The Revised Up-and-Down Procedure:
A Test Method for Determining the
Acute Oral Toxicity of Chemicals

Results of an Independent Peer Review Evaluation Organized by the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) and the National Toxicology Program (NTP) Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM)

National Institute of Environmental Health Sciences
National Institutes of Health
U.S. Public Health Service
Department of Health and Human Services


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Table of Contents - Volume 1 of 2

ICCVAM - NICEATM Overview
Table of Contents
List of Abbreviations
Peer Review Panel Members
Acknowledgements
Preface
Executive Summary

I. Up-and-Down Procedure (UDP) Peer Panel Report, 07/25/2001 Meeting

  1. Introduction
  2. UDP Protocol: Genral Considerations
  3. UDP Protocol: Revised Primary Test
  4. UDP Protocol: Revised Limit Test
  5. UDP Protocol: Supplemental Test for Slope and Confidence Limits
  6. References
    1. Addendum I: Estimating a Point on the Dose-Response Curve
    2. Addendum II: Considerations for Estimating the Slope
    3. Addendum III: Summary of the Statistical Evaluation of the Revised UDP
    4. Addendum IV: Modified Isotonic Estimates of the Dose-Respnse Function

II. UDP Peer Panel Report, 08/21/2001 Meeting

  1. Introduction
  2. Revised Draft UDP Test Guideline (06/20/2001)
  3. Proposed Confidence Interval Procedure
  4. Software Program
  5. References

III. References

Appendices

A.   ICCVAM Test Method Recommendations

B.   Final Revised UDP Test Guideline (U.S. EPA 10/31/2001)

C.   August 2001 Peer Panel Meeting Review Materials

  1. Acute Oral Toxicity: Revised UDP Test Guideline, 07/12/2001
  2. A Proposed Procedure for Calculating Confidence Intervals
  3. Description of the Acute Oral Toxicity Software Program
  4. Evaluation Guidance to the Panel for the Revised UDP

D.   Federal Register Notices for the UDP

  1. Vol. 65, No. 34, February 18, 2000, Request for Data and Nomination of Expert Scientists
  2. Vol. 65, No. 106, June 1, 2000, Notice of Peer Review Panel Meeting and Request for Comments
  3. Vol. 66, No. 121, June 22, 2001, Notice of Availability and Request for Comments
  4. Vol. 66, No. 133, July 21, 2001, Notice of Peer Review Panel Meeting

E.   Summary Minutes and Public Comments from the UDP Meetings

  1. Minutes and Public Comments of the Peer Review Panel Meeting, 07/25/2000 Crystal City, Arlington, VA
  2. Minutes of the Peer Review Panel Meeting, 08/21/2001, Research Triangle Park, NC
  3. Submitted Public Comment for the 08/21/2001 Meeting

Volume 2 of 2

F.   Revised Background Review Document on the UDP (9/01)

Note: The following documents (Appendices G-Q) were appended to the original BRD (01/14/2000) in a similar format. The April 2000 BRD is available on the Up-and-Down Procedure (UDP) page. For the purposes of this final report, selected supporting documents have been retained for inclusion in the following appendices:

G.   Acute Oral Toxicity: Modified UDP (U.S. EPA Revised Test Guideline 425N, 04/2000)

H.   Acute Oral Toxicity: UDP (OECD Test Guideline 425, adopted 21 September 1998)

I.   Acute Oral Toxicity (OECD Test Guideline 401, adopted 24 February 1987)

J.   Development of OECD 425

  1. UDP: Is there a Need for Further Validation?
  2. Rationale for the UDP as Submitted to OECD
  3. Presentation for Test Guideline 425 - UDP

K.   UDP Primary Test: Proposed Revision of the Guideline 425
      'Primary Procedure' for Point Estimation of the LD50

L.   UDP Primary Test: Comparison of Stopping Rules and LD50 Estimators

M.   The UDP Limit Test: Accuracy of In Vivo Limit Dose Tests

N.   Proposed UDP Supplemental Procedure to Estimate Slope and Confidence Interval

  1. Considerations for Supplemental Procedure
  2. Supplemental Procedure to Determine Slope and Confidence Interval
  3. Summary Tables
  4. Simulation Tables and Legends
  5. Additional Simulations: Supplemental Procedures to Determine Slope

O.   The Basis for Revising the UDP

  1. Statistical Basis for Estimating Acute Oral Toxicity
  2. Comparison of Classification Probabilities
  3. Brief Statistical Description of the Method

P.   Selection of the Appropriate Animal Gender for the UDP

  1. Gender Sensitivity of Xenobiotics
  2. Comparison of Male and Female Rat Oral and Dermal LD50 Values
  3. Toxicological Evaluation of Pesticide Hazard to Avian Wildlife
  4. Sex Dependent Metabolism of Xenobiotics

Q.   U.S. Federal Regulations on Acute Toxicity

  1. CPSC Regulations, Administration and Enforcement
  2. OSHA Regulations, Hazard Communication
  3. U.S. EPA Regulations, Pesticide Registration
  4. U.S. EPA Regulations, Pesticide Labeling
  5. U.S. EPA Regulations, Data Requirements
  6. U.S. EPA Regulations, New Uses
  7. U.S. DOT Regulations, Shipping Requirements



This page was last updated January 2, 2002