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1.
Emerg Infect Dis ; 27(4): 1220-1222, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33522478

RESUMO

Coronavirus disease (COVID-19) symptoms can be mistaken for vaccine-related side effects during initial days after immunization. Among 4,081 vaccinated healthcare workers in Israel, 22 (0.54%) developed COVID-19 from 1-10 days (median 3.5 days) after immunization. Clinicians should not dismiss postvaccination symptoms as vaccine-related and should promptly test for COVID-19.


Assuntos
/efeitos adversos , Pessoal de Saúde/estatística & dados numéricos , Vacinação , Adulto , Rotas de Resultados Adversos , /epidemiologia , /métodos , /administração & dosagem , Diagnóstico Diferencial , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/diagnóstico , Feminino , Humanos , Israel/epidemiologia , Masculino , Vacinação/efeitos adversos , Vacinação/métodos , Vacinação/estatística & dados numéricos
2.
Sci Total Environ ; 766: 144249, 2021 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-33421781

RESUMO

Nanoplastics are a growing environmental and public health concern. However, the toxic mechanisms of nanoplastics are poorly understood. Here, we evaluated the effects of spherical polystyrene nanoplastics on reproduction of Daphnia pulex and analyzed the proteome of whole animals followed by molecular and biochemical analyses for the development of an adverse outcome pathway (AOP) for these contaminants of emerging concern. Animals were exposed to polystyrene nanoplastics (0, 0.1, 0.5, 1 and 2 mg/L) via water for 21 days. Nanoplastics negatively impacted cumulative offspring production. A total of 327 differentially expressed proteins (DEPs) were identified in response to nanoplastics which were further validated from gene expression and enzyme activity data. Based on these results, we propose an AOP for nanoplastics, including radical oxygen species production and oxidative stress as the molecular initiating event (MIE); followed by changes in specific signaling pathways (Jak-STAT, mTOR and FoxO) and in the metabolism of glutathione, protein, lipids, and molting proteins; with an end result of growth inhibition and decrease reproductive output. This study serves as a foundation for the development of a mechanistic understanding of nanoplastic toxicity in crustaceans and perhaps other aquatic organisms.


Assuntos
Rotas de Resultados Adversos , Poluentes Químicos da Água , Animais , Daphnia , Microplásticos , Poliestirenos , Proteômica , Poluentes Químicos da Água/toxicidade
3.
PLoS One ; 15(9): e0239799, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32976513

RESUMO

BACKGROUND: To investigate the association between serum 25-hydroxyvitamin D levels and its effect on adverse clinical outcomes, and parameters of immune function and mortality due to a SARS-CoV-2 infection. STUDY DESIGN: The hospital data of 235 patients infected with COVID-19 were analyzed. RESULTS: Based on CDC criteria, among our study patients, 74% had severe COVID-19 infection and 32.8% were vitamin D sufficient. After adjusting for confounding factors, there was a significant association between vitamin D sufficiency and reduction in clinical severity, inpatient mortality serum levels of C-reactive protein (CRP) and an increase in lymphocyte percentage. Only 9.7% of patients older than 40 years who were vitamin D sufficient succumbed to the infection compared to 20% who had a circulating level of 25(OH)D< 30 ng/ml. The significant reduction in serum CRP, an inflammatory marker, along with increased lymphocytes percentage suggest that vitamin D sufficiency also may help modulate the immune response possibly by reducing risk for cytokine storm in response to this viral infection. CONCLUSION: Therefore, it is recommended that improving vitamin D status in the general population and in particular hospitalized patients has a potential benefit in reducing the severity of morbidities and mortality associated with acquiring COVID-19.


