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.

Relevant References

ICCVAM Test Method Recommendations

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