NGRA

ToxStrategies’ professionals have extensive experience supporting the development of Next Generation Risk Assessment (NGRA) frameworks to make safety decisions for both human and environmental health. ToxStrategies has conducted safety evaluations using NGRA approaches for cosmetics, food ingredients, and environmental chemicals. We often interact and collaborate with regulatory, academic, and industry professionals to ensure that the most appropriate science is incorporated into each assessment. Examples of some of the areas where our staff have the relevant experience needed to conduct an NGRA include the following:

  • Developing frameworks to support well- defined problem formulation, development of tiered workflows, and clear decision gate criteria.
  • Characterizing the consumer exposure level
  • Estimating internal systemic doses using physiologically-based kinetic (PBK) modeling
  • Establishing exposure- based waiving thresholds
  • Expertise in incorporating New Approach Methods (NAMS), Integrated Approaches to Testing and Assessment (IATA), and Defined Approaches (DA) into assessment frameworks
  • Using QSAR models and in silico tools to identify existing data, predict toxicological pathways
  • Leveraging read-across approaches
  • Deriving Point of Departure (PoD) using high-throughput bioactivity data from a broad panel of NAMs using a range of dose-response modeling techniques
  • Conducting qualitative and quantitative uncertainty assessment
  • In vitro to in vivo extrapolation (IVIVE) to assess biologically effective doses
  • Deriving bioactivity-exposure ratio (BER) or margin of internal exposure (MoIE)

Specific areas or aspects of expertise include:

  • Developing frameworks and tiered workflows
  • Problem formulation
  • Characterizing human use and consumer exposure level
  • Physiologically-Based Kinetic (PBK) modeling
  • Conducting exposure assessment
  • Applying Threshold of Toxicological Concern (TTC)
  • Applying Dermal Sensitization Threshold (DST)
  • ADME and Metabolic Pathway Analyses
  • Literature searching and systematic literature reviews
  • QSAR models and in silico tools
  • Predicting Modes of Action and Adverse Outcome Pathways
  • Developing and applying read-across approaches
  • Data interpretation and evidence synthesis
  • Study design and monitoring
  • Synthesize systemic toxicity data to evaluate for potential data gaps
  • Deriving Point of Departure (PoD)
  • Deriving Bioactivity-Exposure Ratio (BER)
  • Deriving Margin of Internal Exposure (MoIE)
  • Conducting uncertainty modeling
  • Bayesian Probabilistic Uncertainty
  • PoD model uncertainty and model averaging
  • APROBA
  • Supporting tools
    • Toxtree
    • OECD QSAR Toolbox
    • Comptox Chemoinformatics
    • GenRA
    • DEREK
    • Leadscope Model Applier
    • VEGA
    • EPA T.E.S.T
    • Episuite