STUDIES ON THE COMPARATIVE TOXICITY OF S-(1,2-DICHLOROVINYL)-L-CYSTEINE, S-(1,2-DICHLOROVINYL)-L-HOMOCYSTEINE AND 1,1,2-TRICHLORO-3,3,3-TRIFLUORO-1-PROPENE IN THE FISCHER-344 RAT

The renal tubular toxicity of various halogenated xenobiotics has been attributed to their enzymatic bioactivation to reactive intermediates by S-conjugation. A combination of high resolution proton nuclear mag netic resonance (H-1 NMR) spectroscopy of urine, renal histopathology and more routinely used clinical chemistry methods has been used to ex plore the acute toxic and biochemical effects of S-(1,2-dichlorovinyl) -L-cysteine (DCVC), S-(1,2-dichlorovinyl)-L-homocysteine (DCVHC) and 1 ,1,2-trichloro-3,3,3-trifluoro-1-propene (TCTFP) up to 48 h following their administration to male Fischer 344 (F344) rats. In the absence o f gross renal pathology, H-1 NMR urinalysis revealed increased excreti on of the tricarboxylic acid cycle intermediates citrate and succinate following DCVC administration. In contrast, bath DCVHC and TCTFP prod uced functional defects in the S-2 and S-3 segments of the proximal tu bule that were confirmed histologically. In these cases, H-1 NMR urina lysis revealed increased excretion of glucose, L-lactate, acetate and 3-D-hydroxybutyrate (HB) as well as selective amino aciduria (alanine, valine, glutamate and glutamine). The significance of the proximal ne phropathies induced by DCVHC and TCTFP is discussed in relation to bio chemical observations on other xenobiotics that are toxic by similar m echanisms.