Post on 20-Jul-2020
NAS Green Chemistry Workshop, 20-21 September 2011, Washington DC
The Use of New Toxicological Tools within a Chemical Risk Assessment Framework: An EU
PerspectiveApplying 21st Century Toxicology to Green Chemical and Material Design
National Academy of Sciences Workshop 20
European Commission’s Joint Research Centre
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The Use of New Toxicological Tools within a Chemical Risk Assessment Framework: An EU
PerspectiveCentury Toxicology to Green Chemical and Material Design
National Academy of Sciences Workshop 20 -21 September 2011Sharon Munn
Systems ToxicologyInstitute of Health and Consumer Protection
European Commission’s Joint Research CentreIspra, Italy
NAS Green Chemistry Workshop, 20-21 September 2011, Washington DC
OUTLINE• Introduction to EC’s Joint Research Centre
what we do • Regulatory landscape – setting the scene• Emerging technologies and application to more predictive risk
assessment• Use Cases
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OUTLINEIntroduction to EC’s Joint Research Centre - who we are and
setting the sceneEmerging technologies and application to more predictive risk
NAS Green Chemistry Workshop, 20-21 September 2011, Washington DC
As a Directorate-General of the European Commission,the Joint Research Centre provides customer-driven scientific and technical support to Community policy making
Supporting citizen’s security, healthand environmental protection, safety of food and chemicals, alternative energies, nuclear safety, econometrics, prospective technologies…
JRC - Robust Science for Policy Making3
Robust Science for Policy Making
NAS Green Chemistry Workshop, 20-21 September 2011, Washington DC
IHCP supporting EU legislation involving Risk Assessment- Chemicals, REACH&CLP (DG Enterprise & Industry, DG Environment, ECHA)
- Cosmetics (DG Health & Consumers, DG Enterprise & Industry )
- Biocides (DG Environment, DG Health & Consumers)
- Plant Protection Products (DG Environment,
- Food Safety, inc. GM, Novel (DG Health & Consumers, EFSA)
- General Consumer Product Safety
Cross-cutting legislation and issues- Protection of Animals used for Scientific Purposes. - Safety of Nanomaterials.
- Identification of Endocrine Active/Disrupting (ED) chemicals.- Combination effects of chemical mixtures (CEMC)
Policy Support4
IHCP supporting EU legislation involving Risk Assessment, REACH&CLP (DG Enterprise & Industry, DG Environment, ECHA)
(DG Health & Consumers, DG Enterprise & Industry )
(DG Environment, DG Health & Consumers)
(DG Environment, DG Health & Consumers)
, inc. GM, Novel (DG Health & Consumers, EFSA)
General Consumer Product Safety (DG Health & Consumers)
cutting legislation and issuesused for Scientific Purposes.
Endocrine Active/Disrupting (ED) chemicals.Combination effects of chemical mixtures (CEMC)
Policy Support
NAS Green Chemistry Workshop, 20-21 September 2011, Washington DC
INTERNATIONAL COLLABORATIONS• Agreement signed between IHCP and NCCT of the US Environmental
Protection Agency, to facilitate exchange of research results and materials in relation to the ToxCast programme
• TOX21 Consortium• OECD QSAR Tool Box• OECD Molec Screening & Toxicogenomics• WHO/IPCS MoA framework • ILSI/HESI Risk 21• EPA NexGen• Global Risk Assessment dialogue
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INTERNATIONAL COLLABORATIONSAgreement signed between IHCP and NCCT of the US Environmental Protection Agency, to facilitate exchange of research results and materials in relation to the ToxCast programme
OECD Molec Screening & Toxicogenomics
NAS Green Chemistry Workshop, 20-21 September 2011, Washington DC
Expert judgment of Weight of evidence
Animal model
DEFAULT: hazardous property relevant to humans (qualitative aspect) and humans at least as sensitive as animal (quantitative aspect),
Account for variability and uncertainty in animal model with additional factors
REGULATORY TOXICOLOGY 6
Expert judgment of Weight of evidence
Human
DEFAULT: hazardous property relevant to humans (qualitative aspect) and humans at least as sensitive as animal (quantitative aspect),
Account for variability and uncertainty in animal model with additional factors
REGULATORY TOXICOLOGY - CURRENT MODEL
NAS Green Chemistry Workshop, 20-21 September 2011, Washington DC
WHY CHANGE?• Potential benefits?