Assuntos
Infecções por Coronavirus/diagnóstico , Pneumonia Viral/diagnóstico , Vitamina D/análogos & derivados , Adulto , Rotas de Resultados Adversos , Idoso , Idoso de 80 Anos ou mais , Betacoronavirus , Proteína C-Reativa/metabolismo , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/prevenção & controle , Estudos Transversais , Feminino , Humanos , Imunidade/efeitos dos fármacos , Irã (Geográfico) , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Pandemias/prevenção & controle , Pneumonia Viral/mortalidade , Pneumonia Viral/prevenção & controle , Prognóstico , Resultado do Tratamento , Vitamina D/sangue , Vitamina D/farmacologia , Vitamina D/normas
4.
Arch Toxicol ; 94(10): 3579-3580, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32839845
5.
PLoS One ; 15(7): e0236554, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32716922

RESUMO

The sudden emergence of COVID-19 has brought significant challenges to the care of Veterans. An improved ability to predict a patient's clinical course would facilitate optimal care decisions, resource allocation, family counseling, and strategies for safely easing distancing restrictions. The Care Assessment Need (CAN) score is an existing risk assessment tool within the Veterans Health Administration (VA), and produces a score from 0 to 99, with a higher score correlating to a greater risk. The model was originally designed for the nonacute outpatient setting and is automatically calculated from structured data variables in the electronic health record. This multisite retrospective study of 6591 Veterans diagnosed with COVID-19 from March 2, 2020 to May 26, 2020 was designed to assess the utility of repurposing the CAN score as objective and automated risk assessment tool to promptly enhance clinical decision making for Veterans diagnosed with COVID-19. We performed bivariate analyses on the dichotomized CAN 1-year mortality score (high vs. low risk) and each patient outcome using Chi-square tests of independence. Logistic regression models using the continuous CAN score were fit to assess its predictive power for outcomes of interest. Results demonstrated that a CAN score greater than 50 was significantly associated with the following outcomes after positive COVID-19 test: hospital admission (OR 4.6), prolonged hospital stay (OR 4.5), ICU admission (3.1), prolonged ICU stay (OR 2.9), mechanical ventilation (OR 2.6), and mortality (OR 7.2). Repurposing the CAN score offers an efficient way to risk-stratify COVID-19 Veterans. As a result of the compelling statistical results, and automation, this tool is well positioned for broad use across the VA to enhance clinical decision-making.


Assuntos
Infecções por Coronavirus/terapia , Registros Eletrônicos de Saúde , Pneumonia Viral/terapia , Medição de Risco/métodos , Rotas de Resultados Adversos , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/mortalidade , Tomada de Decisões , Feminino , Hospitais de Veteranos , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Determinação de Necessidades de Cuidados de Saúde , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/mortalidade , Estudos Retrospectivos , Resultado do Tratamento , Estados Unidos , United States Department of Veterans Affairs
7.
Environ Sci Technol ; 54(14): 8491-8499, 2020 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-32584560

RESUMO

A growing number of environmental pollutants are known to adversely affect the thyroid hormone system, and major gaps have been identified in the tools available for the identification, and the hazard and risk assessment of these thyroid hormone disrupting chemicals. We provide an example of how the adverse outcome pathway (AOP) framework and associated data generation can address current testing challenges in the context of fish early life stage tests, and fish tests in general. We demonstrate how a suite of assays covering biological processes involved in the underlying toxicological pathways can be implemented in a tiered screening and testing approach for thyroid hormone disruption, using the levels of assessment of the OECD's Conceptual Framework for the Testing and Assessment of Endocrine Disrupting Chemicals as a guide.


Assuntos
Rotas de Resultados Adversos , Disruptores Endócrinos , Poluentes Ambientais , Animais , Disruptores Endócrinos/toxicidade , Poluentes Ambientais/toxicidade , Peixes , Medição de Risco , Hormônios Tireóideos
9.
Aquat Toxicol ; 222: 105478, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32278258

