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1.
Arch Toxicol ; 98(2): 425-469, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38147116

RESUMO

Fungi of the genus Alternaria are ubiquitous plant pathogens and saprophytes which are able to grow under varying temperature and moisture conditions as well as on a large range of substrates. A spectrum of structurally diverse secondary metabolites with toxic potential has been identified, but occurrence and relative proportion of the different metabolites in complex mixtures depend on strain, substrate, and growth conditions. This review compiles the available knowledge on hazard identification and characterization of Alternaria toxins. Alternariol (AOH), its monomethylether AME and the perylene quinones altertoxin I (ATX-I), ATX-II, ATX-III, alterperylenol (ALP), and stemphyltoxin III (STTX-III) showed in vitro genotoxic and mutagenic properties. Of all identified Alternaria toxins, the epoxide-bearing analogs ATX-II, ATX-III, and STTX-III show the highest cytotoxic, genotoxic, and mutagenic potential in vitro. Under hormone-sensitive conditions, AOH and AME act as moderate xenoestrogens, but in silico modeling predicts further Alternaria toxins as potential estrogenic factors. Recent studies indicate also an immunosuppressive role of AOH and ATX-II; however, no data are available for the majority of Alternaria toxins. Overall, hazard characterization of Alternaria toxins focused, so far, primarily on the commercially available dibenzo-α-pyrones AOH and AME and tenuazonic acid (TeA). Limited data sets are available for altersetin (ALS), altenuene (ALT), and tentoxin (TEN). The occurrence and toxicological relevance of perylene quinone-based Alternaria toxins still remain to be fully elucidated. We identified data gaps on hazard identification and characterization crucial to improve risk assessment of Alternaria mycotoxins for consumers and occupationally exposed workers.


Assuntos
Micotoxinas , Perileno , Humanos , Alternaria/metabolismo , Micotoxinas/toxicidade , Micotoxinas/análise , Mutagênicos/toxicidade , Mutagênicos/metabolismo , Lactonas/toxicidade , Lactonas/metabolismo , Medição de Risco , Contaminação de Alimentos/análise
2.
Environ Res ; 222: 115377, 2023 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-36709869

RESUMO

Exposure to phthalates is widespread in Europe. Phthalates are considered endocrine disrupting compounds and are classified as toxic for reproduction. However how phthalates affect the transcriptome in humans remains largely unknown. To investigate the effects of phthalate exposure on the transcriptomic profile we conducted RNA sequencing on peripheral blood samples from the Norwegian EuroMix cohort. We compared gene expression changes between participants with high, medium, and low exposure of six phthalates and 1,2-cyclohexane dicarboxylic acid diisononyl ester (DINCH). Comparing high and low exposure groups, DINCH was the compound that showed the highest number of differentially expressed genes (126 genes) followed by mono-n-butyl phthalate (MnBP; 89 genes) and mono-iso-nonyl phthalate (MiBP; 70 genes). Distributions between up- or down-regulated genes were similar across the different phthalates and DINCH. All phthalates including DINCH shared common differentially expressed genes ranging from 3 to 37 overlaps. Enriched Gene Ontology (GO) and biological pathway analysis revealed that most of the differentially expressed genes were associated with general cellular metabolism GO terms. MnBP and DINCH, particularly, showed a marked enrichment in various immunological function pathways including neutrophil degranulation, adaptive immune system and signaling by interleukins. Furthermore, the association between genes involved in the peroxisome proliferator activated receptor (PPAR) signaling pathway and phthalates, including DINCH, was evaluated. In total, 15 genes showed positive or negative associations across 5 phthalates and DINCH. MnBP and MiBP were the phthalate metabolites with the highest number of associations: 8 and 4 PPAR signaling pathway genes, respectively. Overall, we have performed an association study between phthalate exposure levels and modulation of transcriptomic profiles in human peripheral blood cells. DINCH, which is often mentioned as a substitute for phthalates, had comparable effects on differential gene expression in peripheral blood cells as phthalates.


