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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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

Toxicological information

Repeated dose toxicity: oral

Currently viewing:

Administrative data

Endpoint:
sub-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:
publication
Title:
The Toxicity and Pharmacodynamics of EGTA: Oral Administration to Rats and Comparisons with EDTA
Author:
Wynn, J.E. et al.
Year:
1970
Bibliographic source:
Toxicology and Applied Pharmacology 16, 807-817 (1970)

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
A 13-week feeding study on rats was performed using 3 different dose groups and one control group. After 13 weeks 50 % of the animals of each group were sacrificed and tissues examined for gross and histopathologic changes. The remaining animals were placed on control diet for 4 weeks. Thereafter animals were sacrificed and examined for gross and histopathologic changes.
GLP compliance:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Disodium dihydrogen ethylenediaminetetraacetate
EC Number:
205-358-3
EC Name:
Disodium dihydrogen ethylenediaminetetraacetate
Cas Number:
139-33-3
Molecular formula:
C10H16N2O8.2Na
IUPAC Name:
disodium dihydrogen 2,2',2'',2'''-(ethane-1,2-diyldinitrilo)tetraacetate
Test material form:
solid

Test animals

Species:
rat
Strain:
other: Holtzman
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 120 ± 6 g
- Diet: Ground Purina Laboratory Chow

Administration / exposure

Route of administration:
oral: feed
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
DIET PREPARATION
The top level (10 %) diet was prepared by adding the appropriate amount of Na2H2EDTA to the basic diet. This was then diluted with the basic diet to prepare the 5 % diet. Lower concentrations were similarly prepared by dilution of the next highest concentration.


Analytical verification of doses or concentrations:
no
Duration of treatment / exposure:
13 weeks
Frequency of treatment:
daily
Doses / concentrationsopen allclose all
Dose / conc.:
500 mg/kg bw/day (nominal)
Remarks:
original data: 1 % ; conversion factor: 20
Dose / conc.:
2 500 mg/kg bw/day (nominal)
Remarks:
original data: 5 % ; conversion factor: 20
Dose / conc.:
5 000 mg/kg bw/day (nominal)
Remarks:
original data: 10 % ; conversion factor: 20
No. of animals per sex per dose:
10
Control animals:
yes, plain diet

Examinations

Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily

BODY WEIGHT: Yes
- Time schedule for examinations: weekly

FOOD CONSUMPTION AND COMPOUND INTAKE :
- Mean food consumption g/animal

WATER CONSUMPTION
- not specified

HAEMATOLOGY: Yes
- Time schedule for collection of blood: at the end of the 4th and 13th week
- Parameters checked: hematocrit, hemoglobin, total and differential white blood cell counts, prothrombin times

CLINICAL CHEMISTRY
- Time schedule for collection of blood: at the end of the 4th and 13th week
- Parameters checked: calcium level

URINALYSIS: Yes
- Time schedule for collection of urine: not specified
- Parameters checked: Calcium

OPHTHALMOSCOPIC EXAMINATION: No
CLINICAL CHEMISTRY: No
NEUROBEHAVIOURAL EXAMINATION: No
Sacrifice and pathology:
GROSS PATHOLOGY: liver, kidney, spleen, lung, heart, urogenital system, digestive organs, and muscle
HISTOPATHOLOGY: Yes

Results and discussion

Results of examinations

Clinical signs:
effects observed, treatment-related
Description (incidence and severity):
500 mg/kg bw/day dose group: nothing abnormal detected
2500 mg/kg bw/day dose group: diarrhea starting at the third day
5000 mg/kg bw/day dose group: animals were emaciated, diarrhea starting at the third day
Mortality:
mortality observed, treatment-related
Description (incidence):
2500 mg/kg bw/day dose group: 2/10 animals died
5000 mg/kg bw/day dose group: 6/10 animals died
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
500 mg/kg bw/day dose group: no difference to the control group
2500; 5000 mg/kg bw/day dose group: statistically significant reduced body weight gain (control: 326 g; 2500 mg/kg bw/day dose group: 185 g; 5000 mg/kg bw/day dose group: 4 g)
Food consumption and compound intake (if feeding study):
effects observed, treatment-related
Description (incidence and severity):
500 mg/kg bw/day dose group: normal food consumption
2500; 5000 mg/kg bw/day dose group: statistically significant lower food consumption than the control
Water consumption and compound intake (if drinking water study):
effects observed, treatment-related
Description (incidence and severity):
500 mg/kg bw/day dose group: nothing abnormal detected
2500 mg/kg bw/day dose group: twice the water consumption of the control
5000 mg/kg bw/day dose group: nothing abnormal detected
Haematological findings:
effects observed, treatment-related
Description (incidence and severity):
after 4 weeks: hematocrits and hemoglobins of the 5000 mg/kg bw/day dose group slightly depressed
after 13 weeks: nothing abnormal detected in any of the groups
Clinical biochemistry findings:
no effects observed
Description (incidence and severity):
serum calcium level did not differ from the control
Urinalysis findings:
effects observed, treatment-related
Description (incidence and severity):
total calcium:
500 mg/kg bw/day dose group: no difference to the control
2500; 5000 mg/kg bw/day dose group: ca. twice as much as in the control
Gross pathological findings:
effects observed, treatment-related
Description (incidence and severity):
500; 2500 mg/kg bw/day dose group: nothing abnormal detected
5000 mg/kg bw/day dose group: pale livers
Histopathological findings: non-neoplastic:
no effects observed

Effect levels

Key result
Dose descriptor:
NOAEL
Effect level:
500 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male
Basis for effect level:
body weight and weight gain
clinical signs
food consumption and compound intake
mortality

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

RECOVERY

Once the survivors were placed on a control diet the diarrhea, when present, subsided within 24 hours. The animal that had previously received 5000 mg/kg bw/day Na2H2EDTA still had low food consumption and died within l week. All other animals survived this 4-week period . The animals that had received 2500 mg/kg bw/ day Na2H2EDTA gained weight more slowly than did the other animals and weighed significantly less than controls at the end of the 4-week withdrawal period. The chelating agent was not detectable in the urine after 2-3 days, nor in the feces after 7 days. The autopsies revealed no significant findings.

- EGTA was better tolerated in the diet than EDTA

Applicant's summary and conclusion