ICCS Human Health
INTERNATIONAL COLLABORATION ON COSMETICS SAFETY
MAPPING / BACKGROUND RESEARCH
List of Services
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Endocrine Disruptors: Identification of the Available In Vitro and In Silico Assays and Approaches to Determine Whether a Given Chemical has the Potential to Cause an Adverse Event as a Direct Consequence of an Endocrine Disruptive Mode of Action.
Establish a combination of assays that is sufficient to assess potential endocrine-disrupting chemicals; determine performance of individual assays; determine if available assays be useful for underpinning endocrine mode of action; determine if an in vitro/in silico framework to assess potential endocrine-disrupting chemicals can be established.
Endocrine Disruptors: Identification of the Available In Vitro and In Silico Assays and Approaches to Determine Whether a Given Chemical has the Potential to Cause an Adverse Event as a Direct Consequence of an Endocrine Disruptive Mode of Action.
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Read Across: Increasing Confidence and Consistency in Analogue Identification, Evaluation, and Assessment Through Case Study for Fragrance Chemicals Through Incorporation of NAMs into Read Across.
Use read across (RAX) informed by NAMs to identify and rate chemical analogues to bring consistency, transparency, and toxicological relevance to RAX; Identifying biological / functional analogues based on modes of action (MoA) data is a parallel effort.
Read Across: Increasing Confidence and Consistency in Analogue Identification, Evaluation, and Assessment Through Case Study for Fragrance Chemicals Through Incorporation of NAMs into Read Across.
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Systemic Toxicity: Informing Toxicologically Relevant Molecular and Cellular Targets Using Expert-Guided AI / Machine Learning (ML) Approach
Enhance our understanding of systemic toxicity Modes of Action (MoAs); expand the coverage of existing Next-Generation Risk Assessment (NGRA) tools; pinpoint potential gaps or needs for higher-tier testing.
Systemic Toxicity: Informing Toxicologically Relevant Molecular and Cellular Targets Using Expert-Guided AI / Machine Learning (ML) Approach
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Systemic Toxicity: Landscape Analysis in Support of ICCS Prioritization of Activities in Systemic Toxicity for Human Safety Assessments
Describe existing efforts, and highlight gaps, challenges, and opportunities, in developing animal-free frameworks for systemic toxicity assessment based on In Vitro, In Chemico, and or In Silico approaches.
Systemic Toxicity: Landscape Analysis in Support of ICCS Prioritization of Activities in Systemic Toxicity for Human Safety Assessments
DEVELOPMENT
List of Services
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Pharmacology Profiling: Including Phase 1 Metabolite Testing in In Vitro Pharmacology Profiling of Test Chemicals
Standardize methods for generating metabolites In Vitro with human and rat liver S9; assess the impact of metabolic capability on target pharmacology activities of cosmetic relevant test chemicals; develop experimental workflow.
Pharmacology Profiling: Including Phase 1 Metabolite Testing in In Vitro Pharmacology Profiling of Test Chemicals
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Cheminformatics: Increase Transparency and Rigor in Read-Across While Reducing Reliance on Expert Judgment
Identify / select / develop tools that permit the selection of quality analogues while supporting their use in a prediction; Incorporation of subsequent NAM assay data into quantitative similarities supporting scientifically sound read-across case studies.
Cheminformatics: Increase Transparency and Rigor in Read-Across While Reducing Reliance on Expert Judgment
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Skin Sensitization: Evaluation of Information From Skin Sensitization New Approach Methodologies not Currently Utilized as Inputs for Available Defined Approaches Within the Next Generation Risk Assessment Framework.
Help address potential uncertainties in defined approach (DA) and risk assessment outcomes, arising from for example in-consistent / borderline or out of domain NAM information, interpretation of the Margin of Exposure (MoE) and the interchangeability of different NAM.
Skin Sensitization: Evaluation of Information From Skin Sensitization New Approach Methodologies not Currently Utilized as Inputs for Available Defined Approaches Within the Next Generation Risk Assessment Framework.
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Toxicogenomics: Create a Universal Intuitive Tool for Toxicogenomics Application that Drives the use of the Technology for Safety Decision Making Among ICCS Members, Partners, and Regulatory Authorities
Develop a user-friendly tool for toxicogenomics applications in grouping and read across, points of departure calculations, and modes of action determination.
Toxicogenomics: Create a Universal Intuitive Tool for Toxicogenomics Application that Drives the use of the Technology for Safety Decision Making Among ICCS Members, Partners, and Regulatory Authorities
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Cheminformatics: Development of a Cheminformatics Platform to Support a Toxicity Global Prediction System (CE- ToxGPS) Based on ChemTunes•ToxGPS®
Develop a workflow that evaluates and integrates chemical descriptors, legacy in vitro and in vivo data on the chemicals of interest plus chemically and biologically similar compounds, plus new data generated.
