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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)
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:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
Cross-reference
- Reason / purpose for cross-reference:
- reference to other study
Data source
Referenceopen allclose all
- Reference Type:
- publication
- Title:
- Teratogenesis Studies with EDTA and its Salts in Rats
- Author:
- Schardein, J.L. et al
- Year:
- 1 981
- Bibliographic source:
- Toxicology and Applied Pharmacology 61, 423-428 (1981)
- Reference Type:
- secondary source
- Title:
- Teratogenesis Studies with EDTA and its Salts in Rats
- Author:
- Schardein, J.L. et al
- Year:
- 1 981
- Bibliographic source:
- Toxicol. Appl. Pharmacol., 61, 423-428, (1981) Cited in: Bibra Bulletin 21, No. 1, pp 12-13, (1982)
Materials and methods
- Principles of method if other than guideline:
- EDTA and four of its salts, disodium, trisodium, calcium di-sodium, and tetrasodium edetate, were studied for teratogenic potential in rats. Equimolar doses based on 1000 mg/kg were given by gastric intubation on days 7 to 14 of gestation. On day 21 of gestation, the dams of each group were sacrificed and litter data for each dam collected.
- GLP compliance:
- no
- Limit test:
- no
Test material
- Reference substance name:
- Edetic acid
- EC Number:
- 200-449-4
- EC Name:
- Edetic acid
- Cas Number:
- 60-00-4
- Molecular formula:
- C10 H16 N2 O8
- IUPAC Name:
- 2,2',2'',2'''-(ethane-1,2-diyldinitrilo)tetraacetic acid
- Test material form:
- solid
Constituent 1
Test animals
- Species:
- rat
- Strain:
- other: CD albino
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charls River Breeding Laboratories
- Weight at study initiation: mean: 241 g
- Diet: Purina Lab Chow ad libitum
- Water: tap water ad libitum
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- other: 0.2 M phosphate buffer
- Details on exposure:
- -pH of dosing solution: 3.9
- Analytical verification of doses or concentrations:
- no
- Details on mating procedure:
- - Impregnation procedure: cohoused
- If cohoused:
- M/F ratio per cage: 1:1
- Proof of pregnancy: vaginal plug, sperm in vaginal smear referred to as day 0 of pregnancy - Duration of treatment / exposure:
- 7 days (day 7 to day 14 of gestation)
- Frequency of treatment:
- equally devided doses twice daily
- Duration of test:
- 21 days
Doses / concentrations
- Dose / conc.:
- 967 mg/kg bw/day (actual dose received)
- Remarks:
- Divided into two eaqual doses
- No. of animals per sex per dose:
- 20
- Control animals:
- yes, concurrent no treatment
- yes, concurrent vehicle
Examinations
- Maternal examinations:
- CAGE SIDE OBSERVATIONS: Yes
BODY WEIGHT: Yes
- Time schedule for examinations: once a week
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes
POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day 21
- Ovaries and uterine content:
- The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Number of implantations: Yes
- Number of early resorptions: Yes
- Number of late resorptions: Yes - Fetal examinations:
- - External examinations: each fetus
- Gross ispection, slicing and visceral abnormalties: 1/3 of the litter
- Skeletal examinations: 2/3 of the litter - Statistics:
- Means and standard errors were calculated for litter size, followed by analysis of variance. Pre- and postimplantation losses, embryonic viability, and fetal survival were evaluated by analysis of covariance. Fetal weights were also evaluated by analysis of covariance following calculation of mean weight/litter by sex, the values representing means and standard errors of mean litter weights. Significant variance by either analysis of variance or covariance was further evaluated by Dunnett's t test to locate the source of variance. Sex distribution was analyzed by partitioned chi^2.
Results and discussion
Results: maternal animals
Maternal developmental toxicity
- Details on maternal toxic effects:
- Maternal toxic effects:yes
Details on maternal toxic effects:
- diarrhea in 80% of the animals: daily after application; it disappeared after the last day of dosing
- depression of activity in 3 animals
- decreased food intake during treatment (see table 1)
- reduced weight gain during treatment; recovery within the post treatment period
Effect levels (maternal animals)
open allclose all
- Dose descriptor:
- LOAEL
- Effect level:
- 967 mg/kg bw/day (actual dose received)
- Basis for effect level:
- other: maternal toxicity
- Dose descriptor:
- NOAEL
- Effect level:
- >= 967 mg/kg bw/day (actual dose received)
- Basis for effect level:
- other: developmental toxicity
Results (fetuses)
- Details on embryotoxic / teratogenic effects:
- Embryotoxic / teratogenic effects:no effects
Details on embryotoxic / teratogenic effects:
- no effects on litter size, sex ratio or mortality index (see table 2)
- no drug related statisticcally significant increase of malformation could be observed in the treated animals.
