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In the European Union, the Chemicals Strategy for Sustainability (CSS) highlights the need to enhance the identification and assessment of substances of concern while reducing animal testing, thus fostering the development and use of New Approach Methodologies (NAMs) such as in silico, in vitro and in chemico. In the United States, the Tox21 strategy aims at shifting toxicological assessments away from traditional animal studies towards target-specific, mechanism-based and biological observations mainly obtained by using NAMs. Many other jurisdictions around the world are also increasing the use of NAMs. Hence, the provision of dedicated non-animal toxicological data and reporting formats as a basis for chemical risk assessment is necessary. Harmonising data reporting is crucial when aiming at re-using and sharing data for chemical risk assessment across jurisdictions. The OECD has developed a series of OECD Harmonised Templates (OHT), which are standard data formats designed for reporting information used for the risk assessment of chemicals relevant to their intrinsic properties, including effects on human health (e.g., toxicokinetics, skin sensitisation, repeated dose toxicity) and the environment (e.g., toxicity to test species and wildlife, biodegradation in soil, metabolism of residues in crops). The objective of this paper is to demonstrate the applicability of the OHT standard format for reporting information under various chemical risk assessment regimes, and to provide users with practical guidance on the use of OHT 201, in particular to report test results on intermediate effects and mechanistic information.
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Organização para a Cooperação e Desenvolvimento Econômico , Pele , Humanos , Medição de Risco/métodosRESUMO
The use of Plant Protection Products (PPPs) is leading to high exposure scenarios with potential risk to soil organisms, including non-target species. Assessment of the effects of PPPs on non-target organisms is one of the most important components of environmental risk assessment (ERA) since they play crucial functions in ecosystems, being main driving forces in different soil processes. As part of the framework, EFSA is proposing the use of the ecosystem services approach for setting specific protection goals. In fact, the services provided by soil organisms can be impacted by the misuse of PPPs in agroecosystems. The aim of this work was to assess PPPs potential risk upon ecosystem services along European soils, considering impacts on earthworms and collembola. Four well-known (2 insecticides-esfenvalerate and cyclaniliprole- and 2 fungicides - picoxystrobin and fenamidone-) worst case application (highest recommended application) were studied; exploring approaches for linked observed effects with impacts on ecosystem services, accounting for their mode of action (MoA), predicted exposure, time-course effects in Eisenia fetida and Folsomia sp. and landscape variability. The selected fungicides exerted more effects than insecticides on E. fetida, whereas few effects were reported for both pesticides regarding Folsomia sp. The most impacted ecosystem services after PPP application to crops appeared to be habitat provision, soil formation and retention, nutrient cycling, biodiversity, erosion regulation, soil remediation/waste treatment and pest and disease regulation. The main factors to be taken into account for a correct PPP use management in crops are discussed.
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Artrópodes , Fungicidas Industriais , Inseticidas , Animais , Ecossistema , Fungicidas Industriais/farmacologia , Inseticidas/toxicidade , Solo , Medição de RiscoRESUMO
Each year, the European Food Safety Authority, supported by a network of experts in the EU Member States, assesses and publishes the environmental risks of 30-40 pesticides active substances. The assessments support hundreds of national risk evaluations for marketing (re-)authorisations of Plant Protection Products. These prospective regulatory evaluations are based on worst-case scenarios in order to provide the high level of protection required by the EU legislations, and establishes the conditions for a correct use of the products including risk mitigations options. However, recent publications suggest that the desired high level of protection may not be achieved with the current risk assessment paradigm. The consideration of larger spatial scales and multiple stressors, including different pesticide uses, could improve the risk assessment process. A next step is the use of these larger spatial scales for evidence-based assessments, evaluating the overall impact of pesticide use on the European environment and biodiversity. Reaching this level would provide science-based support to the National Plans on sustainable use of pesticides and to the broader EU policies defined in the EU Environmental Action Programmes. Recent technological developments, as well as policy efforts, have solved two of the key issues blocking this progress in the past. Data availability and technical capacity for handling Big Data are no longer an unaffordable obstacle. The current proposal presents an alternative environmental risk assessment paradigm, integrating use patterns and pesticides properties with landscape ecotypes and eco-regions, covering the variability of the European agro-environmental conditions. The paradigm is suggested to be implemented in a spatially explicit conceptual model, using the ecosystem services approach and vulnerable key driver species to represent the service providing units. This approach would allow mapping the likelihood and magnitude of the impact of pesticide use on ecosystems functions, environmental resources, and biodiversity at the EU scale.
