Chemical Prioritization | Community Practice | Research Activities | National Center for Computational Toxicology | US EPA

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Chemical Prioritization

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The primary purpose of the EPA Chemical Prioritization Community of Practice (CPCP) is to foster communications on the planning, conduct and interpretation of the ToxCast™ chemical prioritization research project (www.epa.gov/comptox/toxcast).  We look forward to continuing to develop ToxCast™with our many EPA, NTP, NIH, academic, stakeholder and international colleagues.

CPCP meetings are held monthly, typically at EPA's RTP campus, on the fourth Thursday of the month, from 11am-Noon EST/EDT. Teleconferencing is available. Every other month the CPCP meeting is hosted jointly with the NTP Biomolecular Screening Branch, and the NIH Chemical Genomics Center.

For more information on the CPCP, or to be added to the meeting email list, contact either David Dix (dix.david@epa.gov; 919 541 2701) or Keith Houck (houck.keith@epa.gov; 919 541 5519).

Background

The EPA Chemical Prioritization Community of Practice (CPCP) formed in December 2005 to advance research into the utility of computational chemistry, high-throughput screening (HTS) and various toxicogenomic technologies for Agency use. Modern computational chemistry and molecular biology technologies can provide information about the physical and biological properties of large numbers of chemicals. The goal of the CPCP is to advise on the development of a research program within the National Center for Computational Toxicology (NCCT) generating data from these technologies and interpreting it in order to categorize chemicals and predict toxicity. If proven accurate, these toxicity predictions could then be used for prioritization of limited testing resources towards chemicals and endpoints that present the greatest risk to human health and the environment.

The primary function of the CPCP is to advise on the NCCT's planning, conduct and interpretation of a chemical categorization and prioritization research project entitled "ToxCast™". The ToxCast™ project is designed to have the ability to predict, or forecast toxicity. Initially, this has entailed a demonstration project based upon a set of chemicals with a rich toxicological database (e.g., registered pesticides, or the chemicals tested in the National Toxicology Program (NTP) bioassay program). This set of over 300 chemicals represents a number of differing structural classes and phenotypic outcomes (e.g., tumorigens, developmental and reproductive toxicants, neurotoxicants, immunotoxicants). The ToxCast™ project is evaluating chemical properties and effects across a broad spectrum of information domains: physical-chemical properties, predicted biological activities based on existing structure-activity models, biochemical properties based on HTS assays, cell based phenotypic assays, and genomic analysis of cells or organisms. The ultimate goal of the ToxCast™ project is to mine the resulting data for associations between and among the various domains and the known toxicological properties of the base set of chemicals, in order to provide a structured strategy to categorize chemicals, identify potential toxicities and pathways, and to prioritize chemicals for subsequent testing based on that information.

The Community includes individuals from the Office of Research and Development (ORD) Labs and Centers, as well as scientists outside of EPA with expertise in HTS, toxicogenomics, predictive toxicology or bioinformatics. The CPCP is an important point of contact between NCCT, the NTP Biolmolecular Screening Branch and the NIH Chemical Genomics Center (NCGC). The CPCP is chaired by a member of the NCCT, but draws on the expertise of scientists across ORD and the Agency as needed for specific issues.  Community members provide feedback on the planning and execution of the ToxCast™ project.

The charter of the CPCP includes the following functions:

  1. Organize periodic meetings or conference calls (at least quarterly) around specific issues or projects, with goal of identifying state of the science, research needs, consensus positions.
  2. Organize outreach to broader HTS and toxicogenomics scientific community to demonstrate EPA's interest and obtain input and participation.
  3. Report regularly to the Director of the NCCT and the ORD CTISC on issues, progress, and outputs.

Specific goals of the CPCP is to advise on the following:

  1. 1. Development of key partnerships and collaborations with external groups that can facilitate development of the information needed in ToxCast™. These groups include the Office of Air and Radiation (OAR), Office of Prevention Pesticides and Toxic Substances (OPPTS), Office of Water (OW); the NTP and NCGC; the ACC, CropLife, EDF, and other external groups to help develop a consensus on the specific directions and contents of ToxCast™.
  2. Identification of a set of chemicals for the ToxCast™ demonstration project.
  3. Selection of data domains and specific assays based upon pre-existing knowledge and within the available resources.
  4. Selection of key target toxicities for initial focus of the ToxCast™ proof of concept.
  5. The impact of metabolizing capability, or lack thereof, on the efficiency of the screening assays.
  6. Development of a bioinformatic approach to mining the resulting data and identifying signatures of concern.
  7. Reporting the utility of assay results and analysis techniques to categorize pilot chemicals according to known toxicity patterns; revise methods and approaches as dictated by results.
  8. Expanding the ToxCast™ project beyond proof of concept, and carrying out a prospective assessment of the approach using chemicals currently entering a traditional testing process.

Impact

The availability of a biologically and chemically based system (ToxCast™) to categorize chemicals of like properties and activities will provide a number of EPA Program Offices with an extremely useful tool that heretofore has been seriously lacking. ToxCast™ is a major product of the NCCT that addresses the mission of improving the efficiency and effectiveness of hazard identification and risk assessment methodologies employed by the EPA.

CPCP membership

As of February 2008, the CPCP has a membership of over 100 individuals from over 20 public and private sector organizations. Membership will be modified throughout working life of Community as appropriate; to be added to the meeting email list, contact either David Dix (dix.david@epa.gov; 919 541 2701)or Keith Houck (houck.keith@epa.gov; 919 541 5519).

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