The Journal of Toxicological Sciences
Online ISSN : 1880-3989
Print ISSN : 0388-1350
ISSN-L : 0388-1350
Regular Paper
A COMPARATIVE STUDY ON THE RELIABLILITY OF TOXICOKINETIC PARAMETERS FOR PREDICTING HEPATOTOXICITY OF DDT IN RATS RECEIVING A SINGLE OR REPEATED ADMINISTRATION
Naruto TOMIYAMAMomiko WATANABEMakio TAKEDATakanori HARADAHiroko KOBAYASHI
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2003 Volume 28 Issue 5 Pages 403-413

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Abstract

A comparative study on the reliability of toxicokinetic parameters for predicting hepatotoxicity was conducted in male F344 rats receiving a single (106 mg/kg by gavage) or 7-day repeated (1000 ppm in feed, 97 mg/kg/day) administration of p,p'-DDT. DDT was selected as the test substance because it is known as a hepatotoxic agent and its metabolic pathway is well documented. Concentrations of DDT and its metabolites (DDE and DDD) in the plasma, brain, and liver were measured at various time intervals during the study and the results were compared with the area under the concentration-time curve (AUC) in relation to hepatotoxic response. Increases in the absolute and relative (ratio to body weight) liver weights were observed as a typical toxic response after a single or repeated exposure to DDT. The coefficient (R2) of correlation between the increases in the relative liver weight and the concentrations or AUC of DDT and its metabolites in the plasma and liver was estimated. The values of R2 between the relative liver weight and AUC of DDT or the total DDT (T-DDT) in the plasma and liver were found to be more consistent and higher than those with their concentrations in the repeated dose study. In addition, the R2 values in correlation with their AUCs after a single exposure were lower than those in the repeated dose study. These results indicate that the AUC of DDT or T-DDT in the plasma and liver would be more reliable than their concentrations for predicting hepatotoxicity caused by DDT, especially in the repeated dose study.

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© 2003 The Japanese Society of Toxicology
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