ID#

760

Location:

Exhibit Hall

Time of Presentation:

March 11, 2003 - 9:30 a.m.

Category (Subcategory):

In Vitro/Alternative Animal Models, (Biological Modeling)

Establishment of Rat LD50 Reference Values for Chemicals Tested in a Validation Study of In Vitro Cytotoxicity Assays
M.W. Paris^1,2; J.A. Strickland^1,2; R.R. Tice^1,2; W.S. Stokes²
1. ILS, Inc., RTP, NC, USA;
2. NICEATM, NIEHS, RTP, NC, USA;

The Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) and NICEATM convened an international workshop in October 2000 that evaluated the validation status of in vitro methods for predicting acute systemic toxicity. Workshop participants recommended further validation of in vitro methods for predicting rodent and human acute toxicity. NICEATM and ECVAM subsequently designed a multi-laboratory validation study to evaluate two in vitro basal cytotoxicity tests using 72 coded chemicals representing the six globally harmonized acute oral toxicity hazard categories. In order to assess the predictive performance of the in vitro data, it was necessary to establish rodent LD50 reference values for each chemical. LD50 studies were located through literature searches and references from major toxicity databases such as RTECS. Studies were reviewed to identify the most appropriate LD50 reference value for each chemical. Criteria used to select reference LD50 values included: 1) consistency of age, gender, and species with that recommended in current acute oral toxicity testing guidelines, and 2) adequacy of the study based on documentation of experimental parameters such as method of administration, doses used, number of animals and deaths at each dose, and confidence interval for the LD50. Completeness of data for individual chemicals ranged from sparse summaries to detailed GLP compliant studies. Some LD50 values were unsupported by experimental details. The number of available rat oral LD50 values for each chemical ranged from 1 to 29, while oral LD50 values varied by as much as tenfold. Chemical-specific examples of the selection decisions for reference LD50 values will be provided. These reference data will be used to evaluate the extent that in vitro test methods can predict rodent LD50 values. Supported by NIEHS contract N01-ES 85424 and EPA IAG DW-75-93893601-0.