RESUMO
The HESI-coordinated RISK21 roadmap and matrix are tools that provide a transparent method to compare exposure and toxicity information and assess whether additional refinement is required to obtain the necessary precision level for a decision regarding safety. A case study of the use of a pyrethroid, "pseudomethrin," in bed netting to control malaria is presented to demonstrate the application of the roadmap and matrix. The evaluation began with a problem formulation step. The first assessment utilized existing information pertaining to the use and the class of chemistry. At each stage of the step-wise approach, the precision of the toxicity and exposure estimates were refined as necessary by obtaining key data which enabled a decision on safety to be made efficiently and with confidence. The evaluation demonstrated the concept of using existing information within the RISK21 matrix to drive the generation of additional data using a value-of-information approach. The use of the matrix highlighted whether exposure or toxicity required further investigation and emphasized the need to address the default uncertainty factor of 100 at the highest tier of the evaluation. It also showed how new methodology such as the use of in vitro studies and assays could be used to answer the specific questions which arise through the use of the matrix. The matrix also serves as a useful means to communicate progress to stakeholders during an assessment of chemical use.
Assuntos
Exposição Ambiental/efeitos adversos , Mosquiteiros Tratados com Inseticida/efeitos adversos , Piretrinas/toxicidade , Animais , Tomada de Decisões , Exposição Ambiental/análise , Humanos , Modelos Animais , Medição de Risco , Testes de Toxicidade , Estados Unidos , United States Environmental Protection AgencyRESUMO
Genetically modified (GM) crops have achieved success in the marketplace and their benefits extend beyond the overall increase in harvest yields to include lowered use of insecticides and decreased carbon dioxide emissions. The most widely grown GM crops contain gene/s for targeted insect protection, herbicide tolerance, or both. Plant expression of Bacillus thuringiensis (Bt) crystal (Cry) insecticidal proteins have been the primary way to impart insect resistance in GM crops. Although deemed safe by regulatory agencies globally, previous studies have been the basis for discussions around the potential immuno-adjuvant effects of Cry proteins. These studies had limitations in study design. The studies used animal models with extremely high doses of Cry proteins, which when given using the ig route were co-administered with an adjuvant. Although the presumption exists that Cry proteins may have immunostimulatory activity and therefore an adjuvanticity risk, the evidence shows that Cry proteins are expressed at very low levels in GM crops and are unlikely to function as adjuvants. This conclusion is based on critical review of the published literature on the effects of immunomodulation by Cry proteins, the history of safe use of Cry proteins in foods, safety of the Bt donor organisms, and pre-market weight-of-evidence-based safety assessments for GM crops.
Assuntos
Proteínas de Bactérias/genética , Qualidade de Produtos para o Consumidor , Produtos Agrícolas/genética , Endotoxinas/genética , Inocuidade dos Alimentos , Proteínas Hemolisinas/genética , Insetos/crescimento & desenvolvimento , Controle Biológico de Vetores/métodos , Plantas Geneticamente Modificadas/genética , Animais , Toxinas de Bacillus thuringiensis , Proteínas de Bactérias/imunologia , Proteínas de Bactérias/metabolismo , Produtos Agrícolas/imunologia , Produtos Agrícolas/metabolismo , Produtos Agrícolas/parasitologia , Endotoxinas/imunologia , Endotoxinas/metabolismo , Regulação da Expressão Gênica de Plantas , Genótipo , Proteínas Hemolisinas/imunologia , Proteínas Hemolisinas/metabolismo , Interações Hospedeiro-Parasita , Humanos , Insetos/metabolismo , Fenótipo , Plantas Geneticamente Modificadas/imunologia , Plantas Geneticamente Modificadas/metabolismo , Plantas Geneticamente Modificadas/parasitologia , Medição de RiscoRESUMO
In January 2014, an international meeting sponsored by the International Life Sciences Institute/Health and Environmental Sciences Institute and the Canadian Food Inspection Agency titled "Genetic Basis of Unintended Effects in Modified Plants" was held in Ottawa, Canada, bringing together over 75 scientists from academia, government, and the agro-biotech industry. The objectives of the meeting were to explore current knowledge and identify areas requiring further study on unintended effects in plants and to discuss how this information can inform and improve genetically modified (GM) crop risk assessments. The meeting featured presentations on the molecular basis of plant genome variability in general, unintended changes at the molecular and phenotypic levels, and the development and use of hypothesis-driven evaluations of unintended effects in assessing conventional and GM crops. The development and role of emerging "omics" technologies in the assessment of unintended effects was also discussed. Several themes recurred in a number of talks; for example, a common observation was that no system for genetic modification, including conventional methods of plant breeding, is without unintended effects. Another common observation was that "unintended" does not necessarily mean "harmful". This paper summarizes key points from the information presented at the meeting to provide readers with current viewpoints on these topics.
