Bioaccumulation/bioconcentration of pharmaceutical active compounds in aquatic organisms: Assessment and factors database

There is increasing evidence that the presence of certain pharmaceuticals in the environment leads to biota exposure and constitute a potential risk for ecosystems. Bioaccumulation is an essential focus of risk assessment to evaluate at what degree emerging contaminants are a hazard both to the environment and the individuals that inhabit it. The main goals of the present review are 1) to summarize and describe the research and factors that should be taken into account in the evaluation of bioaccumulation of pharmaceuticals in aquatic organisms; and 2) to provide a database and a critical review of the bioaccumulation/bioconcentration factors (BAF or BCF) of these compounds in organisms of different trophic levels. Most studies fall into one of two categories: laboratory-scale absorption and purification tests or field studies and, to a lesser extent, large-scale, semi-natural system tests. Although in the last 5 years there has been considerable progress in this field, especially in species of fish andmolluscs, research is still limited on other aquatic species like crustaceans or algae. This revision includes >230 bioconcentration factors (BCF) and >530 bioaccumulation factors (BAF), determined for 113 pharmaceuticals. The most commonly studied is the antidepressant group, followed by diclofenac and carbamazepine. There is currently no reported accumulation data on certain compounds, such as anti-cancer drugs. BCFs are highly influenced by experimental factors (notably the exposure level, time or temperature). Field BAFs are superior to laboratory BCFs, highlighting the importance of field studies for reliable assessments and in true environmental conditions. BAF data appears to be organ, species and compound-specific. The potential impact on food web transfer is also considered. Among different aquatic species, lower trophic levels and benthic organisms exhibit relatively higher uptake of these compounds.MCIN/AEI/10.13039/501100011033/ (grant: PID2020-117641RB-I00)Consejería de Economía, Conocimiento, EmpresasUniversidad (Spanish regional Government of Andalucia)European funding from ERDF 2014–2020 program (grants B.RNM.362.UGR20 and P20_00556

Bioaccumulation/bioconcentration of pharmaceutical active compounds in aquatic organisms: Assessment and factors database

There is increasing evidence that the presence of certain pharmaceuticals in the environment leads to biota exposure and constitute a potential risk for ecosystems. Bioaccumulation is an essential focus of risk assessment to evaluate at what degree emerging contaminants are a hazard both to the environment and the individuals that inhabit it. The main goals of the present review are 1) to summarize and describe the research and factors that should be taken into account in the evaluation of bioaccumulation of pharmaceuticals in aquatic organisms; and 2) to provide a database and a critical review of the bioaccumulation/bioconcentration factors (BAF or BCF) of these compounds in organisms of different trophic levels. Most studies fall into one of two categories: laboratory-scale absorption and purification tests or field studies and, to a lesser extent, large-scale, semi-natural system tests. Although in the last 5 years there has been considerable progress in this field, especially in species of fish and molluscs, research is still limited on other aquatic species like crustaceans or algae. This revision includes >230 bioconcentration factors (BCF) and >530 bioaccumulation factors (BAF), determined for 113 pharmaceuticals. The most commonly studied is the antidepressant group, followed by diclofenac and carbamazepine. There is currently no reported accumulation data on certain compounds, such as anti-cancer drugs. BCFs are highly influenced by experimental factors (notably the exposure level, time or temperature). Field BAFs are superior to laboratory BCFs, highlighting the importance of field studies for reliable assessments and in true environmental conditions. BAF data appears to be organ, species and compound-specific. The potential impact on food web transfer is also considered. Among different aquatic species, lower trophic levels and benthic organisms exhibit relatively higher uptake of these compounds

Contaminantes emergentes: determinación de fármacos antihipertensivos en aguas superficiales

