Up-and-Down Procedure for Acute Oral Systemic Toxicity Testing
The oral up-and-down procedure (UDP) is an alternative to the traditional LD50 acute oral toxicity test that reduces animal use.
A peer review panel convened during 2000 and 2001 evaluated the validation status of a revised UDP for acute oral toxicity. Following the peer review panel's comments, ICCVAM recommended that the revised UDP should be used instead of the conventional LD50 test to determine the acute oral toxicity hazard of chemicals.
ICCVAM concluded that the revised UDP would reduce and refine animal use. The results of the peer review were used as the basis for two documents adopted in 2001 by the Organisation for Economic Co-operation and Development (OECD):
- A revised test guideline for the UDP
- A guidance document on acute oral toxicity testing
ICCVAM Test Method Recommendations
ICCVAM's recommendations on the revised UDP were transmitted to federal agencies in March 2003. The transmittal letter and agency responses are posted below. The test method recommendations are included as Appendix A of the Peer Review Evaluation Report.
The Revised Up-and-Down Procedure: A Test Method for Determining the Acute Oral Toxicity of Chemicals
(NIH Publication No. 02-4501 - November 2001)
Documents Related 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 to assist in interpreting its results. - 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 unintentionally carried over from the Test Guideline reviewed by the UDP Peer Review Panel in July 2000. - A Proposed Procedure for Calculating Confidence Intervals (May 2001)
- User Manual and AOT Software Program (available on the EPA website)
Transmittal of ICCVAM Recommendations and Agency Responses
Transmittal Letter from Dr. Kenneth Olden to the Agency Heads (March 2003)
Agency Responses
- National Institute of Environmental Health Sciences (NIEHS)
- Letter from Dr. Olden to the NIEHS Record (September 9, 2003)
- Agency for Toxic Substances and Disease Registry (ATSDR)
- Response from Henry Falk, Assistant Administrator (August 25, 2003)
- Consumer Product Safety Commission (CPSC)
- Response from Todd Stevenson, Office of the Secretary (September 9, 2003)
- Environmental Protection Agency (EPA)
- Food and Drug Administration (FDA)
- Response from Mark McClellan, Commissioner of Food and Drugs (September 9, 2003)
- National Cancer Institute (NCI)
- Response from Andrew von Eschenbach, Director (August 25, 2003)
- National Institutes of Health (NIH)
- Response from Elias Zerhouni, Director (September 5, 2003)
- National Institute for Occupational Safety and Health (NIOSH)
- Response from John Howard, Director (September 30, 2003)
- National Library of Medicine (NLM)
- Response from Donald Lindberg, Director (August 8, 2003)
- Occupational Safety and Health Administration (OSHA)
- U.S. Department of Agriculture
- Response from Bobby Acord, Administrator, Animal and Plant Health Inspection Service (September 22, 2003)
- U.S. Department of Defense
- U.S. Department of Energy
- Response from Marvin Frazier, Director, Life Sciences Division (September 24, 2003)
- U.S. Department of the Interior
- Response from Charles Groat, Director, U.S. Geological Survey (August 27, 2003)
- U.S. Department of Transportation