The Bright and Dark Sides of Herbal Infusions: Assessment of Antioxidant Capacity and Determination of Tropane Alkaloids.

Herbal infusions are highly popular beverages consumed daily due to their health benefits and antioxidant properties. However, the presence of plant toxins, such as tropane alkaloids, constitutes a recent health concern for herbal infusions. This work presents an optimized and validated methodology based on the QuEChERS (Quick, Easy, Cheap, Effective, Rugged, and Safe) extraction procedure followed by Ultra-High Performance Liquid Chromatography combined with Time-of-Flight Mass Spectrometry (UHPLC-ToF-MS) for the determination of tropane alkaloids (atropine, scopolamine, anisodamine, and homatropine) in herbal infusions, in accordance with criteria established by Commission Recommendation EU No. 2015/976. One of the seventeen samples was contaminated with atropine, exceeding the current European regulation regarding tropane alkaloids. In addition, this study evaluated the antioxidant capacity of common herbal infusions available on Portuguese markets, indicating the high antioxidant capacity of yerba mate (Ilex paraguariensis), lemon balm (Melissa officinalis), and peppermint (Mentha x piperita).

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.

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.

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.

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

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 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.

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.

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.

Environmental impact of pharmaceuticals from Portuguese wastewaters: geographical and seasonal occurrence, removal and risk assessment.

The occurrence, fate, geographical and seasonal influence and environmental risk assessment of eleven of the most consumed pharmaceuticals in Portugal were studied in wastewater treatment plants (WWTPs) influents and (WWI) and effluents (WWE). WWI and WWE samples, from two sampling campaigns (spring and summer), in 2013, were evaluated in 15 different WWTPs across the country, by solid phase extraction (SPE) and liquid chromatography coupled with tandem mass detection (LC-MS-MS). Lipid regulators were the most frequently found in WWI and WWE (184.1 and 22.3mg/day/1000 inhab., respectively), followed by anti-inflammatories (1339.4 and 15.0mg/day/1000 inhab., respectively), and antibiotics (330.7 and 68.6 mg/day/1000 inhab., respectively). Anxiolytics were the least detected with 3.3 and 3.4 mg/day/1000 inhab. in WWI and WWE, respectively. The mass loads, both in WWI and WWE, were higher in summer than those found during the spring season, being remarkable the high values registered in a region where population triplicates in this time of the year. The mean removal efficiency achieved was of 94.5%, nonetheless, between the different therapeutic groups, as well as within each group, important variations in removal were observed, going from not eliminated to 100%. In the summer higher efficiencies were observed regarding lipid regulators and antibiotics. Furthermore, an important outcome was the evaluation, by means of risk quotients (RQs), of the potential ecotoxicological risk posed by the selected pharmaceuticals to different aquatic organisms, exposed to the effluents studied. Ciprofloxacin, bezafibrate, gemfibrozil, simvastatin and diclofenac showed RQs higher than one, being expected that these pharmaceuticals might pose a threat to the three trophic levels (algae, daphnids and fish) evaluated. These results highlight the importance of these monitoring studies, as required by the Directive 2013/39/EU, in order to minimize their aquatic environmental contamination and support future prioritization measures.

A one-year follow-up analysis of antidepressants in Portuguese wastewaters: occurrence and fate, seasonal influence, and risk assessment.

The occurrence, fate, seasonal influence and environmental risk assessment of four selective serotonin re-uptake inhibitors (SSRIs) antidepressants, citalopram, fluoxetine, paroxetine and sertraline, were studied in 15 different wastewater treatment plants (WWTPs) across Portugal. Influent and effluent samples from four sampling campaigns, in 2013, were extracted through Oasis HLB cartridges, and quantified through liquid chromatography with tandem mass spectrometry (LC-MSn).Results showed that citalopram was the SSRI most frequently found, both in influents and in effluents, with mean mass loads ranging between 14.56 and 9.51 mg/day/1000 inhabitants, respectively. Fluoxetine and sertraline were only detected in influent samples, in lower mean mass loads (14.60 and 1.36 mg/day/1000 inhab., respectively), whereas paroxetine was found in influent and effluent samples (12.61 and 18.90 mg/day/1000 inhab., respectively). WWTPs were not capable of completely removing these pharmaceuticals; nonetheless, the mean removal efficiency was 82.24%. Removal efficiency was lower in winter (74.21%), summer (72.02%), and autumn (81.19%), when compared to spring (100%). Our results translate the variations in SSRI prescription and use between the five Portuguese regions in study. Influent contaminated samples were found in WWTPs from Lisbon, Alentejo, Center and North (28.25, 19.01, 16.55 and 6.98 mg/day/1000 inhab., respectively). In the Algarve region no contaminated samples were found. A seasonal pattern in the presence of SSRIs in influent wastewaters was observed. The SSRIs mass loads in influent wastewaters were higher in autumn, followed by spring, winter, and summer. Finally, the potential ecotoxicological risk posed by SSRIs to different trophic levels of aquatic organisms, exposed to the effluent wastewaters studied was evaluated by means of risk quotients (RQ). Citalopram and paroxetine, the only SSRIs found in these samples, presented RQ lower than 1. According to the results, algae appeared to be the most sensitive followed by fish and daphnids.

Risk assessment of additives through soft drinks and nectars consumption on Portuguese population: a 2010 survey.

