National Toxicology Program

National Toxicology Program

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: (1) replace the Organisation for Economic Cooperation and Development (OECD) UDP test guideline from 1998 and (2) 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.

Transmittal of ICCVAM Recommendations and Agency Responses

Transmittal Letter on Acute Systemic Toxicity from Dr. Kenneth Olden to the Agency Heads (March 21, 2003)

Agency Responses:

Additional Materials from the UDP Evaluation

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