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Overview and Agency Responses
International initiatives to use in vitro cytotoxicity test methods to reduce animal use in acute toxicity
testing were evaluated at the International Workshop on In Vitro Methods for Assessing Acute Systemic Toxicity
in October 2000. Pursuant to this workshop, ICCVAM recommended further evaluation of the use of in vitro
cytotoxicity data as one of the approaches that could be used to estimate the starting doses for rodent acute
oral systemic toxicity studies. To assist in the adoption and implementation of this approach, the Guidance Document
on Using In Vitro Data to Estimate In Vivo Starting Doses for Acute Toxicity was prepared by ICCVAM with the
assistance of the workshop participants.
ICCVAM recommended that near-term validation studies should focus
on two standard basal cytotoxicity assays: one using a human cell system and one using a rodent cell system.
ICCVAM also recommended that long-term research focus on the development of in vitro test methods to assess
biokinetics, metabolism, and organ-specific toxicity so as to improve in vitro predictions of acute oral systemic toxicity.
NICEATM and the European Centre for the Validation of Alternative Methods subsequently designed an
international multi-laboratory validation study
to evaluate the usefulness of two in vitro basal cytotoxicity test methods (one using a rodent cell type and the
other using a human cell type) using a neutral red uptake endpoint for predicting starting doses for acute oral systemic
toxicity tests.
ICCVAM Test Method Recommendations: Appendix I of Workshop Report
View complete Workshop Report (NIH 01-4499 - August 2001)
[PDF -
HTML]
Federal Register Notice:
Report of the International Workshop on In Vitro Methods for Assessing Acute Systemic Toxicity;
Guidance Document on Using In Vitro Data to Estimate In Vivo Starting Doses for Acute Toxicity;
Notice of Availability and Request for Public Comment (66 FR 49686, September 27, 2001)
View Federal Register notice [PDF]
View comments submitted on Federal Register notice
Transmittal ICCVAM Test Method Recommendations on Acute Systemic Toxicity to ICCVAM Agencies
Transmittal Letter on Acute Systemic Toxicity
from Dr. Kenneth Olden to the Agency Heads (March 21, 2003) [PDF]
Agency Responses:
- National Institute of Environmental Health Sciences (NIEHS)
- Letter from Dr. Olden to the NIEHS Record (September 9, 2003) [PDF]
- Agency for Toxic Substances and Disease Registry (ATSDR):
- Response from Henry Falk, Assistant Administrator (August 25, 2003) [PDF]
- Consumer Products Safety Commission (CPSC)
- Environmental Protection Agency (EPA)
- Response from Joseph Merenda, Director, Office of Science Coordination and Policy (December 2, 2003)
[PDF]
- Food and Drug Administration (FDA)
- Response from Mark McClellan, Commissioner of Food and Drugs (September 9, 2003)
[PDF]
- National Cancer Institute (NCI)
- Response from Andrew von Eschenbach, Director (August 25, 2003) [PDF]
- National Institutes of Health (NIH)
- Response from Elias Zerhouni, Director (September 5, 2003) [PDF]
- National Institute for Occupational Safety and Health (NIOSH)
- Response from John Howard, Director (September 30, 2003) [PDF]
- National Library of Medicine (NLM)
- Response from Donald Lindberg, Director (August 8, 2003) [PDF]
- Occupational Safety and Health Administration (OSHA)
- Response from John Henshaw, Office of the Assistant Secretary [PDF]
- U.S. Department of Agriculture
- Response from Bobby Acord, Administrator, Animal and Plant Health Inspection Service (September 22, 2003)
[PDF]
- U.S. Department of Defense
- Response from Charles Holland, Deputy Undersecretary of Defense for Science and Technology
(September 30, 2003) [PDF]
- U.S. Department of Energy
- Response from Marvin Frazier, Director, Life Sciences Division (September 24, 2003)
[PDF]
- U.S. Department of the Interior
- Response from Charles Groat, Director, U.S. Geological Survey (August 27, 2003)
[PDF]
- U.S. Department of Transportation
- Response from Samuel Bonasso, Acting Director, Research and Special Programs Administration (May 7, 2003)
[PDF]
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