B.M.Y. designed the experiments and interpreted the results. A.D.D. performed the experiments with input from W.E.B. W.E.B. and B.M.Y. designed the stabilization method. A.D.D. and W.E.B. developed the realtime implementation of the stabilized BCI. A.D.D. and W.E.B. performed the analyses and wrote the manuscript. E.R.O., E.C.T.-K. and A.D.D. implanted the electrode arrays used for the experiments. All authors provided feedback on the manuscript.

This article provides a review of available information on the chemistry, environmental toxicology, and mammalian toxicology of nitrilotriacetic acid (NTA). The ability of NTA to chelate metal ions such as Mg++ and Ca++ into water soluble complexes makes NTA useful as an additive to boiler water, as a builder in laundry detergents, and as a stabilizer in textile, paper, and pulp processing. Environmental fate studies show NTA biodegrades in wastewater treatment plants, in natural waters, and in soils under a wide variety of conditions. Studies on the environmental effects of NTA indicate that no adverse effects occur in treatment plants or receiving waters at anticipated levels. Monitoring programs have established that only low steady-state concentrations of NTA occur in natural waters as a result of NTA usage. In mammalian systems, NTA is not metabolized and is excreted rapidly by filtration in the kidney. No reproductive, teratogenic, or adverse bone effects have been observed at highly exaggerated doses. In numerous genotoxicity assay systems, both in vivo and in vitro, NTA is nongenotoxic. Chronic oral exposure of rodents to high doses of NTA is associated with tumorigenicity in, and restricted to, the urinary tract. The urinary tract tumors are the consequence of chronic toxicity that is caused by changes in Zn and Ca distributions between the urinary tract tissues and urine at high doses of NTA. Thresholds for the effects of NTA on Zn and Ca distributions are 10(5) to 10(6) greater than the possible maximum human exposure resulting from the low levels of NTA that are known to occur in the environment.