Assuntos
Poluentes Ambientais , Ácidos Ftálicos , Humanos , Exposição Ambiental/análise , Receptores Ativados por Proliferador de Peroxissomo , Ácidos Dicarboxílicos , Reprodução
3.
Molecules ; 28(9)2023 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-37175378

RESUMO

(1) Background: Citrus honey constitutes a unique monofloral honey characterized by a distinctive aroma and unique taste. The non-targeted chemical analysis can provide pivotal information on chemical markers that differentiate honey based on its geographical and botanical origin. (2) Methods: Within the PRIMA project "PLANT-B", a metabolomics workflow was established to unveil potential chemical markers of orange blossom honey produced in case study areas of Egypt, Italy, and Greece. In some of these areas, aromatic medicinal plants were cultivated to enhance biodiversity and attract pollinators. The non-targeted chemical analysis and metabolomics were conducted using ultra-high-performance liquid chromatography high-resolution mass spectrometry (UHPLC-HRMS). (3) Results: Forty compounds were disclosed as potential chemical markers, enabling the differentiation of the three orange blossom honeys according to geographical origin. Italian honey showed a preponderance of flavonoids, while in Greek honey, terpenoids and iridoids were more abundant than flavonoids, except for hesperidin. In Egyptian honey, suberic acid and a fatty acid ester derivative emerged as chemical markers. New, for honey, furan derivatives were identified using GC-MS in Greek samples. (4) Conclusions: The application of UHPLC-HRMS metabolomics combined with an elaborate melissopalynological analysis managed to unveil several potential markers of Mediterranean citrus honey potentially associated with citrus crop varieties and the local indigenous flora.


Assuntos
Citrus sinensis , Citrus , Mel , Cromatografia Gasosa-Espectrometria de Massas , Cromatografia Líquida de Alta Pressão , Mel/análise , Citrus sinensis/química , Espectrometria de Massas , Flores/química , Flavonoides/análise , Biomarcadores/análise , Metabolômica
4.
Arch Toxicol ; 96(1): 211-229, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34778935

RESUMO

Within the EuroMix project, we have previously developed an adverse outcome pathway (AOP)-based in vitro assay toolbox to investigate the combined effects of liver steatosis-inducing compounds in human HepaRG hepatocarcinoma cells. In this study, we applied the toolbox to further investigate mixture effects of combinations, featuring either similarly acting or dissimilarly acting substances. The valproic acid structural analogs 2-propylheptanoic acid (PHP) and 2-propylhexanoic acid (PHX) were chosen for establishing mixtures of similarly acting substances, while a combination with the pesticidal active substance clothianidin (CTD) was chosen for establishing mixtures of dissimilarly acting compounds. We first determined relative potency factors (RPFs) for each compound based on triglyceride accumulation results. Thereafter, equipotent mixtures were tested for nuclear receptor activation in transfected HepG2 cells, while gene expression and triglyceride accumulation were investigated in HepaRG cells, following the proposed AOP for liver steatosis. Dose addition was observed for all combinations and endpoints tested, indicating the validity of the additivity assumption also in the case of the tested mixtures of dissimilarly acting substances. Gene expression results indicate that the existing steatosis AOP can still be refined with respect to the early key event (KE) of gene expression, in order to reflect the diversity of molecular mechanisms underlying the adverse outcome.


Assuntos
Rotas de Resultados Adversos , Carcinoma Hepatocelular , Fígado Gorduroso , Neoplasias Hepáticas , Fígado Gorduroso/induzido quimicamente , Fígado Gorduroso/metabolismo , Células Hep G2 , Humanos
5.
Molecules ; 27(19)2022 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-36235169

RESUMO

Bees in search of diet sources intensively fly within a radius of up to 3 km, encountering nectar, pollen, and water sources which are potentially contaminated. Consequently, their products can provide valuable information about potential pollution. In the current study, 27 macro and trace elements, including the most hazardous ones, were measured in bees, honey, wax, pollen, and larvae, obtained from seven explicitly industrial areas in eastern regions of Slovakia, using a validated ICP-MS method. All the analysed elements were detected at least in one matrix. The detected concentrations of toxic elements, such as Hg, Pb, and Cd were in some cases higher in wax and bee samples, compared with honey, larvae, and pollen. In particular, Pb and Hg maximum concentrations were detected in the wax samples from Posa (3193 µg/kg) and Strázske_A (90 µg/kg). In addition, adult bees accumulated more elements than larvae, while wax and adult bees seemed more suitable for monitoring macro and trace elements in the surrounding environment. Statistical analysis emphasizing bees and wax correlated Cd with the Strázske area, possibly attributed to the intensified industrial activity in this region.


