Subacute nephrotoxicity and induction of renal cell carcinoma in mice treated with ferric nitrilotriacetate

Abstract

We investigated the induction of renal tumors by the ferric complex of nitrilotriacetic acid (Fe-NTA) in male and female A/J mice. Fifty-three male and 21 female mice received i.p. injections of Fe-NTA, 1.8 to 2.7 mg of iron/kg of body weight/day, 6 days a wk for 12 wk, at the longest. Ten male and ten female mice received nitrilotriacetic acid (NTA) i.p. at the dose equivalent to the NTA portion of Fe-NTA for the same period of time. Twenty male and 20 female mice left untreated served as the controls. Twenty-eight of the 53 Fe-NTA-treated male mice died within 14 days of the treatment. Renal proximal tubular cell necrosis was the major autopsy finding in these mice. On the other hand, all the Fe-NTA-treated female mice and NTA-treated male and female mice survived the 12 wk of treatment. Renal tubular cell carcinoma had developed in 15 of the 25 male mice and in one of the 21 female mice by the 420th day after the start of the experiment. The NTA-treated and control mice did not develop any tumors. In conclusion there is no species specificity in rats or mice in the induction of the renal carcinoma by Fe-NTA, but male mice are far more susceptible to both the acute or subacute toxicity and carcinogenic effect of Fe-NTA than are female mice.