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Diss Factsheets
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EC number: 200-449-4 | CAS number: 60-00-4
- 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
![](https://echa.europa.eu./o/diss-blank-theme/images/factsheets/A-REACH/factsheet/print_toxicological-information.png)
Repeated dose toxicity: oral
Administrative data
- Endpoint:
- chronic toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 977
Materials and methods
- Principles of method if other than guideline:
- A bioassay for possible carcinogenicity was conducted by administering the test material in feed to B6C3F1 mice. The chemical was administered to 50 males and 50 females at low and high concentrations, for 103 weeks. Matched-control groups were composed of 20 males and 20 females. Animals were analysed for mortality, clinical signs, histopathological as well as gross pathological changes.
- GLP compliance:
- no
- Limit test:
- no
Test material
- Reference substance name:
- Trisodium hydrogen ethylenediaminetetraacetate
- EC Number:
- 205-758-8
- EC Name:
- Trisodium hydrogen ethylenediaminetetraacetate
- Cas Number:
- 150-38-9
- Molecular formula:
- C10H16N2O8.3Na
- IUPAC Name:
- trisodium hydrogen 2,2',2'',2'''-(ethane-1,2-diyldinitrilo)tetraacetate
- Test material form:
- solid
Constituent 1
Test animals
- Species:
- mouse
- Strain:
- B6C3F1
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Breeding Laboratories, Wilmington, USA
- Weight at study initiation: 19-22 g
- Age at study initiation: 28 days
- Housing: five per cage in solid polycarbonate cages
- Diet: prepared from Wayne Lab Blox Meal (Allied Mills, Inc.) ad libitum
- Water: acidulated water ad libitum
- Acclimation period: 14 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-25°C
- Humidity (%): 45-55%
- Air changes (per hr): 15 times per hour
- Photoperiod (hrs dark / hrs light): 16/8
Administration / exposure
- Route of administration:
- oral: feed
- Vehicle:
- unchanged (no vehicle)
- Details on oral exposure:
- DIET PREPARATION
- Rate of preparation of diet (frequency): 2 times/week
- Mixing appropriate amounts with (Type of food): Wayne Lab Blox Meal (Allied Mills, Inc.)
- Storage temperature of food: 4°C
- Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- - Analyses were performed, using FDA methods to determine the efficiency of the mixing procedure and the stability of the test chemical in feed. Recoveries were found to be 90.3 ± 1.4% of the theoretical value at 7,500 ppm EDTA and 90.4 ± 3.4% of the theoretical value at 3,750 ppm. It was concluded from these results that the preparations contained reasonably accurate concentrations of EDTA and were mixed homogeneously, and that the chemical was stable in feed for at least a week.
- Duration of treatment / exposure:
- 103 weeks
- Frequency of treatment:
- daily
Doses / concentrationsopen allclose all
- Dose / conc.:
- 3 750 ppm
- Remarks:
- 469 mg/kg bw/day
(conversion factor according to EU risk assessment)
- Dose / conc.:
- 7 500 ppm
- Remarks:
- 938 mg/kg bw/day
(conversion factor according to EU risk assessment)
- No. of animals per sex per dose:
- 50 (except for the control, which consisted of only 20 animals)
- Control animals:
- yes, plain diet
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: twice daily
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: twice daily
BODY WEIGHT: Yes
- Time schedule for examinations: approximately once a month - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes; all major organs, not specified but presumably all organs used for histopathology: skin, lymph nodes, mammary gland, salivary gland, bone marrow, trachea, lungs and bronchi, heart, thyroids, parathyroids, esophagus, stomach, small intestine, large intestine, liver, gallbladder, pancreas, spleen, kidneys, adrenals, urinary bladder, prostate or uterus, testis or ovary, brain, and pituitary.
HISTOPATHOLOGY: Yes;
skin, lymph nodes, mammary gland, salivary gland, bone marrow, trachea, lungs and bronchi, heart, thyroids, parathyroids, esophagus, stomach, small intestine, large intestine, liver, gallbladder, pancreas, spleen, kidneys, adrenals, urinary bladder, prostate or uterus, testis or ovary, brain, and pituitary. - Statistics:
- - Statistical tests of differences in survival between groups are compared using the method of Cox (1972) for two groups and an extension of this method by Tarone (1975) for more than two groups.