– Ethical - reduce reliance on in vivo– Regulators need faster cheaper methods to screen many chemicals
already in the environment to identify the bad actors which require risk management –
– Product designers need {same}many chemicals to deselect bad actors from product development and prevent entry into the environment
– More predictive/accurate risk assessment from bettter understanding of why chemicals are toxic
Undesirable scenario
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WHY CHANGE?
in vivo testing in animals. Regulators need faster cheaper methods to screen many chemicals already in the environment to identify the bad actors which require
{same} faster cheaper methods to screen many chemicals to deselect bad actors from product development and prevent entry into the environment -More predictive/accurate risk assessment from bettter understanding
Undesirable scenario
Desirable scenario
NAS Green Chemistry Workshop, 20-21 September 2011, Washington DC
Regulatory Drivers: Challenges and Opportunities• DIRECTIVE 2010/63/EU OF THE EUROPEAN PARLIAMENT
AND OF THE COUNCIL of 22 September 2010 on the protection of animals used for scientific purposes (replacing 86/609/EEC)– Chapter V. Avoidance of duplication and alternative approaches– 3Rs: replacement, reduction, refinement– EU Reference Lab (ECVAM) to coordinate and promote
development and use of alternatives
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Regulatory Drivers: Challenges and OpportunitiesDIRECTIVE 2010/63/EU OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL of 22 September 2010 on the protection of animals used for scientific purposes (replacing
Chapter V. Avoidance of duplication and alternative approaches3Rs: replacement, reduction, refinementEU Reference Lab (ECVAM) to coordinate and promote development and use of alternatives
NAS Green Chemistry Workshop, 20-21 September 2011, Washington DC
Strong regulatory incentive in product legislation
Ø Directive on Cosmetic products 76/768marketing. Following provisions introducedØ A testing ban of finished cosmetic productsØ A testing ban on ingredients or combinationsØ A marketing ban since March 2009, it isand their ingredients which have been testedproducts.
ØExtension of deadline to MarchØRepeated dose toxicity (carcinogenicityØReproductive toxicityØToxicokinetics
Regulatory Drivers: Challenges and Opportunities 9
Strong regulatory incentive in product legislation
768/EEC introduces a ban on testing andintroduced by Dir. 2003/15/EC
products since September 2004combinations of ingredients since March 2009.
prohibited in the EU to market cosmetic productstested on animals, irrespective of the origin of these
March 2013 for complex endpoints(carcinogenicity and skin sensitisation)
Regulatory Drivers: Challenges and Opportunities - Cosmetics
NAS Green Chemistry Workshop, 20-21 September 2011, Washington DC
2013 MARKETING BAN
State of the Art Review"Alternative (non-animal) methods for cosmetics testing: current status and future prospects—2010" in Archives of Toxicology: Vol 85, (5) (2011), p367 http://ec.europa.eu/consumers/sectors/cosmetics/files/pdf/animal_testing/final_report_at_en.pdf• MAIN FINDINGS
–Advanced methods and approaches hold a lot of promise for the future development of more predictive risk assessment, based on improved understanding of how toxic substances reach the target cells/organs (toxicokinetics) and perturb critical biological pathways.–The central importance of toxicokinetics is underlined
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2013 MARKETING BAN – COSMETICS
animal) methods for cosmetics testing: current status and 2010" in Archives of Toxicology: Vol 85, (5) (2011), p367
http://ec.europa.eu/consumers/sectors/cosmetics/files/pdf/animal_testing/final
Advanced methods and approaches hold a lot of promise for the future development of more predictive risk assessment, based on improved understanding of how toxic substances reach the target cells/organs (toxicokinetics) and perturb critical biological pathways.
