National Toxicology Program

National Toxicology Program
http://ntp.niehs.nih.gov/go/41494

Nominations for Reference Chemicals for Metabolism Assays

The National Toxicology Program Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM), on behalf of the Organisation for Economic Co-operation and Development (OECD) Validation Management Group—Non-Animal (VMG-NA) expert working group, requests the nomination of reference chemicals. Appropriate chemicals with supporting data will be used to validate in vitro metabolizing systems with the potential to interact with estrogen or androgen receptors. Specifically, chemicals are needed to characterize the usefulness and limitations of in vitro metabolizing systems for use in conjunction with estrogen receptor and androgen receptor transactivation assays.

Please submit data via email to NICEATM by June 2, 2014. You may use this Microsoft Excel form or submit data as Microsoft Word documents. Those submitting information should include name, affiliation, mailing address, phone, fax, email address, and sponsoring organization (if any) with the submission (columns A and B in Excel form). Name and Chemical Abstracts Service registry number (if available) should be specified for each chemical (columns D and E of Excel form).

Federal Register notice announcing the public forum (May 13, 2014) (view as webpage)

Considerations for selection of appropriate chemicals include the ability of a chemical to interact with the estrogen receptor or androgen receptor (column F in Excel form) as an agonist or antagonist (column G in Excel form). Additional considerations (specify in columns H, I, and J in Excel form as appropriate) include:

  • Potential for metabolism to make a chemical either more potent (bioactivation) or less potent (detoxification)
  • Likelihood of metabolism occurring in relevant routes of exposure and target organs
  • Likelihood of metabolism occurring over a range of doses: information on the ratio of the half maximal effective or inhibitory concentration (EC50 or IC50, respectively) of parent to daughter metabolites will be useful and there is a particular need for information pertaining to substances where biotransformation yields a very small or very large ratio of EC50/IC50 of parent to daughter metabolites
  • Stability, preferably with real-time curves and consequent exposure significance of likely metabolites
  • Diversity of likely and predominant biotransformative pathways
  • Diversity of chemical types, use classes, and consequent applicability domains

Relevant references from the published literature will be very helpful (provide information on these in columns K and L of Excel form). However, data from past or ongoing validation studies, data in databases, or unpublished data is also welcomed.

For further information, please contact Dr. Warren Casey at NICEATM or Dr. Miriam Jacobs, OECD data request coordinator.

NTP is located at the National Institute of Environmental Health Sciences, part of the National Institutes of Health.