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Política Ambiental , Poluentes Ambientais , Marketing , Praguicidas , Conservação dos Recursos Naturais , Ecossistema , Monitoramento Ambiental , Estudos Prospectivos , Medição de RiscoRESUMO
Glyphosate is the most widely used herbicide worldwide. It is a broad spectrum herbicide and its agricultural uses increased considerably after the development of glyphosate-resistant genetically modified (GM) varieties. Since glyphosate was introduced in 1974, all regulatory assessments have established that glyphosate has low hazard potential to mammals, however, the International Agency for Research on Cancer (IARC) concluded in March 2015 that it is probably carcinogenic. The IARC conclusion was not confirmed by the EU assessment or the recent joint WHO/FAO evaluation, both using additional evidence. Glyphosate is not the first topic of disagreement between IARC and regulatory evaluations, but has received greater attention. This review presents the scientific basis of the glyphosate health assessment conducted within the European Union (EU) renewal process, and explains the differences in the carcinogenicity assessment with IARC. Use of different data sets, particularly on long-term toxicity/carcinogenicity in rodents, could partially explain the divergent views; but methodological differences in the evaluation of the available evidence have been identified. The EU assessment did not identify a carcinogenicity hazard, revised the toxicological profile proposing new toxicological reference values, and conducted a risk assessment for some representatives uses. Two complementary exposure assessments, human-biomonitoring and food-residues-monitoring, suggests that actual exposure levels are below these reference values and do not represent a public concern.
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Carcinógenos/toxicidade , Glicina/análogos & derivados , Herbicidas/toxicidade , Animais , Monitoramento Ambiental/métodos , União Europeia , Glicina/toxicidade , Humanos , Agências Internacionais , Valores de Referência , Medição de Risco/métodos , Roedores , Fatores de Tempo , Testes de Toxicidade/métodos , GlifosatoRESUMO
There is growing concern about the presence of endocrine disrupting chemicals (EDCs) in cosmetics. We aimed to identify the main cosmetic ingredients with suspected endocrine-disrupting properties, and analyse their presence in current marketed products. Particular attention was given to products intended for susceptible (due to physiological status) and vulnerable (due to specific pathologies) groups with a view to informing cosmetologists and related health professionals of the scientific basis and current status of any concerns. Suspected EDCs used as cosmetic ingredients, included in lists published by regulatory agencies, were documented and investigated by weight of evidence analysis based on endocrine-related toxicity studies. In total, 49 suspected EDCs were identified from a sample of over a thousand cosmetic products marketed in the European Union. Suspected EDCs were found in approximately one third of products, with a similar frequency in products intended for susceptible and vulnerable groups. Avobenzone (CAS number:70356-09-1), octisalate (CAS number: 118-60-5), and butylated hydroxytoluene (CAS number: 128-37-0) were mostly commonly identified. The presence of EDCs was particularly high for sun care cosmetic products. Our results highlight potentially significant exposure through cosmetics to substances currently studied by regulatory institutions as suspected endocrine disrupters. EDCs are not yet universally regulated, and informing health professionals and educating the population as a precaution are options to reduce individual exposure levels, especially in vulnerable and susceptible groups. Special recommendations are needed for products intended for oncological patients.
