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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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

Carcinogenicity

Currently viewing:

Administrative data

Endpoint:
carcinogenicity: oral
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Pre-GLP study; study meets generally accepted scientific principles
Cross-reference
Reason / purpose for cross-reference:
reference to same study

Data source

Reference
Reference Type:
publication
Title:
Safety evaluation studies of Calcium EDTA
Author:
Oser BL, Oser M, Spencer HC
Year:
1963
Bibliographic source:
Toxicol. Appl. Pharmacol. 5, 142-162

Materials and methods

Test guideline
Qualifier:
no guideline available
Principles of method if other than guideline:
Two year feeding study in rats in combination with a 5-generation study (see also section 7.8.1 and 7.5.1)
GLP compliance:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Sodium calcium edetate
EC Number:
200-529-9
EC Name:
Sodium calcium edetate
Cas Number:
62-33-9
Molecular formula:
C10H12CaN2O8.2Na
IUPAC Name:
calcium disodium 2,2',2'',2'''-(ethane-1,2-diyldinitrilo)tetraacetate
Test material form:
other: a solution in water was used
Details on test material:
A 25% solution of Ca-EDTA was used.

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
The rats were housed individually in raised-bottom cages, fresh water being available at all times.

Administration / exposure

Route of administration:
oral: feed
Vehicle:
water
Details on exposure:
The basal diet for the rats was a mixture of natural foods supplemented with inorganic salts and vitamins. Its composition resembles the food consumption pattern of the United States population with respect to the ratios of milk, meat, and grain components. Vitamins and minerals were present at levels adequate for normal growth and development. The test material was added at such levels as to provide 50, 125, and 250 mg calcium EDTA (anhydrous basis) per kilogram body weight of rat per day. Because of the initially high and gradually diminishing ratio of food intake to body weight during the period between weaning and maturity, adjustments of the proportion of test material in the diet were made biweekly up to the eleventh week. Since the food intake of rats at this time is normally stabilized at approximately 50 g per kilogram body weight, the concentration of test material was kept constant for the remainder of the study.
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
In the studies reported, a 25% solution of calcium EDTA was used. Two samples were prepared and stored in polyethylene bottles
at room temperature. Portions for use in the experimental work were withdrawn as needed. Analytical studies demonstrated that these solutions
were stable throughout the period covered by this work.
Duration of treatment / exposure:
Two years
Frequency of treatment:
Daily
Post exposure period:
No
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 50, 125 and 250 mg/kg bw
No. of animals per sex per dose:
25
Details on study design:
See section 7.5.1
Positive control:
No

Examinations

Observations and examinations performed and frequency:
See section 7.5.1
Sacrifice and pathology:
See section 7.5.1

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
no effects observed
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
not examined
Haematological findings:
no effects observed
Clinical biochemistry findings:
no effects observed
Urinalysis findings:
no effects observed
Behaviour (functional findings):
not examined
Organ weight findings including organ / body weight ratios:
no effects observed
Gross pathological findings:
no effects observed
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
no effects observed
Details on results:
Except for mammary tumors which are fairly common in females with a history of continuous breeding, the character and number of tumors
observed indicated them to be of an incidental nature. They occurred with a frequency comparable to that usually seen in this colony.

Effect levels

Dose descriptor:
NOAEL
Effect level:
>= 250 mg/kg bw/day
Based on:
test mat.
Basis for effect level:
other: NOAEL

Applicant's summary and conclusion

Conclusions:
Except for mammary tumors which are fairly common in females with a history of continuous breeding, the character and number of tumors
observed indicated them to be of an incidental nature. They occurred with a frequency comparable to that usually seen in this colony.