Software to Integrate Chemical Exposures and Health Effects
Durham, N.C., March 25, 2019—ScitoVation, a solution leader recognized as an industry expert in cell-based assays and computational methods, today announced the release of the Population Lifecourse Exposure-To-Health-Effects Model (PLETHEM) package, a free, open-source platform that makes pharmacokinetic modeling approaches more accessible to chemical safety practitioners. PLETHEM provides a quantitative bridge between external chemical exposure and internal dose to better understand and evaluate potential health effects at realistic levels of exposure.
This open-source package, which was funded by the Long-Range Research Initiative (LRI) of the American Chemistry Council (ACC), was developed by ScitoVation. ScitoVation collaborated with scientists at the US Environmental Protection Agency (EPA) to link the PLETHEM package to EPA’s high-throughput toxicokinetics (HTTK) R package.
To assess the potential health risks of chemicals, knowledge of chemical hazards is integrated with information on chemical exposure. Understanding the potential hazards of chemicals has received significant attention over the years but evaluating exposure potential has received much less attention. For screening level safety evaluations, estimating exposures at the site of contact may be sufficient. For detailed risk assessments, it is also important to link the external dose of a chemical to an internal blood or tissue concentration, this process is called toxicokinetics. PLETHEM, built around a core physiologically based pharmacokinetic (PBPK) model using knowledge of absorption, distribution, metabolism and excretion, is designed for this purpose.
PLETHEM can be used to address numerous exposure challenges commonly encountered by toxicologists and others making decisions about chemical safety, including extrapolation of chemical safety data from new approach methodologies (NAMs) to equivalent human exposures.
“High throughput in vitro screening and computational methods allow toxicology to be more agile and responsive. However, these methods generate very large quantities of new types of data. Tools like PLETHEM and EPA’s HTTK R package — which facilitates in vitro-in vivo extrapolation using physiologically-based toxicokinetic models — allow the integration of new approach methodologies into more traditional contexts for safety evaluation,” said EPA scientist Dr. John Wambaugh.
PLETHEM is designed to make pharmacokinetic modeling more intuitive to practitioners by providing a menu-driven interface and workflows for common tasks. “ScitoVation has a long history of expertise in pharmacokinetic modeling, but it has traditionally been difficult for non-experts to use PBPK modeling, HT-IVIVE, and related tools in their decision making. We are excited about the potential of PLETHEM to change that”, says ScitoVation’s Dr. Patrick McMullen.
EPA ‘s HTTK R package estimates chemical concentrations in humans. The package can currently use human in vitro data to make predictions for hundreds of chemicals (available here: doi.org/10.23645/epacomptox.6062791.v1).
ScitoVation helps clients assess chemical compound safety using innovative science, next-generation technology, and professional expertise. ScitoVation is known for partnership, flexibility, and proven success in its work to develop safer and more effective pharmaceuticals, food ingredients, agricultural chemicals, commodity chemicals, and consumer products. Being recognized as industry experts in the use of New Approach Methods (NAMs) who have pioneered cell-based and computational methods to provide leading-edge solutions, ScitoVation’s results are scientifically sound and withstand scrutiny, including from peer-reviewers and regulators.