Mycotoxins in Rice Correlate with Other Contaminants? A Pilot Study of the Portuguese Scenario and Human Risk Assessment.

Rice is the second most important cereal crop and is vital for the diet of billions of people. However, its consumption can increase human exposure to chemical contaminants, namely mycotoxins and metalloids. Our goal was to evaluate the occurrence and human exposure of aflatoxin B1 (AFB1), ochratoxin A (OTA), zearalenone (ZEN), and inorganic arsenic (InAs) in 36 rice samples produced and commercialized in Portugal and evaluate their correlation. The analysis of mycotoxins involved ELISA, with limits of detection (LODs) of 0.8, 1 and 1.75 µg kg-1 for OTA, AFB1, and ZEN, respectively. InAs analysis was carried out by inductively coupled plasma mass spectrometry (ICP-MS; LOD = 3.3 µg kg-1). No sample showed contamination by OTA. AFB1 was present in 2 (4.8%) samples (1.96 and 2.20 µg kg-1), doubling the European maximum permitted level (MPL). Concerning ZEN, 88.89% of the rice samples presented levels above the LOD up to 14.25 µg kg-1 (average of 2.75 µg kg-1). Regarding InAs, every sample presented concentration values above the LOD up to 100.0 µg kg-1 (average of 35.3 µg kg-1), although none surpassed the MPL (200 µg kg-1). No correlation was observed between mycotoxins and InAs contamination. As for human exposure, only AFB1 surpassed the provisional maximum tolerable daily intake. Children were recognized as the most susceptible group.

Incidence of symptomatic gallstones after bariatric surgery: the impact of expectant management.

BACKGROUND: Bariatric surgery is the most effective treatment for sustained weight reduction and obesity-related comorbidities. The development of gallstones as a result of rapid weight loss is a well-known consequence of bariatric procedures. It remains unclear, if there is an increased risk of these gallstones becoming symptomatic. METHODS: A retrospective analysis of 505 consecutive patients submitted to either Roux-en-Y Gastric Bypass or Sleeve Gastrectomy between January and December 2019 was performed. The aim of our study was to determine the incidence of symptomatic cholelithiasis in asymptomatic patients with their gallbladder in situ after bariatric surgery and to identify potential risk factors for its development. RESULTS: Of the 505 patients included, 79 (15.6%) underwent either previous cholecystectomy. (n = 67, 84.8%) or concomitant cholecystectomy during bariatric surgery (n = 12, 15.2%). Among the remaining 426 (84.4%) patients, only 8 (1.9%) became symptomatic during the 12-month follow-up period. When compared with patients who remained asymptomatic, they had a higher median preoperative BMI (47.0 vs. 42.8, p = 0.046) and prevalence of cholelithiasis on preoperative ultrasound (62.5% vs. 10.7%, p = 0.001). Multivariate analysis revealed preoperative BMI and cholelithiasis on preoperative ultrasound as independent risk factors for symptomatic biliary disease (OR 1.187, 95%CI 1.025-1.376, p = 0.022 and OR 10.720, 95%CI 1.613-71.246, p = 0.014, respectively). CONCLUSION: Considering a low incidence of symptomatic gallstones after bariatric surgery, concomitant cholecystectomy should only be performed in symptomatic patients undergoing bariatric surgery. Preoperative factors, such as a higher BMI and positive ultrasound for cholelithiasis, may be related to the development of symptomatic gallstones.

Risk Assessment of Nine Coccidiostats in Commercial and Home-Raised Eggs.

The poultry industry, in order to prevent and control coccidiosis caused by Eimeria spp., widely uses coccidiostats as feed additives. The main objective of this study was to evaluate the presence of nine coccidiostats in 62 egg samples by UHPLC-MS/MS. Overall, detection frequency and average concentration were 90.3% (56/62) and 106.3 µg kg-1, respectively. Only diclazuril and nicarbazin were detected. Diclazuril, only found in home-raised eggs, showed an overall detection frequency of 8.1% (5/62), with average and maximum concentrations of 0.46 ± 1.90 µg kg-1 and 13.6 µg kg-1, respectively. Nicarbazin presented an overall higher frequency, 88.7% (55/62), with levels up to 744.8 µg kg-1. Additionally, four samples (6.5%) presented both nicarbazin and diclazuril. Home-raised egg samples (n = 28) showed a detection frequency of 89.3%, with nicarbazin found in more samples (85.7% vs. 17.9%) and at higher levels (266.3 ± 169.4 µg kg-1 vs. 0.91 ± 2.78 µg kg-1) when compared to diclazuril. In supermarket samples (n = 34), only nicarbazin was detected in 31 samples (91.1%), with an average of 167.6 ± 62.2 µg kg-1. Considering the average contamination scenario, consumers' health should not be adversely affected by egg consumption. In every scenario considered, children were the most vulnerable population group.

