Nephrotoxicity and Renal Cell Carcinoma After Use of Iron- and Aluminum-Nitrilotriacetate Complexes in Rats2

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Abstract
Wistar male rats were tested for nephrotoxicity and carcinogenicity after administration of ferric nitrilotriacetate [(NTA) CAS: 139-13-9] (Fe-NTA) [No. of rats (n)=24] and AI-NTA (n=24). The control rats were given AICI3 (n=10), NTA (n=10), and saline (n = 10). Sublethal doses of Fe-NTA [5–7 mg Fe/kg (body wt)] and AI-NTA [1.5–2.0 mg AI/kg (body wt)] were chosen and injected ip for 3 months. AICI3 and NTA were given in equivalent doses and saline was given in equivalent volumes. All the rats given Fe-NTA or AI-NTA had a depressed weight gain, polyuria, and glucosuria from the 1st week. Histologically, acute tubular necrosis and regenerating epithelial cells were observed. Regenerative atypical epithelial cells in the renal cortex were seen at the termination of Fe-NTA or AI-NTA administration. Control rats had no remarkable changes. After 1 year, primary renal cell carcinoma and metastases to liver, lung, and peritoneum were observed only in Fe-NTA-treated rats (14 of 18 surviving rats). On the contrary, there were no tumors in AI-NTA-treated rats (none of 12 surviving rats). The results suggest that nephrotoxicity and renal cell carcinoma are two independent phenomena from AI-NTA treatment and that a long-term sublethal dose of AI-NTA is not related to renal carcinogenicity.

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