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Cosméticos , Disruptores Endócrinos , Humanos , Disruptores Endócrinos/química , Disruptores Endócrinos/toxicidade , Cosméticos/efeitos adversos , Cosméticos/química , Hidroxitolueno ButiladoRESUMO
BACKGROUND: Regular monitoring of the air pollutant nitrogen dioxide (NO2), an indicator for traffic-related emissions, is a priority in urban environments. The health impacts associated with NO2 exposure are the result of a combination of factors, including concentration, duration of exposure, and interactions with other pollutants. WHO has established air quality guidelines based on epidemiological studies. OBJECTIVE: This study develops a new concept "Health Impact Pathways (HIPs)" using adversity as a probabilistic indicator of health effects. For this purpose, it integrates available toxicological and epidemiological information, using Adverse Outcome Pathways (AOPs), in order to understand chemical-biological interactions and their consequences on health. METHODS: Literature review and meta-analysis of toxicological data supported by expert judgment were performed to establish: a) adversity pathways, b) quantitative criteria for scoring the observed toxicological effects (adversity indicators), c) NO2 exposure - adversity relationship for both long-term (1-36 months) and shortterm (1-7 days). The NO2 daily concentrations from January 2001 to December 2022, were obtained from Madrid city Air Quality network monitoring database. Adversity levels were compared with relative risk levels for all-cause and respiratory mortality estimated using linear equations from WHO 2021 guidelines. RESULTS: Non-linear relations were obtained for all long- and short-term NO2 related adversity indicators; for long-term effects, the best fitting was obtained with a modified Haber's law model with an exponential coefficient for the exposure time of 0.25. Estimations are presented for a set of case studies for Madrid city, covering temporal and spatial variability. A clear improvement trend along the two decades was observed, as well as high inter- and intra-station variability; the adversity indicators provided integrated information on the temporal and spatial evolution of population level risk. DISCUSSION: The proposed HIP conceptual approach offers promising advances for integrating experimental and epidemiological data. The next step is linking the concentration-adversity relationship with population health impacts through probability estimations, the preliminary estimations confirm the need for assessing independently different population groups.
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The webinar series and workshop titled "Trust Your Gut: Establishing Confidence in Gastrointestinal Models An Overview of the State of the Science and Contexts of Use" was co-organized by NICEATM, NIEHS, FDA, EPA, CPSC, DoD, and the Johns Hopkins Center for Alternatives to Animal Testing (CAAT) and hosted at the National Institutes of Health in Bethesda, MD, USA on October 11-12, 2023. New approach methods (NAMs) for assessing issues of gastrointestinal tract (GIT)- related toxicity offer promise in addressing some of the limitations associated with animal-based assessments. GIT NAMs vary in complexity, from two-dimensional monolayer cell line-based systems to sophisticated 3-dimensional organoid systems derived from human primary cells. Despite advances in GIT NAMs, challenges remain in fully replicating the complex interactions and processes occurring within the human GIT. Presentations and discussions addressed regulatory needs, challenges, and innovations in incorporating NAMs into risk assessment frameworks; explored the state of the science in using NAMs for evaluating systemic toxicity, understanding absorption and pharmacokinetics, evaluating GIT toxicity, and assessing potential allergenicity; and discussed strengths, limitations, and data gaps of GIT NAMs as well as steps needed to establish confidence in these models for use in the regulatory setting.
Non-animal methods to assess whether chemicals may be toxic to the human digestive tract promise to complement or improve on animal-based methods. These approaches, which are based on human or animal cells and/or computer models, are faced with their own technical challenges and need to be shown to predict adverse effects in humans. Regulators are tasked with evaluating submitted data to best protect human health and the environment. A webinar series and workshop brought together scientists from academia, industry, military, and regulatory authorities from different countries to discuss how non-animal methods can be integrated into the risk assessment of drugs, food additives, dietary supplements, pesticides, and industrial chemicals for gastrointestinal toxicity.
