Cross-Species and Cross-Route Comparisons of Acute Lethal Doses: Further Results of Analysis of a Large Database. L. R. Rhomberg and L. C. Caprario, Center for Risk Analysis, Harvard School of Public Health, Boston, MA 02115
Recently, Rhomberg and Wolff (Risk Anal.18(6):741, 1998) presented analyses of comparative oral lethal doses among mammalian species based on a large database (Registry of Toxic Effects of Chemical Substances®) of values abstracted from the literature. Here, we expand and extend those results by examining comparative median lethal doses (LD50 values) among 9 mammalian species when doses are administered not orally, but as single injections by various routes: intravenous, intraperitoneal, and intramuscular. Pairwise species comparisons based on up to 3,139 agents parallel previous findings on oral exposures, namely, that scaling the dose amount in proportion to the species’ body mass (mg/kg) leads to good prediction of lethal dose across differently sized mammals. Moreover, for a given species, systematic differences in lethal dose exist among routes of administration, with LD50 decreasing (i.e., potency increasing) as one goes from oral to intramuscular to intraperitoneal to intravenous administration, a result explicable in terms of the decreasing importance of the absorption phase through the series. We discuss the implications of our results for route-to-route and species-to-species extrapolation.
Go to . . .
1999 SRA Table of Contents
1999 SRA Author Index
Main Abstracts Menu Page
RiskWorld Home Page