Assuntos
Mel , Mercúrio , Oligoelementos , Animais , Abelhas , Cádmio , Mel/análise , Chumbo , Néctar de Plantas , Oligoelementos/análise , Água , Ceras
6.
Int J Mol Sci ; 22(9)2021 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-34063053

RESUMO

Increased soil salinity, and therefore accumulation of ions, is one of the major abiotic stresses of cultivated plants that negatively affect their growth and yield. Among Medicago species, only Medicago truncatula, which is a model plant, has been extensively studied, while research regarding salinity responses of two important forage legumes of Medicago sativa (M. sativa) and Medicago arborea (M. arborea) has been limited. In the present work, differences between M. arborea, M. sativa and their hybrid Alborea were studied regarding growth parameters and metabolomic responses. The entries were subjected to three different treatments: (1) no NaCl application (control plants), (2) continuous application of 100 mM NaCl (acute stress) and (3) gradual application of NaCl at concentrations of 50-75-150 mM by increasing NaCl concentration every 10 days. According to the results, M. arborea maintained steady growth in all three treatments and appeared to be more resistant to salinity. Furthermore, results clearly demonstrated that M. arborea presented a different metabolic profile from that of M. sativa and their hybrid. In general, it was found that under acute and gradual stress, M. sativa overexpressed saponins in the shoots while M. arborea overexpressed saponins in the roots, which is the part of the plant where most of the saponins are produced and overexpressed. Alborea did not perform well, as more metabolites were downregulated than upregulated when subjected to salinity stress. Finally, saponins and hydroxycinnamic acids were key players of increased salinity tolerance.


Assuntos
Hibridização Genética , Medicago/metabolismo , Medicago/fisiologia , Metaboloma , Tolerância ao Sal , Metabolismo Secundário , Análise de Variância , Medicago/crescimento & desenvolvimento , Raízes de Plantas/metabolismo , Brotos de Planta/metabolismo , Caules de Planta/anatomia & histologia , Análise de Componente Principal
7.
Molecules ; 26(2)2021 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-33467182

RESUMO

Chemical composition of propolis depends on the plant source and thus on the geographic and climatic characteristics of the site of collection. The aim of this study was to investigate the chemical profile of Greek and Chinese propolis extracts from different regions and suggest similarities and differences between them. Untargeted ultrahigh-performance liquid chromatography coupled to hybrid quadrupole-Orbitrap mass spectrometry (UHPLC-HRMS) method was developed and 22 and 23 propolis samples from Greece and China, respectively, were analyzed. The experimental data led to the observation that there is considerable variability in terms of quality of the distinctive propolis samples. Partial least squares - discriminant analysis (PLS-DA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) models were constructed and allowed the identification of significant features for sample discrimination, adding relevant information for the identification of class-determining metabolites. Chinese samples overexpressed compounds that are characteristic of the poplar type propolis, whereas Greek samples overexpress the latter and the diterpenes characteristic of the Mediterranean propolis type.


Assuntos
Metabolômica , Própole/análise , China , Cromatografia Líquida de Alta Pressão , Grécia , Espectrometria de Massas
8.
BMC Ecol ; 20(1): 57, 2020 11 06.
Artigo em Inglês | MEDLINE | ID: mdl-33158433