The central importance of toxicokinetics is underlined
NAS Green Chemistry Workshop, 20-21 September 2011, Washington DC
Regulatory Drivers: Challenges and Opportunities
Strong regulatory incentives introduced in product legislation• REACH (EC1907/2006) introduces the 3Rs principle by
avoidance of duplication of testingconcept of generating information by means other than the standard tests in the testing annexes (sostandard testing regime)– REACH Guidance on ITS and use of QSARs (2008)
http://guidance.echa.europa.eu/docs/guidance_document/information_requirements_en.htm
– The use of alternatives to testing on animals for the REACH Regulation 2011http://echa.europa.eu/publications/alternatives_test_animals_2011_en.asp
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Regulatory Drivers: Challenges and Opportunities - REACH
Strong regulatory incentives introduced in product legislationintroduces the 3Rs principle by
avoidance of duplication of testing and introducing the concept of generating information by means other than the standard tests in the testing annexes (so-called ‘adaptation’ of
REACH Guidance on ITS and use of QSARs (2008) http://guidance.echa.europa.eu/docs/guidance_document/information
The use of alternatives to testing on animals for the REACH
http://echa.europa.eu/publications/alternatives_test_animals_2011_e
NAS Green Chemistry Workshop, 20-21 September 2011, Washington DC
Plant Protection Products (Regulation 1107/2009)• active substances only approved if free of ED properties or exposure negligible.• by end of 2013, the EC (DG ENV) must present criteria for evaluation of substances to
identify possible ED properties.
REACH (Regulation 1907/2006)• information on endocrine disrupting (ED) properties might be asked by the competent Authorities
during substance evaluation. • possible inclusion of substances in Annex XIV if weight of evidence shows that it has
properties (similar to CMR- and PB-type concerns)
Biocides (Regulation COM(2009)267, revision)• active substances with ED properties "on the basis of …. Community or internationally agreed
test guidelines" are possible candidates for substitution, may lose lowmore complete risk characterisation.
EDCs and legislation12
Plant Protection Products (Regulation 1107/2009)active substances only approved if free of ED properties or exposure negligible.by end of 2013, the EC (DG ENV) must present criteria for evaluation of substances to
information on endocrine disrupting (ED) properties might be asked by the competent Authorities
possible inclusion of substances in Annex XIV if weight of evidence shows that it has ED type concerns)
Biocides (Regulation COM(2009)267, revision)"on the basis of …. Community or internationally agreed
are possible candidates for substitution, may lose low-risk status, might require
EDCs and legislation
NAS Green Chemistry Workshop, 20-21 September 2011, Washington DC
Political mandate to take action (2009)• Council of EU MS Environment Ministers invited the European Commission
(EC) "to consider appropriate modifications, guidelines and assessment methods, and report back to the Council by early 2012 at the latest".
State of the science• State of the Art Report on Mixture Toxicity presented in June 2010
conclude that sufficient information is available to start developing technical guidelines which could be applied across the different pieces of EU legislation.
Scientific opinion• Scientific Committees supporting DG Health and Consumers (DG SANCO)
expected to issue their views and recommendations shortly.
Political impetus • Danish Environment Minister - "Policy options for assessing the combined
effects of groups of substances [..] will be among Denmark's environmental policy priorities during its presidency of the EU in the first half of 2012".
CEMCs and legislation13
Political mandate to take action (2009)Council of EU MS Environment Ministers invited the European Commission (EC) "to consider appropriate modifications, guidelines and assessment methods, and report back to the Council by early 2012 at the latest".
State of the Art Report on Mixture Toxicity presented in June 2010 - DG ENV conclude that sufficient information is available to start developing technical guidelines which could be applied across the different pieces of EU legislation.
Scientific Committees supporting DG Health and Consumers (DG SANCO) expected to issue their views and recommendations shortly.
