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The EU-ToxRisk project: An integrated program driving mechanism-based toxicity testing and risk assessment
Toxicology Letters 280S (2017) S56–S57
Contents lists available at ScienceDirect
Toxicology Letters journal homepage: www.elsevier.com/locate/toxlet
Hands-on risk assessment in the 21st century: reports from the front line
S23-01 The HESI Risk 21 project: An innovative tool in risk assessment
S23-02 The EU-ToxRisk project: An integrated program driving mechanism-based toxicity testing and risk assessment
Alan Boobis 1 , Michelle Embry 2 , Timothy Pastoor 3 Bob van de Water 1
Centre for Pharmacology & Therapeutics, Imperial College London, London, United Kingdom 2 ILSI Health and Environmental Sciences Institute (HESI), Washington, DC, United States 3 Pastoor Science Communication, LLC, Greensboro, NC, United Kingdom Whilst current approaches to the risk assessment of chemicals have served us well, they need to be updated to reflect advances in science and to better address the needs of risk assessment. The ILSI Health and Environmental Sciences Institute (HESI) has therefore developed Risk Assessment in the 21st Century (RISK21), a framework for the scientific, transparent and efficient assessment of chemical risk to human health. The RISK21 framework was designed around the way in which chemical risk assessment information is obtained and used. It is a problem formulation-based, exposure driven, tiered approach that enables an informed decision to be made on the risk to human health when sufficient information is obtained. Two case studies were developed to illustrate application of the framework. In the first, a new ‘nth’ in class insecticide was assessed for use in treatment of mosquito bed nets to help prevent malaria. Existing knowledge from similar chemicals and their use patterns was used to direct the testing strategy and help in making recommendations. In the second case study, a large number of chemicals had been detected in surface and ground water. As these might enter drinking water they needed to be prioritised for their potential human health concern. Approaches to use of the framework for assessing possible cumulative risk from these chemicals were also developed. These case studies established the utility of the framework in assessing the value of available information and what, if any, additional information would be needed to enable conclusions on chemical safety. http://dx.doi.org/10.1016/j.toxlet.2017.07.139
0378-4274/
Leiden Academic Centre for Drug Research, Leiden University, Leiden, Netherlands The EU-ToxRisk aims to drive a paradigm shift in toxicology towards an animal-free, mechanism-based integrated approach to chemical safety assessment. The project will unite all relevant disciplines and stakeholders to establish: (i) pragmatic, solid read-across procedures incorporating mechanistic and toxicokinetic knowledge; and (ii) ab initio hazard and risk assessment strategies of chemicals with little background information. The project is focused on repeated dose systemic toxicity (liver, kidney, lung and nervous system) as well as developmental/reproduction toxicity. Different human tiered test systems are integrated to balance speed, cost and biological complexity. Advanced technologies, including high throughput transcriptomics, RNA interference, and high throughput microscopy, will provide quantitative and mechanistic underpinning of toxic events. The project combines in silico tools and in vitro assays by computational modelling approaches. The EU-ToxRisk work plan is structured along a broad spectrum of case studies, driven by the cosmetics, (agro)-chemical, pharma industry together with regulators. The approach involves iterative training, testing, optimization and validation phases to establish fitfor-purpose integrated approaches to testing and assessment with key EU-ToxRisk methodologies. The presentation will highlight the main results of the project so far, exemplified by two case studies focused around solutions for biological read-across-based risk assessment using liver steatotis induced by various valproic analogues on the one hand and neuronal toxicity caused by mitotoxic pesticides and insecticides on the other hand as proof-of-concept studies. http://dx.doi.org/10.1016/j.toxlet.2017.07.140
Contents lists available at ScienceDirect
Toxicology Letters journal homepage: www.elsevier.com/locate/toxlet
Hands-on risk assessment in the 21st century: reports from the front line
S23-01 The HESI Risk 21 project: An innovative tool in risk assessment
S23-02 The EU-ToxRisk project: An integrated program driving mechanism-based toxicity testing and risk assessment
Alan Boobis 1 , Michelle Embry 2 , Timothy Pastoor 3 Bob van de Water 1
Centre for Pharmacology & Therapeutics, Imperial College London, London, United Kingdom 2 ILSI Health and Environmental Sciences Institute (HESI), Washington, DC, United States 3 Pastoor Science Communication, LLC, Greensboro, NC, United Kingdom Whilst current approaches to the risk assessment of chemicals have served us well, they need to be updated to reflect advances in science and to better address the needs of risk assessment. The ILSI Health and Environmental Sciences Institute (HESI) has therefore developed Risk Assessment in the 21st Century (RISK21), a framework for the scientific, transparent and efficient assessment of chemical risk to human health. The RISK21 framework was designed around the way in which chemical risk assessment information is obtained and used. It is a problem formulation-based, exposure driven, tiered approach that enables an informed decision to be made on the risk to human health when sufficient information is obtained. Two case studies were developed to illustrate application of the framework. In the first, a new ‘nth’ in class insecticide was assessed for use in treatment of mosquito bed nets to help prevent malaria. Existing knowledge from similar chemicals and their use patterns was used to direct the testing strategy and help in making recommendations. In the second case study, a large number of chemicals had been detected in surface and ground water. As these might enter drinking water they needed to be prioritised for their potential human health concern. Approaches to use of the framework for assessing possible cumulative risk from these chemicals were also developed. These case studies established the utility of the framework in assessing the value of available information and what, if any, additional information would be needed to enable conclusions on chemical safety. http://dx.doi.org/10.1016/j.toxlet.2017.07.139
0378-4274/
Leiden Academic Centre for Drug Research, Leiden University, Leiden, Netherlands The EU-ToxRisk aims to drive a paradigm shift in toxicology towards an animal-free, mechanism-based integrated approach to chemical safety assessment. The project will unite all relevant disciplines and stakeholders to establish: (i) pragmatic, solid read-across procedures incorporating mechanistic and toxicokinetic knowledge; and (ii) ab initio hazard and risk assessment strategies of chemicals with little background information. The project is focused on repeated dose systemic toxicity (liver, kidney, lung and nervous system) as well as developmental/reproduction toxicity. Different human tiered test systems are integrated to balance speed, cost and biological complexity. Advanced technologies, including high throughput transcriptomics, RNA interference, and high throughput microscopy, will provide quantitative and mechanistic underpinning of toxic events. The project combines in silico tools and in vitro assays by computational modelling approaches. The EU-ToxRisk work plan is structured along a broad spectrum of case studies, driven by the cosmetics, (agro)-chemical, pharma industry together with regulators. The approach involves iterative training, testing, optimization and validation phases to establish fitfor-purpose integrated approaches to testing and assessment with key EU-ToxRisk methodologies. The presentation will highlight the main results of the project so far, exemplified by two case studies focused around solutions for biological read-across-based risk assessment using liver steatotis induced by various valproic analogues on the one hand and neuronal toxicity caused by mitotoxic pesticides and insecticides on the other hand as proof-of-concept studies. http://dx.doi.org/10.1016/j.toxlet.2017.07.140