Assuntos
Produtos Agrícolas/genética , Alimentos Geneticamente Modificados , Plantas Geneticamente Modificadas/genética , Qualidade de Produtos para o Consumidor , Humanos , Medição de RiscoRESUMO
The HESI RISK21 project formed the Dose-Response/Mode-of-Action Subteam to develop strategies for using all available data (in vitro, in vivo, and in silico) to advance the next-generation of chemical risk assessments. A goal of the Subteam is to enhance the existing Mode of Action/Human Relevance Framework and Key Events/Dose Response Framework (KEDRF) to make the best use of quantitative dose-response and timing information for Key Events (KEs). The resulting Quantitative Key Events/Dose-Response Framework (Q-KEDRF) provides a structured quantitative approach for systematic examination of the dose-response and timing of KEs resulting from a dose of a bioactive agent that causes a potential adverse outcome. Two concepts are described as aids to increasing the understanding of mode of action-Associative Events and Modulating Factors. These concepts are illustrated in two case studies; 1) cholinesterase inhibition by the pesticide chlorpyrifos, which illustrates the necessity of considering quantitative dose-response information when assessing the effect of a Modulating Factor, that is, enzyme polymorphisms in humans, and 2) estrogen-induced uterotrophic responses in rodents, which demonstrate how quantitative dose-response modeling for KE, the understanding of temporal relationships between KEs and a counterfactual examination of hypothesized KEs can determine whether they are Associative Events or true KEs.
Assuntos
Carcinógenos/toxicidade , Modelos Teóricos , Medição de Risco/métodos , Toxicologia/métodos , Animais , Carcinógenos/química , Carcinógenos/metabolismo , Relação Dose-Resposta a Droga , Humanos , Especificidade da Espécie , Estados Unidos , United States Environmental Protection AgencyRESUMO
The Health and Environmental Sciences Institute (HESI)-coordinated Risk Assessment in the 21st Century (RISK21) project was initiated to develop a scientific, transparent, and efficient approach to the evolving world of human health risk assessment, and involved over 120 participants from 12 countries, 15 government institutions, 20 universities, 2 non-governmental organizations, and 12 corporations. This paper provides a brief overview of the tiered RISK21 framework called the roadmap and risk visualization matrix, and articulates the core principles derived by RISK21 participants that guided its development. Subsequent papers describe the roadmap and matrix in greater detail. RISK21 principles include focusing on problem formulation, utilizing existing information, starting with exposure assessment (rather than toxicity), and using a tiered process for data development. Bringing estimates of exposure and toxicity together on a two-dimensional matrix provides a clear rendition of human safety and risk. The value of the roadmap is its capacity to chronicle the stepwise acquisition of scientific information and display it in a clear and concise fashion. Furthermore, the tiered approach and transparent display of information will contribute to greater efficiencies by calling for data only as needed (enough precision to make a decision), thus conserving animals and other resources.
