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EC number: 205-187-4 | CAS number: 135-37-5
- 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
Developmental toxicity / teratogenicity
Administrative data
- Endpoint:
- developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: meets generally acceptable scientific standards, well documented and accepted for assessment
Cross-reference
- Reason / purpose for cross-reference:
- reference to same study
Data source
Reference
- Reference Type:
- publication
- Title:
- Unnamed
- Year:
- 1 971
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 414 (Prenatal Developmental Toxicity Study)
- Deviations:
- not specified
- Principles of method if other than guideline:
- Prenatal development study as part of a combined Reproduction and Teratology Studies
- GLP compliance:
- no
- Limit test:
- no
Test material
- Reference substance name:
- Trisodium nitrilotriacetate
- EC Number:
- 225-768-6
- EC Name:
- Trisodium nitrilotriacetate
- Cas Number:
- 5064-31-3
- Molecular formula:
- C6H9NO6.3Na
- IUPAC Name:
- trisodium 2,2',2''-nitrilotriacetate
- Details on test material:
- - Name of test material (as cited in study report): Trisodium nitrilotriacetate
- Substance type: pure substance
- Purity: not further specified
Constituent 1
Test animals
- Species:
- rabbit
- Strain:
- New Zealand White
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
Rabbit study
- Virgin New Zealand Does
- Age 5-6 months old
- Source: Sweetwater Rabbitry, Hillsboro, Ohio
- Housing: caged individually
- Diet (e.g. ad libitum): Purina Chow ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimatisation period: 18 days
ENVIRONMENTAL CONDITIONS
Carefully controlled environment
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- water
- Analytical verification of doses or concentrations:
- not specified
- Details on mating procedure:
- - Impregnation procedure: artificial insemination after an 18-day acclimatisation period.
- Semen was collected from eight bucks with an artificial vagina and used undiluted to impregnate all 120 does.
- Inseminations were done over a 10-day period with two does from each group being inseminated daily.
- The day of insemination was designated day 0. - Duration of treatment / exposure:
- Daily during days 7-16 of gestation / during organogenesis
- Frequency of treatment:
- Daily
- Duration of test:
- 18 days of acclimatisation
Max 10 days of insemination
Treatment during days 7-16 of gestation
On day 28, the does were sacrificed.
Doses / concentrations
- Remarks:
- Doses / Concentrations:
0, 2.5, 25, 100, and 250 mg/kg bw day
Basis:
analytical conc.
All does, except the untreated controls, were weighed every 3 days during pregnancy so that dosages could be adjusted.
- No. of animals per sex per dose:
- 120 animals in total
20 animals per dose group - Control animals:
- yes, concurrent no treatment
- yes, concurrent vehicle
Results and discussion
Results: maternal animals
Maternal developmental toxicity
- Details on maternal toxic effects:
- Maternal toxic effects:no effects
Details on maternal toxic effects:
Mild diarrhea at the highest dose levels (> 25 mg7kg/d) when Na3NTA was administered by gavage or in the feed. This effect may be related to the poor absorption of NTA in the rabbit.
Effect levels (maternal animals)
- Dose descriptor:
- NOAEL
- Effect level:
- >= 250 mg/kg bw/day (nominal)
- Based on:
- act. ingr.
- Basis for effect level:
- other: no maternal toxicity
Results (fetuses)
- Details on embryotoxic / teratogenic effects:
- Embryotoxic / teratogenic effects:no effects
Effect levels (fetuses)
- Dose descriptor:
- NOAEL
- Effect level:
- >= 250 mg/kg bw/day (actual dose received)
- Based on:
- act. ingr.
- Sex:
- male/female
- Basis for effect level:
- other: no developmental toxicity
Overall developmental toxicity
- Developmental effects observed:
- no
Any other information on results incl. tables
As a result there were no significant differences in the average numbers of corpora lutea, resorptions, live and dead fetuses or in the average fetal body weights between treatment groups and controls. Also, no significant differences were seen in the number with gross abnormalities, skeletal or soft-tissue defects. For some detailed data see table 1.