RESUMO

BACKGROUND: Invasive plant species pose a significant threat for fragile isolated ecosystems, occupying space, and consuming scarce local resources. Recently though, an additional adverse effect was recognized in the form of its secondary metabolites entering the food chain. The present study is elaborating on this subject with a specific focus on the Nicotiana glauca Graham (Solanaceae) alkaloids and their occurrence and food chain penetrability in Mediterranean ecosystems. For this purpose, a targeted liquid chromatography electrospray tandem mass spectrometric (LC-ESI-MS/MS) analytical method, encompassing six alkaloids and one coumarin derivative, utilizing hydrophilic interaction chromatography (HILIC) was developed and validated. RESULTS: The method exhibited satisfactory recoveries, for all analytes, ranging from 75 to 93%, and acceptable repeatability and reproducibility. Four compounds (anabasine, anatabine, nornicotine, and scopoletin) were identified and quantified in 3 N. glauca flowers extracts, establishing them as potential sources of alien bio-molecules. The most abundant constituent was anabasine, determined at 3900 µg/g in the methanolic extract. These extracts were utilized as feeding treatments on Apis mellifera honeybees, resulting in mild toxicity documented by 16-18% mortality. A slightly increased effect was elicited by the methanolic extract containing anabasine at 20 µg/mL, where mortality approached 25%. Dead bees were screened for residues of the N. glauca flower extracts compounds and a significant mean concentration of anabasine was evidenced in both 10 and 20 µg/mL treatments, ranging from 51 to 92 ng/g per bee body weight. Scopoletin was also detected in trace amounts. CONCLUSIONS: The mild toxicity of the extracts in conjunction with the alkaloid and coumarin residual detection in bees, suggest that these alien bio-molecules are transferred within the food chain, suggesting a chemical invasion phenomenon, never reported before.


Assuntos
Alcaloides , Nicotiana , Alcaloides/toxicidade , Animais , Abelhas , Ecossistema , Reprodutibilidade dos Testes , Espectrometria de Massas em Tandem
9.
Mar Drugs ; 17(10)2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31575010

RESUMO

Chlorophenols (CPs) are environmental pollutants that are produced through various anthropogenic activities and introduced in the environment. Living organisms, including humans, are exposed to these toxic xenobiotics and suffer from adverse health effects. More specifically, 2,4-dichlorophenol (2,4-DCP) is released in high amounts in the environment and has been listed as a priority pollutant by the US Environmental Protection Agency. Bioremediation has been proposed as a sustainable alternative to conventional remediation methods for the detoxification of phenolic compounds. In this work, we studied the potential of fungal strains isolated as symbionts of marine invertebrates from the underexplored mesophotic coral ecosystems. Hence, the unspecific metabolic pathways of these fungal strains are being explored in the present study, using the powerful analytical capabilities of a UHPLC-HRMS/MS. The newly identified 2,4-DCP metabolites add significantly to the knowledge of the transformation of such pollutants by fungi, since such reports are scarce.


Assuntos
Organismos Aquáticos/microbiologia , Clorofenóis/metabolismo , Fungos/metabolismo , Invertebrados/microbiologia , Poluentes Químicos da Água/metabolismo , Animais , Antozoários/metabolismo , Biodegradação Ambiental , Ecossistema , Humanos , Redes e Vias Metabólicas/fisiologia , Fenóis/metabolismo , Simbiose/fisiologia , Xenobióticos/metabolismo
10.
Chem Res Toxicol ; 31(8): 784-798, 2018 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-29995386

RESUMO

Adverse outcome pathways (AOPs) describe causal relationships between molecular perturbation and adverse cellular effects and are being increasingly adopted for linking in vitro mechanistic toxicology to in vivo data from regulatory toxicity studies. In this work, a case study was performed by developing a bioassay toolbox to assess key events in the recently proposed AOP for chemically induced liver steatosis. The toolbox is comprised of in vitro assays to measure nuclear receptor activation, gene and protein expression, lipid accumulation, mitochondrial respiration, and formation of fatty liver cells. Assay evaluation was performed in human HepaRG hepatocarcinoma cells exposed to the model compound cyproconazole, a fungicide inducing steatosis in rodents. Cyproconazole dose-dependently activated RARα and PXR, two molecular initiating events in the steatosis AOP. Moreover, cyproconazole provoked a disruption of mitochondrial functions and induced triglyceride accumulation and the formation of fatty liver cells as described in the AOP. Gene and protein expression analysis, however, showed expression changes different from those proposed in the AOP, thus suggesting that the current version of the AOP might not fully reflect the complex mechanisms linking nuclear receptor activation and liver steatosis. Our study shows that cyproconazole induces steatosis in human liver cells in vitro and demonstrates the utility of systems-based approaches in the mechanistic assessment of molecular and cellular key events in an AOP. AOP-driven in vitro testing as demonstrated can further improve existing AOPs, provide insight regarding molecular mechanisms of toxicity, and inform predictive risk assessment.