Assuntos
Exposição Ambiental , Nível de Saúde , Saúde Pública , Medição de Risco/métodos , Tomada de Decisões , Exposição Ambiental/efeitos adversos , Exposição Ambiental/prevenção & controle , Humanos , National Academy of Sciences, U.S. , Saúde Pública/métodos , Saúde Pública/tendências , Segurança , Reino Unido , Estados UnidosRESUMO
Abstract The RISK21 integrated evaluation strategy is a problem formulation-based exposure-driven risk assessment roadmap that takes advantage of existing information to graphically represent the intersection of exposure and toxicity data on a highly visual matrix. This paper describes in detail the process for using the roadmap and matrix. The purpose of this methodology is to optimize the use of prior information and testing resources (animals, time, facilities, and personnel) to efficiently and transparently reach a risk and/or safety determination. Based on the particular problem, exposure and toxicity data should have sufficient precision to make such a decision. Estimates of exposure and toxicity, bounded by variability and/or uncertainty, are plotted on the X- and Y-axes of the RISK21 matrix, respectively. The resulting intersection is a highly visual representation of estimated risk. Decisions can then be made to increase precision in the exposure or toxicity estimates or declare that the available information is sufficient. RISK21 represents a step forward in the goal to introduce new methodologies into 21st century risk assessment. Indeed, because of its transparent and visual process, RISK21 has the potential to widen the scope of risk communication beyond those with technical expertise.
Assuntos
Exposição Ambiental , Substâncias Perigosas/toxicidade , Medição de Risco/métodos , Tomada de Decisões , Exposição Ambiental/efeitos adversos , Exposição Ambiental/prevenção & controle , Substâncias Perigosas/química , Humanos , Modelos Teóricos , Probabilidade , Relação Quantitativa Estrutura-Atividade , Segurança , Reino Unido , Estados Unidos , United States Environmental Protection AgencyRESUMO
Quantitative methods for estimation of cancer risk have been developed for daily, lifetime human exposures. There are a variety of studies or methodologies available to address less-than-lifetime exposures. However, a common framework for evaluating risk from less-than-lifetime exposures (including short-term and/or intermittent exposures) does not exist, which could result in inconsistencies in risk assessment practice. To address this risk assessment need, a committee of the International Life Sciences Institute (ILSI) Health and Environmental Sciences Institute conducted a multisector workshop in late 2009 to discuss available literature, different methodologies, and a proposed framework. The proposed framework provides a decision tree and guidance for cancer risk assessments for less-than-lifetime exposures based on current knowledge of mode of action and dose-response. Available data from rodent studies and epidemiological studies involving less-than-lifetime exposures are considered, in addition to statistical approaches described in the literature for evaluating the impact of changing the dose rate and exposure duration for exposure to carcinogens. The decision tree also provides for scenarios in which an assumption of potential carcinogenicity is appropriate (e.g., based on structural alerts or genotoxicity data), but bioassay or other data are lacking from which a chemical-specific cancer potency can be determined. This paper presents an overview of the rationale for the workshop, reviews historical background, describes the proposed framework for assessing less-than-lifetime exposures to potential human carcinogens, and suggests next steps.
Assuntos
Carcinógenos/toxicidade , Exposição Ambiental/normas , Mutagênicos/toxicidade , Bioensaio/métodos , Carcinógenos/administração & dosagem , Bases de Dados Factuais , Árvores de Decisões , Relação Dose-Resposta a Droga , Determinação de Ponto Final , Contaminação de Alimentos/análise , Guias como Assunto , Produtos Domésticos/efeitos adversos , Humanos , Mutagênicos/administração & dosagem , National Institute of Environmental Health Sciences (U.S.) , Neoplasias/induzido quimicamente , Praguicidas/efeitos adversos , Medição de Risco , Fatores de Tempo , Estados Unidos , United States Environmental Protection Agency , United States Food and Drug AdministrationRESUMO
The public health and environmental communities will face many challenges during the next decade. To identify significant issues that might be addressed as part of the International Life Sciences Institute (ILSI) Health and Environmental Sciences Institute (HESI) scientific portfolio, an expert group of key government, academic, and industry scientists from around the world were assembled in 2009 to map the current and future landscape of scientific and regulatory challenges. The value of the scientific mapping exercise was the development of a tool which HESI, individual companies, research institutions, government agencies, and regulatory authorities can use to anticipate key challenges, place them into context, and thus strategically refine and expand scientific project portfolios into the future.
