Other Validation Study Documents
Project Coordinators: Dr. Judy Strickland and
Mr. Michael Paris
The In Vitro Cytotoxicity Validation Study was a joint effort of NICEATM and the European Centre
for the Validation of Alternative Methods (ECVAM).
It generated data using in vitro basal cytotoxicity assays with rodent (mouse fibroblast 3T3)
and human (normal human keratinocyte) cells to predict rodent in vivo LD50 data and human in vivo
lethal blood concentration data so as to further the development of in vitro predictive models for human acute toxicity.
IC20, IC50, and IC80 values were generated by testing 72 chemicals using the in vitro basal cytotoxicity test methods.
The IC50 values were used with
IC50-LD50 regression formulas developed from Registry of Cytotoxicity to predict starting doses for
acute oral toxicity tests (i.e., the Up-and-Down Procedure and the Acute Toxic Class method).
Please refer to the Background Review Document for more study information on the prediction
of rodent acute oral toxicity using the in vitro basal cytotoxicity test methods.
The ICx values and human
lethal and sublethal blood concentrations will be used by ECVAM to develop a human prediction model.
Study Objectives
- Further standardize and optimize the in vitro cytotoxicity test method protocols to maximize test method reliability
(intralaboratory repeatability, intra- and inter-laboratory reproducibility)
- Assess the accuracy of the standardized in vitro cytotoxicity test methods for estimating rodent
oral LD50 values across the five United Nations Globally Harmonised System of Classification and Labelling of Chemicals (GHS) categories
of acute oral toxicity, as well as unclassified toxicities
- Estimate the reduction and refinement in animal use achievable
from using in vitro test methods to identify starting doses for in vivo acute toxicity
tests
- Develop high quality in vitro acute oral lethality and in vitro cytotoxicity test method databases
that can be used to support investigations of
other in vitro test methods necessary to improve the prediction of in vivo acute oral lethality
Additional Documents
- Report of the International Workshop on In Vitro Methods for Assessing Acute
Systemic Toxicity. 2001.
[NIH Publication No. 01-4499]
[PDF (2.4 MB) or
HTML]
- Guidance Document on Using In Vitro Data to Estimate In Vivo Starting Doses for
Acute Toxicity. 2001.
[NIH Publication No. 01-4500]
[PDF (432 K) or
HTML]
- LD50 Database [Excel Spreadsheet]
- IC50 and LD50 Database [Excel Spreadsheet]
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