This study investigated whether the Portuguese population is at risk of exceeding ADI levels for acesulfame-K, saccharin, aspartame, caffeine, benzoic and sorbic acid through an assessment of dietary intake of additives and specific consumption of four types of beverages, traditional soft drinks and soft drinks based on mineral waters, energetic drinks, and nectars. The highest mean levels of additives were found for caffeine in energetic drinks, 293.5mg/L, for saccharin in traditional soft drinks, 18.4 mg/L, for acesulfame-K and aspartame in nectars, with 88.2 and 97.8 mg/L, respectively, for benzoic acid in traditional soft drinks, 125.7 mg/L, and for sorbic acid in soft drinks based on mineral water, 166.5 mg/L. Traditional soft drinks presented the highest acceptable daily intake percentages (ADIs%) for acesulfame-K, aspartame, benzoic and sorbic acid and similar value for saccharin (0.5%) when compared with soft drinks based on mineral water, 0.7%, 0.08%, 7.3%, and 1.92% versus 0.2%, 0.053%, 0.6%, and 0.28%, respectively. However for saccharin the highest percentage of ADI was obtained for nectars, 0.9%, in comparison with both types of soft drinks, 0.5%. Therefore, it is concluded that the Portuguese population is not at risk of exceeding the established ADIs for the studied additives.

Assessment of the in-vivo drug release from pellets film-coated with a dispersion of high amylose starch and ethylcellulose for potential colon delivery.

OBJECTIVES: The aim of this study was to test the ability of a colon targeting system comprising pellets film-coated with a dispersion of high amylose starch (Hylon VII) and ethylcellulose (Surelease) (1 : 2 w/w) to deliver a model drug (5-aminosalicylic acid; 5-ASA) in vivo into the colon of rabbits. An uncoated pellet formulation was used as a control. METHODS: Six New Zealand female rabbits, approximately 2 kg, were randomly divided into two groups. Pellet formulations containing 50 mg/kg of 5-ASA were filled into hard gelatin capsules size 4, and were administered orally using a cannula. The rabbits were fasted for 12 h before, and throughout, the study but had free access to water. Blood samples were collected, through a catheter inserted into the marginal vein of the ear, at pre-determined times and the plasma analysed by a validated HPLC method with fluorescence detection. RESULTS: Analysis of the 5-ASA plasma levels following administration of the uncoated pellets showed a C(max) of 2.38 +/- 0.49 microg/ml at 2 h post administration confirming that this system released the drug at an unspecific site, most likely in the rabbits' stomach and proximal small intestine. On the other hand, the coated formulation showed a delayed drug absorption (C(max) 0.22 +/- 0.19 microg/ml and t(max) of 8 h), suggesting that the coating is able to prevent drug release in the stomach and small intestine, but allowing drug release in the colon. The coated pellets were retrieved from the rabbits' faeces after the 24-h study. They had a drug content of < 40%, suggesting that the film-coating had been digested by the bacterial amylases of the colon and the drug was released specifically in the colon of the rabbits. CONCLUSIONS: Results from this study showed that the proposed drug delivery system has the potential to deliver drugs specifically into the colon.

Regulatory approach on environmental risk assessment. Risk management recommendations, reasonable and prudent alternatives.

Current knowledge shows that residues of human medicinal products at trace quantities are widespread in aquatic systems. The sewage treatment plants are pointed out as the major source discharge of these compounds on the environment. In this context, it has been worldwide recognised that the environmental impact of medicinal products have to be evaluated, according to recent EU legislation and regulatory guidance. The strategy of the global risk assessment includes primarily a pre-screening based on the estimation of exposure concentrations of drugs in the wastewater. The present paper addresses the decision-maker frontier of the ecologically relevant endpoints. Risk management recommendation and reasonable and prudent alternatives are discussed to minimise the possible environmental impact.

Assessment of pesticide residues in honey samples from portugal and Spain.

Fifty samples of honey collected from local markets of Portugal and Spain during year 2002 were analyzed for 42 organochlorine, carbamate, and organophosphorus pesticide residues. An analytical procedure based on solid-phase extraction with octadecyl sorbent followed by gas chromatography-mass spectrometry (GC-MS), for organochlorines, and by liquid chromatography-atmospheric pressure chemical ionization-mass spectrometry (LC-APCI-MS), for organophosphorus and carbamates, has been developed. Recoveries of spiked samples ranged from 73 to 98%, except for dimethoate (40%), with relative standard deviations from 3 to16% in terms of repeatability, and from 6 to 19% in terms of reproducibility. Limits of quantification were from 0.003 to 0.1 mg kg(-)(1). Most of the pesticides found in honey were organochlorines. Among them, gamma-HCH was the most frequently detected in 50% of the samples, followed by HCB in 32% of the samples and the other isomers of HCH (alpha-HCH and beta-HCH) in 28 and 26% of the samples, respectively. Residues of DDT and their metabolites were detected in 20% of the samples. Of the studied carbamates, both methiocarb and carbofuran were detected in 10% of the samples, pirimicarb in 4% and carbaryl in 2%. The only organophosphorus pesticides found were heptenophos in 16%, methidathion in 4%, and parathion methyl in 2% of honey samples. Results indicate that Portuguese honeys were more contaminated than Spanish ones. However, honey consumers of both countries should not be concerned about the amounts of pesticide residues found in honeys available on the market.