Assuntos
Saúde Ambiental/legislação & jurisprudência , Diretrizes para o Planejamento em Saúde , Prioridades em Saúde/tendências , Saúde Pública/tendências , Toxicologia/tendências , Academias e Institutos , Governo , Humanos , Indústrias , Medição de Risco/tendênciasRESUMO
The two-year cancer bioassay in rodents remains the primary testing strategy for in-life screening of compounds that might pose a potential cancer hazard. Yet experimental evidence shows that cancer is often secondary to a biological precursor effect, the mode of action is sometimes not relevant to humans, and key events leading to cancer in rodents from nongenotoxic agents usually occur well before tumorigenesis and at the same or lower doses than those producing tumors. The International Life Sciences Institute (ILSI) Health and Environmental Sciences Institute (HESI) hypothesized that the signals of importance for human cancer hazard identification can be detected in shorter-term studies. Using the National Toxicology Program (NTP) database, a retrospective analysis was conducted on sixteen chemicals with liver, lung, or kidney tumors in two-year rodent cancer bioassays, and for which short-term data were also available. For nongenotoxic compounds, results showed that cellular changes indicative of a tumorigenic endpoint can be identified for many, but not all, of the chemicals producing tumors in two-year studies after thirteen weeks utilizing conventional endpoints. Additional endpoints are needed to identify some signals not detected with routine evaluation. This effort defined critical questions that should be explored to improve the predictivity of human carcinogenic risk.
Assuntos
Testes de Carcinogenicidade/métodos , Carcinógenos/toxicidade , Bases de Dados Factuais , Neoplasias Experimentais/induzido quimicamente , Animais , Feminino , Humanos , Fenômenos do Sistema Imunitário/efeitos dos fármacos , Masculino , Camundongos , Neoplasias Experimentais/imunologia , Neoplasias Experimentais/patologia , Neoplasias Experimentais/prevenção & controle , Ratos , Ratos Endogâmicos F344 , Medição de Risco/métodosRESUMO
To predict important strategic issues in product safety during the next 10 years, the Health and Environmental Sciences Institute (HESI) of the International Life Sciences Institute initiated a mapping exercise to evaluate which issues are likely to be of societal, scientific, and regulatory importance to regulatory authorities, the HESI membership, and the scientific community at large. Scientists representing government, academia, and industry participated in the exercise. Societal issues identified include sensitive populations, alternative therapies, public education on the precautionary principle, obesity, and aging world populations. Scientific issues identified include cancer testing, children's health, mixtures and co-exposures, sensitive populations, idiosyncratic reactions, "omics" or bioinformatics, and environmental toxicology. Regulatory issues identified include national and regional legislation on chemical safety, exposure inputs, new technologies, transitioning new science into regulations and guidelines, conservative default factors, data quality, and sensitive populations. Because some issues were identified as important in all three areas (e.g. sensitive populations), a comprehensive approach to assessment and management is needed to ensure consideration of societal, scientific, and regulatory implications. The resulting HESI Combined Challenges Map is not intended to offer a universal description of challenges in safety assessment, nor is it intended to address, advocate, or manage the prioritized issues. Rather, the map focuses on and predicts issues likely to be central to the strategic agendas of individual companies and regulatory authorities in the developed world. Many of these issues will become increasingly important in the future in rapidly developing economies, such as India and China. The scientific mapping exercise has particular value to the toxicology community because it represents the contributions of key scientists from around the world from government, academia, and industry.
Assuntos
Ecologia/métodos , Saúde Ambiental/métodos , Monitoramento Ambiental , Saúde Pública/tendências , Medição de Risco/métodos , Ecologia/legislação & jurisprudência , Ecologia/tendências , Exposição Ambiental/prevenção & controle , Saúde Ambiental/legislação & jurisprudência , Saúde Ambiental/tendências , Humanos , Medição de Risco/legislação & jurisprudência , Medição de Risco/tendênciasRESUMO
The International Life Sciences Institute (ILSI) Health and Environmental Sciences Institute (HESI) established a Biomonitoring Technical Committee in 2002 to define and characterize appropriate scientific use(s) of biomonitoring tools and/or biomonitoring data needed to characterize exposure to chemicals, and to explore mechanisms for integrating biomonitoring exposure data and toxicology data into a robust risk assessment process. This paper summarizes the Technical Committee's initiatives and perspectives on improving the quality, value, application, and interpretation of human biomonitoring data for exposure and risk assessment purposes. Scientific outreach, collaborative partners, and new projects are described.