Table 1: Effect of various levels of Trisodium nitrilotriacetate given by intubation on reproduction and embryogeny in the New Zealand rabbit on days 7-16 of pregnancy
Parameter | No treatment | Water treatment | 2,5 mg/kg bw/day | 25 mg/kg bw/day | 100 mg/kg bw/day | 250 mg/kg bw/day |
Average no. of: | ||||||
Corpora lutea | 11.2 | 10.1 | 10.5 | 10.9 | 11.2 | 10.5 |
Resorptions | 0.9 | 0.9 | 0.6 | 0.9 | 0.7 | 0.5 |
Live foetuses | 7.1 | 7.4 | 8.0 | 8.0 | 8.5 | 7.7 |
Average foetal weight (g) | 33.8 | 31.9 | 33.3 | 32.9 | 31.7 | 34.5 |
No. of dead foetuses | 0 | 2 | 3 | 6 | 2 | 3 |
Incidence of soft-tissue defects and no. examined | 3.2 (95) | 0 (78) | 0 (102) | 2.2 (89) | 3.0 (100) | 3.0 (102) |
Incidence of defects (%*): | ||||||
Hydroureter | 1.0 | – | – | 2.2 | 2.0 | 1.0 |
Hydronephrosis | – | – | – | 1.1 | – | 1.0 |
Distended bladder | 2.1 | – | – | – | – | – |
Umbilical hernia | 1.0 | – | – | – | – | 1.0 |
Cleft palate | – | – | – | – | 1.0 | – |
Hydrocephaly | – | – | – | – | 1.0 | – |
Acephaly | – | – | – | – | – | 1.0 |
Hypoplastic ovary | 1.0 | – | – | – | – | – |
Muscle contracture | – | – | – | – | – | 1.0 |
Incidence of skeletal defects (%) and no. examined: | 8.9 (45) | 5.6 (36) | 2.0 (50) | 8.5 (47) | 5.7 (53) | 6.0 (50) |
Missing twelfth rib | 2.2 | 2.8 | 2.0 | 8.5 | – | – |
Fusion of fourth and fifth sternebrae | 6.7 | 2.8 | – | – | 5.7 | 2.0 |
Fused fourth and fifth fibs, fight side | 2.2 | – | – | – | – | – |
*One animal may have had more than one defect.
No significant differences in the numbers of corpora lutea, resorptions or live foetuses. The number of dead foetuses in the group treated with 25 mg/kg was somewhat high, but this number was not significantly higher than the number of dead foetuses in the water-dosed control animals. Furthermore, the lack of a dose-response relationship between the levels of Trisodium nitrilotriacetate and the number of dead foetuses indicated that the deaths were due to some cause other than the Trisodium nitrilotriacetate. Similarly, no statistical differences were seen in the weights of the foetuses or in the number with congenital defects.
As with the soft-tissue defects, there were no significant differences in skeletal defects.
Some variations in the numbers of sternebrae and ribs were scattered throughout the groups, but these appeared to be within the normal range for the rabbit. Otherwise, the only abnormalities of the skeleton were a missing twelfth rib in seven foetuses, fused ribs in one foetus and vertical fusion of the fourth and fifth sternebrae in eight foetuses. These were distributed randomly throughout test and control groups.
No gross pathology was seen in the dams at laparotomy. Since no histological differences were seen in the tissues of rats in the much longer study (see Nolen et al 1971 - NTA - DevelopTox-rats, 7.8.2), no histopathology was done on these animals.
Applicant's summary and conclusion
- Conclusions:
- No substance-related effect on the development of the fetuses was observed in rabbits receiving Na3NTA up to 250 mg/kg/d.
- Executive summary:
In a developmental toxicity study Na3NTA was administered to female New Zealand dams at dose levels of 0, 2.5, 25, 100, and 250 mg/kg/d from days 7 through 16 of gestation.
As a result there were no significant differences in the average numbers of corpora lutea, resorptions, live and dead fetuses or in the average fetal body weights between treatment groups and controls. Also, no significant differences were seen in the number with gross abnormalities, skeletal or soft-tissue defects.
The developmental toxicity study in the rabbits is sufficiently well documented and satisfies main guideline requirements for a developmental toxicity studies in rabbits.
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