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Up-and-Down Procedure for Acute Oral Systemic Toxicity Testing

A peer review panel meeting to evaluate the validation status of a revised Up-and-Down Procedure (UDP) for acute oral toxicity was held in July 2000 and was followed by a teleconference in August 2001. The Panel endorsed revisions to further reduce the number of animals needed to estimate a median lethal dose (LD50) necessary for hazard classification and labeling of chemicals and products.

In agreement with the peer review panel, ICCVAM recommended that the revised UDP test guideline should

  • Replace the Organisation for Economic Cooperation and Development (OECD) UDP test guideline from 1998
  • Be used instead of the conventional LD50 test to determine the acute oral toxicity hazard of chemicals

ICCVAM concluded that use of the revised UDP test guideline will reduce and refine animal use. Results of the peer review were used as the basis for a revised OECD Test Guideline for the UDP and for a Guidance Document on Acute Oral Toxicity Testing that were adopted in December 2001.

ICCVAM's recommendations to use the revised UDP in place of the conventional LD50 test were transmitted to federal agencies in March 2003. The transmittal letter and agency responses are posted below. The ICCVAM test method recommendations are included as Appendix A of the Peer Review Evaluation Report.

Documents Relevant to the UDP Evaluation
  • Agenda and minutes of the July 2000 Peer Review Panel meeting
  • Minutes of the August 2000 UDP Peer Review Panel teleconference
  • Relevant references
  • Toxicology Summary: Performance of the Up-and-Down Procedure (November 2001)
    This summary was developed in response to recommendations from the UDP Panel at their August 21, 2001 meeting. It is intended to accompany the Up-and-Down Procedure (UDP) test guideline and the AOT425StatPgm program and assist the user in interpreting its output.
  • Revised Draft UDP Test Guideline (July 2001)
    On July 12, 2001, the phrase 'OECD' was removed from the title of this document. The previous title was inadvertently carried over from the Test Guideline that was reviewed by the UDP Peer Review Panel in July 2000. This document is a revised draft version of the Up-and-Down Procedure Test Guideline that is currently being considered by the U.S. EPA for incorporation into their acute oral toxicity guidelines.
  • A Proposed Procedure for Calculating Confidence Intervals (May 2001)
  • User Manual and AOT Software Program (available on the U.S. EPA web site)
  • Public Comment submitted prior to the August 2001 teleconference
    • I. Pate, ICI PLC, Central Toxicology Laboratory, UK (August 10, 2001)
Transmittal of ICCVAM Recommendations and Agency Responses

Transmittal Letter from Dr. Kenneth Olden to the Agency Heads (March 2003)

Agency Responses