Carcinogenesis and Chronic Toxicity of Nitrilotriacetic Acid in Swiss Mice2

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Abstract
Swiss mice were treated orally for 26 weeks with 5 g nitrilotriacetic acid (NTA)/liter, 5 g NTA plus 1 g NaNO2/liter, or 2 g N-nitrosoiminodiacetic acid (NIDA)/liter, and killed at 35–36 weeks. Control animals received either no treatment, 1 g NaNO2/liter, or 0.1 g N-nitro-sopiperidine (NP)/liter as a positive control. Approximately 80 mice in each experimental group were divided equally by sex. Animals were studied mainly for induction of lung adenomas by the Shimkin screening method; other pathologic lesions were also evaluated by extensive light microscopy. There was no significant increase in lung adenomas or other tumors (mainly malignant lymphoma) in mice treated with NTA or NTA plus NaNO2 when the sexes were compared separately. NP-treated mice showed a tenfold increase in lung adenomas/mouse compared with controls. Mice treated with NIDA had a statistically significant decrease in tumorigenesis compared with other groups. No renal or osseous changes were detected by light microscopy. Other pathologic lesions were equally distributed in all experimental groups. NTA did not appear to be carcinogenic in Swiss mice in these tests.

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