RESUMO

This study was undertaken to systematically assess the utilities and performance of ontology-based semantic analysis in adverse outcome pathway (AOP) research. With an increasing number of AOPs developed by scientific domain experts to organize toxicity information and facilitate chemical risk assessment, there is a pressing need for objective approaches to evaluate the biological coherence and quality of these AOPs. Powered by ontologies covering a wide range of biological domains, abundant phenotypic data annotated ontologically, and some sophisticated knowledge computing tools, semantic analysis has great potential in this area of application. With the events in the AOP-Wiki first annotated into logical definitions and then grouped into phenotypic profiles by individual AOPs, the coherence and quality of AOPs were assessed at several levels: paired key event relationships (KER), all possible event pair combinations within AOPs, and the phenotypic profiles of AOPs, genes, biological pathways, human diseases, and selected chemicals. The semantic similarities were assessed at all these levels based on a unified cross-species vertebrate phenotype ontology encompassing the logical definitions of AOP events as well as many other domain ontologies. A substantial number of KERs and AOPs in the AOP-Wiki were found to be semantically coherent. These same coherent AOPs also mapped to many more genes, pathways, and diseases biologically aligned with the intended chain of events therein leading to their respective adverse outcomes. Significantly, these findings imply that semantic analysis should also have utilities in developing future AOPs by selecting candidate events from either the existing AOP-Wiki events or a broader collection of ontology terms semantically similar to the molecular initiating events or adverse outcomes of interest. In addition, semantic analysis enabled AOP networks to be constructed at the level of phenotypic profiles based on similarities, complementing those based on event sharing by bringing genes, pathways, diseases, and chemicals into the networks too-thus greatly expanding the biological scope and our understanding of AOPs.


Assuntos
Rotas de Resultados Adversos , Pesquisa Biomédica/métodos , Semântica , Toxicologia/métodos , Animais , Ontologias Biológicas , Humanos , Fenótipo , Medição de Risco
10.
Yakugaku Zasshi ; 140(4): 481-484, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-32238628

RESUMO

The latest chemical management policies require toxicological evaluation of marketed but untested chemicals. Furthermore, in Europe, for animal welfare reasons sales of cosmetics and raw materials for which animal experiments were conducted were totally banned, in 2013. Responding to these regulatory trends, a strong demand exists to develop new in vitro test methods and to improve in silico prediction models for safety assessments. In recent years, the development of adverse outcome pathways (AOPs) has been actively promoted in the Organisation for Economic Co-operation and Development (OECD). Since it is difficult to replace a particular in vivo animal test with a single in vitro test method or in silico prediction model, integrated approaches to testing and assessment (IATA) have been studied based on AOP information. With regard to skin sensitization, several in vitro test methods that measure key events of AOP have been established, and integrated strategies using in vitro tests have been examined using AOP. Currently, numerous AOPs are under development for a wide range of complex toxicity endpoints in the OECD AOP program. The AOPs are expected to contribute to the development of many accurate in vitro test methods and to establish IATA as well as to evaluate safety in humans of many substances, including household chemicals, food-related chemicals, cosmetics, and pharmaceuticals.


Assuntos
Rotas de Resultados Adversos , Segurança Química , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Medição de Risco/métodos , Experimentação Animal , Alternativas aos Testes com Animais , Animais , Simulação por Computador , Humanos , Técnicas In Vitro
11.
Yakugaku Zasshi ; 140(4): 485-489, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-32238629

RESUMO

The Organisation for Economic Co-operation and Development (OECD) has initiated the adverse outcome pathway (AOP) Development Program in which the concept of AOP is applied to evaluate the safety of molecules such as chemicals. This program aims to assist regulatory needs and construct a knowledge base by accumulating AOP case studies. AOP consists of a molecular initiating event (MIE) as the initiating event of the pathway; key events (KEs) as the events themselves, such as cellular-molecular interactions; and adverse outcome (AO), such as signaling transduction-induced toxicity, as adverse events. KEs are extracted as important events at various levels, such as the molecular, cellular, tissue, organ, individual, and species levels; measurement of KEs and key event relationships (KERs), including mechanisms, plausibility, species differences, and empirical support information, are gathered. The development status of the AOP relating to histone deacetylase inhibition-induced testicular toxicity, currently being reviewed by the OECD, has been introduced. The AOP describing malignancies by Wnt ligand stimulation and Wnt signaling activation using gene expression network analysis-based mechanisms in molecular pathway elucidation has been suggested.


