Chemical Risk Assessment (original) (raw)
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Accelerating the Pace of Chemical Risk Assessment
Chemical research in toxicology, 2018
Changes in chemical regulations worldwide have increased the demand for new data on chemical safety. New approach methodologies (NAMs) are defined broadly here as including in silico approaches and in chemico and in vitro assays, as well as the inclusion of information from the exposure of chemicals in the context of hazard [European Chemicals Agency, " New Approach Methodologies in Regulatory Science ", 2016]. NAMs for toxicity testing, including alternatives to animal testing approaches, have shown promise to provide a large amount of data to fill information gaps in both hazard and exposure. In order to increase experience with the new data and to advance the applications of NAM data to evaluate the safety of data-poor chemicals, demonstration case studies have to be developed to build confidence in their usability. Case studies can be used to explore the domains of applicability of the NAM data and identify areas that would benefit from further research, development, a...
Chemical Risk Assessment: Traditional vs Public Health Perspectives
American journal of public health, 2017
Preventing adverse health effects of environmental chemical exposure is fundamental to protecting individual and public health. When done efficiently and properly, chemical risk assessment enables risk management actions that minimize the incidence and effects of environmentally induced diseases related to chemical exposure. However, traditional chemical risk assessment is faced with multiple challenges with respect to predicting and preventing disease in human populations, and epidemiological studies increasingly report observations of adverse health effects at exposure levels predicted from animal studies to be safe for humans. This discordance reinforces concerns about the adequacy of contemporary risk assessment practices for protecting public health. It is becoming clear that to protect public health more effectively, future risk assessments will need to use the full range of available data, draw on innovative methods to integrate diverse data streams, and consider health endpo...
evaluated eight approaches for selecting genes for POD derivation and three previously proposed approaches (the lowest pathway BMD, and the mean and median BMD of all genes). The relationship between transcriptional BMDs derived using these 11 approaches and PODs derived from apical data that might be used in chemical risk assessment was examined. Transcriptional BMD values for all 11 approaches were remarkably aligned with corresponding apical PODs, with the vast majority of toxicogenom-ics PODs being within tenfold of those derived from api-cal endpoints. We identified at least four approaches that produce BMDs that are effective estimates of apical PODs across multiple sampling time points. Our results support that a variety of approaches can be used to derive reproducible transcriptional PODs that are consistent with PODs produced from traditional methods for chemical risk assessment.
4.6 Toxicogenomics and biology-based modeling framework for health risk assessment
Human & Experimental Toxicology, 2009
The Scientific Steering Committee 87 Declaration of Como 89 Provisional Definition of an Evidence-Based Toxicology 91 1 Fundamentals of a an evidence-based toxicology 1.1 Opening statement T Hartung 93 1.2 Aspects of test assessment S Hoffmann 95 1.3 Consensus, opinion, and evidence-based sciencethree methods of reaching conclusions in toxicology P Guzelian 97 1.4 Comparing medicine with toxicology -a mapping of knowledge creation, concepts and basic epistemology C Griesinger 101 2. Evidence-based medicine -a possible model for evidence-based toxicology? 2.1 Translation of evidence-based medicine into practice EAM Neugebauer 105 2.2 Evidence-based health care and the Cochrane Collaboration RW Scherer 109 3. Core problems and case studies 3.1 Key challenges of toxicology ME Cebrián 113 3.2 Quantification of uncertainty within and between species and the role of uncertainty factors L Edler 115 3.3 Trovafloxacin: a case study of idiosyncratic or iatrogenic liver toxicity -molecular mechanisms and lessons for pharmacotoxicity J Borlak 119 4 Toxicological decision-making on hazards and risksstatus quo and way forward 4.1 Current concepts and schemes of science-driven toxicological decisionmaking -an overview C Portier 123 4.2 Applying an evidence-based approach: arsenic as a health risk E Silbergeld 127 4.3 In-vitro genotoxicity tests to detect carcinogenicity: a systematic review L Müller 131 4.4 The proposed replacement of the no observed adverse effect level with benchmark dose levels in food risk assessment L Edler 135 4.5 Evidence-based individual toxicological analysis P Guzelian 136 4.6 Toxicogenomics and biology-based modeling framework for health risk assessment D Sarigiannis 139 4.7 Biological modeling as a method for data evaluation and integration in toxicology HA Barton 143 4.8 Current schemes for decision-making in toxicology C Griesinger, S Hoffmann, A Kinsner, S Coecke and T Hartung 147 4.9 Current information sources for hazard identification C Griesinger, S Hoffmann, A Kinsner, S Coecke and T Hartung 149 5 Steps toward an evidence-based toxicology 5.1 Evidence-based tools in toxicological basic research C Griesinger, S Hoffmann, A Kinsner, S Coecke and T Hartung 151 5.2 Evidence-based tools in toxicological hazard identification C Griesinger, S Hoffmann, A Kinsner, S Coecke and T Hartung 153 5.3 Evidence-based tools in toxicological decision-making C Griesinger, S Hoffmann, A Kinsner, S Coecke and T Hartung 155 5.4 Possible improvement of information sources on hazard and risk C Griesinger, S Hoffmann, A Kinsner, S Coecke and T Hartung 157 5.5 Standardization: an efficient tool to support evidence-based toxicology A Pirlet 159 5.6 An online portal to evidence-based toxicology A Kinsner-Ovaskainen, C Griesinger, S Hoffmann, S Coecke, G Bowe, C Campana and T Hartung 161 6 Conclusions I Kimber 163 7 Annex 7.1 Suggested Charge Questions for Break-out group work 165
