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EC number: 205-759-3 | CAS number: 150-39-0
- 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
Key value for chemical safety assessment
Carcinogenicity: via oral route
Link to relevant study records
- Endpoint:
- carcinogenicity: oral
- Type of information:
- migrated information: read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Study meets generally accepted scientific principles For read-across justification refer to section 13.
- Principles of method if other than guideline:
- A bioassay for possible carcinogenicity was conducted by administering the test material in feed to Fischer 344 rats. 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
- Species:
- rat
- Strain:
- Fischer 344
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Schmidt, Madison, Wisconsin, USA
- Weight at study initiation: 85-110 g
- Age at study initiation: 28 days
- Housing: four 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 - Route of administration:
- oral: feed
- Vehicle:
- unchanged (no vehicle)
- Details on exposure:
- DIET PREPARATION
- Rate of preparation of diet (frequency): 3 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
- Post exposure period:
- none
- Remarks:
- Doses / Concentrations:
248; 495 mg/kg bw/day (original data: 3,750 ppm 7,500 ppm; conversion according to EU risk assessment)
Basis:
nominal in diet - No. of animals per sex per dose:
- 50 (except for the control, which consisted of only 20 animals)
- Control animals:
- yes, plain diet
- 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 - Histopathological findings: neoplastic:
- effects observed, treatment-related
- Details on results:
- MORTALITY
The male rats exhibited a negative dose-related trend in survival with the probability level of P = 0.103; the treated and control groups of male rats can thus be considered as comparable to each other in survival. The female rats also exhibited a negative dose-related trend in survival, but in this case the effect was statitstically significant (p =0.029).
CLINICAL SIGNS
No significant signs were observed among test animals during the first year of the study. In the 6 months preceding termination of the test, corneal opacities, ascites, and urine stains, occurred in both treatment and control groups.
BODY WEIGHT AND WEIGHT GAIN
Average body weights of treated male and female rats were comparable to those of the matched controls throughout the study.
GOSS PATHOLOGY
Inflammatory and degenerative changes were observed in about the same frequency in all groups. These lesions appeared to be related to age and no to the administration of the chemical.
HISTOPATHOLOGY: NEOPLASTIC
A high incidence of neoplasms occurred in the reproductive and endocrine systems and lower in the hematopoietic, respiratory, integumentary, and digestive systems. No neoplasms were observed in the nervous, musculoskeletal, or urinary systems or in organs of special sense. A number of tumors occurred in other organ systems of both sexes, controls as well as treated animals.
No tumor appeared in a statistically significant positive trend in either dose groups or sexes. A variety of endocrine tumors were found, some types occurring only in treated animals. However, these tumors occurred in low numbers and have frequently been seen in untreated animals in other studies. Therefore, they are probably unrelated to treatment .
Males:
Interstitial-cell tumors of the testes were observed in nearly all male rats in each feeding group. This high incidence of interstitial-cell tumors in both treated and control animals reflects this commonly occurring age-related lesion in the male Fischer 344 rat.
Females:
The distribution of neoplasms in the reproductive system among control and treated rats was random, the tumors occurred mainly in the uterus . The majority of these were endometrial stromal polyps. However, one adenocarcinoma and one leiomyosarcoma occurred at 495 ppm. An ovarian cystadenoma was detected in a single 248 ppm-dose rat - Dose descriptor:
- NOAEL
- Effect level:
- >= 500 mg/kg bw/day (nominal)
- Sex:
- male/female
- Remarks on result:
- other: Effect type: carcinogenicity (migrated information)
- Dose descriptor:
- NOAEL
- Effect level:
- >= 500 mg/kg bw/day (nominal)
- Sex:
- male/female
- Remarks on result:
- other: Effect type: toxicity (migrated information)
Reference
Table 1: Analyses of the Incidence of Primary Tumors at Specific Sites in Male Rats Fed EDTA Trisodium Salt in the Diet |
Morphology (p-value) | Control | 248 mg/kg bw/day | 495 mg/kg bw/day |
Hematopoietic System: Leukemia, Malignant Lymphoma and Lymphocytic Leukemia | 3/20 (n.s.) | 4/50 (n.s.) | 4/50 (n.s.) |
Weeks to first observed tumor: | 76 | 104 | 102 |
Adrenal: Pheochromocytoma | 2/20 (n.s.) | 5/49 (n.s.) | 4/50 (n.s.) |
Weeks to first observed tumor: | 104 | 104 | 67 |
Thyroid: C-cell Adenoma | 0/17 (n.s.) | 6/35 (p = 0 0.08) | 3/38 (n.s.) |
Weeks to first observed tumor: | - | 104 | 67 |
Pituitary: Chromophobe Adenoma | 0/18 | 3/47 (n.s.) | 5/44 (n.s.) |
Weeks to first observed tumor: | - | 88 | 104 |
Lung: Alveolar/Bronchiolar Adenoma and Carcinoma | 1/18 (n.s.) | 2/50 (n.s.) | 3/49 (n.s.) |
Weeks to first observed tumor: | 104 | 95 | 67 |
Liver: hepatocellular Adenoma and Neoplastic Nodule | 0/20 (n.s.) | 1/48 (n.s.) | 1/50 (n.s.) |
Weeks to first observed tumor: | - | 104 | 104 |
Testis: Interstitial-cell Tumor | 19/20 (n.s.) | 43/50 (n.s.) | 44/50 (n.s.) |
Weeks to first observed tumor: | 88 | 85 | 95 |
Table 2 Analyses of the Incidence of Primary Tumors at Specific Sites in Female Rats Fed EDTA Trisodium Salt in the Diet |
Morphology (p-value) | Control | 248 mg/kg bw/day | 495 mg/kg bw/day |
Hematopoietic System: Leukemia, Malignant Lymphoma and Lymphocytic Leukemia | 1/20 (n.s.) | 8/50 (n.s.) | 0/50 (n.s.) |
Weeks to first observed tumor: | 104 | 80 | - |
Adrenal: Pheochromocytoma | 1/20 (n.s.) | 1/49 (n.s.) | 1/48 (n.s.) |
Weeks to first observed tumor: | 98 | 104 | 104 |
Thyroid: C-cell Adenoma | 0/11 (n.s.) | 0/36 (n.s.) | 1/37 (n.s.) |
Weeks to first observed tumor: | - | - | 104 |
Pituitary: Chromophobe Adenoma | 6/19 (n.s.) | 10/48 (n.s.) | 11/50 (n.s.) |
Weeks to first observed tumor: | 95 | 104 | 104 |
Lung: Alveolar/Bronchiolar Adenoma and Carcinoma | 0/20 (n.s.) | 3/48 (n.s.) | 2/48 (n.s.) |
Weeks to first observed tumor: | - | 104 | 104 |
Liver: Neoplastic Nodule | 0/20 (n.s.) | 1/48 (n.s.) | 0/48 (n.s.) |
Weeks to first observed tumor: | - | 104 | - |
Uterus: Endometrial Stromal Polyp | 5/20 (n.s.) | 6/50 (n.s.) | 7/50 (n.s.) |
Weeks to first observed tumor: | 104 | 96 | 85 |
Mammary Gland: Fibroadenoma | 4/20 (n.s.) | 3/50 (n.s.) | 3/50 (n.s.) |
Weeks to first observed tumor: | 85 | 96 | 97 |
- Not all animals were examined pathologically, due to cannibalism or advanced state of autolysis.
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 500 mg/kg bw/day
- Study duration:
- chronic
- Species:
- rat
- Quality of whole database:
- Also mouse study available with a higher NOAEL.
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
Negative findings were obtained in tests for gene mutation / mutagenicity. In-vivo carcinogenicity studies in the rat and mouse have not revealed any statistical significant increace in tumour type or incidence.
Non-classification is justified on the basis of negative findings in accordance with Regulation (EC) No. 1272/2008.
Additional information
A study in the rat on a structural analogue of the substance revealed a high incidence of neoplasms occurring in the reproductive and endocrine systems and a lower incidence in the hematopoietic, respiratory, integumentary, and digestive systems. No neoplasms were observed in the nervous, musculoskeletal, or urinary systems or in organs of special sense. A number of tumours occurred in other organ systems of both sexes, controls as well as treated animals. No tumour appeared in a statistically significant positive trend in either dose groups or sexes. A study with the same substance in the mouse revealed a variety of neoplasms in both treated and control animals that were well known from historical controls of the same strain. There was a high incidence of tumors in the hematopoictic, endocrine, digestive, and respiratory systems. The incidence of neoplasms in other systems was variable. For all tumour types observed no statistical significance were seen between incidences in treated and control groups.
Justification for selection of carcinogenicity via oral route endpoint:
Well performed study in rats with a structurally related substances meeting generally accepted scientific principles
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