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Alternativas aos Testes com Animais , Trato Gastrointestinal , Humanos , Alternativas aos Testes com Animais/métodos , Animais , Modelos Biológicos , Medição de Risco/métodos , Testes de Toxicidade/métodosRESUMO
The use of pyrethroids is very broad and shows increasing trends. Human biomonitoring studies represent the best approach for realistic risk estimations, but their interpretation requires a tiered approach. A previous HBM4EU study indicated levels in European children groups just around the threshold for concern, requiring further refinement. The main difficulty is that several pyrethroids with different toxicity potencies generate the same urinary metabolites. As diet is the main pyrethroid source for the general population, EU food monitoring data reported by EFSA have been used to estimate the relative contribution of each pyrethroid. The main contributors were cypermethrin for DCCA and 3-PBA and lambda-cyhalothrin for CFMP. Urinary levels predicted from food concentration according to the EFSA diets were mostly within the range of measured levels, except 3-PBA and CFMP levels in children, both below measured levels. The predicted lower levels for 3-PBA can be explained by the very low Fue value, initially proposed as conservative, but that seems to be unrealistic. The discrepancies for CFMP are mostly for the highest percentiles and require further assessments. The refined assessments included the revision of the previously proposed human biomonitoring guidance values for the general population, HBM-GV Gen Pop, following recent toxicological reevaluations, and the estimation of hazard quotients (HQs) for each individual pyrethroid and for the combined exposure to all pyrethroids. All HQs were below 1, indicating no immediate concern, but attention is required, particularly for children, with HQs in the range of 0.2-0.3 for the highly exposed group. The application of probabilistic methods offers assessments at the population level, addressing the variability in exposure and risk and providing relevant information for Public Health impact assessments and risk management prioritization.
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Human health and animal health risk assessment of combined exposure to multiple chemicals use the same steps as single-substance risk assessment, namely problem formulation, exposure assessment, hazard assessment and risk characterisation. The main unique feature of combined RA is the assessment of combined exposure, toxicity and risk. Recently, the Scientific Committee of the European Food Safety Authority (EFSA) published two relevant guidance documents. The first one "Harmonised methodologies for the human health, animal health and ecological risk assessment of combined exposure to multiple chemicals" provides principles and explores methodologies for all steps of risk assessment together with a reporting table. This guidance supports also the default assumption that dose addition is applied for combined toxicity of the chemicals unless evidence for response addition or interactions (antagonism or synergism) is available. The second guidance document provides an account of the scientific criteria to group chemicals in assessment groups using hazard-driven criteria and prioritisation methods, i.e., exposure-driven and risk-based approaches. This manuscript describes such principles, provides a brief description of EFSA's guidance documents, examples of applications in the human health and animal health area and concludes with a discussion on future challenges in this field.
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Ração Animal , Inocuidade dos Alimentos , Animais , Humanos , União Europeia , Inocuidade dos Alimentos/métodos , Medição de Risco/métodos , Previsões , Ração Animal/análiseRESUMO
This publication is linked to the following EFSA Supporting Publications articles: http://onlinelibrary.wiley.com/doi/10.2903/sp.efsa.2023.EN-8441/full, http://onlinelibrary.wiley.com/doi/10.2903/sp.efsa.2023.EN-8440/full, http://onlinelibrary.wiley.com/doi/10.2903/sp.efsa.2023.EN-8437/full.
