Using HPV Chemical Data to Develop QSARs for Non‐HPV Chemicals: Opportunities to Promote More Efficient Use of Chemical Testing Resources

Abstract

There are opportunities to use data developed for High Production Volume (HPV) chemicals to save chemical testing resources for non-HPV chemicals. First, data being developed for HPV chemicals could reduce chemical testing resources for non-HPV chemicals, if the data can be used to develop and validate Quantitative Structure Activity Relationships (QSARs) that can be used to make predictions for non-HPV chemicals. Second, strategies need to be developed to identify chemicals for which QSARs may not make reliable predictions and appropriate tests need to be conducted so that these and related chemicals can be included in more robust QSAR predictions. This paper illustrates the chemical testing resources that could be saved by using QSAR predictions and discusses guidelines and issues that need to be addressed before using data from HPV chemicals to develop QSARs for non-HPV chemicals.

Improving Opportunities for Regulatory Acceptance of QSARs: The Importance of Model Domain, Uncertainty, Validity and Predictability

“…The proposed Registration, Evaluation and Authorization of Chemicals (REACH) in Europe has stimulated a renewed interest in the application of QSARs to predict physical and chemical properties, environmental fate, ecological effects and health effects of chemicals to promote more cost-effective use of chemical testing resources [46]. Important characteristics of QSARs are model domain, uncertainty, validity and predictability as influenced by model sensitivity and model specificity.…”

Use of QSARs in international decision-making frameworks to predict health effects of chemical substances.

“…QSARs for skin permeability are well reviewed by Moss et al (2002) and Walker et al (2003). The passage of chemicals across the skin may be viewed as a passive diffusion process.…”

“…Walker et al (2003) described the regulatory application of QSARs to predict dermal absorption of compounds. The permeability coefficient was predicted by a series of simple QSARs that were based either on hydrophobicity and molecular size or on hydrophobicity alone.…”

Use of Physicochemical Property Limits to Develop Rules for Identifying Chemical Substances with no Skin Irritation or Corrosion Potential

“…The GHS testing and assessment strategy includes application of validated in vitro and (Q)SAR models prior to any consideration of animal testing. While validated in vitro models are already available for skin corrosion and will be validated within the next few years for skin irritation, the present status of (Q)SAR modelling in toxicology [16] led to guidelines for development and use of such models [17] as well as proposals how to promote their use [18]. However, specific (Q)SARs fitting directly into the testing and assessment strategy of the GHS are at present not available.…”