Nitrilotriacetic acid

Genetic toxicity: in vitro

Administrative data

Endpoint:

genetic toxicity in vitro

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Data source

Reference

Reference 1

Title:

No information

Author:

IARC

Year:

1999

Bibliographic source:

IARC NTA mono73-19 (1999)

Reference 2

Title:

No information

Author:

Anonymous

Year:

2000

Bibliographic source:

IUCLID4 data set for trisodiumnitrilotriacetate, 18 February 2000, page 173-217 and 260-261

Materials and methods

Test guideline

Guideline:

other: see summary

GLP compliance:

not specified

Type of assay:

other: a number of different in vitro and in vivo tests

Test material

Test material information

Constituent 1

Reference substance name:

Nitrilotriacetic acid

EC Number:

205-355-7

EC Name:

Nitrilotriacetic acid

Cas Number:

139-13-9

Molecular formula:

C6H9NO6

IUPAC Name:

2-[bis(carboxymethyl)amino]acetic acid

Results and discussion

Test results

Species / strain:

other: see summary below

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Any other information on results incl. tables

The IARC monograph on nitrilotriacetic acid (volume 73, chapter 19) from 1999, which is attached in section 13, summarizes the genotoxic effects as follows (see also table 1 of the monograph). The cytotoxicity studies can be found on page 260 -261 of the IUCLID4 data set which is attached in section 13, the genotoxicity studies on page 173 -217.

Nitrilotriacetic acid did not induce reverse mutation in Escherichia coli and did not

induce gene mutation in either Saccharomyces cerevisiae or Schizosaccharomyces pombe.

It did not induce sex-linked recessive lethal mutation or dominant lethal mutation but

induced aneuploidy in Drosophila melanogaster. It did not induce sister chromatid

exchange or chromosomal aberrations in Chinese hamster cells in vitro. It did not induce

dominant lethal mutation but induced aneuploidy in mice in vivo.

Nitrilotriacetic acid, disodium salt did not induce gene mutation in mouse lymphoma

L5178Y tk+/– cells or sister chromatid exchange in Chinese hamster lung V79 cells

in vitro. It did not induce oxidative DNA damage in rat kidney cells in vivo.

Nitrilotriacetic acid, trisodium salt gave negative results in the bacterial SOS DNA

repair assay but induced differential toxicity in various repair-deficient Escherichia coli

WP2 strains. It did not induce gene mutation in Salmonella typhimurium TA100, TA1535,

TA1537, TA1538 or TA98 or in E. coli WP2 uvrA with or without exogenous metabolic

activation. It did not induce gene conversion, crossing-over, forward mutation or aneuploidy

in yeast and fungi without exogenous metabolic activation or gene conversion or

forward mutation with exogenous metabolic activation. Nitrilotriacetic acid, trisodium salt

induced micronuclei and chromosomal aberrations in plant cells, but it did not give rise to

micronuclei in Chinese hamster lung cells in vitro. It weakly induced somatic mutation in

D. melanogaster. It did not induce unscheduled DNA synthesis in rat primary hepatocytes

in the absence of metabolic activation. Nitrilotriacetic acid, trisodium salt did not induce

gene mutation at the hprt locus of Chinese hamster lung V79 cells without exogenous

metabolic activation or at the tk locus of mouse lymphoma L5178Y cells with or without

exogenous metabolic activation. It did not induce sister chromatid exchange in Chinese

hamster ovary cells or mouse lymphocytes in vitro. Nitrilotriacetic acid, trisodium salt

induced chromosomal aberrations in rat-kangaroo kidney cells in vitro without exogenous

metabolic activation and gene mutation in human cells in vitro. It did not induce sister

chromatid exchange or chromosomal aberration in human lymphocytes in vitro. It did not

induce micronuclei or aneuploidy in vivo in mice treated with a single intraperitoneal

injection.

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.

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.