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One of the aims of the European Human Biomonitoring Initiative, HBM4EU, was to provide examples of and good practices for the effective use of human biomonitoring (HBM) data in human health risk assessment (RA). The need for such information is pressing, as previous research has indicated that regulatory risk assessors generally lack knowledge and experience of the use of HBM data in RA. By recognising this gap in expertise, as well as the added value of incorporating HBM data into RA, this paper aims to support the integration of HBM into regulatory RA. Based on the work of the HBM4EU, we provide examples of different approaches to including HBM in RA and in estimations of the environmental burden of disease (EBoD), the benefits and pitfalls involved, information on the important methodological aspects to consider, and recommendations on how to overcome obstacles. The examples are derived from RAs or EBoD estimations made under the HBM4EU for the following HBM4EU priority substances: acrylamide, o-toluidine of the aniline family, aprotic solvents, arsenic, bisphenols, cadmium, diisocyanates, flame retardants, hexavalent chromium [Cr(VI)], lead, mercury, mixture of per-/poly-fluorinated compounds, mixture of pesticides, mixture of phthalates, mycotoxins, polycyclic aromatic hydrocarbons (PAHs), and the UV-filter benzophenone-3. Although the RA and EBoD work presented here is not intended to have direct regulatory implications, the results can be useful for raising awareness of possibly needed policy actions, as newly generated HBM data from HBM4EU on the current exposure of the EU population has been used in many RAs and EBoD estimations.
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Monitoramento Biológico , Mercúrio , Humanos , Monitoramento Ambiental/métodos , Políticas , Medição de RiscoRESUMO
Biologically active substances could reach the aquatic compartment when livestock wastes are considered for recycling. Recently, the standardized FETAX assay has been questioned, and some researchers have considered that the risk assessment performed on fish could not be protective enough to cover amphibians. In the present study a Xenopus laevis acute assay was developed in order to compare the sensitivity of larvae relative to fish or FETAX assays; veterinary medicines (ivermectin, oxytetracycline, tetracycline, sulfamethoxazole, and trimethoprim) and essential metals (zinc, copper, manganese, and selenium) that may be found in livestock wastes were used for the larvae exposure. Lethal (LC(50)) and sublethal effects were estimated. Available data in both, fish and FETAX studies, were in general more protective than values found out in the current study, but not in all cases. Moreover, the presence of nonlethal effects, caused by ivermectin, zinc, and copper, suggested that several physiological mechanisms could be affected. Thus, this kind of effects should be deeply investigated. The results obtained in the present study could expand the information about micropollutants from livestock wastes on amphibians.
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Bioensaio/métodos , Bioensaio/normas , Conservação dos Recursos Naturais/métodos , Testes de Mutagenicidade/métodos , Testes de Mutagenicidade/normas , Teratogênicos/toxicidade , Xenopus laevis/fisiologia , Animais , Larva , Sensibilidade e Especificidade , Entorses e DistensõesRESUMO
Plant Protection Products (PPP) raise concerns as their application may cause effects on some soil organisms considered non-target species which could be highly sensitive to some pesticides. The European Food and Safety Authority (EFSA), in collaboration with the Joint Research Centre (JRC) of the European Commission, has developed guidance and a software tool, Persistence in Soil Analytical Model (PERSAM), for conducting soil exposure assessments. EFSA PPR Panel has published recommendations for the risk assessment of non-target soil organisms. We have used PERSAM for calculating PPPs predicted environmental concentrations (PECs); and used the estimated PEC for assessing potential risks using Toxicity Exposure Ratios (TER) for selected soil organisms and good agricultural practices. Soil characteristics and environmental variables change along a latitudinal axis through the European continent, influencing the availability of PPP, their toxicity upon soil biota, and hence, impacting on the risk characterization. Although PERSAM includes as input geographical information, the information is aggregated and not further detailed in the model outputs. Therefore, there is a need to develop landscape based environmental risk assessment methods addressing regional variability. The objective was to integrate spatially explicit exposure (PECs) and effect data (biological endpoints i.e. LC50, NOEC, etc.) to estimate the risk quotient (TER) of four PPP active substances (esfenvalerate, cyclaniliprole, picoxystrobin, fenamidone) on non-target species accounting European landscape and agricultural variability. The study was focused on the effects produced by the above-mentioned pesticides on two soil organisms: E. fetida earthworms and Folsomia sp. collembolans. After running PERSAM assuming a worst case application of PPPs, PECs in total soil and pore water were obtained for different depths in northern, central and southern European soils. With this data, soil variability and climatic differences among soils divided in three large Euroregions along a latitudinal transect (Northern, Central, Southern Europe) were analysed. Summarising, a trend to accumulate higher PECs and TERs in total soil was observed in the north decreasing towards the south. Higher PECs and TERs could be expected in pore water in southern soils, decreasing towards the north. The risk disparity between pollutant concentrations at different soils compartments should be taken into account for regulatory purposes, as well as the potential landscape variabilities among different Euroregions.