Occurrence of zearalenone in dairy farms - A study on the determinants of exposure and risk assessment.

The Azorean dairy industry is based on a semi-intensive model. Due to the few storage facilities and the large climatic fluctuations that characterize the Azores, the complete feed mixture (total mixed ration - TMR) is susceptible to the proliferation of a variety of fungi and mycotoxin contamination. Thus, chronic ingestion of these xenobiotics may lead to increased susceptibility to disease, loss of reproductive performance and, in the case of dairy cattle, decreased productivity and quality of milk produced. Since it is impossible to eliminate completely the presence of mycotoxins, it is essential to ensure the implementation of strategies to reduce their concentration in products intended for food and feed, as well as to monitor and control the levels present in food. This study aimed to evaluate the occurrence zearalenone (ZEA) in feed (TMR) in four dairy cattle farms on the Azorean Island of São Miguel and relate it to the occurrence of this mycotoxin in the milk produced, by associating several production and health indicators translated by the monthly milk contrast. To this end, the monthly milk contrast data, the determination of ZEA in the ingested feed and the (individual) milk samples from the four farms included in the study were used. Eighty-three (98.8%) of the milk samples under study had detectable ZEA levels (1.56 ± 1.36 µg/L), higher than reported in previous similar studies. Although ZEA concentration was not significantly associated with any production indicator analyzed (days in milk, age at calving, milk yield, protein content, butyrate content, somatic cell concentration and urea), it was found that the production regime and type of feed management is a major factor in the exposure of animals to high mycotoxin contents. Further studies are recommended to ensure continued monitoring and reduction of the risk associated with exposure of animals and humans to ZEA.

Risk Assessment of Nine Coccidiostats in Commercial and Home Raised Poultry.

For the first time, this paper aimed to evaluate nine ionophore and synthetic coccidiostat residues in poultry muscle samples, obtained from different production types, by solid-liquid extraction followed by liquid chromatography with tandem mass spectrometry (LC-MS/MS). The fully validated methodology was successfully applied to a total of 101 chicken and turkey samples obtained from canteens, supermarkets, and home productions in Portugal. Halofuginone, diclazuril, decoquinate, narasin, lasalocid, and salinomycin were detected in 20.8% of the samples. Home raised samples showed a greater frequency, 47.1%. The synthetic coccidiostats halofuginone, diclazuril, and decoquinate were found in averages of 0.7 µg kg-1,2.9 µg kg-1, and 3.7 µg kg-1, respectively, while averages of 1.2 µg kg-1, 1.6 µg kg-1, and 1.3 µg kg-1 were found regarding the ionophores narasin, lasalocid, and salinomycin. As for the risk assessment, values lower than 8.06% of the acceptable daily intake (ADI) were observed, indicating that exposure to coccidiostats through consumption of poultry meat does not represent risk to consumers.

A crise pandémica a vários ritmos / The pandemic crisis at various paces / La crisis de la pandemia a varios ritmos

18 meses após o início da pandemia global, vislumbram-se centelhas de esperança graças à descoberta da vacina e ao processo de vacinação,ambos realizados em tempo recorde, nos países mais desenvolvidos; simultaneamente, o horizonte encobre-se com as muitas sombras que constituem a iniquidade mundial no acesso à inoculação. E mesmo nos países mais desenvolvidos, sobretudo no plano individual, desenham-se sinais de preocupação como sejam as medidas eventualmente excessivas e desproporcionais no combate à pandemia, acompanhadas talvez por sentimentos de resignação em relação às várias proibições decretadas ou ingerências na vida privada e familiar o que, no seu conjunto, colocamà prova a tradição democrática e liberal ocidental.Importa levar a cabo uma reflexão bioética, que se caracterize pelo rigor da informação, por um reforçado respeito pela Declaração Universal dos Direitos Humanos e pelo cumprimento dos princípios e valores plasmados na Declaração Universal de Direitos Humanos e Bioética, da UNESCO, com vista a contribuir para os Objetivos de Desenvolvimento Sustentável das Nações Unidas.