"Policy options for assessing the combined effects of groups of substances [..] will be among Denmark's environmental policy priorities during its presidency of the EU in the first half of 2012".
CEMCs and legislation
NAS Green Chemistry Workshop, 20-21 September 2011, Washington DC
SCREENING AND PRIORITISATION • Situations where animal data not mandatory or impractical, need
predictive screening tools to identify potential bad actors [PBTs, vPvBs, CMRs, EDs]. – Prioritisation of water contaminants under Water Framework Directive– Asssessment of pesticide metabolites in food or feed– Prioritisation of lower tonnage substances for evaluation in REACH
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SCREENING AND PRIORITISATION –USE CASESSituations where animal data not mandatory or impractical, need predictive screening tools to identify potential bad actors [PBTs,
Prioritisation of water contaminants under Water Framework DirectiveAsssessment of pesticide metabolites in food or feedPrioritisation of lower tonnage substances for evaluation in REACH
NAS Green Chemistry Workshop, 20-21 September 2011, Washington DC
WHAT’S NEW
Emerging technologies and application to more predictive risk assessment
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WHAT’S NEW
Emerging technologies and application to more predictive risk assessment
NAS Green Chemistry Workshop, 20-21 September 2011, Washington DC
Computational Toxicology
Automation of in vitro methods
HTS/HCA
3D in vitrotissue models
PBBK Models
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EMERGING TECHNOLOGIES
Human stem cells
genomics, proteomics,
metabonomics
tissue models
PBBK Models
NAS Green Chemistry Workshop, 20-21 September 2011, Washington DC
Strategy - Hypothesis-driven MoA– Purpose driven approach to design of test systems based on mode of
action of chemicals– Identify critical events in mode of action upstream from apical
endpoint – Develop methods (in vitro) for measuring such critical events– Form chemical categories based on structure
activity relationships– Provide data for modelling, grouping and prediction. – Use of in vitro/in silico/in vivo in combination – Extrapolate from in vitro dose concentration response to in vivo dose
response
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driven MoA-based approachPurpose driven approach to design of test systems based on mode of
Identify critical events in mode of action upstream from apical
Develop methods (in vitro) for measuring such critical eventsForm chemical categories based on structure-activity and activity-
Provide data for modelling, grouping and prediction. Use of in vitro/in silico/in vivo in combination – learning feedbackExtrapolate from in vitro dose concentration response to in vivo dose
NAS Green Chemistry Workshop, 20-21 September 2011, Washington DC
Biochemical / Metabolic PathwaysCourtesy of Roche
Disturbance
Toxicological effect
Systemic toxicity deals with a complex system
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Systemic toxicity deals with a complex system
NAS Green Chemistry Workshop, 20-21 September 2011, Washington DC
MechanismsS.
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Mechanisms in Drug-Induced Hepatotoxicity. Russmann, Current Med. Chemistry, 2009, 16, 3041-3053
NAS Green Chemistry Workshop, 20-21 September 2011, Washington DC
Applying MOA-based approach in the laboratory
• An in vitro testing strategy to identifyhepatotoxic in humans and to associate(MoA) categories.– Using HepaRG metabolically competent– High Content Analysis (HCA) using
number of parameters at the same– Categorize chemicals according to– Comparison between in vitro and
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based approach in the laboratory
identify chemicals that are potentiallyassociate them with specific Mode-of-Action
competent cell lineusing automated cell imaging to measure
same timeto their responses
and in vivo data
NAS Green Chemistry Workshop, 20-21 September 2011, Washington DC
Cell Count ROS Intensity
Nuclear Intensity
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4
8
11 4Not Toxic
Cell Count ROS Intensity
Nuclear Intensity
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9
4
8
11 4Not Toxic
Cell culturing and differentiation
Data AnalysisChemicals
categorization
In vitro Workflow21
Cell treatment: HTS (92 chemicals, qHTS format, 16 conc, 1:2 dil.)
