High-Throughput Toxicokinetics (httk) R Package
Overview
EPA researchers develop models to help estimate the amount of a chemical in the body which could lead to an effect. These estimates, along with exposure and hazard data, help inform predictions about chemical risks facing the public.
EPA researchers recently released an updated software package called the high-throughput toxicokinetics (httk) R package with new data and models which can be used to estimate chemical concentrations in humans.
The package currently uses human in vitro data to make predictions about the fate of chemicals in humans, rats, mice, dogs, and rabbits.
To make useful predictions about chemical risks facing the public, scientists need three types of data: dosimetry (which is included in the httk package), hazard, and exposure. Dosimetry is the amount inside and interacting with the body, hazard is the amount of a chemical that could lead to toxicity, and exposure is the amount of a chemical present in the environment.
Dosimetry Data: EPA researchers have been collecting toxicokinetic data for more than ten years using animal-free methods originally developed for pharmaceuticals. Researchers measure how much of a chemical attaches to proteins or cells in the body and how long before the body transforms and/or eliminates a substance. This data is used in the httk R package which can be used to estimate the concentration of a chemical in the human body or animal which could lead to an effect.
Hazard Data: As part of the New Approach Methods (NAMs) Work Plan, EPA is committed to reducing the use of animals to test chemicals. EPA researchers use high-throughput screening technologies to generate chemical biological activity data. This data can be coupled with historical data from animal toxicity tests to help predict the potential for chemical toxicity. The data generated from high-throughput screening from EPA efforts such as ToxCast can be converted into a human (or other animal) equivalent amount that a person would be exposed to.
Exposure Data: A wide variety of exposure relevant data are necessary to support chemical safety decision making. For many chemicals and product types, there remains critical gaps in exposure information. EPA researchers collect and curate existing exposure-relevant data, conduct laboratory experiments to collect measured data, harmonize meta-data (i.e., descriptive data), and expand established databases (e.g., Chemical and Products Database (CPDat)) in order to fill these gaps. EPA researchers use this information to develop methods, data, tools, models, and approaches to generate exposure and dosimetry estimates for chemicals and mixtures found in commerce and in the environment.
R Package
Access: httk: High-Throughput Toxicokinetics R Package
EPA scientists plan to continue improving the accuracy of the HTTK R Package. New models are being developed to describe absorption through the skin, exposure to aerosols (clouds of droplets), partial oral absorption, and human pregnancy.