18 months after the start of the global pandemic, sparks of hope can be glimpsed thanks to the discovery of the vaccine and the vaccination process, both conductedin record time, in the most developed countries; at the same time, the horizon is obscured by shadows that constitute the world's iniquity in access to inoculation. And even in the most developed countries, especially at the individual level, there are signs of concern such as the eventually excessive and disproportionate measures to combat the pandemic, perhaps accompanied by feelings of resignation in relation to the various prohibitions and interference in the right to private and family life,which, overall, puts a great test to the western democratic and liberal tradition. It is important to conducta bioethical reflection, characterized by the rigor of information, by a reinforced respect for the Universal Declaration of Human Rights and by the fulfillment of the principles and values enshrined in the UNESCO Universal Declaration of Human Rights and Bioethics, with a view to contributing for the United Nations Sustainable Development Goals.

A 18 meses del inicio de la pandemia mundial, se vislumbran chispas de esperanza gracias al descubrimiento de la vacuna y al proceso de vacunación, ambos realizados en tiempo récord, en los países más desarrollados; al mismo tiempo, el horizonte se oscurece por las muchas sombras que constituyen la iniquidad del mundo en el acceso a la inoculación. E incluso en los países más desarrollados, especialmente a nivel individual, hay señales de preocupación como las eventualmente excesivas y desproporcionadas medidas para combatir la pandemia, quizás acompañadas de sentimientos de resignación en relación a las diversas prohibiciones decretadas o injerencias en el ámbito de la vida privada y familiar que, en general, pone a prueba la tradición democrática y liberal occidental. Es importante realizar una reflexión bioética, caracterizada por el rigor de lainformación, por un reforzado respeto a la Declaración Universal de Derechos Humanos y por el cumplimiento de los principios y valores consagrados en la Declaración Universal de Derechos Humanos y Bioética de la UNESCO, con miras a contribuir a los Objetivos de Desarrollo Sostenible de Naciones Unidas.

Carmines (E120) in coloured yoghurts: a case-study contribution for human risk assessment.

Carmines (E120) are used worldwide as natural food colouring agents of animal origin, with a widespread application, including yoghurts. Despite being considered safe for human health, carmines are known to cause allergic reactions. Our goal was to evaluate the presence of carmines in different yoghurts with a label declaration of E120, purchased in Portugal, and, for the first time, to assess the human risk. The analytical methodology, recommended by JECFA, was based on acid hydrolysis of the samples followed by spectrophotometric UV-Vis analysis at 494 nm. This methodology allowed for a limit of quantification (LOQ) of 39.0 mg/kg and recovery rates higher than 97.7%. All the samples had carmines at levels above the LOQ, ranging between 43.8 and 193.8 mg/kg, with an average of 125.2 ± 34.5 mg/kg. In total, 8 (26.7%) samples exceeded the European Union (EU) maximum permitted level (MPL) established for carmines in this foodstuff, 150 mg/kg. Solid yoghurts presented higher average levels, 137.2 mg/kg, when compared to liquid samples, 107.2 mg/kg, with a significant statistical difference (p= 0.0236) being observed. No significant statistical difference was observed between white and private labels, whose average levels were very similar, 125.4 vs 125 mg/kg, respectively. Although some samples were above the allowable values, the estimated daily intake (EDI), designed for the different scenarios of different yoghurt types, did not exceed the established ADI, 5 mg/kg bw/day. According to the obtained results, carmine ingestion through the consumption of yoghurt poses low risk to the Portuguese consumers. However, children were the most vulnerable population group with a calculated risk value of up to 10% considering the mean content scenario. These first findings point out the need to reinforce surveillance programmes and monitoring studies, contributing to an increased awareness regarding carmine exposure, however it must be emphasised that yoghurt has evident nutritional benefits depending on a healthful consumer choice.

Urine biomonitoring of glyphosate in children: Exposure and risk assessment.