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Oligoquetos , Praguicidas , Poluentes do Solo , Agricultura , Animais , Praguicidas/análise , Praguicidas/toxicidade , Medição de Risco , Solo , Poluentes do Solo/análise , Poluentes do Solo/toxicidade , Água/análiseRESUMO
This chapter aims to introduce the reader to the basic principles of environmental risk assessment of chemicals and highlights the usefulness of tiered approaches within weight of evidence approaches in relation to problem formulation i.e., data availability, time and resource availability. In silico models are then introduced and include quantitative structure-activity relationship (QSAR) models, which support filling data gaps when no chemical property or ecotoxicological data are available. In addition, biologically-based models can be applied in more data rich situations and these include generic or species-specific models such as toxicokinetic-toxicodynamic models, dynamic energy budget models, physiologically based models, and models for ecosystem hazard assessment i.e. species sensitivity distributions and ultimately for landscape assessment i.e. landscape-based modeling approaches. Throughout this chapter, particular attention is given to provide practical examples supporting the application of such in silico models in real-world settings. Future perspectives are discussed to address environmental risk assessment in a more holistic manner particularly for relevant complex questions, such as the risk assessment of multiple stressors and the development of harmonized approaches to ultimately quantify the relative contribution and impact of single chemicals, multiple chemicals and multiple stressors on living organisms.
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Ecossistema , Ecotoxicologia , Simulação por Computador , Relação Quantitativa Estrutura-Atividade , Medição de RiscoRESUMO
Pyrethroids are a major insecticide class, suitable for biomonitoring in humans. Due to similarities in structure and metabolic pathways, urinary metabolites are common to various active substances. A tiered approach is proposed for risk assessment. Tier I was a conservative screening for overall pyrethroid exposure, based on phenoxybenzoic acid metabolites. Subsequently, probabilistic approaches and more specific metabolites were used for refining the risk estimates. Exposure was based on 95th percentiles from HBM4EU aligned studies (2014-2021) covering children in Belgium, Cyprus, France, Israel, Slovenia, and The Netherlands and adults in France, Germany, Israel, and Switzerland. In all children populations, the 95th percentiles for 3-phenoxybenzoic acid (3-PBA) exceeded the screening value. The probabilistic refinement quantified the risk level of the most exposed population (Belgium) at 2% or between 1-0.1% depending on the assumptions. In the substance specific assessments, the 95th percentiles of urinary concentrations in the aligned studies were well below the respective human biomonitoring guidance values (HBM-GVs). Both information sets were combined for refining the combined risk. Overall, the HBM data suggest a low health concern, at population level, related to pyrethroid exposure for the populations covered by the studies, even though a potential risk for highly exposed children cannot be completely excluded. The proposed tiered approach, including a screening step and several refinement options, seems to be a promising tool of scientific and regulatory value in future.