Assuntos
Rotas de Resultados Adversos , Fígado Gorduroso/induzido quimicamente , Fungicidas Industriais/toxicidade , Triazóis/toxicidade , Bioensaio , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Fígado Gorduroso/metabolismo , Expressão Gênica , Células HEK293 , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Humanos , Mitocôndrias Hepáticas/efeitos dos fármacos , Modelos Biológicos , Reação em Cadeia da Polimerase , Receptores Citoplasmáticos e Nucleares/metabolismo , Medição de Risco , Triglicerídeos/metabolismo
11.
Int J Mol Sci ; 18(4)2017 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-28417904

RESUMO

Triadimefon is a widely used triazole fungicide known to cause severe developmental defects in several model organisms and in humans. The present study evaluated in detail the developmental effects seen in zebrafish embryos exposed to triadimefon, confirmed and expanded upon previous phenotypic findings and compared them to those observed in other traditional animal models. In order to do this, we exposed embryos to 2 and 4 µg/mL triadimefon and evaluated growth until 120 h post-fertilization (hpf) through gross morphology examination. Our analysis revealed significant developmental defects at the highest tested concentration including somite deformities, severe craniofacial defects, a cleft phenotype along the three primary neural divisions, a rigorously hypoplastic or even absent mandible and a hypoplastic morphology of the pharyngeal arches. Interestingly, massive pericardial edemas, abnormal shaped hearts, brachycardia and inhibited or absent blood circulation were also observed. Our results revealed that the presented zebrafish phenotypes are comparable to those seen in other organism models and those derived from human observations as a result of triadimefon exposure. We therefore demonstrated that zebrafish provide an excellent system for study of compounds with toxic significance and can be used as an alternative model for developmental toxicity studies to predict effects in mammals.


Assuntos
Embrião não Mamífero/efeitos dos fármacos , Desenvolvimento Embrionário/efeitos dos fármacos , Teratogênicos/toxicidade , Peixe-Zebra , Animais , Osso e Ossos/efeitos dos fármacos , Anormalidades Congênitas/etiologia , Modelos Animais , Especificidade de Órgãos , Organogênese/efeitos dos fármacos , Triazóis/toxicidade
12.
J Xenobiot ; 14(2): 701-716, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38921650

RESUMO

The monitoring of contaminants in fish species is pivotal for fishes' health and reproduction, as well as for human health. In the specific work, three major categories of contaminants, pesticides, pharmaceuticals, and macro and trace elements, were investigated in two major fish species, Dicentrarchus labrax and Solea solea, collected from Thermaikos Gulf, in Greece. To achieve this goal, three analytical methods using LC-MS/MS, GC-MS/MS, and ICP-MS were developed, validated, and applied to the collected fish samples. The results indicated a very low prevalence of caffeine and acetaminophen, both not exceeding 3.8 µg/kg fish. Similarly, thiabendazole, cypermethrin, and tricyclazole (pesticides) were found in a concentration range of 0.9 to 13.7 µg/kg fish, while in one D. labrax sample, traces of the metabolite of organochlorine pesticide DDT, o,p'-DDE were detected. Al, Mn, Fe, Zn, and Sr were the predominant trace elements in a concentration range of 500-20,000 µg/kg fish. Macro elements levels varied from 280 to 5405 mg/kg fish. Health risk assessment did not unveil an unacceptable risk for the human health of adults, apart from one sample presenting Hg above the regulatory levels. On the contrary, for children, the calculated hazard quotient values for Hg in all cases and for two As detections were higher than the threshold value of 1, indicating a potential risk.