Endpoints Measurement: HCS(cell loss, DNA content, steatosis, ROS, caspase3, cyt c)
In vitro Workflow
NAS Green Chemistry Workshop, 20-21 September 2011, Washington DC
Neuronal Electrophysiology
• Microelectrode arrays– Measuring electrical activity in neuronal cells– Rat embryonic cortical neurons– Measure effects at sub-cytotoxic concentrations in specialised
cells– Functional assay based on a “living sample” which can be
monitored over time (low dose chronic toxicity studies).– Combinations of chemicals -– Network of communicating cells not amenable to automation
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Neuronal Electrophysiology - “the in vitro EEG”
Measuring electrical activity in neuronal cellsRat embryonic cortical neurons
cytotoxic concentrations in specialised
Functional assay based on a “living sample” which can be monitored over time (low dose chronic toxicity studies).
- Mixture effectsNetwork of communicating cells not amenable to automation
NAS Green Chemistry Workshop, 20-21 September 2011, Washington DC
MEA chipNeuronal Electrophysiology- “the in vitro EEG”
Analysis
firing rate
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MEA chip
Signal acquisition
Signal processing
NAS Green Chemistry Workshop, 20-21 September 2011, Washington DC
Computational Toxicology
ChemicalReactivity
Mathematical Modelling
Complex Networks
( )
−⋅+
−⋅= i
ii
ii
tAtAtI21
expexp 21 ττ
StructureActivity/Prop.
Relations
Data & Info Management
Biophysics & PBBK
Biostatistics
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Computational Toxicology
Structure-Activity/Prop.
Relations
Exploit existing data !
Read AcrossApplicability
Domains
Chemical Categories
Data & Info Management
NAS Green Chemistry Workshop, 20-21 September 2011, Washington DC
Human bioconcentration factor
A. Tonnelier, S. Coecke, J-M Zaldívar, Screening of chemicals for human bioaccumulation potential with a physiologically based toxicokinetic model;
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Human bioconcentration factor
M Zaldívar, Screening of chemicals for human bioaccumulation potential with a physiologically based toxicokinetic model; submitted
NAS Green Chemistry Workshop, 20-21 September 2011, Washington DC 26
NAS Green Chemistry Workshop, 20-21 September 2011, Washington DC
Repeated dose toxicity
Acrylamide, fibroblasts (3T3), NRU, repeat
“Towards the replacement of repeated dose systemic toxicity testing on animals”
6 projects, 70 institutions, 5 years,1 coord action, 50 MEuro, public
“Safety Assessment Ultimately Replacing Animal Testing”
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Repeated dose toxicity
Acrylamide, fibroblasts (3T3), NRU, repeat-dose, every 24h for 96h
“Towards the replacement of repeated dose systemic toxicity testing on animals”
6 projects, 70 institutions, 5 years,1 coord action, 50 MEuro, public-private partnership
“Safety Assessment Ultimately Replacing Animal Testing”
NAS Green Chemistry Workshop, 20-21 September 2011, Washington DC
“Safety Evaluation Ultimately Replacing Animal Testing” SEURAT
The SEURAT strategy is to adopt a toxicological modeto describe how any substance may adversely affect human health, and to use this knowledge to develop complimentary theoretical, computational and experimental (in vitro) models that predict quantitative points of departure needed for safety assessment.
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“Safety Evaluation Ultimately Replacing Animal Testing” SEURAT
The SEURAT strategy is to adopt a toxicological mode-of-action framework to describe how any substance may adversely affect human health, and to use this knowledge to develop complimentary theoretical, computational and experimental (in vitro) models that predict quantitative points of departure needed for safety assessment.