Assuntos
Rotas de Resultados Adversos , Segurança Química , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Redes Reguladoras de Genes/genética , Animais , Humanos
12.
Yakugaku Zasshi ; 140(4): 491-498, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-32238630

RESUMO

Because the liver is the primary target organ for chemicals and pharmaceuticals, evaluation of these substances' liver toxicity is of critical importance. New evaluation methods without animal testing (i.e., in vitro and/or in silico) are eagerly anticipated, both for animal welfare and for decreasing cost. Also, the importance of mechanistic interpretation of the output derived from non-animal testing has been increasing. Accordingly, we investigated the potential for evaluating liver toxicity by applying the adverse outcome pathway (AOP) concept using gene set enrichment analysis (GSEA) from gene expression (GEx) data. A case study targeting hepatocellular fatty degeneration (HFD) is reported and discussed. We first identified the events detectable in an in vitro system by comparing the GEx data from the rat primary hepatocyte (in vitro) and rat liver (in vivo) treated with a chemical with the ability to induce HFD as one of the phenotypes in a 28-day repeated-dose toxicity test. Then, the scores based on GSEA were calculated after establishing the gene sets for each event leading to HFD. As a result, the mechanistic information leading to HFD was obtained from the score calculated based on the GSEA and the usefulness of the transcriptome-driven evaluation using AOP was demonstrated.


Assuntos
Rotas de Resultados Adversos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Testes de Toxicidade/métodos , Transcriptoma , Tecido Adiposo/metabolismo , Alternativas aos Testes com Animais , Bem-Estar do Animal , Animais , Simulação por Computador , Expressão Gênica , Hepatócitos/metabolismo , Humanos , Técnicas In Vitro , Ratos
13.
Yakugaku Zasshi ; 140(4): 499-505, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-32238631

RESUMO

Toxicity testing is critical for new drug and chemical development process. A clinical study, experimental animal models, and in vitro study are performed to evaluate the safety of a new drug. The limitations of these methods include extensive time for toxicity testing, an ethical problem, and high costs of experimentation. Therefore computational methods are considered useful for estimating chemical toxicity. In silico toxicity prediction is one of the toxicity assessments that uses computational methods to predict and stimulate the toxicity of chemicals. In silico study aims to contribute to effective development of new drug and chemical design. In this study, quantitative structure-activity relationship (QSAR) models will be used to predict toxicities based on chemical structural parameters. Because toxicities are complicated physiological phenomena, a similar toxicity expression might cause a different pathway. Also, since many drugs with unknown mechanisms of actions are available, the application of artificial intelligence (AI)-which uses sophisticated algorithms- is increasingly used to predict toxicities. Recently, the QSAR model was applied to determine complex relations between chemical structures and toxicities. However, accuracy of QSAR for toxicity prediction remains an important issue. International competitions funded by public institutions can address this issue. Two important toxicity challenges were organized in the past decade; this article presents issues of toxicity based on these challenges.


Assuntos
Rotas de Resultados Adversos , Inteligência Artificial , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Relação Quantitativa Estrutura-Atividade , Alternativas aos Testes com Animais , Animais , Simulação por Computador , Modelos Animais , Testes de Toxicidade/métodos
15.
Medicina (Kaunas) ; 56(3)2020 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-32183082

RESUMO

Background: Left ventricular assist device (LVAD) therapy has improved the clinical outcomes in advanced heart failure patients, however, this may differ between countries. We aimed to compare outcomes between Japanese and US LVAD cohorts. Methods: For 416 consecutive LVAD patients who received HeartMate II LVAD implantation and completed a one-year follow-up, age-matched Japanese patients (the Japanese registry for mechanically assisted circulatory support (J-MACS) group) and the US patients were compared for their clinical outcomes. Results: 154 J-MACS patients and 77 US patients were compared. Survival, free from hemocompatibility-related adverse events (HRAEs) in the J-MACS was statistically comparable with the US (75% vs. 63%, p = 0.79). J-MACS had more disabling strokes than the US (0.221 vs. 0.052/patient-year, p = 0.005), whereas there was less nonsurgical bleeding (0.045 vs. 0.117/patient-year, p = 0.024). The net hemocompatibility score was statistically comparable between the groups (1.54 vs. 1.19 points/patient, p = 0.99). Post-LVAD prothrombin time with international normalized ratio (INR) <1.5 (odds ratio 4.07) was a risk factor for HRAEs in J-MACS, whereas INR >3.0 (odds ratio 5.71) was a risk factor in the US (p < 0.05 for both). Conclusion: In the age-matched cohorts, the J-MACS group experienced more strokes, while the US group had more bleedings. "Tailor-made" therapeutic strategy might be required for each country, given the unique variation of HRAE incidence among each country.


