INTRODUCTION: Reactive metabolite-mediated toxicity is frequently limited to the 
organ where the electrophilic metabolites are generated. Some reactive 
metabolites, however, might have the ability to translocate from their site of 
formation. This suggests that for these reactive metabolites, investigations 
into the role of organs other than the one directly affected could be relevant 
to understanding the mechanism of toxicity.
AREAS COVERED: The authors discuss the physiological and biochemical factors 
that can enable reactive metabolites to cause toxicity in an organ distal from 
the site of generation. Furthermore, the authors present a case study which 
describes studies that demonstrate that S-(1,2-dichlorovinyl)-L-cysteine 
sulfoxide (DCVCS) and N-acetyl-S-(1,2-dichlorovinyl-L-cysteine sulfoxide 
(N-AcDCVCS), reactive metabolites of the known trichloroethylene metabolites 
S-(1,2-dichlorovinyl)-L-cysteine (DCVC), and 
N-acetyl-S-(1,2-dichlorovinyl)-L-cysteine (N-AcDCVC), are generated in the liver 
and translocate through the circulation to the kidney to cause nephrotoxicity.
EXPERT OPINION: The ability of reactive metabolites to translocate could be 
important to consider when investigating mechanisms of toxicity. A mechanistic 
approach, similar to the one described for DCVCS and N-AcDCVCS, could be useful 
in determining the role of circulating reactive metabolites in extrahepatic 
toxicity of drugs and other chemicals. If this is the case, intervention 
strategies that would not otherwise be feasible might be effective for reducing 
extrahepatic toxicity.