VOL.: 73 (1999) (p. 385)
Nitrilotriacetic acid
CAS No.:
Chem. Abstr. Name: N,N-Bis(carboxymethyl)glycine
Nitrilotriacetic acid, sodium salt
CAS No.:
Chem. Abstr. Name: N,N-Bis(carboxymethyl)glycine, sodium salt
Nitrilotriacetic acid, monosodium salt
CAS No.:
Chem. Abstr. Name: N,N-Bis(carboxymethyl)glycine, monosodium salt
Nitrilotriacetic acid, disodium salt
CAS No.:
Chem. Abstr. Name: N,N-Bis(carboxymethyl)glycine, disodium salt
Nitrilotriacetic acid, disodium salt, monohydrate
CAS No.:
Chem. Abstr. Name: N,N-Bis(carboxymethyl)glycine, disodium salt, monohydrate
Nitrilotriacetic acid, trisodium salt
CAS No.:
Chem. Abstr. Name: N,N-Bis(carboxymethyl)glycine, trisodium salt
Nitrilotriacetic acid, trisodium salt, monohydrate
CAS No.:
Chem. Abstr. Name: N,N-Bis(carboxymethyl)glycine, trisodium salt, monohydrate
Exposure to nitrilotriacetic acid and its salts occurs during their production, formulation and use in synthetic laundry and dishwashing detergents and related products as metal chelating and sequestering agents.
5.2 Human carcinogenicity data
No data were available to the Working Group.
5.3 Animal carcinogenicity data
Nitrilotriacetic acid was tested for carcinogenicity by oral administration in the diet to mice and rats. It induced renal tubular tumours (adenomas and adenocarcinomas) in mice of each sex and in male rats and transitional-cell and squamous-cell carcinomas of the urinary bladder, hepatocellular adenomas and adrenal phaeochromocytomas in female rats.
The trisodium salt was tested for carcinogenicity in mice and rats by oral administration. When administered in the diet as the monohydrate, it induced haematopoietic tumours in male mice and benign and malignant tumours of the urinary system (kidney, ureter and bladder) in rats of each sex. When administered in drinking-water to male rats, it induced renal tubular adenomas and adenocarcinomas.
In two-stage studies of carcinogenicity in male rats treated by oral administration, nitrilotriacetic acid and its trisodium salt increased the incidence of urinary-tract tumours after pretreatment with various N-nitrosamines.
5.4 Other relevant data
Nitrilotriacetic acid is absorbed in mammals, but it is not metabolized and is excreted rapidly by filtration in the kidney.
Orally administered nitrilotriacetic acid and its trisodium salt were nephrotoxic to rats and mice of each sex. Toxicity occurs at high doses and appears to be due to Zn++ accumulation secondary to the chelating properties of nitrilotriacetic acid; administration of Zn++ accentuated the nephrotoxicity of the acid. Urothelial cytotoxicity and regenerative hyperplasia were seen in male and female rats but not in mice, and only at doses higher than those that produced nephrotoxicity. The mechanism is unclear but appears to involve cellular Ca++ depletion secondary to the chelating effect of nitrilotriacetic acid. Urinary microcrystals were also produced.
Nitrilotriacetic acid does not induce developmental toxicity in rats, rabbits or mice exposed during gestation and gave negative results in short-term assays to screen for teratogenesis in two cellular assays in Drosophila larvae and frog embryos.
No data were available on the genetic and related effects of nitrilotriacetic acid or its salts in humans. Nitrilotriacetic acid and its disodium and trisodium salts were not genotoxic in experimental systems in vivo, except that the acid induced aneuploidy in mouse germ cells. Neither the acid nor its salts were genotoxic in mammalian cells in vitro and they were not mutagenic to bacteria.
5.5 Evaluation
There is inadequate evidence in humans for the carcinogenicity of nitrilotriacetic acid and its salts.
There is sufficient evidence in experimental animals for the carcinogenicity of nitrilotriacetic acid and its salts.
Overall evaluation
Nitrilotriacetic acid and its salts are possibly carcinogenic to humans (Group 2B).
For definition of the italicized terms, see Preamble Evaluation.Previous evaluation: Vol. 48 (1990)
Synonyms
Nitrilotriacetic acid
Nitrilotriacetic acid, sodium salt
Nitrilotriacetic acid, monosodium salt
Nitrilotriacetic acid, disodium salt, monohydrate
Nitrilotriacetic acid, trisodium salt
Nitrilotriacetic acid, trisodium salt, monohydrate
See Also:
Toxicological Abbreviations
Nitrilotriacetic Acid and its Salts (IARC Summary & Evaluation, Volume 48, 1990)