum toxicity of a compound, generally underestimated the ecotoxicity of the analyzed pharmaceuticals. This could possibly be because some pharmaceuticals can react through specific modes of action. Nonetheless, it should be noted that 95% prediction intervals spread over approximately four orders of magnitude for both tested QSAR models specifically for pharmaceuticals.

Occurrence, fate and environmental risk assessment of pharmaceutical compounds in soils amended with organic wastes

One of the most common ways of getting rid of sewage sludge is land spreading on agricultural fields as a source of nutrients and organic matter. However, sewage sludge may be contaminated with pharmaceuticals and can represent a cause of environmental contamination. The objectives of this study was (i) to determine the occurrence and the fate of pharmaceuticals such as antibiotics belonging to different classes: antibiotics (sulfadiazine, sulfamethoxazole, sulfamethoxypyridazine, ciprofloxacin, norfloxacin, tylosin, trimethoprim), anti-inflammatories (diclofenac) and anticonvulsants (carbamazepine) in the soil after spreading stabilized sludge (composted, limed and digested) and solid digestat, (ii) to evaluate agronomic benefits and (iii) to determine the potential ecotoxicological consequences of pharmaceutical compounds on the environment using a risk quotient approach. For this purpose, four different types of sludge samples, coming from the same treatment plant but submitted to different stabilization processes, were incorporated into three soils with different physicochemical characteristics and pedogenetic factors. The obtained results highlighted that the sludge treatments have a great influence on sludge contamination. Once applied onto the soil, the agronomic benefits will depend on the soil’s properties as well as the sludge’s characteristics. The risks concerning the ecotoxicity of pharmaceuticals, found in the sludge, are low but not insignificant.

Ecotoxicological Modeling, Ranking and Prioritization of Pharmaceuticals Using QSTR and i-QSTTR Approaches: Application of 2D and Fragment Based Descriptors.

There is a huge lack of experimental data on ecotoxicity of pharmaceuticals, while existing resources are insufficient to gather these data against all possible environmental endpoints. Computational tools such as quantitative structure-toxicity relationship (QSTR) can help us to a great extent to overcome this problem through filling of data gaps. In the current study, QSTR models have been developed for toxicity of 260 diverse pharmaceuticals on three different trophic level species namely algae, daphnia and fish, using partial least squares (PLS) regression approach with 2D descriptors selected through a genetic algorithm approach in order to study underlying chemical features responsible for the observed acute toxicity. The final obtained statistically reliable QSTR models were extensively validated following the OECD guidelines. Interspecies quantitative structure-toxicity-toxicity (QSTTR) models were also developed using genetic algorithm followed by multiple linear regression (GA-MLR) approach to check for the pattern of responses observed as we move across the hierarchy of genetics in different taxonomical class. The obtained interspecies models were finally utilized to fill the data gaps for 260 pharmaceuticals, where experimental data were missing for at least one of the endpoints. Finally, a prioritized list for 7106 existing drug like substances was prepared by predicting their acute toxicity using developed QSTR models.

Effect of Environmental Factors on the Ecotoxicity of Pharmaceuticals and Personal Care Products

In recent years, pharmaceuticals and personal care products (PPCPs) have emerged as significant pollutants of aquatic environments and have been detected at levels in the range of ng/L to μg/L. The source of PPCPs is humans and livestock that have been administered pharmaceuticals and subsequently excreted them via urine and feces. Unlike agricultural chemicals, the environmental dynamics of PPCPs is not examined and they would undergo structural transformation by environmental factors, e.g., sunlight, microorganisms and treatments in sewage treatment plants (STPs). Processing at STPs can remove various PPCPs; however, they are not removed completely and some persist in the effluents. In this study, we examined the degradation of 9 pharmaceuticals (acetaminophen, amiodarone, dapsone, dexamethasone, indomethacin, raloxifene, phenytoin, naproxen, and sulindac) by sunlight or UV, and investigated the ecotoxicological variation of degradation products. Sunlight (UVA and UVB) degraded most pharmaceuticals, except acetaminophen and phenytoin. Similar results were obtained with UVB and UVA. All the pharmaceuticals were photodegraded by UVC, which is used for sterilization in STPs. Ecotoxicity assay using the luminescent bacteria test (ISO11348) indicated that UVC irradiation increased the toxicity of acetaminophen and phenytoin significantly. The photodegraded product of acetaminophen was identified as 1-(2-amino-5-hydroxyphenyl)ethanone and that of phenytoin as benzophenone, and the authentic compounds showed high toxicity. Photodegraded products of PPCPs are a concern in ecotoxicology.