Assuntos
Biomarcadores/análise , Monitoramento Ambiental/métodos , Conferências de Consenso como Assunto , Monitoramento Ambiental/normas , Saúde Global , Humanos , Internacionalidade , Controle de Qualidade , Medição de Risco/métodosRESUMO
Biomonitoring programs in the United States and Europe demonstrate the vast array of data that are publicly available for the evaluation of exposure trends, identification of susceptible populations, detection of emerging chemical risks, the conduct of epidemiology studies, and evaluation of risk reduction strategies. To cultivate international discussion on these issues, the ILSI Health and Environmental Sciences Institute convened a scientific session at its annual meeting in January 2006 on "Integration of Biomonitoring Exposure Data into the Risk Assessment Process." This Forum paper presents perspectives from session speakers on the biomonitoring activities of the Centers for Disease Control and Prevention, the U.S. Environmental Protection Agency, the National Research Council Committee on Human Biomonitoring for Environmental Toxicants, the German Commission on Human Biomonitoring, and the Health and Environmental Sciences Institute Biomonitoring Technical Committee. Speakers noted that better estimates of biological concentrations of substances in the tissues of human populations can be combined with other exposure indices, as well as epidemiological and toxicologic data, to improve risk estimates. With this type of combined data, the potential also exists to define exposure levels at which hazard and risk are of minimal concern. Limitations in interpreting biomonitoring data were discussed, including the need for different criteria for applying biomonitoring data for exposure assessment, risk assessment, risk management, or disease prevention purposes. As efforts and resources are expended to improve the ability to apply biomonitoring exposure data in the risk assessment process, it is equally important to communicate the significance of such data to the public.
Assuntos
Monitoramento Ambiental , Alemanha , Órgãos Governamentais , Medição de Risco , Estados UnidosRESUMO
A pilot toxicology database system has been created which is accessible on-line via the world-wide web or in-house via an intranet. It is intended to be suitable as a source of toxicological information and to support structure-activity relationship studies, and it can be searched on chemical structural and substructural as well as toxicological and physico-chemical data. Successful completion of the pilot has led to an ongoing project to develop and expand the system.
Assuntos
Bases de Dados como Assunto , Toxicologia , Estudos de Viabilidade , Cooperação Internacional , Projetos Piloto , Software , Relação Estrutura-AtividadeRESUMO
FutureTox II, a Society of Toxicology Contemporary Concepts in Toxicology workshop, was held in January, 2014. The meeting goals were to review and discuss the state of the science in toxicology in the context of implementing the NRC 21st century vision of predicting in vivo responses from in vitro and in silico data, and to define the goals for the future. Presentations and discussions were held on priority concerns such as predicting and modeling of metabolism, cell growth and differentiation, effects on sensitive subpopulations, and integrating data into risk assessment. Emerging trends in technologies such as stem cell-derived human cells, 3D organotypic culture models, mathematical modeling of cellular processes and morphogenesis, adverse outcome pathway development, and high-content imaging of in vivo systems were discussed. Although advances in moving towards an in vitro/in silico based risk assessment paradigm were apparent, knowledge gaps in these areas and limitations of technologies were identified. Specific recommendations were made for future directions and research needs in the areas of hepatotoxicity, cancer prediction, developmental toxicity, and regulatory toxicology.