Estudios recientes han mostrado la presencia de un amplio grupo de principios activos farmacológicos en el medioambiente procedentes principalmente de la descarga de estaciones depuradoras de aguas residuales. Entre ellos, son de especial interés aquellos empleados en el tratamiento de enfermedades crónicas, como los fármacos antihipertensivos, no sólo debido a su consumo continuado, sino además a su potente mecanismo de acción, lo que los hace especialmente peligrosos para el medioambiente. En este trabajo se ha optimizado y validado una metodología analítica, basada en la extracción en fase sólida y determinación mediante cromatografía líquida con detector de espectrometría de masas de triple cuadrupolo, para la determinación de los tres fármacos antihipertensivos más consumidos (irbesartán, telmisartán y valsartán) en aguas superficiales. Las recuperaciones obtenidas se situaron entre el 84 y el 101 %. La precisión, medida en unidades de desviación estándar relativa, fue inferior al 10 % y los límites de detección se situaron entre 0.24 y 2.01 ng/L.Recent studies have reported the presence of a broad spectrum of pharmaceutical compounds in several environmental compartments, where they mainly end up due to discharges of effluent wastewater. Among them, pharmaceuticals designed to treat chronic diseases, including hypertensive pharmaceuticals, are of special interest, not only due to its continued consumption, but also for their potent mechanism of action, which makes them especially dangerous for the environment. In this work, an analytical method, based on solid phase extraction and determination by liquid chromatography with triple quadrupole mass spectrometry detector, has been optimized and validated for the determination of three of the most consumed antihypertensive pharmaceuticals (irbesartan, telmisartan and valsartan) on surface water samples. The recoveries obtained were between 84 and 101%. Precision, expressed as relative standard deviation, was < 10%, and limits of detection were between 0.24 and 2.01 ng/L.Ministerio de Economía y Competitividad. Proyecto CGL2013-44402-

Exposición a agentes químicos: determinación de bisfenol A en cabello humano

El bisfenol A (BPA) es un monómero comúnmente empleado en la fabricación de plásticos, PVC, envases alimentarios, juguetes o papel térmico, siendo los alimentos que han estado en contacto con plásticos la principal vía de exposición humana. El carácter nocivo del BPA, que posee actividad como disruptor endocrino, ha sido objeto de numerosos estudios. La exposición humana a este contaminante se ha evaluado fundamentalmente mediante su determinación en matrices biológicas como plasma, suero y orina. Actualmente, los estudios de biomonitorización tienden hacia el uso de matrices no invasivas como pueden ser el cabello, uñas, orina o saliva. De entre las citadas matrices, el cabello parece ser una de las matrices de mayor interés ya que posee una gran estabilidad, proporciona información sobre exposición a corto y a largo plazo, desde semanas hasta meses o años en función de la longitud del cabello. Además, su contenido lipídico (2-4%) la convierte en una matriz de interés para la biomonitorización de compuestos lipofílicos. En este trabajo se presenta el desarrollo de un método analítico para la extracción y determinación de BPA de cabello humano. El tratamiento de la muestra consistió en tres etapas: lavado, hidrólisis y extracción. La determinación se realizó mediante cromatografía líquida de alta resolución acoplada a espectrometría de masas de triple cuadrupolo. El método se validó en términos de recuperación, precisión, linealidad y límites de detección y cuantificación. Se obtuvo una recuperación >77% y una precisión, expresada como desviación estándar relativa, <4%. Los límites de detección y cuantificación fueron de 1.8 ng g-1 y 6.1 ng g-1, respectivamente. Finalmente, se comprobó la aplicabilidad del método en muestras de cabello de seis individuos de la ciudad de Sevilla, donde se detectó la presencia de BPA en cinco de las seis muestras analizadas.Bisphenol A (BPA) is a chemical product common used as a component for the manufacture of plastics, PVC, food packaging, toys or thermal paper, being foods that have been in contact with plastics the main route of human exposure to BPA. The harmfulness of BPA, which has activity as endocrine disruptor , has been subject of numerous studies. The human exposure to this pollutant has been evaluated maninly through its determination in biological matrices such as plasma, serum and urine. Human hair seems to be one of the biological matrices of interest; it is a non-invasive matrix besides having great stability. In addition, its lipid content (2-4%) makes it an interesting matrix for biomonitoring lipophilic compounds. The aim of our study was to develop an analytical method for the extraction and determination of (BPA) in human hair. The treatment of the sample consisted on three stages: washing, hydrolysis and extraction. The analytical determination was carried out by liquid chromatography tandem mass spectrometry. The method was validated in terms of recovery, precision, linearity and limits of detection and quantification. A recovery >77% and precision, expressed as relative standard deviation, <4% was obtained. Limits of detection and quantification were 1.8 ng g-1 and 6.1 ng g-1, respectively. Finally, the applicability of the method was tested in hair samples of six volunteers from Seville city, where BPA was detected in five out of the six samples analyzed

Occurrence of pharmaceuticals and their metabolites in sewage sludge and soil: A review on their distribution and environmental risk assessment

