Elemental alterations during the exposure of 1,2-dichloroethane (EDC), Disulfiram (DSF), and EDC-DSF to male Sprague-Dawley rats

Abstract

Trace elements participate in the organ specific impact of 1,2-dichloroethane (EDC) and Disulfiram (tetraethylthiuram disulfide; Antabuse (DSF] administered singly or together, on male Sprague-Dawley rats exposed by diet (AIN-76) to DSF (0 and 0.15% for 10 d before and during exposure to EDC) and by inhalation to EDC (0, 153, 304, 455 ppm (v/v); 7 h/d for 5 d/wk for 30 exposure days). Kidney, liver, spleen, and testes at exposure d 30 as well as progressive urine samples were examined for elemental content by simultaneous inductively coupled plasma atomic emission spectroscopy. Each compound singly or together produced EDC dose related (r greater than or equal to 0.8) changes in metal content in organs relative to controls. There were increases induced by EDC alone for P and Sr in the liver and decreases for Fe, Mg, and P in the spleen. EDC in DSF-exposed animals caused increases in Ca, Cu, Fe, Mn, and S and a decrease in K in the liver; increases in Ca, Cu, Fe, Mn, Mo, P, and S and a decrease of Zn in the testes; an increase in Fe and a decrease in K in the spleen; and an increase of P in the kidney. DSF alone increased Cu in the liver but decreased it in the testes and kidney; Pb was increased in the liver and kidney and Zn in the liver, spleen, and kidney; Al and Si were increased also in the liver, S in the spleen, and K in the kidney; Mn and Na were decreased in the kidney. The organs showing histopathology (the liver and testes) both showed increases in Ca, Cu, Fe, Mn, and S. Metals in urine characterized a "shock" impact of the initial exposure by initial excretion of Na and retention of most other elements. After steady state (greater than 12 d), EDC alone caused increases for Sr and Zn; for EDC-DSF, EDC also decreased Na in addition to the changes elicited by DSF alone (increases in S and Zn and a decrease for Cu). The results were interpreted from the perspective of the effects of metals on the glutathione detoxicative pathway, the concentration of free diethyldithiocarbamate in urine, and an interaction with bone. Mechanisms of action of EDC, DSF, and EDC-DSF must include consideration of trace elements in addition to organic intermediates, metabolites, and enzymes.