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 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 toxicity.
NICEATM and the European Centre for the Validation of Alternative Methods (ECVAM) subsequently designed a 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
toxicity tests.
ICCVAM Test Method Recommendations on Acute Systemic Toxicity
- ICCVAM Test Method Recommendations: Appendix I of Workshop Report
- View complete Workshop Report (NIH 01-4499 - August 2001)
[PDF -
HTML]
Agency Responses
|
