Acute toxicity of 1,2-dibromo-3-chloropropane in the F344 male rat: I. Dose-response relationships and differences in routes of exposure

Single treatments of F344 male rats with the nematocide 1,2-dibromo-3-chloropropane (DBCP) produced acute injury to the kindney, epididymis, testis, and liver. Severity was proportional to the size of the dose administered, but the kidney was adversely affected at a lowere single dose (40 mg/kg) than was the testis or liver (80 mg/kg). Primary target cells in the kidney were proximal tubular epithelia in the outer medulla. Disturbances in renal function included impaired tubular reabsorption (e.g., glucose, fluid, and electrolyte transport) and reduced glomerular filtration. Mild, hepatocellular swelling was produced by 40 mg/kg DBCP, while the leakage of intracellular enzymes into the blood, and centrolobular hepatocellular necrosis occurred after 80 and 120 mg/kg, respectively. The acute testicular lesion was characterized by degeneration and desquamation of the caput epididymal (head of the epididymis) epithelium and by disruption of the seminiferous tubular architecture; these effects were more severe after 120 mg/kg than after 80 mg/kg. Comparisons of the acute toxicity of DBCP following repeated sc, po (by gavage), and ip administration (40 mg/kg daily for 4 days) failed to reveal qualitative differences attributable to the route of exposure. However, the severity of the renal lesion appeared comparatively greatest when treatment occurred sc. These results indicate that DBCP is a cytotoxicant for epididymal and renal proximal tubular epithelia and, since lesions were produced by repeated exposure to acutely subtoxic doses, suggest that its effects on these tissues may be cumulative.