The recycling and recovery of organic matter and nutrients from sewage sludge for application in agricultural soils is gaining interest, while the presence of pharmaceutically active compounds (PhACs) in this matrix may have a great impact on the environment and human health. The aim of this review paper is to outline recent research on the occurrence of PhACs and their metabolites in sewage treatment lines. A total of 32 classes of therapeutic groups including 180 PhACs and 45 metabolites have been included. In a first part, a summary of the analytical methods with a critical overview of the extraction and determination techniques, quality control issues and methodological challenges for their determination is included. Subsequently, the study gives a snapshot of the concentration levels and distribution patterns found in primary, secondary, digested (aerobically and anaerobically), dehydrated and composted sludge. Data have been systematically summarized and categorized according to matrix type, treatment processes available for PhAC degradation in sludge, and geographical areas. Our literature review showed that antimicrobials, antibiotics, non-steroidal anti-inflammatory drugs (NSAIDs), antidepressants and antidiabetics were the most abundant PhACs found in sludge matrices.Overall, attenuation of PhACs concentrations occurs during sludge stabilization, in particular during anaerobic digestion and composting. PhAC sorption onto sludge is strongly affected by the physicochemical properties, the sludge matrix and the operating and environmental conditions. Lastly, the paper discusses the impact of PhACs on sludge-amended agricultural land. The potential ecotoxicological risk associated with the presence of PhACs in amended soil is medium-low for most PhACs. The most critical compounds found in sludge-amended soil are ciprofloxacin, 17α-ethinylestradiol, 17β-estradiol, and triclocarban and triclosan.Spanish Ministry of Economy, Industry and Competitiveness Project CTM2017-82778-

Thermodynamic and Kinetic Investigation of the Adsorption and Desorption of Trimethoprim and Its Main Metabolites in Mediterranean Crop Soils

The adsorption–desorption processes of organic pollutants into the soil are one of the main factors influencing their potential environmental risks and distribution in the environment. In the present work, the adsorption–desorption behavior of an antibiotic, trimethoprim (TMP), and two of its main metabolites, 3-desmethyltrimethoprim (DM-TMP) and 4-hydroxytrimethoprim (OH-TMP), were assessed in three Mediterranean agricultural soils with different physicochemical characteristics. Results showed that the adsorption kinetic is performed in two steps: external sorption and intraparticle diffusion. The adsorptions of the studied compounds in soils were similar and fitted to the three models but were better fitted to a linear model. In the case of DM-TMP and OH-TMP, their adsorptions were positively correlated with the soil organic matter. In addition, desorption was higher in less organic matter soil (from 1.3 to 30.9%). Furthermore, the desorptions measured for the TMP metabolites were lower than those measured in the case of TMP (from 2.0 and 4.0% for OH-TMP and DM-TMP, respectively, to 9.0% for TMP).Ministerio de Ciencia e Innovación PID2020-117641RB-I0

Multiresidue method for the determination of critically and highly important classes of antibiotics and their metabolites in agricultural soils and sewage sludge

In this paper, a method is proposed for the determination of antibiotics classified by the World Health Organization as critically important (four macrolides and three quinolones) and highly important (one tetracycline, one diaminopyridine, and three sulfonamides) and eight of their metabolites. The method is based on ultrasound-assisted extraction, dispersive solid-phase extraction clean-up, and analytical determination by liquid chromatography–tandem mass spectrometry. Variables affecting each stage of the analytical method were thoroughly optimised. The method was validated for its application to sewage sludge from different treatment stages (non-treated sludge: primary and secondary sludge; and treated sludge: digested sludge and compost) and to agricultural soil. Limits of quantification were in the range of 0.03–7.50 ng g−1 dry weight (dw) for most of the compounds. Accuracy values were in the range of 70–102%. Precision was below 17%. The application of the method to real samples revealed that macrolides and fluoroquinolones were the antibiotic classes at the highest concentrations in all types of samples. The lowest concentrations of antibiotics were measured in compost (highest concentration: 27 ng g−1 dw, corresponding to norfloxacin) and soil samples (highest concentration: 93 ng g−1 dw, corresponding to a metabolite of clarithromycin). The proposed method is the first developed to date for the determination of multiclass antibiotics and their main metabolites in sludge from different treatment stages. The method can provide a useful tool for obtaining information about antibiotics in sewage sludge prior to its application to agricultural soils and in agricultural soils.Ministerio de Ciencia e Innovación PID2020-117641RB-I0