- Statistical analysis of the incidence of tumors was made using the Fisher exact test (Cox, 1970) to compare a control group to a group of treated animals at each dose. In addition, the Armitage and Cochran test for linear trend in proportions, with continuity correction (Armitage, 1971), was used.
Results and discussion
Results of examinations
- Details on results:
- MORTALITY
No statistically significant difference in survival between the different groups in both sexes. (males: 5/50 (10%) of the low-dose group, 2/50 (4%) of the high-dose group, and 1/20 (5%) of the control; females: 0/50 low-dose female mice, 1/20 (5%) of the control group and 3/50 (6%) of the high-dose group)
CLINICAL SIGNS
Ataxia occurred in a low-dose male at 8 months, and ascites was noted in mice of both sexes during the second year of the study.
BODY WEIGHT AND WEIGHT GAIN
In male mice only the high-dose group showed throughout most of the test period a decrease in average body weight compared to the controls. In female mice average body weights of the treatment groups were depressed in a dose-related manner during the test period, although the effect was small. No individual data given. No information whether this effect is statistically relevant is available.
GROSS PATHOLOGY
Nothing reported.
HISTOPATHOLOGY: NEOPLASTIC
A variety of neoplasms was observed in both treated and control animals. Each type observed has been encountered previously as a spontaneous lesion in the mouse. However, the incidence of neoplasms in all groups was high in the hematopoietic, endocrine, digestive, and respiratory systems. The incidence of neoplasms in other systems was variable. (See table 1 and 2 below)
Effect levels
- Dose descriptor:
- NOAEL
- Effect level:
- >= 938 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- body weight and weight gain
- clinical signs
- gross pathology
- histopathology: non-neoplastic
- mortality
Target system / organ toxicity
- Critical effects observed:
- not specified
Any other information on results incl. tables
Table 1: Analyses of the Incidence of Primary Tumors at Specific Sites in Male Mice Fed EDTA Trisodium Salt in the Diet
Morphology (p-value) | Control | 625 mg/kg bw/day | 1250 mg/kg bw/day | |
Hematopoietic System: Malignant Lymphoma | 2/20 (n.s.) | 7/46 (n.s.) | 7/48 (n.s.) | |
Thyroid: C-cell Adenoma | 0/10 (n.s.) | 1/29 (n.s.) | 1/33 (n.s.) | |
Pituitary: Chromophobe Adenoma | 1/13 (n.s.) | 0/19 (n.s.) | 1/26 (n.s.) | |
Lung: Alveolar/Bronchiolar Adenoma and Carcinoma | 2/18 (0.096) | 2/50 (n.s.) | 3/49 (n.s.) | |
Liver: Hepatocellular Adenoma and Neoplastic Nodule | 3/19 (n.s.) | 10/44 (n.s.) | 10/47 (n.s.) |
Table 2: Analyses of the Incidence of Primary Tumors at Specific Sites in Female Mice Fed EDTA Trisodium Salt in the Diet
Morphology (p-value) | Control | 625 mg/kg bw/day | 1250 mg/kg bw/day |
Hematopoietic System: Malignant Lymphoma | 5/19 (n.s.) | 11/49 (n.s.) | 12/47 (n.s.) |
Thyroid: C-cell Adenoma | 1/12 (n.s.) | 3/33 (n.s.) | 1/34 (n.s.) |
Pituitary: Chromophobe Adenoma | 2/12 (n.s.) | 6/34 (n.s.) | 4/29 (n.s.) |
Lung: Alveolar/Bronchiolar Adenoma and Carcinoma | 0/19 (n.s.) | 3/47 (n.s.) | 3/49 (n.s.) |
Liver: Hepatocellular Adenoma and Neoplastic Nodule | 0/19 (n.s.) | 1/46 (n.s.) | 1/47 (n.s.) |
Applicant's summary and conclusion
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.
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