The use of glyphosate has been increasing over the years, making it one of the most consumed herbicides in the world. Although children are considered a vulnerable population, only four previous published studies determined glyphosate in the urine of non-occupationally exposed children. The paucity of epidemiological data and biomonitoring surveys are considered major gaps, that hinder the implementation of science driven policies in the protection of public health. The aim of the present study was to determine glyphosate in the urine of 41 Portuguese children (2-13 years old) and identify potential determinants of exposure. Glyphosate was detected in 95.1% of the samples (1.77 ± 0.86 µg/L), up to a maximum value of 4.35 µg/L. Glyphosate concentrations were higher in the urine of children aged 7-9 years, living near agricultural areas (<1 km), with a higher percentage of consumption of home-produced foods, and whose parents applied herbicides in the backyard. Risk assessment revealed an exposure representing 1-5.58% of the established Acceptable Daily Intake (ADI) of glyphosate (0.5 mg/kg bw/day). The results should be further analyzed considering the age of the participants, for which no adjusted ADI exists. This was the first published report of glyphosate exposure in the urine of Portuguese children.

Translation, cross-cultural adaptation and validation of the Brazilian Portuguese version of the Victorian Institute of Sports Assessment for Gluteal Tendinopathy patient reported-outcome measure (VISA-G.BR).

BACKGROUND: Different outcome measures can be used to assess pain and disability in individuals with Greater Trochanteric Pain Syndrome (GTPS), including the Victorian Institute of Sports Assessment for Gluteal Tendinopathy (VISA-G), Oswestry Disability Index (ODI), Patient Specific Functional Scale (PSFS) and Global Perceived Effect (GPE). OBJECTIVE: To translate, cross-culturally adapt and validate VISA-G to Brazilian Portuguese and to evaluate the measurement properties of the VISA-G.BR, ODI, GPE, and PSFS in individuals with GTPS. DESIGN: This is a longitudinal clinimetric study. METHODS: Sixty-eight individuals with GTPS participated in this study. The questionnaires VISA-G.BR, ODI, PSFS, and GPE were administered to participants at the initial assessment, 24-48 h and 30 days after the initial assessment. Internal consistency and construct validity for the VISA-G.BR were assessed. Reliability, agreement, ceiling and floor effect, and responsiveness were described for all instruments. RESULTS: The Cronbach Alpha for internal consistency value for VISA-G.BR was 0.65. The construct validity analysis showed a strong correlation value between ODI and VISA-G.BR (r = -0.77). The agreement analysis performed for all questionnaires showed standard error of measurement values ranging from 0.64 (PSFS) to 4.2 (VISA-G.BR). GPE scale had a floor effect. The responsiveness analysis performed for all questionnaires showed low values of effect size ranging from -0.07 to 0.3. CONCLUSION: The VISA-G.BR is a valid and reliable instrument to assess the disability of individuals with GTPS. The ODI and PSFS instruments can also be used in the evaluation of this population.

Global trends of epidemiological research in livestock tuberculosis for the last four decades.

Animal tuberculosis (TB) caused by Mycobacterium tuberculosis complex (MTC) bacteria remains as one of the most significant infectious diseases of livestock, despite decades of eradication programmes and research efforts, in an era where the livestock sector is among the most important and rapidly expanding commercial agricultural segments worldwide. This work provides a global overview of the spatial and temporal trends of reported scientific knowledge of TB in livestock, aiming to gain insights into research subtopics within the animal TB epidemiology domain and to highlight territorial inequalities regarding data reporting and research outputs over the years. To deliver such information, peer-reviewed reports of TB studies in livestock were retrieved from the Web of Science and Google Scholar, systematized and dissected. The validated data set contained 443 occurrence observations, covering the 1981-2020 period (39 years). We highlight a clear move towards transdisciplinary areas and the One Health approach, with a global temporal increase in publications combining livestock with wildlife and/or human components, which reflect the importance of non-prototypical hosts as key to understanding animal TB. It becomes evident that cattle is the main host across works from all continents; however, many regions remain poorly surveyed. TB research in livestock in low-/middle-income countries is markedly growing, reflecting changes in animal husbandry, but also mirroring the globalization era, with a marked increase in international collaboration and capacitation programmes for scientific and technological development. This review gives an overview of the most prolific continents, countries and research fields in animal TB epidemiology, clearly outlining knowledge gaps and key priority topics. The estimated growth trend of livestock production until 2050, particularly in Asia and Africa, in response to human population growth and animal-protein demand, will require further investment in early surveillance and adaptive research to accommodate the higher diversity of livestock species and MTC members and raising the possibility to fine-tune funding schemes.

