Evaluation of In Vitro Cytotoxicity Test Methods
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. Following this workshop, ICCVAM recommended further evaluation of the use of in vitro cytotoxicity data 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 tests using human and rodent cell systems.
To improve in vitro predictions of acute oral systemic toxicity, ICCVAM also recommended that long-term research focus on the development of in vitro test methods to assess biokinetics, metabolism, and organ-specific toxicity.
NICEATM and the European Centre for the Validation of Alternative Methods (ECVAM, now known as EURL ECVAM) designed an international multi-laboratory validation study to evaluate the usefulness of the two recommended in vitro basal cytotoxicity tests for predicting starting doses for acute oral systemic toxicity tests.
ICCVAM Test Method Recommendations
Transmittal of ICCVAM Recommendations and 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 Products Safety Commission (CPSC)
Response from Todd Stevenson, Office of the Secretary (September 9, 2003)
- Environmental Protection Agency (EPA)
Response from Joseph Merenda, Director, Office of Science Coordination and Policy (December 2, 2003)
- 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)
Response from John Henshaw, Office of the Assistant Secretary
- U.S. Department of Agriculture
Response from Bobby Acord, Administrator, Animal and Plant Health Inspection Service (September 22, 2003)
- U.S. Department of Defense
Response from Charles Holland, Deputy Undersecretary of Defense for Science and Technology (September 30, 2003)
- 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
Response from Samuel Bonasso, Acting Director, Research and Special Programs Administration (May 7, 2003)