EPA Opens Access to New Toxicity Database

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EPA Opens Access to New Toxicity Database

V. Cilento Johnson, Guest Science Writer

Published: June 22, 2010

The U.S. Environmental Protection Agency (EPA) recently announced the public availability of a new database of toxicity information. Toxicity Reference Database, or ToxRefDB, contains the results of nearly two billion dollars worth of traditional in vivo animal toxicity studies conducted over the last thirty years.

Scientists and other interested parties can query a specific chemical and obtain—in this one source—all publicly available toxicity data and previously unpublished experimental studies concerning cancer, developmental, and reproductive animal toxicity. The database also includes pesticide toxicity registration data that at one time was available only in hard copy format. The types of toxicity information now in ToxRefDB, combined with information on metabolism and exposure, have formed the basis for the risk assessment of pesticides. Comprehensive data sets from the toxicity profiles for the active ingredients in pesticides can aid in bridging from in vivo to in vitro toxicology (Martin, et al., 2009).

In an April 2010 EPA press release Dr. Robert Kavlock, the director of the agency’s National Center for Computational Toxicology (NCCT), noted that “tens of thousands of chemicals are in commerce and current chemical testing is expensive and time consuming. Results from chemical testing are scattered throughout different sources. ToxRefDB allows the public to search, find and compare available studies about chemical toxicity and potential health effects.”

In a recent paper, Martin et al. (2009) noted pathologies for 273 of the 310 chemical profiles that were generated based on long-term rodent bioassays. They also noted chemical effects in the liver, kidney, thyroid, testis, lung, and spleen. From their observations, they selected 26 primarily tissue-specific pathology end points to uniformly classify the 310 chemicals. This information from ToxRefDB serves as a primary source of reference data for the validation of ToxCast, the EPA’s high-throughput program for chemical screening and prioritization. The ToxCast database has also been recently made available to the public.

ToxCast currently includes more than 500 automated chemical screening assays which are used to assess the ways that chemical exposure affects biological processes and whether this exposure causes adverse health effects. By using screening tests from ToxCast, scientists can avoid expensive and lengthy in vivo tests.

Recently, the EPA announced it will continue validating ToxCast by screening over 100 compounds that have been provided by Pfizer, GlaxoSmithKline, Sanofi-Aventis, and Merck. These drug candidates were never brought to market because they exhibited different levels and types of toxicity during the early stages of clinical trials; the drug companies supplied this data along with the chemicals themselves. Data from the clinical trials and toxicity endpoints from ToxRefDB will help EPA choose the most predictive ToxCast screening tests and biological profiles. Once completed, the tests and profiles will be used in future screening to predict potential chemical toxicity in humans.

ToxRefDB and the ToxCast database are part of EPA’s Aggregated Computational Toxicology Resource, or ACToR database. ACToR contains over 500 public data sources that provide information on hazard, exposure, and potential risks to human health and the environment for more than 500,000 chemicals. It is a support tool utilized by NCCT, the EPA division that developed the Computational Toxicology Research Program (CompTox) in order to efficiently assess potential toxicity risks of chemicals. The goal of CompTox is to provide fast, automated screening tests for assessing chemical toxicity.

The chemical toxicity testing results provided by ToxCast combined with the in vivo animal testing results provided by ToxRefDB are available to the general public and can be accessed without cost, as follows:

ToxCast: http://www.epa.gov/ncct/toxcast/
ToxRefDB: http://actor.epa.gov/toxrefdb/faces/Home.jsp

Public access to this information can potentially benefit ongoing toxicity research and reduce dependency on toxicity testing in animals.

Martin, M.T., Judson, R.S., Reif, D.M., Kavlock, R.J. & Dix, D.J. (2009). Profiling Chemicals Based on Chronic Toxicity Results from the U.S. EPA ToxRef Database. Environ. Health Perspect. 117(3):392-9. Available here.