ATLA::Alternatives to Laboratory Animals

Volume 28, Number 2

The high production volume chemical challenge program: the rodent LD50 and its possible replacement.

ATLA 28, 259-270, March/April 2000

Herbert S. Rosenkranz and Albert R. Cunningham

Department of Environmental Occupational Health, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA 15261, USA

SUMMARY

The High Production Volume Chemical Challenge Program provides an opportunity to re-examine the usefulness and informational value of tests currently used to obtain preliminary hazard identification data. With a view to assessing the mechanistic information provided by the rodent LD50 test and to ascertain the possibility of replacing it with other "more acceptable" assays, we used a recently developed approach to determine the relationship of the LD50 assay to other toxicological protocols. Our analyses indicate that, of the assays examined, the LD50 was significantly related to toxicity in cultured cells and to binding at the Ah receptor.

Keywords: LD50, replacement, cell toxicity, structure-activity relationship (SAR)