13.
Heliyon ; 10(1): e23564, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38187233

RESUMO

The steady conditions of temperature, humidity and air flux within beehives make them a valuable location for conducting environmental monitoring of pollutants such as PAHs. In this context, the selection of an appropriate apicultural matrix plays a key role in these monitoring studies, as it maximizes the information that will be obtained in the analyses while minimizing the inaccurate results. In the present study, three apicultural matrices (honey bees, pollen and propolis) and two passive samplers (APIStrips and silicone wristbands) are compared in terms of the number and total load of PAHs detected in them. Samplings took place in a total of 11 apiaries scattered in Austria, Denmark, and Greece, with analyses performed by GC-MS/MS. Up to 14 different PAHs were identified in silicone wristbands and pollen, whereas the remaining matrices contained a maximum of five contaminants. Naphthalene, 1-methylnaphthalene, 2-methylnaphthalene, and pyrene were found to be the most prevalent substances in the environment. Recovery studies were also performed; these suggested that the chemical structure of APIStrips is likely to produce very strong interactions with PAHs, thus hindering the adequate desorption of these substances from their surface. Overall, silicone wristbands placed inside the beehives proved the most suitable matrix for PAH monitoring through honey bee colonies.

14.
Foods ; 12(4)2023 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-36832781

RESUMO

BACKGROUND: Bees encounter a plethora of environmental contaminants during nectar and pollen collection from plants. Consequently, after their entrance into the beehives, the transfer of numerous pollutants to apicultural products is inevitable. METHODS: In this context, during the period of 2015-2020, 109 samples of honey, pollen, and beebread were sampled and analyzed for the determination of pesticides and their metabolites. More than 130 analytes were investigated in each sample by applying two validated multiresidue methods (HPLC-ESI-MS/MS and GC-MS/MS). RESULTS: Until the end of 2020, 40 determinations were reported in honey, resulting in a 26% positive to at least one active substance. The concentrations of pesticides ranged from 1.3 ng/g to 785 ng/g honey. For seven active substances in honey and pollen, maximum residue limits (MRLs) exceedances were observed. Coumaphos, imidacloprid, acetamiprid, amitraz metabolites (DMF and DMPF), and tau-fluvalinate were the predominant compounds detected in honey, while several pyrethroids such as λ-cyhalothrin, cypermethrin, and cyfluthrin were also found. Pollen and beebread, as expected, accumulated a higher number of active substances and metabolites (32 in total), exhibiting almost double the number of detections. CONCLUSIONS: Although the above findings verify the occurrence of numerous pesticide and metabolite residues in both honey and pollen, the human risk assessment in the majority of the cases does not raise any concerns, and the same applies to bee risk assessment.

15.
Toxics ; 11(5)2023 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-37235216

RESUMO

This paper reviews key elements in the assessment of human health effects from combined exposure to multiple chemicals taking into consideration current knowledge and challenges to identify areas where scientific advancement is mostly needed and proposes a decision-making scheme on the basis of existing methods and tools. The assumption of dose addition and estimation of the hazard index (HI) is considered as a starting point in component-based risk assessments. When, based on the generic HI approach, an unacceptable risk is identified, more specific risk assessment options may be implemented sequentially or in parallel depending on problem formulation, characteristics of the chemical group under assessment, exposure levels, data availability and resources. For prospective risk assessments, the reference point index/margin of exposure (RPI/MOET) (Option 1) or modified RPI/normalized MOET (mRPI/nMOET) (Option 2) approaches may be implemented focusing on the specific mixture effect. Relative potency factors (RPFs) may also be used in the RPI approach since a common uncertainty factor for each mixture component is introduced in the assessment. Increased specificity in the risk assessment may also be achieved when exposure of selected population groups is considered (Option 3/exposure). For retrospective risk assessments, human biomonitoring data available for vulnerable population groups (Option 3/susceptibility) may present more focused scenarios for consideration in human health risk management decisions. In data-poor situations, the option of using the mixture assessment factor (MAF) is proposed (Option 4), where an additional uncertainty factor is applied on each mixture component prior to estimating the HI. The magnitude of the MAF may be determined by the number of mixture components, their individual potencies and their proportions in the mixture, as previously reported. It is acknowledged that implementation of currently available methods and tools for human health risk assessment from combined exposure to multiple chemicals by risk assessors will be enhanced by ongoing scientific developments on new approach methodologies (NAMs), integrated approaches to testing and assessment (IATA), uncertainty analysis tools, data sharing platforms, risk assessment software as well as guideline development to meet legislative requirements.