Assuntos
Simulação por Computador , Técnicas In Vitro , Toxicologia/métodos , Toxicologia/tendências , Congressos como Assunto , Valor Preditivo dos Testes , Sociedades Científicas , Estados UnidosRESUMO
The scope of allergy risk is diverse considering the myriad ways in which protein allergenicity is affected by physiochemical characteristics of proteins. The complexity created by the matrices of foods and the variability of the human immune system add additional challenges to understanding the relationship between sensitization potential and allergy disease. To address these and other issues, an April 2012 international symposium was held in Prague, Czech Republic, to review and discuss the state-of-the-science of sensitizing properties of protein allergens. The symposium, organized by the Protein Allergenicity Technical Committee of the International Life Sciences Institute's Health and Environmental Sciences Institute, featured presentations on current methods, test systems, research trends, and unanswered questions in the field of protein sensitization. A diverse group of over 70 interdisciplinary scientists from academia, government, and industry participated in the symposium. Experts provided overviews on known mechanisms by which proteins in food may cause sensitization, discussed experimental models to predict protein sensitizing potential, and explored whether such experimental techniques may be applicable in regulatory settings. Three accompanying reviews address critical factors and methods for assessing allergic sensitization: 1) food-and protein-related factors; 2) host-specific factors and 3) screening methods, i.e., the ability of experimental models to predict the sensitizing potential of proteins and whether such models are applicable within regulatory settings.
RESUMO
The practice of toxicology is changing rapidly, as demonstrated by the response to the 2007 NRC report on "Toxicity Testing in the 21(st) Century." New assays are being developed to replace animal testing; yet the use of data from these assays in decision making is not clear. A Health and Environmental Sciences Institute committee held a May 2011 workshop to discuss approaches to identifying adverse effects in the context of the NRC report. Scientists from industry, government, academia, and NGOs discussed two case studies and explored how information from new, high data content assays developed for screening can be used to differentiate adverse effects from adaptive responses. The terms "adverse effect" and "adaptive response" were defined, as well as two new terms, the relevant pathways of toxicological concern (RPTCs) and relevant responses for regulation (RRRs). RPTCs are biochemical pathways associated with adverse events and need to be elucidated before they are used in regulatory decision making. RRRs are endpoints that are the basis for risk assessment and may or may not be at the level of pathways. Workshop participants discussed the criteria for determining whether, at the RPTC level, an effect is potentially adverse or potentially indicative of adaptability, and how the use of prototypical, data-rich compounds could lead to a greater understanding of RPTCs and their use as RRRs. Also discussed was the use of RPTCs in a weight-of-evidence approach to risk assessment. Inclusion of data at this level could decrease uncertainty in risk assessments but will require the use of detailed dosimetry and consideration of exposure context and the time and dose continuum to yield scientifically based decisions. The results of this project point to the need for an extensive effort to characterize RPTCs and their use in risk assessment to make the vision of the 2007 NRC report a reality.
Assuntos
Toxicologia , História do Século XXI , Medição de Risco , Testes de ToxicidadeRESUMO
Assessing the risk profiles of potentially sensitive populations requires a "tool chest" of methodological approaches to adequately characterize and evaluate these populations. At present, there is an extensive body of literature on methodologies that apply to the evaluation of the pediatric population. The Health and Environmental Sciences Institute Subcommittee on Risk Assessment of Sensitive Populations evaluated key references in the area of pediatric risk to identify a spectrum of methodological approaches. These approaches are considered in this article for their potential to be extrapolated for the identification and assessment of other sensitive populations. Recommendations as to future research needs and/or alternate methodological considerations are also made.