Effect of UV irradiation on the ecotoxicity of pharmaceuticals in aquatic environment

Effect of UV irradiation on the ecotoxicity of pharmaceuticals in aquatic environment

New indexes for compound prioritization and complexity quantification on environmental monitoring inventories

Lists of compounds resulting from environmental monitoring may be conveniently represented in a very general way using Pareto distributions, after ranking them on descending order according to their concentration or hazard quotient expressed as percentages, depending on whether the objective of the monitoring is focussed on mass load occurrence or risk assessment respectively. Ranked distributions are characterized using appropriate indexes, such as h (Hirsch), well known in other disciplines like bibliometry. Furthermore, to such ordered distributions, simple numerical power type equations relating rank order and occurrence probability can be fitted, following the so-called power or Zipf law. Both h indices and the characteristic power law exponents are interpreted as measures of complexity of the overall mixture. On the other hand, compounds included within the h index may be seen as the most relevant in the mixture, thus providing a reasonable indication of what is worth analyzing. These concepts have been applied, as case study, to the characterization of the pharmaceutical compounds found in the input and output streams of wastewater treatment plants. Whereas both the concentration load and ecotoxicity of pharmaceuticals in WWTPs obviously decrease in the output of the treatment (influent > effluent, sludge), complexity quantified using the proposed indexes does not follow the same trend, being this behaviour common to the three plants examined. The joint combination of h compounds of the three plants studied allowed optimizing the list of compounds to be analyzed, which must be considered the key ones for the scenario under study.

Ecotoxicity of selected pharmaceuticals of urban origin discharged to the Saint-Lawrence river (Québec, Canada): a review.

Twelve pharmaceuticals comprising anti-inflammatory agents (ibuprofen, naproxen), lipid regulators (bezafibrate, gemfibrozil), an anti-convulsant (carbamazepine), antibiotics (sulfamethoxazole, sulfapyridine, oxytetracycline, novobiocin, trimethoprim), a stimulant (caffeine) and a nicotine metabolite (cotinine) were identified in the final effluent of a major wastewater treatment plant (WWTP) based in the Montreal area (Quebec, Canada) discharging to the Saint-Lawrence River. Their measured concentrations ranged from 33 (carbamazepine) to 22187 ng/L (caffeine) in the Montreal WWTP effluent and from 58 (cotinine) to 85000 (ibuprofen) ng/L based on maximum concentrations found in other municipal effluents as reported elsewhere. In general, elimination of these drugs by wastewater treatment is purported to be fairly efficient for ibuprofen, naproxen, bezafibrate, gemfibrozil and caffeine. In contrast, carbamazepine, sulfamethoxazole, sulfapyridine and oxytetracycline appear more resistant to treatment whereas removal efficiency for novobiocin, trimethoprim and cotinine is either unclear or unknown. Despite the degree to which they are eliminated in WWTps, their presence in urban effluents discharging to surface waters is common. To estimate their potential risk to aquatic biota, we undertook acute/chronic toxicity testing with a suite of small-scale bioassays representing four taxonomic groups (bacteria, algae, invertebrates and fish) and complemented our results with those published in the literature. When all acute and chronic toxicity tests were combined, their toxicity responses spanned over five orders of magnitude. Barring caffeine and cotinine, all others are clearly recognized as toxic based on the EU-Directive 93/67/EEC classification, but their concentrations measured in WTTPs are too low to cause acute or chronic effects on an individual basis. Sulfamethoxazole, naproxen and ibuprofen, however, were found to produce toxic effects at concentrations that are <= one order of magnitude to those found in municipal effluents. In general, bioassay responses displayed a wide range of sensitivity that justifies continuing use of representative species within test batteries to properly appraise the toxic potential of pharmaceuticals. We also showed that exposure of Hydra attenuata to caffeine for 48 h induced xanthine oxidoreductase activity which may in turn lead to production of oxidative stress at concentrations close to those present in urban effluents. Future studies on the ecotoxicity of pharmaceuticals should therefore also seek to include appropriate biomarkers to assess possible adverse long-term effects to biota resulting from the biotransformation of drugs.