Gradient

Product Stewardship and Safety

Predictive Toxicology

Overview
Example Projects
Experts

Overview

Regulatory bodies across the globe are simultaneously calling for higher throughput substance characterization and use of emerging non-animal testing technologies.  Predictive toxicology describes a multidisciplinary approach to chemical toxicity evaluation that uses a suite of alternative testing methods to forecast the effects of a chemical in biological systems.  This approach offers many advantages to traditional hazard assessment methods, such as reducing the reliance on lengthy animal studies and associated costs.  Predictive toxicology strategies can be tailored to meet specific client goals and applied to environmental and human health risk assessment or chemical hazard identification, as well as for safer product design, pharmaceutical safety assessment, and regulatory compliance or comment.

Gradient's predictive toxicology services draw upon many areas of expertise, including the use of iterative read-across strategies, evaluation and interpretation of available in vitro toxicity data, application of in silico computational toxicology programs (e.g. expert rule-based and quantitative structure activity relationship [QSAR] programs), and pathway-based toxicology for predicting unknown chemical toxicity.  We have extensive experience applying and documenting read-across methods for chemical toxicity assessment, including for more complex substances (e.g., UVCBs), as well as using predictive software programs such as EPI Suite, Derek Nexus, Toxtree, and the OECD Toolbox for hazard characterization and interpretation.  In addition to these in silico tools, Gradient also assists clients with interpretation and application of other 'Next Generation' risk assessment methods, including high throughput in vitro testing, and adverse outcome pathway (AOP) and mode of action (MoA) analysis.

Test Tubes

 

 

 

Example Projects

Product Safety Evaluation for a Consumer Product

Full Description

Gradient assisted a wearable consumer product company in evaluating potentially leachable chemicals for a specific toxicological endpoint. When chemical specific data was lacking, Gradient evaluated possible chemicals for toxicological read-across. Gradient employed various in silico programs (e.g. Derek Nexus, Toxtree) to provide support for a weight-of-evidence hazard and risk assessment conclusion for chemicals with conflicting data. We also helped identify potential substitute materials for future product development.

Management of a Global Chemical Portfolio

Full Description

In support of hazard assessments conducted for the purposes of regulatory compliance, Gradient identified chemicals suitable for read-across for over 700 substances when chemical-specific data were unavailable. To leverage the breadth of the chemical portfolio, we established chemical groups based on structural features and/or functional use.

Ecological Risk Assessment Screening Framework for Pharmaceutical Ingredients

Full Description

Ecological Risk Assessment Screening Framework for Pharmaceutical Ingredients Gradient developed a screening protocol to evaluate ecological risks from societal use of products manufactured by a global personal care product company. The protocol relied on appropriate QSAR models and toxicity databases, and enabled rapid screening of large numbers of organic and inorganic product ingredients without the need for additional experimental data. The protocol can be used to identify ingredients with the potential to pose environmental risks.

Comments on US EPA Draft Rules Regarding Use of Non-Animal Testing

Full Description

In coordination with the Humane Society of the United States (HSUS), Gradient provided written comments to US EPA regarding the draft chemical prioritization and risk evaluation rules, including the use of alternatives to animal testing for chemical hazard evaluation. We provided a framework that articulates the purpose and merits of alternatives to animal testing, and the types of non-animal tests that US EPA will recommend.

Updated Naphthalene Toxicology and Risk Evaluation Using Recent Studies and US EPA's ToxCast Data

Full Description

Gradient updated a toxicity and risk evaluation for naphthalene, incorporating naphthalene toxicity assay information from US EPA's ToxCast database and applying a naphthalene physiologically based pharmacokinetic (PBPK) model to determine naphthalene inhalation concentrations for humans that would lead to the relevant activity concentrations in the ToxCast assays. We compared these inhalation concentrations to typical naphthalene exposure concentrations in the population. Our analysis will be useful in review of US EPA's upcoming revised toxicity and risk assessment for naphthalene.

Experts

Lisa A. Bailey Read Bio

Joel M. Cohen Read Bio

Tom A. Lewandowski Read Bio

Daniella M. Pizzurro Read Bio

James W. Rice Read Bio

Jiaru Zhang Read Bio