The use of
EDBPHA as a potential
iron chelator in cases of
hemochromatosis provided impetus for investigating its toxicology. Because a reddish coloration of excreta was observed during subchronic administration of the
drug to dogs, measurements of
iron concentrations in blood, excreta, and hematopoietic tissues were made. Groups of beagle dogs of both sexes were injected i.v. with
EDBPHA doses of 6, 12, or 18 mg/kg or were given capsules containing doses of 30, 100, or 240 mg/kg for 14 days. Control dogs received either saline i.v. or empty
gelatin capsules orally. In addition to the monitoring of toxicological effects,
iron levels in plasma, urine, feces, liver, spleen, and kidney were monitored before
drug, at the end of treatment, and after a 16-day recovery period. In the absence of
hemoglobin and hematocrit changes, i.v.
EDBPHA reduced renal
iron 40% and hepatic
iron 15% to 25% without altering splenic
iron. Serum
iron rose 34% to 54%, urinary
iron 80% to 119%, and fecal
iron 23% to 41%. Oral
EDBPHA did not induce changes in tissue
iron or excreta
iron, but serum
iron was increased 22% to 29%. These alterations in
iron concentrations were transient and may be related to
iron redistribution and inactivation of
drug by liver.