Cheminformatics: Development of a Cheminformatics Platform to Support a Toxicity Global Prediction System (CE- ToxGPS) Based on ChemTunes•ToxGPS®
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Genotoxicity: Development of a Novel Skin-Based Photogenotoxicity Assay
Integrate the 3D skin phototoxicity assay (OECD TG 498) with the reconstructed skin micronucleus (RSMN) assay; fills a gap with a predictive In Vitro model to evaluate the photoclastogenic potential of chemicals, and in skin.
Genotoxicity: Development of a Novel Skin-Based Photogenotoxicity Assay
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Internal Exposure: Inhalation TTC (Threshold of Toxicological Concern) Project, Led by Inhalation Expert Team (ET Inh)
Define threshold values for airborne compounds below which inhalation exposure is of low to negligible risk to human health and are predictive of lifetime exposures.
Internal Exposure: Inhalation TTC (Threshold of Toxicological Concern) Project, Led by Inhalation Expert Team (ET Inh)
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Internal Exposure: Alternative Approaches to Build a Valid PBPK Model for use in Cosmetic Human Safety Assessment.
Evaluation of pharmacokinetic (PK) analog and physiologically based pharmacokinetic (PBPK) modeling read across concept; Develop guidance on analog selection; develop chemical specific PBPK model.
Internal Exposure: Alternative Approaches to Build a Valid PBPK Model for use in Cosmetic Human Safety Assessment.
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Internal Exposure: Pilot Study to Evaluate a Methodology to Characterize the Kinetics of Serum Protein Binding to Inform Decision Making for Hepatic Clearance IVIVE for PBK Modelling
Investigate the feasibility of measuring association/dissociation constants as source of data to inform on the likely effect of differences in protein binding In Vitro and In Vivo on metabolism clearance extrapolation.
Internal Exposure: Pilot Study to Evaluate a Methodology to Characterize the Kinetics of Serum Protein Binding to Inform Decision Making for Hepatic Clearance IVIVE for PBK Modelling
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Higher Tier Evaluation: Botanical Based Thresholds of Toxicological Concern – Guidance for Application to Botanical Mixtures
Establish practical strategies to assist safety assessment of botanical mixtures by evaluating current TTC approaches and developing a relevant working framework.
Higher Tier Evaluation: Botanical Based Thresholds of Toxicological Concern – Guidance for Application to Botanical Mixtures
STANDARDIZATION / VALIDATION
List of Services
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Pharmacology Profiling: Completion of Feasibility Study on Pharmacology Profiling of Cosmetic Relevant Chemicals
Develop an in vitro pharmacology profiling toolbox which informs the assessment of systemic toxicity mode of action of cosmetic ingredients; provides quantitative data on an In Vitro bioactivity points of departure that can aid NGRAs.
Pharmacology Profiling: Completion of Feasibility Study on Pharmacology Profiling of Cosmetic Relevant Chemicals
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Skin Sensitization: Uncertainty Assessment in the Skin Sensitization NGRA
Description of NAM-based skin sensitization NGRA uncertainty sources, including hierarchies and interdependencies; NGRA case study demonstrating the application and appropriateness of the Margin of Exposure (MoE) approach.
Skin Sensitization: Uncertainty Assessment in the Skin Sensitization NGRA
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Skin Sensitization: Skin Sensitization Assessment Options for Lipophilic Compounds, Mixtures and Polymers
Enable the assessment of skin sensitization adverse outcome pathway (AOP) Key Event 2 (keratinocytes activation, resulting in upregulation of inflammatory cytokines and chemokines, and induction of cytoprotective gene pathways) for challenging compounds.
Skin Sensitization: Skin Sensitization Assessment Options for Lipophilic Compounds, Mixtures and Polymers
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Genotoxicity: Improving the Predictive Capacity of the In Vitro Genotoxicity Testing Battery: Improving External Metabolic Systems to Better Reflect the Human Situation, as well as Realistic Exposure Scenarios.
Apply a more human and tissue-relevant metabolic system to in vitro genotoxicity assays; proof-of-concept studies using above chemicals for with genotoxic potential is known to be impacted by Phase 2 metabolism (bioactivated or detoxified).
Genotoxicity: Improving the Predictive Capacity of the In Vitro Genotoxicity Testing Battery: Improving External Metabolic Systems to Better Reflect the Human Situation, as well as Realistic Exposure Scenarios.
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Internal Exposure: Development of an Internal Threshold of Toxicological Concern (iTTC)
Supports the final aspects associated with the development of TTCs based on internal exposure, (e.g., the chemical concentration in plasma) for use in a next generation safety assessment framework.
Internal Exposure: Development of an Internal Threshold of Toxicological Concern (iTTC)
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Internal Exposure: Development of Guidance for the Generation of Fraction Unbound in Plasma (Fup) Data for Cosmetics Relevant “Difficult to Test Chemicals” for PBK Model Parameterization
Evaluation of Fup methodologies; Guidance, decision criteria and workflows to support fup data generation for highly protein bound and/or highly hydrophobic chemicals.