16.
Evid Based Toxicol ; 1(1): 1-15, 2023 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-38264543

RESUMO

This protocol describes the design and development of a tool for evaluation of the internal validity of in vitro studies, which is needed to include the data as evidence in systematic reviews and chemical risk assessments. The tool will be designed specifically to be applied to cell culture studies, including, but not restricted to, studies meeting the new approach methodology (NAM) definition. The tool is called INVITES-IN (IN VITro Experimental Studies INternal validity). In this protocol, three of the four studies that will be performed to create the release version of INVITES-IN are described. In the first study, evaluation of existing assessment tools will be combined with focus group discussions to identify how characteristics of the design or conduct of an in vitro study can affect its internal validity. Bias domains and items considered to be of relevance for in vitro studies will be identified. In the second study, group agreement on internal validity domains and items of importance for in vitro studies will be identified via a modified Delphi methodology. In the third study, the draft version of the tool will be created, based on the data on relevance and importance of bias domains and items collected in Studies 1 and 2. A separate protocol will be prepared for the fourth study, which includes the user testing and validation of the tool, and collection of users' experience.

17.
Front Toxicol ; 5: 1116707, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37342468

RESUMO

The environmental impact on health is an inevitable by-product of human activity. Environmental health sciences is a multidisciplinary field addressing complex issues on how people are exposed to hazardous chemicals that can potentially affect adversely the health of present and future generations. Exposure sciences and environmental epidemiology are becoming increasingly data-driven and their efficiency and effectiveness can significantly improve by implementing the FAIR (findable, accessible, interoperable, reusable) principles for scientific data management and stewardship. This will enable data integration, interoperability and (re)use while also facilitating the use of new and powerful analytical tools such as artificial intelligence and machine learning in the benefit of public health policy, and research, development and innovation (RDI). Early research planning is critical to ensuring data is FAIR at the outset. This entails a well-informed and planned strategy concerning the identification of appropriate data and metadata to be gathered, along with established procedures for their collection, documentation, and management. Furthermore, suitable approaches must be implemented to evaluate and ensure the quality of the data. Therefore, the 'Europe Regional Chapter of the International Society of Exposure Science' (ISES Europe) human biomonitoring working group (ISES Europe HBM WG) proposes the development of a FAIR Environment and health registry (FAIREHR) (hereafter FAIREHR). FAIR Environment and health registry offers preregistration of studies on exposure sciences and environmental epidemiology using HBM (as a starting point) across all areas of environmental and occupational health globally. The registry is proposed to receive a dedicated web-based interface, to be electronically searchable and to be available to all relevant data providers, users and stakeholders. Planned Human biomonitoring studies would ideally be registered before formal recruitment of study participants. The resulting FAIREHR would contain public records of metadata such as study design, data management, an audit trail of major changes to planned methods, details of when the study will be completed, and links to resulting publications and data repositories when provided by the authors. The FAIREHR would function as an integrated platform designed to cater to the needs of scientists, companies, publishers, and policymakers by providing user-friendly features. The implementation of FAIREHR is expected to yield significant benefits in terms of enabling more effective utilization of human biomonitoring (HBM) data.

18.
EFSA J ; 21(1): e07728, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36694841

RESUMO

Copper is an essential micronutrient and also a regulated product used in organic and in conventional farming pest management. Both deficiency and excessive exposure to copper can have adverse health effects. In this Scientific Opinion, the EFSA 2021 harmonised approach for establishing health-based guidance values (HBGVs) for substances that are regulated products and also nutrients was used to resolve the divergent existing HBGVs for copper. The tightly regulated homeostasis prevents toxicity manifestation in the short term, but the development of chronic copper toxicity is dependent on copper homeostasis and its tissue retention. Evidence from Wilson disease suggests that hepatic retention is indicative of potential future and possibly sudden onset of copper toxicity under conditions of continuous intake. Hence, emphasis was placed on copper retention as an early marker of potential adverse effects. The relationships between (a) chronic copper exposure and its retention in the body, particularly the liver, and (b) hepatic copper concentrations and evidence of toxicity were examined. The Scientific Committee (SC) concludes that no retention of copper is expected to occur with intake of 5 mg/day and established an Acceptable Daily Intake (ADI) of 0.07 mg/kg bw. A refined dietary exposure assessment was performed, assessing contribution from dietary and non-dietary sources. Background copper levels are a significant source of copper. The contribution of copper from its use as plant protection product (PPP), food and feed additives or fertilisers is negligible. The use of copper in fertilisers or PPPs contributes to copper accumulation in soil. Infant formula and follow-on formula are important contributors to dietary exposure of copper in infants and toddlers. Contribution from non-oral sources is negligible. Dietary exposure to total copper does not exceed the HBGV in adolescents, adults, elderly and the very elderly. Neither hepatic copper retention nor adverse effects are expected to occur from the estimated copper exposure in children due to higher nutrient requirements related to growth.