NAS Green Chemistry Workshop, 20-21 September 2011, Washington DC
The Building Blocks of SEURAT
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Stem cell differentiation for providing humanspecific target cells
Identification and investigation of human biomarkers
Delivery of computational tools to predict the effects of chemicals based on silico calculations and estimation techniques
Development of systems biological tools for organotypic human cell cultures
Supporting integrated data analysis and servicing of alternative testing methods in toxicologyCluster level Coordinating and Support Action
Development of a hepatic microfluidic bioreactor
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The Building Blocks of SEURAT-1
coach-arttic@eurtd.com29
Stem cell differentiation for providing human-based organ
Identification and investigation of human biomarkers
Delivery of computational tools to predict the effects of chemicals based on in calculations and estimation techniques
Development of systems biological tools for organotypic human cell
Supporting integrated data analysis and servicing of alternative testing
Cluster level Coordinating and Support Action
Development of a hepatic microfluidic bioreactor
NAS Green Chemistry Workshop, 20-21 September 2011, Washington DC
VALIDATION
• Validation– an intrinsic part of the scientific process– needs to be ‘fit for purpose’’ depending on how data will
ultimately be used - screening, weight of evidence, or critical data in regulatory decision
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VALIDATION
an intrinsic part of the scientific processneeds to be ‘fit for purpose’’ depending on how data will
screening, weight of evidence, or critical data in regulatory decision-making
NAS Green Chemistry Workshop, 20-21 September 2011, Washington DC
Test definition
Within-lab reproducibility
Transferability
Between-lab reproducibility
Predictive capacity
Applicability domain
Performance standards
VALIDATION
ECVAM Modular Approach31
Reliability
Relevance
Validation Managem
ent
Independent Peer Review
VALIDATION
ECVAM Modular Approach
NAS Green Chemistry Workshop, 20-21 September 2011, Washington DC
Use of automation in validation
NRU 3T3 cytotoxicity assay- first example of formal ECVAM validation activity involving an automated assay
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Use of automation in validation
NAS Green Chemistry Workshop, 20-21 September 2011, Washington DC
ICCVAM/NICEATM Coordinated Study• Reporter gene assay - ER binding.• Agonist and antagonist formats.• 78 chemicals in test set.• 3 test labs (manual) inc. ECVAM.• Peer review March 2011.
“LUMI-CELL” Automation
• qHTS format with 96-well plates.• 16 plates/concentrations, DL of 2. • 44 chemicals per plate, 2 replicates.• 3 biological repeats.• pos/neg control, fixed conc, 4 replicates.• Acceptance and normalisation criteria needed adapting.
Automation at IHCP
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ICCVAM/NICEATM Coordinated Study
C1
C16
C2
CELL” Automation
Acceptance and normalisation criteria needed adapting.
NAS Green Chemistry Workshop, 20-21 September 2011, Washington DC
HARMONISED PLATFORM FOR DATA EXCHANGE
OECD harmonised template 201• IHCP in collaboration with OECD and ECHA are now
developing a new harmonised template to capture in vitro/in silico data as ‘íntermediate effects’ within a toxicity pathway/mode of action framework
• Building a taxonomy of intermediate effects which may ultimately be identified as key events in a mode of action/adverse outcome pathway
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HARMONISED PLATFORM FOR DATA EXCHANGE
IHCP in collaboration with OECD and ECHA are now developing a new harmonised template to capture in vitro/in silico data as ‘íntermediate effects’ within a toxicity pathway/mode of action frameworkBuilding a taxonomy of intermediate effects which may ultimately be identified as key events in a mode of action/adverse outcome pathway
NAS Green Chemistry Workshop, 20-21 September 2011, Washington DC
USE CASES IN HAZARD ASSESSMENT• A model-based prioritisation exercise for the European Water Framework
Directive. • Computational models for prediction of nanoparticle toxicity.