Evaluación de la contaminación atmosférica por PAH mediante biomonitorización

En este trabajo se ha optimizado y validado un método analítico para la determinación de los dieciséis hidrocarburos aromáticos policíclicos (PAHs) clasificados como contaminantes prioritarios por la Agencia de Protección Medioambiental de Estados Unidos, en hojas de naranjo amargo. El método propuesto se aplicó a la evaluación de la idoneidad de las hojas de naranjo como bioindicador de la contaminación urbana debido a estas sustancias. Se tomaron muestras en diez calles con diferente densidad de tráfico y en tres parques urbanos. Se detectaron catorce de los dieciséis PAHs. Las concentraciones medidas en las calles de alta densidad de tráfico fueron similares a las medidas en las calles de bajo tráfico. Las concentraciones medidas en las hojas tomadas en los parques fueron inferiores. Se emplearon las relaciones de diagnóstico para identificar y evaluar las posibles fuentes de emisión de estos contaminantes. Los resultados obtenidos señalan al tráfico como principal fuente de contaminación. Basándonos en estos resultados, la hoja de naranjo amargo parece ser un prometedor, además de económico, muestreador pasivo para la evaluación de la contaminación urbana debido a los PAHs.In this work an analytical method has been optimized a validated for the determination of the sixteen polycyclic aromatic hydrocarbons (PAHs) classified as priority pollutants by Unites States Environmental Protection Agency (EPA), on bitter orange leaves. The method has been applied to the evaluation of the suitability of leaves of bitter orange tree as a bioindicator of urban atmospheric pollution by these contaminants. Leaves of bitter orange trees were collected from 13 sampling points in Seville city (South of Spain). Sampling points were located in high-density traffic streets (n=5), in low-density traffic streets (n=5) and in urban parks (n=3). Fourteen of the sixteen PAH monitored were detected in bitter orange leaves. The concentrations in high-density traffic streets were similar to those in low-density traffic streets. Lower concentrations were found in leaves from parks. PAH diagnostic ratios were applied to identify and to assess pollution emission sources. Diagnostic ratios obtained were consistent with traffic emissions as the main source of PAH to urban air. Based on the obtained results, leaves from bitter orange trees appears to be a promising inexpensive passive sampler for the evaluation of urban pollution due to PAHs

Approach to the Dynamic of Carbamazepine and its Main Metabolites in Soil Contamination through the Reuse of Wastewater and Sewage Sludge

The release of pharmaceutically active compounds to the soils through the application of sewage sludge and the irrigation with wastewater, or even with surface water, is constant. The adsorption of these compounds onto the soil is one of the key factors affecting their fate in the environment and their potential environmental risks. In this work, the adsorption of carbamazepine (CBZ) and its metabolites, 3-hydroxy-carbamazepine (3OH-CBZ), carbamazepine-10,11-dihydro-10,11-epoxide (EP-CBZ), and 10,11-dihydro-10-hydroxycarbamazepine (10OH-CBZ), in three Mediterranean soils was evaluated using single-solute and four-solute experiments. The highest adsorptions were measured for 3OH-CBZ, followed by CBZ, EP-CBZ, and 10OH-CBZ, in that order. A high influence of the physicochemical characteristics of the compounds, pH, and soil characteristics in the adsorption of the studied compounds was observed and corroborated by the statistical analysis of the results. Moreover, a good fit was observed in the three isotherm models evaluated (linear, Freundlich, and Langmuir) in single-solute experiments (R2 > 0.90). However, a decrease of the measured adsorptions and a worse fit to the isotherm models were observed in the case of multiple-solute experiments. This could be mainly due to the competition established between the studied compounds for the active sites of the soils.Ministerio de Economía y Competitividad CTM2017-82778-

Biomonitoring parabens in dogs using fur sample analysis – Preliminary studies

Parabens are widely used in the food, cosmetics and pharmaceutical industry and are widespread in the environment. As endocrine disruptors, parabens have adverse effects on living organisms. However, knowledge of the exposure of domestic animals to parabens is extremely scarce. Therefore, this study assessed the exposure level of dogs to three parabens commonly used in industry (i.e. methylparaben - MeP, ethylparaben - EtP and propylparaben - PrP) using fur sample analysis in liquid chromatography-tandem mass spectrometry. The presence of parabens has been noted in the samples collected from all dogs included in the study (n = 30). Mean concentrations of MeP, EtP and PrP in the fur of dogs were 176 (relative standard deviation – RSD = 127.48%) ng/g dry weight (dw), 48.4 (RSD = 163.64%) ng/g dw and 79.8 ng/g dw (RSD = 151.89%), respectively. The highest concentrations were found for MeP (up to 1023 ng/g dw). Concentrations of MeP and EtP in males were statistically higher than those in females (p < 0.05). Statistically significantly higher concentration levels of PrP in young animals (up to three years old) were also found. This is the first study concerning the use of fur samples to evaluate the exposure of domestic animals to parabens. The results indicate that an analysis of the fur may be a useful tool of paraben biomonitoring in dogs. The presence of parabens in the canine fur also suggests that these substances may play a role in veterinary toxicology. However, many aspects connected with this issue are not clear and require further study