Effect of exposure routes on the relationships of lethal toxicity to rats from oral, intravenous, intraperitoneal and intramuscular routes

The lethal toxicity values (log 1/LD50) of 527 aliphatic and aromatic compounds in oral, intravenous, intramuscular and intraperitoneal routes were used to investigate the relationships of log 1/LD50 from different exposure routes. Regression analysis shows that the log 1/LD50 values are well correlated between intravenous and intraperitoneal or intramuscular injections. However, the correlations between oral and intravenous or intraperitoneal routes are relatively poor. Comparison of the average residuals indicates that intravenous injection is the most sensitive exposure route and oral administration is the least sensitive exposure route. This is attributed to the difference in kinetic process of toxicity testing. The toxic effect of a chemical can be similar or significantly different between exposure routes, depending on the absorption rates of chemicals into blood. Inclusion of hydrophobic parameter and fractions of ionic forms can improve the correlations between intravenous and intraperitoneal or oral routes, but not between intraperitoneal and oral routes. This is due to the differences of absorption rate in different exposure environments from different routes. Several factors, such as experimental uncertainty, metabolism and toxic kinetics, can affect the correlations between intravenous and intraperitoneal or oral routes. (C) 2015 Elsevier Inc. All rights reserved.