Integrative Review of Managed Entry Agreements: Chances and Limitations.

BACKGROUND AND OBJECTIVE: Managed entry agreements (MEAs) consist of a set of instruments to reduce the uncertainty and the budget impact of new high-priced medicines; however, there are concerns. There is a need to critically appraise MEAs with their planned introduction in Brazil. Accordingly, the objective of this article is to identify and appraise key attributes and concerns with MEAs among payers and their advisers, with the findings providing critical considerations for Brazil and other high- and middle-income countries. METHODS: An integrative review approach was adopted. This involved a review of MEAs across countries. The review question was 'What are the health technology MEAs that have been applied around the world?' This review was supplemented with studies not retrieved in the search known to the senior-level co-authors including key South American markets. It also involved senior-level decision makers and advisers providing guidance on the potential advantages and disadvantages of MEAs and ways forward. RESULTS: Twenty-five studies were included in the review. Most MEAs included medicines (96.8%), focused on financial arrangements (43%) and included mostly antineoplastic medicines. Most countries kept key information confidential including discounts or had not published such data. Few details were found in the literature regarding South America. Our findings and inputs resulted in both advantages including reimbursement and disadvantages including concerns with data collection for outcome-based schemes. CONCLUSIONS: We are likely to see a growth in MEAs with the continual launch of new high-priced and often complex treatments, coupled with increasing demands on resources. Whilst outcome-based MEAs could be an important tool to improve access to new innovative medicines, there are critical issues to address. Comparing knowledge, experiences, and practices across countries is crucial to guide high- and middle-income countries when designing their future MEAs.

Selected Pharmaceuticals in Different Aquatic Compartments: Part II-Toxicity and Environmental Risk Assessment.

Potential risks associated with releases of human pharmaceuticals into the environment have become an increasingly important issue in environmental health. This concern has been driven by the widespread detection of pharmaceuticals in all aquatic compartments. Therefore, 22 pharmaceuticals, 6 metabolites and transformation products, belonging to 7 therapeutic groups, were selected to perform a review on their toxicity and environmental risk assessment (ERA) in different aquatic compartments, important issues to tackle the water framework directive (WFD). The toxicity data collected reported, with the exception of anxiolytics, at least one toxicity value for concentrations below 1 µg L-1. The results obtained for the ERA revealed risk quotients (RQs) higher than 1 in all the aquatic bodies and for the three trophic levels, algae, invertebrates and fish, posing ecotoxicological pressure in all of these compartments. The therapeutic groups with higher RQs were hormones, antiepileptics, anti-inflammatories and antibiotics. Unsurprisingly, RQs values were highest in wastewaters, however, less contaminated water bodies such as groundwaters still presented maximum values up to 91,150 regarding 17α-ethinylestradiol in fish. Overall, these results present an important input for setting prioritizing measures and sustainable strategies, minimizing their impact in the aquatic environment.

Ochratoxin A in Beers Marketed in Portugal: Occurrence and Human Risk Assessment.

Ochratoxin A (OTA) is produced by fungi present in several agricultural products with much relevance to food safety. Since this mycotoxin is widely found in cereals, beer has a potential contamination risk. Therefore, it was deemed essential to quantify, for the first time, the levels of OTA in beer, a cereal-based product that is marketed in Portugal, as well as to calculate the human estimated weekly intake (EWI) and risk assessment. A total of 85 samples were analyzed through immunoaffinity clean-up, followed by liquid chromatography-fluorescence detection (LC-FD). This analytical methodology allowed a limit of quantification (LOQ) of 0.43 µg/L. The results showed that 10.6% were contaminated at levels ranging between

Ochratoxin A and Portuguese children: Urine biomonitoring, intake estimation and risk assessment.

