Preliminary Toxicity Findings in Dogs and Rodents Given the Iron Chelator Ethylenediamine-N,N'-bis(2-hydroxyphenylacetic acid) (EDHPA)

Preliminary Toxicity Findings in Dogs and Rodents Given theIron Chelator Ethylenediamine N,N'-bis(2-hydroxyphenylaceticacid) (EDHPA). ROSENKRANTZ, H., METTERVILLE, J. J., AND FLEISCHMAN,R. W. (1986). Fundam. Appl. Toxicol 6, 292–298. Becauseof a projected pilot study with EDHPA in Cooley's anemia patients,animal studies with emphasis on reversibility of potential toxicsigns were performed. Young dogs were treated iv with 6–18mg/kg or orally with 30–240 mg/kg for 14 days followedby a 16-day recovery period. Drug-induced emesis, elevated BUNchanges in kidney, spleen, and thymus weights diminished duringrecovery. One deceased dog exhibited nephrotoxicity consistingof tubular necrosis and deposition of the iron—EDHPA complex.The latter was observed in the excreta of survivors but kidneydamage was not evident. Atrophy of the spleen and thymus inthe deceased dog was consistent with less intense organ weightchanges in recovered survivors. In the absence of morphologicchanges after recovery, the precise effect on the immune systemis unknown. The iv LD50 was 53 mg/kg for rats and mice. No rodentdeaths occurred at an oral dose of 6000 mg/kg An elevated BUNand changes in kidney, spleen, and thymus weights were confirmedin rodents given iv doses of 5–20 mg/kg or oral dosesof 150–600 mg/kg for 5 days. It is cautioned that duringthe use of EDHPA derivatives that the functions of the renaland immune systems be monitored.