On the incorporation of chemical-specific information in risk assessment
Toxicology Letters, 2008
This paper describes the evolution of chemical risk assessment from its early dependence on generic default approaches to the current situation in which mechanistic and biokinetic data are routinely incorporated to support a more chemical-specific approach. Two methodologies that have played an important role in this evolution are described: mode-of-action evaluation and physiologically based biokinetic (PBBK) modelling. When used together, these techniques greatly increase the opportunity for the incorporation of biokinetic and mechanistic data in risk assessment. The resulting risk assessment approaches are more appropriately tailored to the specific chemical and are more likely to provide an accurate assessment of the potential hazards associated with human exposures. The appropriate application of PBBK models in risk assessment demands well-formulated statements about the chemical mode of action. It is this requirement for an explicit, mechanistic hypothesis that gives biologically motivated models their power, but at the same time serves as the greatest impediment to the acceptance of a chemical-specific risk assessment approach by regulators. The chief impediment to the regulatory acceptance and application of PBBK models in risk assessment is concern about uncertainties associated with their use. To some extent such concerns can be addressed by the development of generally accepted approaches for model evaluation and quantitative uncertainty analysis. In order to assure the protection of public health while limiting the economic and social consequences of over-regulation, greater dialogue between researchers and regulators is crucially needed to foster an increased use of emerging scientific information and innovative methods in chemical risk assessments.
A walk in the PARC: developing and implementing 21st century chemical risk assessment in Europe
Archives of Toxicology, 2023
Current approaches for the assessment of environmental and human health risks due to exposure to chemical substances have served their purpose reasonably well. Nevertheless, the systems in place for different uses of chemicals are faced with various challenges, ranging from a growing number of chemicals to changes in the types of chemicals and materials produced. This has triggered global awareness of the need for a paradigm shift, which in turn has led to the publication of new concepts for chemical risk assessment and explorations of how to translate these concepts into pragmatic approaches. As a result, nextgeneration risk assessment (NGRA) is generally seen as the way forward. However, incorporating new scientific insights and innovative approaches into hazard and exposure assessments in such a way that regulatory needs are adequately met has appeared to be challenging. The European Partnership for the Assessment of Risks from Chemicals (PARC) has been designed to address various challenges associated with innovating chemical risk assessment. Its overall goal is to consolidate and strengthen the European research and innovation capacity for chemical risk assessment to protect human health and the environment. With around 200 participating organisations from all over Europe, including three European agencies, and a total budget of over 400 million euro, PARC is one of the largest projects of its kind. It has a duration of seven years and is coordinated by ANSES, the French Agency for Food, Environmental and Occupational Health & Safety. Keywords Next-generation risk assessment (NGRA) • Chemicals • Safety assessment • Exposure assessment • Hazard characterisation • Human biomonitoring (HBM) • New approach methods (NAM)
Toxics
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. R...
Toxicogenomic profiling of chemically exposed humans in risk assessment
Mutation Research/Reviews in Mutation Research, 2010
Gene-environment interactions contribute to complex disease development. The environmental contribution, in particular low-level and prevalent environmental exposures, may constitute much of the risk and contribute substantially to disease. Systematic risk evaluation of the majority of human chemical exposures, has not been conducted and is a goal of regulatory agencies in the U.S. and worldwide. With the recent recognition that toxicological approaches more predictive of effects in humans are required for risk assessment, in vitro human cell line data as well as animal data are being used to identify toxicity mechanisms that can be translated into biomarkers relevant to human exposure studies. In this review, we discuss how data from toxicogenomic studies of exposed human populations can inform risk assessment, by generating biomarkers of exposure, early effect, and/or susceptibility, elucidating mechanisms of action underlying exposure-related disease, and detecting response at low doses. Good experimental design incorporating precise, individual exposure measurements, phenotypic anchors (pre-disease or traditional toxicological markers), and a range of relevant exposure levels, is necessary. Further, toxicogenomic studies need to be designed with sufficient power to detect true effects of the exposure. As more studies are performed and incorporated into databases such as the Comparative Toxicogenomics Database (CTD) and Chemical Effects in Biological Systems (CEBS), data can be mined for classification of newly tested chemicals (hazard identification), and, for investigating the dose-response, and interrelationship among genes, environment and disease in a systems biology approach (risk characterization).