Assuntos
Rotas de Resultados Adversos/estatística & dados numéricos , Desenho de Equipamento/normas , Insuficiência Cardíaca/cirurgia , Coração Auxiliar/efeitos adversos , Teste de Materiais/métodos , Adulto , Desenho de Equipamento/estatística & dados numéricos , Feminino , Humanos , Japão , Masculino , Teste de Materiais/estatística & dados numéricos , Pessoa de Meia-Idade , Estudos Prospectivos , Sistema de Registros/estatística & dados numéricos , Resultado do Tratamento , Estados Unidos
16.
Environ Int ; 138: 105673, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32217427

RESUMO

This paper presents a framework for organizing and accessing mechanistic data on chemical interactions. The framework is designed to support the assessment of risks from combined chemical exposures. The framework covers interactions between chemicals that occur over the entire source-to-outcome continuum including interactions that are studied in the fields of chemical transport, environmental fate, exposure assessment, dosimetry, and individual and population-based adverse outcomes. The framework proposes to organize data using a semantic triple of a chemical (subject), has impact (predicate), and a causal event on the source-to-outcome continuum of a second chemical (object). The location of the causal event on the source-to-outcome continuum and the nature of the impact are used as the basis for a taxonomy of interactions. The approach also builds on concepts from the Aggregate Exposure Pathway (AEP) and Adverse Outcome Pathway (AOP). The framework proposes the linking of AEPs of multiple chemicals and the AOP networks relevant to those chemicals to form AEP-AOP networks that describe chemical interactions that cannot be characterized using AOP networks alone. Such AEP-AOP networks will aid the construction of workflows for both experimental design and the systematic review or evaluation performed in risk assessments. Finally, the framework is used to link the constructs of existing component-based approaches for mixture toxicology to specific categories in the interaction taxonomy.


Assuntos
Rotas de Resultados Adversos , Projetos de Pesquisa , Medição de Risco
17.
Environ Health ; 19(1): 23, 2020 02 24.
Artigo em Inglês | MEDLINE | ID: mdl-32093744

RESUMO

BACKGROUND: In light of the vulnerability of the developing brain, mixture risk assessment (MRA) for the evaluation of developmental neurotoxicity (DNT) should be implemented, since infants and children are co-exposed to more than one chemical at a time. One possible approach to tackle MRA could be to cluster DNT chemicals in a mixture on the basis of their mode of action (MoA) into 'similar' and 'dissimilar', but still contributing to the same adverse outcome, and anchor DNT assays to common key events (CKEs) identified in DNT-specific adverse outcome pathways (AOPs). Moreover, the use of human in vitro models, such as induced pluripotent stem cell (hiPSC)-derived neuronal and glial cultures would enable mechanistic understanding of chemically-induced adverse effects, avoiding species extrapolation. METHODS: HiPSC-derived neural progenitors differentiated into mixed cultures of neurons and astrocytes were used to assess the effects of acute (3 days) and repeated dose (14 days) treatments with single chemicals and in mixtures belonging to different classes (i.e., lead(II) chloride and methylmercury chloride (heavy metals), chlorpyrifos (pesticide), bisphenol A (organic compound and endocrine disrupter), valproic acid (drug), and PCB138 (persistent organic pollutant and endocrine disrupter), which are associated with cognitive deficits, including learning and memory impairment in children. Selected chemicals were grouped based on their mode of action (MoA) into 'similar' and 'dissimilar' MoA compounds and their effects on synaptogenesis, neurite outgrowth, and brain derived neurotrophic factor (BDNF) protein levels, identified as CKEs in currently available AOPs relevant to DNT, were evaluated by immunocytochemistry and high content imaging analysis. RESULTS: Chemicals working through similar MoA (i.e., alterations of BDNF levels), at non-cytotoxic (IC20/100), very low toxic (IC5), or moderately toxic (IC20) concentrations, induce DNT effects in mixtures, as shown by increased number of neurons, impairment of neurite outgrowth and synaptogenesis (the most sensitive endpoint as confirmed by mathematical modelling) and increase of BDNF levels, to a certain extent reproducing autism-like cellular changes observed in the brain of autistic children. CONCLUSIONS: Our findings suggest that the use of human iPSC-derived mixed neuronal/glial cultures applied to a battery of assays anchored to key events of an AOP network represents a valuable approach to identify mixtures of chemicals with potential to cause learning and memory impairment in children.