Internal Exposure: Development of Guidance for the Generation of Fraction Unbound in Plasma (Fup) Data for Cosmetics Relevant “Difficult to Test Chemicals” for PBK Model Parameterization
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Internal Exposure: Enabling In Vitro to In Vivo Extrapolation (IVIVE) for Human Skin S9 Metabolism
Develop best practices for skin S9 and scaling factor to use for IVIVE; create workflow for IVIVE for skin metabolism.
Internal Exposure: Enabling In Vitro to In Vivo Extrapolation (IVIVE) for Human Skin S9 Metabolism
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External Exposure: Comparing Consumer and Occupational Exposure to Cosmetic Ingredients
This project will test the hypothesis that consumer exposure to cosmetic ingredients is higher (and therefore protective of) workers involved in manufacture and/or formulation could provide an additional strategy for registrants to consider as adaptation to animal testing.
External Exposure: Comparing Consumer and Occupational Exposure to Cosmetic Ingredients
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Skin Sensitization: Evaluation and Optimization of Skin Sensitization NGRA for Natural Complex Substances (NCS)
This project will evaluate and amend as necessary the existing NGRA framework so that it considers better the specific characteristics of NCS to enable more accurate and reliable skin sensitization risk assessment of these substances.
Skin Sensitization: Evaluation and Optimization of Skin Sensitization NGRA for Natural Complex Substances (NCS)
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Toxicogenomics: Method Standardization of Computational Approaches to Transcriptomics Data Processing and Concentration-Response Analyses
This project will assess the variation in different toxicogenomics parameter choices and methods to make evidence-informed decisions as to which methods should be included on chemicals relevant to the cosmetics industry.
Toxicogenomics: Method Standardization of Computational Approaches to Transcriptomics Data Processing and Concentration-Response Analyses
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Toxicogenomics: Variety of Technologies for Omics Data Generation: Limits and Recommendation for Safety Evaluation of Cosmetic Ingredients
This project will explore usefulness of each toxicogenomics technology for safety assessment of cosmetic compounds, and also establish best practices on advantages and limitations of each selected technology for sequencing data generation in relation to risk assessment.
Toxicogenomics: Variety of Technologies for Omics Data Generation: Limits and Recommendation for Safety Evaluation of Cosmetic Ingredients
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External Exposure: Closing Data Gaps in Parameters for Inhalation Exposure Assessment
The project will fill data gaps for the main inhalation exposure parameters (e.g. particle size distribution, airborne fraction) to faciliate a refined and more realistic inhalation exposure assessment.
External Exposure: Closing Data Gaps in Parameters for Inhalation Exposure Assessment
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Internal Exposure: Evaluation of Extended Clearance Classification System (ECCS) for Rational In Vitro Testing and Reliable PBK Modeling
The project will develop and validate a tiered testing strategy specifically for cosmetic ingredient internal exposure assessment, and thereby maximize the use of available non-animal data in a purposeful fashion, ensuring the development of robust and reliable PBK models.
Internal Exposure: Evaluation of Extended Clearance Classification System (ECCS) for Rational In Vitro Testing and Reliable PBK Modeling
ACCEPTANCE
Acceptance
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Genotoxicity: Development of OECD Test Guidelines for the Reconstructed Skin Comet and Micronucleus Assays.
Support OECD efforts to draft harmonized test guidelines.
Genotoxicity: Development of OECD Test Guidelines for the Reconstructed Skin Comet and Micronucleus Assays.
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Eye Irritation: Testing of Additional Surfactants to Increase the Confidence of the OECD - Submitted Defined Approach (DA) to Support Regulatory Acceptance
Enable the extension of the OECD guideline to include surfactants.
Eye Irritation: Testing of Additional Surfactants to Increase the Confidence of the OECD - Submitted Defined Approach (DA) to Support Regulatory Acceptance
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Endocrine Disruptors: Collaboration with Vrije Universiteit Brussel (VUB), Under the European Partnership for the Assessment of Risks from Chemicals (PARC) to Assess Methodologies Used for Endocrine Activity Evaluation of Cosmetic Ingredients and Other Chemicals.
Identify In Vitro assays to address the endocrine disruptive potential, understand whether these assays are fit for purpose for endocrine-disrupting chemicals (i.e., can predict the In Vivo situation) and determine if the data from these assays could be used to build a safety dossier.
Endocrine Disruptors: Collaboration with Vrije Universiteit Brussel (VUB), Under the European Partnership for the Assessment of Risks from Chemicals (PARC) to Assess Methodologies Used for Endocrine Activity Evaluation of Cosmetic Ingredients and Other Chemicals.
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Skin Sensitization: Regulatory Acceptance of a Defined Approach (DA) and Next Generation Risk Assessment (NGRA) Framework for Skin Sensitization
Inclusion of DA and refined NGRA framework into international guidelines and regulations (e.g., SCCS Notes of Guidance).
Skin Sensitization: Regulatory Acceptance of a Defined Approach (DA) and Next Generation Risk Assessment (NGRA) Framework for Skin Sensitization