(A total of 1084 pups from drug-treated dams were examined. These were compared to 237 pups from 19 dams treated with the vehicle and 278 pups from 20 untreated dams. In addition, 752 pups from dams treated with edetic acid and its salts together with 165 and 191 pups from the vehicle and untreated control groups, respectively, were cleared and examined for skeletal defects. Twenty-four pups from the drug-treated groups had abnormalities. These included 20 with bifid vertebrae, 1 with agenesis of the ribs, 2 with inhibition of osteogenesis of the skull or ribs, and 1 with malformed ribs.
There was no definitive pattern regarding treatment with a particular compound and the occurrence of anomalies. None of the pups in the vehicle control group had abnormalities while 8 untreated control pups exhibited some major defect. One untreated control fetus was stunted and had multiple abnormalities including eye defect, ectrodactyly, and a curly tail. Histological examination of the eyes revealed a cataract in one eye and a dysmorphic lens and retina in the other. Five additional control pups had bifid vertebrae while 2 had malformed vertebrae or sternebrae.)
Effect levels (fetuses)
open allclose all
- Dose descriptor:
- NOAEL
- Effect level:
- >= 967 mg/kg bw/day (actual dose received)
- Basis for effect level:
- other: teratogenicity
- Dose descriptor:
- NOAEL
- Effect level:
- >= 967 mg/kg bw/day (actual dose received)
- Basis for effect level:
- other: embryotoxicity
- Dose descriptor:
- NOAEL
- Effect level:
- >= 967 mg/kg bw/day (actual dose received)
- Basis for effect level:
- other: fetotoxicity
Overall developmental toxicity
- Developmental effects observed:
- not specified
Any other information on results incl. tables
Table 1: Food consumption and weight gain in rats treated with EDTA and EDTA salts on days 7 through 14 of gestation
Days | Control (untreated) | Vehicle Control | 967 mg/kg bw/day EDTA | 1243 mg/kg bw/day Na2 EDTA | 1245 mg/kg bw/day Na3 EDTA | 1340 mg/kg bw/day CaNa2 EDTA | 1374 mg/kg bw/day Na4 EDTA |
Mean food consumption (g/day) | |||||||
0-7 | 20.7 | 21.4 | 19.9 | 20.4 | 19.9 | 20.4 | 19.0 |
7-14 | 22.3 | 22.5 | 18.4 | 17.5 | 19.1 | 20.9 | 18.5 |
14-21 | 24.7 | 25.3 | 26.7 | 27.2 | 25.7 | 26.5 | 25.6 |
Mean body weight gain (g) | |||||||
0-7 | 31.9 | 35.1 | 37.6 | 35.6 | 33.2 | 37.2 | 26.9 |
7-14 | 28.5 | 26.1 | 16.5 | 13.7 | 20.4 | 25.1 | 18.3 |
14-21 | 102.7 | 93.3 | 104.4 | 100.2 | 98.4 | 108.1 | 94.2 |
Table 2: Reproductive data in dams recieving EDTA and EDTA salts on days 7 through 14 of gestation
Fetuses | ||||||||||
Sex | Body weight (mean g ± SE) | Number | ||||||||
Treatment | No of dams | Litter size (mean ± SE) | Post implantation loss (%) | M | F | M | F | Dead | live | Resorbed |
Control (untreated) | 20 | 14.0 ± 0.4 | 4 | 52 | 48 | 5.3 ± 0.1 | 5.6 ± 0.1 | 1 | 278 | 12 |
Vehicle Control | 19 | 12.5 ± 0.1 | 3 | 50 | 50 | 5.3 ± 0.1 | 5.7 ± 0.1 | 0 | 237 | 7 |
967 mg/kg bw/day EDTA | 17 | 12.7 ± 0.6 | 3 | 49 | 51 | 5.5 ± 0.1 | 5.7 ± 0.1 | 0 | 216 | 6 |
1243 mg/kg bw/day Na2 EDTA | 19 | 12.6 ± 0.4 | 1 | 56 | 44 | 5.4 ± 0.1 | 5.6 ± 0.1 | 0 | 202 | 3 |
1245 mg/kg bw/day Na3 EDTA | 18 | 12.4 ± 1.0 | 8 | 48 | 52 | 5.4 ± 0.2 | 5.7 ± 0.1 | 0 | 210 | 11 |
1340 mg/kg bw/day CaNa2 EDTA | 17 | 13.5 ± 0.4 | 2 | 52 | 48 | 5.3 ± 0.1 | 5.6 ± 0.1 | 0 | 230 | 4 |
1374 mg/kg bw/day Na4 EDTA | 19 | 11.9 ± 0.7 | 4 | 47 | 52 | 5.2 ± 0.1 | 5.5 ± 0.1 | 0 | 226 | 10 |
- 2 dams had to be killed due to dosing errors
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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