Assuntos
Rotas de Resultados Adversos , Poluentes Ambientais/toxicidade , Síndromes Neurotóxicas/etiologia , Neurotoxinas/toxicidade , Disruptores Endócrinos/toxicidade , Humanos , Células-Tronco Pluripotentes Induzidas/efeitos dos fármacos , Metais Pesados/toxicidade , Células-Tronco Neurais/efeitos dos fármacos , Praguicidas/toxicidade , Bifenilos Policlorados/toxicidade , Medição de Risco , Testes de Toxicidade
18.
Food Chem Toxicol ; 138: 111185, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32058012

RESUMO

A model and data toolbox is presented to assess risks from combined exposure to multiple chemicals using probabilistic methods. The Monte Carlo Risk Assessment (MCRA) toolbox, also known as the EuroMix toolbox, has more than 40 modules addressing all areas of risk assessment, and includes a data repository with data collected in the EuroMix project. This paper gives an introduction to the toolbox and illustrates its use with examples from the EuroMix project. The toolbox can be used for hazard identification, hazard characterisation, exposure assessment and risk characterisation. Examples for hazard identification are selection of substances relevant for a specific adverse outcome based on adverse outcome pathways and QSAR models. Examples for hazard characterisation are calculation of benchmark doses and relative potency factors with uncertainty from dose response data, and use of kinetic models to perform in vitro to in vivo extrapolation. Examples for exposure assessment are assessing cumulative exposure at external or internal level, where the latter option is needed when dietary and non-dietary routes have to be aggregated. Finally, risk characterisation is illustrated by calculation and display of the margin of exposure for single substances and for the cumulation, including uncertainties derived from exposure and hazard characterisation estimates.


Assuntos
Método de Monte Carlo , Medição de Risco , Rotas de Resultados Adversos , Animais , Benchmarking , Análise de Dados , Bases de Dados Factuais , Exposição Ambiental , Substâncias Perigosas , Humanos , Modelos Estatísticos , Nível de Efeito Adverso não Observado , Relação Quantitativa Estrutura-Atividade , Incerteza
20.
Zhonghua Yu Fang Yi Xue Za Zhi ; 54(2): 219-223, 2020 Feb 06.
Artigo em Chinês | MEDLINE | ID: mdl-32074714

RESUMO

Risk assessment is a necessary technical means to protect human health and environmental safety. Traditional risk assessment based on toxicity data obtained from animal experiments was difficult to meet the need for risk assessment for a large number of chemicals due to the low throughput, long cycle, high cost and uncertainty of extrapolation to human exposure dose. The proposed risk assessment frameworks, the model of action (MOA) and the adverse outcome pathway (AOP), pointed the way for us to develop new and efficient evaluation methods. In this review, the basic concepts and contents of MOA and AOP, as well as the relationship between them, were introduced. Taking acrylamide (AA) as an example, this review briefly described the application of MOA/AOP framework in chemical risk assessment, so as to provide theoretical guidance for better application of MOA/AOP framework in chemical risk assessment.


Assuntos
Acrilamida/toxicidade , Medição de Risco/métodos , Rotas de Resultados Adversos , Humanos , Testes de Toxicidade
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