Quantitative Structure-Activity Relationship (QSAR) Modeling

Scientists at ToxStrategies  use a variety of open-source and commercial Quantitative Structure-Activity Relationship (QSAR) models, based on expert rules and statistical approaches, to evaluate potential human or environmental health hazards of chemicals as part of our computational toxicology offerings The use of QSAR models is a key tool in 21st century approaches to hazard identification and risk assessment.  Whether informing data gaps for specific hazard endpoints or predicting potential hazards, such as for prioritizing commercial discovery and development of novel, untested compounds across a wide array of endpoints, ToxStrategies’ scientists provide custom solutions to meet our clients’ global regulatory toxicology and product stewardship needs.  

Integration of QSAR results using expert judgment within context can be used across sectors to support: 

  • Research and development 
  • Product stewardship 
  • Regulatory submissions (within the U.S. and abroad) 
  • Compliance with UN GHS and EU CLP regulations 
  • US EPA Sustainable Futures models and TSCA submission support 
  • EFSA food additive submissions 
  • ICH M7 drug impurity assessments 
  • Others 

QSAR methods can be used to address endpoints related to human health and the environment, including: 

  • Bacterial and mammalian mutagenicity, clastogenicity, DNA reactivity, genotoxic and non-genotoxic carcinogenicity 
  • Repeat-dose and targetorgan toxicities, such as hepatoxicity 
  • Acute toxicity, such as oral LD50 or skin and eye irritation/corrosion potential  
  • Skin sensitization 
  • Reproductive and developmental toxicity 
  • Estrogen/androgen/thyroid receptor activity  
  • Acute and chronic aquatic toxicity 
  • Chemical persistence/bioaccumulation potential 
  • Physicochemical properties of data-poor compounds  
  • Cramer classification assessments (e.g., foods, cosmetics, extractable and leachable substances) 
  • Qualitative and quantitative read-across assessments (including analogue/surrogate identification and justification) to fill data gaps 

Expertise in ICH M7 evaluations for pharmaceutical products:  

  • Access to Lhasa Ltd. Derek Nexus (knowledge-based) and Leadscope Model Applier (statistics-based) QSAR models 
  • ICH M7-compliant evaluation to complement assessment of drug synthesis processes, including starting materials, intermediates, and known impurities  
  • Evaluation of single impurities in drug products  
  • Leverage of data from ICH M7 evaluations to support drug impurity qualifications 
  • Use of Lhasa Derek and/or Leadscope Model Applier to support lead optimization in drug development