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The risk assessment of pesticide residues in food is a key priority in the area of food safety. Most jurisdictions have implemented pre-marketing authorization processes, which are supported by prospective risk assessments. These prospective assessments estimate the expected residue levels in food combining results from residue trials, resembling the pesticide use patterns, with food consumption patterns, according to internationally agreed procedures. In addition, jurisdictions such as the European Union (EU) have implemented large monitoring programs, measuring actual pesticide residue levels in food, and are supporting large-scale human biomonitoring programs for confirming the actual exposure levels and potential risk for consumers. The organophosphate insecticide chlorpyrifos offers an interesting case study, as in the last decade, its acceptable daily intake (ADI) has been reduced several times following risk assessments by the European Food Safety Authority (EFSA). This process has been linked to significant reductions in the use authorized in the EU, reducing consumers' exposure progressively, until the final ban in 2020, accompanied by setting all EU maximum residue levels (MRL) in food at the default value of 0.01 mg/kg. We present a comparison of estimates of the consumer's internal exposure to chlorpyrifos based on the urinary marker 3,5,6-trichloro-2-pyridinol (TCPy), using two sources of monitoring data: monitoring of the food chain from the EU program and biomonitoring of European citizens from the HB4EU project, supported by a literature search. Both methods confirmed a drastic reduction in exposure levels from 2016 onwards. The margin of exposure approach is then used for conducting retrospective risk assessments at different time points, considering the evolution of our understanding of chlorpyrifos toxicity, as well as of exposure levels in EU consumers following the regulatory decisions. Concerns are presented using a color code, and have been identified for almost all studies, particularly for the highest exposed group, but at different levels, reaching the maximum level, red code, for children in Cyprus and Israel. The assessment uncertainties are highlighted and integrated in the identification of levels of concern.
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Environmental risk assessment is a key process for the authorization of pesticides, and is subjected to continuous challenges and updates. Current approaches are based on standard scenarios and independent substance-crop assessments. This arrangement does not address the complexity of agricultural ecosystems with mammals feeding on different crops. This work presents a simplified model for regulatory use addressing landscape variability, co-exposure to several pesticides, and predicting the effect on population abundance. The focus is on terrestrial vertebrates and the aim is the identification of the key risk drivers impacting on mid-term population dynamics. The model is parameterized for EU assessments according to the European Food Safety Authority (EFSA) Guidance Document, but can be adapted to other regulatory schemes. The conceptual approach includes two modules: (a) the species population dynamics, and (b) the population impact of pesticide exposure. Population dynamics is modelled through daily survival and seasonal reproductions rates; which are modified in case of pesticide exposure. All variables, parameters, and functions can be modified. The model has been calibrated with ecological data for wild rabbits and brown hares and tested for two herbicides, glyphosate and bromoxynil, using validated toxicity data extracted from EFSA assessments. Results demonstrate that the information available for a regulatory assessment, according to current EU information requirements, is sufficient for predicting the impact and possible consequences at population dynamic levels. The model confirms that agroecological parameters play a key role when assessing the effect of pesticide exposure on population abundance. The integration of laboratory toxicity studies with this simplified landscape model allows for the identification of conditions leading to population vulnerability or resilience. An Annex includes a detailed assessment of the model characteristics according to the EFSA scheme on Good Modelling Practice.
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Praguicidas , Agricultura , Animais , Ecossistema , Inocuidade dos Alimentos , Mamíferos , Praguicidas/análise , Praguicidas/toxicidade , Coelhos , Medição de RiscoRESUMO
Several medicinal products for human use are currently under consideration as potential treatment for COVID-19 pandemic. As proposals cover also prophylactic use, the treatment could be massive, resulting in unprecedent levels of antiviral emissions to the aquatic environment. We have adapted previous models and used available information for predicting the environmental impact of representative medicinal products, covering the main groups under consideration: multitarget antiparasitic (chloroquines and ivermectin), glucocorticoids, macrolide antibiotics and antiviral drugs including their pharmacokinetic boosters. The retrieved information has been sufficient for conducting a conventional environmental risk assessment for the group of miscellaneous medicines; results suggest low concern for the chloroquines and dexamethasone while very high impact for ivermectin and azithromycin, even at use levels well below the default value of 1% of the population. The information on the ecotoxicity of the antiviral medicines is very scarce, thus we have explored an innovative pharmacodynamic-based approach, combining read-across, quantitative structure-activity relationship (QSAR), US EPA's Toxicity Forecaster (ToxCast) in vitro data, pharmacological modes of action, and the observed adverse effects. The results highlight fish sublethal effects as the most sensitive target and identify possible concerns. These results offer guidance for minimizing the environmental risk of treatment medication for COVID-19.