Assuntos
Modelos Biológicos , Saúde Pública/métodos , Testes de Toxicidade/métodos , Adolescente , Adulto , Fatores Etários , Biomarcadores/metabolismo , Criança , Pré-Escolar , Relação Dose-Resposta a Droga , Exposição Ambiental , Monitoramento Ambiental , Predisposição Genética para Doença , Regulamentação Governamental , Política de Saúde , Humanos , Lactente , Recém-Nascido , Farmacocinética , Saúde Pública/legislação & jurisprudência , Medição de Risco , Fatores de RiscoRESUMO
Although rarely occurring in humans, hemangiosarcomas (HS) have become important in evaluating the potential human risk of several chemicals, including industrial, agricultural, and pharmaceutical agents. Spontaneous HS arise frequently in mice, less commonly in rats, and frequently in numerous breeds of dogs. This review explores knowledge gaps and uncertainties related to the mode of action (MOA) for the induction of HS in rodents, and evaluates the potential relevance for human risk. For genotoxic chemicals (vinyl chloride and thorotrast), significant information is available concerning the MOA. In contrast, numerous chemicals produce HS in rodents by nongenotoxic, proliferative mechanisms. An overall framework is presented, including direct and indirect actions on endothelial cells, paracrine effects in local tissues, activation of bone marrow endothelial precursor cells, and tissue hypoxia. Numerous obstacles are identified in investigations into the MOA for mouse HS and the relevance of the mouse tumors to humans, including lack of identifiable precursor lesions, usually late occurrence of the tumors, and complexities of endothelial biology. This review proposes a working MOA for HS induced by nongenotoxic compounds that can guide future research in this area. Importantly, a common MOA appears to exist for the nongenotoxic induction of HS, where there appears to be a convergence of multiple initiating events (e.g., hemolysis, decreased respiration, adipocyte growth) leading to either dysregulated angiogenesis and/or erythropoiesis that results from hypoxia and macrophage activation. These later events lead to the release of angiogenic growth factors and cytokines that stimulate endothelial cell proliferation, which, if sustained, provide the milieu that can lead to HS formation.
Assuntos
Hemangiossarcoma/patologia , Animais , Carcinógenos/toxicidade , DNA/efeitos dos fármacos , Cães , Hemangiossarcoma/induzido quimicamente , Hemangiossarcoma/epidemiologia , Humanos , Camundongos , Neovascularização Patológica/patologia , Neovascularização Fisiológica/fisiologia , Receptores Ativados por Proliferador de Peroxissomo/agonistas , Ratos , Medição de Risco , Especificidade da Espécie , Cloreto de Vinil/toxicidadeRESUMO
Better understanding of toxicological mechanisms, enhanced testing capabilities, and demands for more sophisticated data for safety and health risk assessment have generated international interest in improving the current testing paradigm for agricultural chemicals. To address this need, the ILSI Health and Environmental Sciences Institute convened a large and diverse group of international experts to develop a credible and viable testing approach that includes scientifically appropriate studies that are necessary without being redundant, and that emphasize toxicological endpoints and exposure durations that are relevant for risk assessment. Benefits of the proposed approach include improved data for risk assessment, greater efficiency, use of fewer animals, and better use of resources. From the outset of this endeavor, it was unanimously agreed that a tiered approach should be designed to incorporate existing knowledge on the chemistry, toxicology, and actual human exposure scenarios of the compound, with integration of studies on metabolism/kinetics, life stages, and systemic toxicities. Three international task forces were charged with designing study types and endpoints on metabolism/kinetics, life stages, and systemic toxicities to be used in the tiered approach. This tiered testing proposal departs from the current standardized list of hazard studies used by many national authorities, and represents the first comprehensive effort of its kind to scientifically redesign the testing framework for agricultural chemicals.
Assuntos
Agroquímicos/toxicidade , Gestão da Segurança , Humanos , Medição de RiscoRESUMO
A proposal has been developed by the Agricultural Chemical Safety Assessment (ACSA) Technical Committee of the ILSI Health and Environmental Sciences Institute (HESI) for an improved approach to assessing the safety of crop protection chemicals. The goal is to ensure that studies are scientifically appropriate and necessary without being redundant, and that tests emphasize toxicological endpoints and exposure durations that are relevant for risk assessment. Incorporation of pharmacokinetic studies describing absorption, distribution, metabolism, and excretion is an essential tool for improving the design and interpretation of toxicity studies and their application for safety assessment. A tiered approach is described in which basic pharmacokinetic studies, similar to those for pharmaceuticals, are conducted for regulatory submission. Subsequent tiers provide additional information in an iterative manner, depending on pharmacokinetic properties, toxicity study results, and the intended uses of the compound.