Ochratoxin A (OTA) is a mycotoxin detected worldwide. Urine biomonitoring is a more realistic and non-invasive way to assess exposure when compared to traditional methods based on food occurrence and consumption data. Few studies have investigated children's exposure to OTA, although it is a more susceptible population. Our main goal was the OTA biomonitoring in urine of Portuguese children to better characterize the health risk of this population. The validated analytical methodology was based on an immunoaffinity clean-up, followed by LC-FD. First morning samples were collected, between 2018 and 2019, from 85 healthy children, 41 boys and 44 girls, aging between 2 and 13 years old. Overall, from the 85 analysed samples 79 (92.94%) were found positive. The average OTA concentration level was of 0.020 ng/mL (29.41 ng/g of creatinine), with a maximum value of 0.052 ng/mL (114.45 ng/g of creatinine). No statistical differences were found between the OTA contamination levels, the anthropometric data and dietary habits considered. Depending on the excretion rate considered for the PDI calculation, the risk assessed for the average OTA contamination varied from 10% to 194%, indicating a potential concern. This is the first study regarding OTA exposure in Portuguese children, showing their clear exposure.

Ochratoxin A in the Portuguese Wine Market, Occurrence and Risk Assessment.

Ochratoxin A (OTA) is mainly found in cereals and cereal-based foodstuffs, but also in wine. Being one of the most consumed alcoholic drinks in Portugal and one of the main sources of human exposure to OTA, wine monitoring and exposure studies are essential. The analytical methodology consisted of the direct injection of the filtered samples into the liquid chromatograph, equipped with fluorescent detection (LC-FLD). Linearity was adequate, both in mobile phase and in matrix-matched solutions, with R2 values higher than 0.997. The limits of detection were 0.08 and 0.39 µg/L for white and red wine, respectively and recoveries were above 91.9%. One hundred wine samples acquired on the Portuguese market were investigated. In 5 samples the OTA was detected, with the red wine presenting higher frequency of contamination. Regarding the risk to human health it was observed that the estimated weekly intake (EWI) is considerably lower than the established tolerable weekly intake (TWI).

Risk assessment of fluoroquinolones from poultry muscle consumption: Comparing healthy adult and pre-school populations.

Antibiotics, especially fluoroquinolones (FQs), have been largely used in animal husbandry namely poultry production. Therefore, this study aimed to identify, quantify and estimate the daily intake for adult and 3-year-old populations of the FQs norfloxacin (NOR), ciprofloxacin (CIP) and enrofloxacin (ENR) through poultry muscle consumption. The results showed detection frequencies of 78% and 62% in supermarket and school canteen samples, respectively. Of the 182 analysed samples, 4 did not comply with ENR maximum residue level (MRL), and 9 were contaminated with NOR, not allowed as a veterinary medicine of food-producing animals. The highest estimated daily intake value was obtained for the 3-year-old population regarding the sum of ENR and CIP (0.46 µg kg-1 day-1); value substantially lower than the established acceptable daily intake (2.0 µg kg-1 day-1). Although the low risk found, the high detection frequencies support the apprehension of the different international organizations, towards the emergence of human bacterial resistances to FQs originated from poultry production.

The decision-making process in Brazil's ratification of the World Health Organization Framework Convention on Tobacco Control. / O processo decisório de ratificação da Convenção-Quadro para o Controle do Tabaco da Organização Mundial da Saúde no Brasil.

Tobacco consumption is a leading cause of various types of cancer and other tobacco-related diseases. In 2003, the World Health Assembly adopted the World Health Organization Framework Convention on Tobacco Control (WHO-FCTC), which aims to protect citizens from the health, social, environmental, and economic consequences of tobacco consumption and exposure to tobacco smoke. The Convention was to be ratified by the Member States of the WHO; in Brazil's case, ratification involved the National Congress, which held public hearings in the country's leading tobacco growing communities (municipalities). The current study analyzes this decision-making process according to the different interests, positions, and stakeholders. In methodological terms, this is a qualitative study based on document research, drawing primarily on the shorthand notes from the public hearings. We analyze the interests and arguments for and against ratification. The article shows that although preceded by intense debates, the final decision in favor of ratification was made by a limited group of government stakeholders, characterizing a decision-making process similar to a funnel.

Pharmacopollution and Household Waste Medicine (HWM): how reverse logistics is environmentally important to Brazil.

