Scientific Tools and Methods

The research supported and catalyzed by ACC LRI has led to the development of a number of methods and tools to investigate and characterize toxicity, exposures, dosimetry, and risks. Information on the ACC LRI tools and methods can be accessed via the hyperlinks below.

LRI Tools and Methods: Exposure Science

Exposure science focuses on understanding the fate and transport of chemicals from sources of manufacturing, use and disposal and includes studies of exposure scenarios, behaviors and use patterns related to contact and interactions with, and uptake by, environmental receptors and humans. Research support from ACC’s LRI has contributed to the exposure science methods and tools listed below. Click on the hyperlinks to learn more about each method.

Tool/Method	Organization and Description
In Vitro to In Vivo Extrapolation (IVIVE)	SciotoVation IVIVE model for extrapolating in vitro measured metabolism values to predicted in vivo values is fully integrated into PLETHEM. New step-by-step User Guide now available here.
Population Lifecourse Exposure-to-Health-Effects Model (PLETHEM)	ScitoVation PLETHEM is a modular open source modeling platform that provides users the ability to create, share, and audit PBPK models and connect them to existing exposure tools. Developed by ScitoVation with funding from ACC and under a Memorandum of Understanding with EPA-NCCT. New step-by-step User Guides now available for: Forward dosimetry Deriving biomonitoring equivalents Conducting route to route extrapolation Reverse Dosimetry Developing kinetically derived MTDs
Risk Assessment, Identification, and Ranking (RAIDAR)	ARC Arnot Research & Consulting RAIDAR is an evaluative, regional-scale, mass balance model for screening level exposure and risk assessment. The model simulates chemical fate and transport in the environment, bioaccumulation in a range of species, food web bioaccumulation, far-field exposures to humans and representative ecological species, and effects (risk). Developed by Jon Arnot.
Risk Assessment, Identification, and Ranking-Indoor and Consumer Exposure (RAIDAR-ICE)	ARC Arnot Research & Consulting RAIDAR-ICE adapts the RAIDAR technique particularly for human exposure via indoor use or direct application of chemicals.

LRI Tools and Methods: Exposure Science

Epidemiology is the study and analysis of the patterns, causes, and effects of diseases. Research support from ACC’s LRI has contributed to the epidemiology methods and tools listed below. Click on the hyperlinks to learn more about each method.

Tool/Methods	Organization and Description
Evaluation of reverse causality in epidemiological associations	ScitoVation Quantitative bias analysis for epidemiological associations of perfluoroalkyl substance serum concentrations and early onset of menopause.

LRI Tools and Methods: Ecological & Environmental

Ecological and environmental science focuses on understanding the potential impacts of chemicals released to environmental media, such as air, water and soil, and how such exposures may influence environmental receptors. Research support from ACC’s LRI has contributed to the ecological and environmental exposure science methods and tools listed below. Click on the hyperlinks to learn more about each method.

More information to come.

LRI Tools and Methods: Pathways and Mechanisms of Action

Research of toxicity pathways and mechanisms of action of chemicals focuses on understanding the moleciular and biological interactions of chemicals with living organisms and the dose-related relationships of such interactions with cellular and organ-level events in pathways of causally related events that may lead to adverse health effects. Listed below are methods and tools that research support from ACC’s LRI has contributed to. Click on the hyperlinks to learn more about each method.

Tool/Methods	Organization and Description
Mode of Action Visualization (MoAviz)	ScitoVation MoAviz is a browser-based applet for summarizing, exploring and interpreting gene expression and other high-throughput data

LRI Tools and Methods: Technology and Assessments

Understanding the potential risk of exposures to chemicals requires integration of scientific evidence from epidemiological studies, laboratory animal investigations, and mechanistic research with knowledge of exposure and dosimetery. ACC’s LRI has contributed to the development and improvement of a wide variety of technologies and assessment methods focused in improving risk-based approaches for evaluating chemicals. Click on the hyperlinks to learn more about each method.

Tool/Method	Organization and Description
Predictive Analytics Toolkit (PAT)	ACC This toolkit facilitates automated development and testing of predictive models utilizing machine learning. Outputs include a table of outcomes from each predictive model, confusion matrices, an outcome classification dendrogram, and calibration curves.
Quantitative weight of evidence to assess confidence in potential modes of action	ACC A proof of concept extension of the MoA framework is proposed for scoring confidence in the supporting data to improve scientific justification for MoA use in characterizing hazards and selecting dose-response extrapolation methods for specific chemicals.
Threshold of Toxicological Concern (TTC) applet	ScitoVation This searchable applet provides TTC values, classes, and Kroes decisions for six classes of chemicals.