Registration Dossier
Registration Dossier
Data platform availability banner - registered substances factsheets
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.
The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.
Diss Factsheets
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 205-355-7 | CAS number: 139-13-9
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Carcinogenicity
Administrative data
Description of key information
Effect level expressed as the acid
Key value for chemical safety assessment
Carcinogenicity: via oral route
Link to relevant study records
- Endpoint:
- carcinogenicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 1977
- Reliability:
- 2 (reliable with restrictions)
- Guideline:
- other: Stanford Research Institute / NCI
- GLP compliance:
- not specified
- Species:
- rat
- Strain:
- Fischer 344
- Sex:
- male/female
- Route of administration:
- oral: feed
- Duration of treatment / exposure:
- 2 years
- Frequency of treatment:
- continuous
- Post exposure period:
- none
- Remarks:
- Doses / Concentrations:
0.02, 0.2 and 2% (15, 150 and 1500 mg/kg bw per day) as Na3NTA.H2O
Basis:
nominal in diet - No. of animals per sex per dose:
- 24 per sex per test group plus another 24 per sex for the control group
- Control animals:
- yes, concurrent no treatment
- Details on results:
- Hydronephrosis was pronounced at the highest dose-level. No renal and bladder tumours were observed in the controls and lower-dose groups but 1 papilloma in a female at 0.2%.
All other tumours occurred in the highest dose-level (acc. to IARC):
RCN TCC(R) TCC (U)
male (high dose) 4/24 4/24 8/24
female (high dose) 4/24 6/24 5/24
RCN = renal tubular-cell neoplasms (adenoma + carc.)
TCC = transitional-cell carcinoma, renal (R) and urinary (U)
Metastases arisen from primary tumours of the urinary tract were found in 5/24 animals each of both sexes.
A revision of histological sections from NCI study (Alden, Kanerva, 1982) substantiated recent findings from Procter & Gamble and may have resulted in a different appreciation by P&G (Anderson et al., 1982):
CONCLUSION: High doses of NTA initiate a sequential series of toxic events vi two pathways, a specific and an age-related unspecific one. Doses
of NTA that do not induce toxicity do not induce tubular tumours.
With respect to tumour formation, the adoption of a dietary chronic NOAEL of 0.2% (ca. 150 mg/kg bw*d) is justified (see also TSCATS,
OTS 0545297) - Dose descriptor:
- NOAEL
- Effect level:
- 100 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: Effect level expressed as the acid
- Remarks on result:
- other: Effect type: carcinogenicity (migrated information)
Reference
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed
- Dose descriptor:
- NOAEL
- 100 mg/kg bw/day
- Study duration:
- chronic
- Species:
- rat
Carcinogenicity: via inhalation route
Endpoint conclusion
- Endpoint conclusion:
- no study available
Carcinogenicity: via dermal route
Endpoint conclusion
- Endpoint conclusion:
- no study available
Justification for classification or non-classification
The IARC monograph on nitrilotriacetic acid (volume 73, chapter 19) from 1999, which is attached in section 13, summarizes the carcinogenic effects as follows:
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.
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.
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.
Nitrilotriacetic acid and its salts are possibly carcinogenic to humans
Note: the effect level is expressed as the acid
Additional information
The IARC monograph on nitrilotriacetic acid (volume 73, chapter 19) from 1999, which is attached in section 13, summarizes the carcinogenic effects as follows:
Nitrilotriacetic acid was tested for carcinogenicity by oral administration in the diet
in mice and rats. It induced renal-cell adenocarcinomas in mice of each sex, renal-cell
tumours in male rats and transitional-cell and squamous-cell carcinomas of the urinary
bladder, hepatocellular adenomas and adrenal phaeochromocytomas in female rats.
Nitrilotriacetic acid, 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 adenomas and adenocarcinomas.
In two-stage carcinogenicity studies in male rats by oral administration, nitrilotriacetic
acid and its trisodium salt increased the incidence of urinary-tract tumours after
pretreatment with various N-nitrosamines (IARC, 1990).
The nephrocarcinogenic effects of nitrilotriacetic acid in rats and mice appear to be
related to dose-dependent changes in Zn++ homeostasis. Orally administered nitrilotriacetic
acid and its trisodium salt were nephrotoxic to rats and mice of each sex. The toxicity
occurs at high doses and appears to be due to Zn++ accumulation secondary to the
chelating properties of nitrilotriacetic acid. Administration of zinc nitrilotriacetic acid or
Zn++ accentuated the nephrotoxicity of nitrilotriacetic acid.
Nitrilotriacetic acid has urothelial effects only in rats and at doses higher than those
required for nephrotoxicity and proliferative effects. Although the mechanism of induction
of the urothelial effects is not known, they are not related to Zn++ homeostasis but rather
correlate with depletion of cellular calcium and possibly the formation of nitrilotriacetic
acid-containing microcrystals.
The renal and urothelial effects of nitrilotriacetic acid are associated with cellular
toxicity and regenerative hyperplasia. Its toxic, regenerative proliferative and tumorigenic
effects occur only at high doses. No direct genotoxic effect appears to be
involved.
None of 12 renal-cell carcinomas in rats treated with ferric nitrilotriacetate acid had
mutations in codons 12, 13 or 61 of the H-, K- and N-ras genes. Only one high-grade
tumour contained a CGC→CTC transversion in codon 246 of the p53 gene (Nishiyama
et al., 1995).
Carcinogenicity: via oral route (target organ): urogenital: kidneys
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.