– Development of computational models to predict the behaviour of nanomaterials in biological systems to allow researchers to streamline and prioritise the toxicological testing of nanomaterials. http://ihcp.jrc.ec.europa.eu/our_labs/computational_toxicology/computationalpredict-nanoparticle-toxicity
• Prospects for the use of computational methods in the toxicological assessment of chemicals in food. – JRC update of results obtained in the PESTISAR project, performed during 2009
the EFSA.• A framework for assessing in silico toxicity predictions: Case studies with
selected pesticides. http://ihcp.jrc.ec.europa.eu/our_labs/computational_toxicology/publications
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USE CASES IN HAZARD ASSESSMENTbased prioritisation exercise for the European Water Framework
Computational models for prediction of nanoparticle toxicity. Development of computational models to predict the behaviour of nanomaterials in biological systems to allow researchers to streamline and prioritise the toxicological testing of
http://ihcp.jrc.ec.europa.eu/our_labs/computational_toxicology/computational-models-
Prospects for the use of computational methods in the toxicological assessment
JRC update of results obtained in the PESTISAR project, performed during 2009-2010 for
toxicity predictions: Case studies with
http://ihcp.jrc.ec.europa.eu/our_labs/computational_toxicology/publications
NAS Green Chemistry Workshop, 20-21 September 2011, Washington DC
Hazard:• Persistence(BIOWIN, BIOHCWIN and OECD Povand LRTP screening tool)• Bioaccumulation(EPI BCFBAF, CAESARBioaccumulation, JRC QSAR BCF)• Toxicity(3 ADMET QSAR Toxicity models)
Risk Ratio =
RISK
Daginnus, K. et al, Int. J. Environ. Res. Public Health
Use of computational methods to evaluate over 2000 substances for the European Water Framework Directive
Identification of Priority Hazardous Substances36
Exposure:• EU production level(IUCLID and SPIN databases)• Use(IUCLID database)•Environmental data/Multimedia modelling(ECETOC TRA tool and OECD Pov and LRTP screening tool)
Risk Ratio = PECPNEC
RISK
Daginnus, K. et al, Int. J. Environ. Res. Public Health 2011, 8, 435-455
Use of computational methods to evaluate over 2000 substances for the European Water Framework Directive
Identification of Priority Hazardous Substances
NAS Green Chemistry Workshop, 20-21 September 2011, Washington DC
European Partnership for Alternative Approaches to Animal Testing• Public/Private partnership between the European Commission,
European trade associations, and companies from seven industry sectors. – The partners are committed to pooling knowledge and resources to accelerate the
development, validation and acceptance of alternative approaches to further the replacement, reduction and refinement (3Rs) of animal use in regulatory testing.
Lead theme for 2011 "Integrated Testing Strategies and their impact on the 3Rs"
• Integrated Testing Strategies for more scienceanimal-reduction approaches.
http://ec.europa.eu/enterprise/epaa/index_en.htm
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European Partnership for Alternative Approaches to Animal TestingPublic/Private partnership between the European Commission, European trade associations, and companies from seven industry
The partners are committed to pooling knowledge and resources to accelerate the development, validation and acceptance of alternative approaches to further the replacement, reduction and refinement (3Rs) of animal use in regulatory testing.
Lead theme for 2011 "Integrated Testing Strategies and their impact on the
Integrated Testing Strategies for more science-based, faster throughput and
http://ec.europa.eu/enterprise/epaa/index_en.htm
NAS Green Chemistry Workshop, 20-21 September 2011, Washington DC
CONCLUDING REMARKS• Strong regulatory drivers to find alternative approaches less
reliant on animals• Adopt toxicological mode of action framework as a strategy
within which to apply new knowledge and tools• Recognise importance of reliability and relevance of results• Apply in vitro/in silico/in vivo in integrated manner• Increased interaction between disciplines but also industry cross
sector sharing of ideas and data• Establishment of in vitro to in vivo extrapolation models
importance of toxicokinetics
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CONCLUDING REMARKSStrong regulatory drivers to find alternative approaches less
Adopt toxicological mode of action framework as a strategy within which to apply new knowledge and toolsRecognise importance of reliability and relevance of resultsApply in vitro/in silico/in vivo in integrated mannerIncreased interaction between disciplines but also industry cross-sector sharing of ideas and dataEstablishment of in vitro to in vivo extrapolation models –
NAS Green Chemistry Workshop, 20-21 September 2011, Washington DC
Thank you
Sharon.Munn@ec.europa.eu
http://ihcp.jrc.ec.europa.eu/
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