ToxStrategies is a leader in using new approach methods (NAMs) to support our clients with alternatives to traditional animal testing for substance safety assessments. We are highly experienced in integrating and interpreting NAM data from in vitro, in chemico, and in silico methods to study potential adverse effects of various substances. Under our Center of Excellence for 21st Century Toxicology (21CT) we have accumulated years of experience assisting clients with designing and interpreting NAM data, synthesizing evidence, and using real-world evidence (RWE) analytics to support safety assessments. As such, we are highly skilled at implementing testing strategies that incorporate NAMs, and have developed training materials for clients on effectively using NAMs for safety evaluations. Our capabilities include:
In Silico Methods and Read-Across
- Quantitative structure activity relationship modeling (e.g., QSAR Toolbox, VEGA-QSAR, Leadscope Model Applier, Derek Nexus, EPA T.E.S.T)
- Cramer classification assessments (e.g., foods, cosmetics, extractable and leachable substances)
- Qualitative read-across assessments (including analogue/surrogate identification and justification) to fill data gaps
- Read-across and analogue identification, evaluation and justification
- Environmental fate and persistence predictions (e.g., EpiSuite, EcoSar)
- In silico metabolic predictions with Meteor from Lhasa Ltd.
Physiologically-Based Pharmacokinetic (PBPK) Models and In Vitro to In Vivo Extrapolation (IVIVE)
- Generalized model development, application, and evaluation for multiple substance parameterization
- Example: Open-source R package httk containing a framework for high-throughput PK/TK modeling suitable for parameterizing multiple substance and species
- In vitro to In vivo Extrapolation (IVIVE)
- Incorporation of inter-individual variability
- Quantification of uncertainty/error/confidence and sensitivity analysis of models
- Integration of high-throughput PBPK and IVIVE models
In Vitro and In Chemico Testing and Data Evaluation
- Design and interpretation of human-relevant and animal-free testing strategies such as in vitro dermal absorption evaluations following OECD 428 test guideline, eye irritation testing, in vitro pharmacological profiling, and transcriptomic evaluations
- Study placement and monitoring
- Curation and interpretation of high-throughput screening data (e.g., EPA ToxCast, etc.)
Evidence Synthesis and Evaluation
- Systematic identification and assessment of existing mechanistic data using categorical and pathway-based approaches
- Critical appraisal for reliability and data quality assessments
- Integration of in vitro and in vivo studies to develop weight-of-evidence conclusions
- Use of OECD Integrated Approaches to Testing and Assessment (IATA) for combing multiple sources of information to evaluate substance toxicity
Training on Methods and Processes Considering NAMs
- Development of best practice guidance documents for using NAM data for safety assessments
- Development of case studies demonstrating using NAM data with in vivo data for safety support
- Development of webinars and virtual trainings related to novel approaches for unique chemistries (e.g, polymers, botanicals)
For more on ways ToxStrategies can help you with NAMs approaches, please reach out to us at: info@ToxStrategies.com