19.
EFSA J ; 21(10): e08312, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37908452

RESUMO

EFSA Strategy 2027 outlines the need for fit-for-purpose protocols for EFSA generic scientific assessments to aid in delivering trustworthy scientific advice. This EFSA Scientific Committee guidance document helps address this need by providing a harmonised and flexible framework for developing protocols for EFSA generic assessments. The guidance replaces the 'Draft framework for protocol development for EFSA's scientific assessments' published in 2020. The two main steps in protocol development are described. The first is problem formulation, which illustrates the objectives of the assessment. Here a new approach to translating the mandated Terms of Reference into scientifically answerable assessment questions and sub-questions is proposed: the 'APRIO' paradigm (Agent, Pathway, Receptor, Intervention and Output). Owing to its cross-cutting nature, this paradigm is considered adaptable and broadly applicable within and across the various EFSA domains and, if applied using the definitions given in this guidance, is expected to help harmonise the problem formulation process and outputs and foster consistency in protocol development. APRIO may also overcome the difficulty of implementing some existing frameworks across the multiple EFSA disciplines, e.g. the PICO/PECO approach (Population, Intervention/Exposure, Comparator, Outcome). Therefore, although not mandatory, APRIO is recommended. The second step in protocol development is the specification of the evidence needs and the methods that will be applied for answering the assessment questions and sub-questions, including uncertainty analysis. Five possible approaches to answering individual (sub-)questions are outlined: using evidence from scientific literature and study reports; using data from databases other than bibliographic; using expert judgement informally collected or elicited via semi-formal or formal expert knowledge elicitation processes; using mathematical/statistical models; and - not covered in this guidance - generating empirical evidence ex novo. The guidance is complemented by a standalone 'template' for EFSA protocols that guides the users step by step through the process of planning an EFSA scientific assessment.

20.
Food Chem Toxicol ; 161: 112826, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35063474

RESUMO

Bee pollen contains a diversity of bioactive components. Nevertheless, since pollen is retrieved from a variety of plants, including the cultivated ones which are subjected to agrochemical treatments, its contamination is unavoidable. In this context, 45 samples of pollen were analysed with optimized analytical methods for trace and macro elements (ICP-MS), pesticides and metabolites residues (LC & GC-MS/MS) content. According to the results, potassium and iron were the most abundant in terms of concentration and frequency of detection, while the contribution of the most hazardous elements, such as lead, arsenic, cadmium and mercury, to the total concentration of trace elements was lower than 1%. For pesticides, coumaphos was the most frequently detected in the examined samples (22%), followed by propargite, azoxystrobin, dimethoate and cypermethrin. Non-carcinogenic health risk assessment demonstrated in the majority of cases negligible risk for adults and children. On the contrary, carcinogenic risk assessment considering a worst case scenario disclosed nickel and in less extent chromium and arsenic, as risk drivers, exhibiting in several samples carcinogenic risk values for adults above the safety threshold. Yet, regarding that both adults and children unlikely will daily consume such pollen quantities, especially on a long-term basis, an overestimation of risk should be appraised.


Assuntos
Minerais/toxicidade , Resíduos de Praguicidas/toxicidade , Praguicidas/toxicidade , Pólen/química , Animais , Abelhas , Monitoramento Ambiental/métodos , Análise de Alimentos , Contaminação de Alimentos , Humanos , Minerais/química , Resíduos de Praguicidas/química , Praguicidas/química , Fatores de Risco
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