Pharmacopollution is a public health and environmental outcome of some active pharmaceutical ingredients (API) and endocrine-disrupting compounds (EDC) dispersed through water and/or soil. Its most important sources are the pharmaceutical industry, healthcare facilities (e.g., hospitals), livestock, aquaculture, and households (patients' excretion and littering). The last source is the focus of this article. Research questions are "What is the Household Waste Medicine (HWM) phenomenon?", "How HWM and pharmacopollution are related?", and "Why is a reverse logistic system necessary for HWM in Brazil?" This article followed the seven steps proposed by Rother (2007) for a systematic review based on the Cochrane Handbook and the National Health Service (NHS) Center for Reviews Dissemination (CDR) Report. The HWM phenomenon brings many environmental, public health, and, social challenges. The insufficient data is a real challenge to assessing potential human health risks and API concentrations. Therefore, the hazard of long-term exposure to low concentrations of pharmacopollutants and the combined effects of API mixtures is still uncertain. HWM are strongly related to pharmacopollution, as this review shows. The Brazilian HWM case is remarkable because it is the fourth pharmaceutical market (US$ 65,971 billion), with a wide number of private pharmacies and drugstores (3.3: 10,000 pharmacy/inhabitants), self-medication habits, and no national take-back program. The HWM generation is estimated in 56.6 g/per capita, or 10,800 t/year. The absence of a reverse logistics for HWM can lead to serious environmental and public health challenges. The sector agreement for HWM is currently under public consultation.

A critical evaluation of different parameters for estimating pharmaceutical exposure seeking an improved environmental risk assessment.

A critical evaluation of the European Medicines Agency (EMA) Guideline on Environmental Risk Assessment (ERA) was performed on 16 of Portugal's most consumed pharmaceuticals in wastewater effluents (WWEs), the main route for aquatic contamination. The predicted environmental concentrations (PECs) were formulated based on the Guideline, after incorporating several refinements. The best approach was selected by comparing the measured environmental concentrations (MECs) to the PECs in WWEs. Finally, risk was assessed by comparing PECs to predicted no-effect concentrations (PNECs). The results showed that the default value of the penetration factor (Fpen) used by the EMA (0.01) was surpassed and that national consumption and excretion data were the two most important parameters for PEC calculations. The risk quotient between PECs and PNECs was higher than 1 for 12 pharmaceuticals, indicating a risk to all three trophic levels of aquatic organisms (algae, daphnids and fish). To improve the current ERA framework, suggestions were made for incorporating consumption and excretion data, changing the default value of Fpen to 0.04 and adding a safety factor of 10. Moreover, this evaluation should be performed for pharmaceuticals already on the market, and future ERAs should incorporate a risk-benefit analysis, an important risk-management step.

SSRIs antidepressants in marine mussels from Atlantic coastal areas and human risk assessment.

Selective serotonin reuptake inhibitors (SSRIs) are among the most prescribed antidepressants nation and worldwide. Their presence in the aquatic environment is known, causing growing pressures in heavily populated coastal areas. For instance, disruption of invertebrate endocrine systems has been described. Since discrete seawater sampling may not be suitable to evaluate such environmental risk, we aimed to assess SSRIs and metabolites in wild Mytilus galloprovincialis, and assess risk to human health. A total of 1225 mussels were sampled during one year along the Portuguese Atlantic coast. Each freeze-dried pool of 25 specimens was analyzed, in duplicate, by solid phase extraction (SPE) and liquid chromatography with tandem mass spectrometry (LC-MSn). Approximately 70% of the samples were contaminated with at least one, and up to 4 from the 7 targeted compounds. The cumulative SSRIs and metabolites content in mussels ranged between 3.17 and 33.93ngg-1 dry weight, in a mean level of 14.68±9.69ngg-1. Norfluoxetine was the most recurring SSRI and the one with the highest mean concentration, 13.52ngg-1. Although some differences were found between different sampling periods and locations, those were not statistically significant (p>0.05) and no correlation was found between wet weight and mean contamination levels. Regarding risk to human health following consumption of these filter-feeders, when considering the average sample contamination of positive samples and the average Portuguese and European consumption, the ratio between the estimated daily intake (EDI) and the acceptable daily intake (ADI) ranged from 0.45 to 5.50%, and from 1.60 to 19.41%, respectively. Therefore, although the resultant risk is lower for the Portuguese consumer than for the average EU consumer, apparently, no appreciable risk to human health is expected.