Sodium calcium edetate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1957

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: This study was conducted prior to GLP and guidelines but well documented and sufficient data is available for the interpretation of study results.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1957

Report date:

1957

Materials and methods

Test guideline

Qualifier:

no guideline available

Principles of method if other than guideline:

A standard acute oral toxicity test was carried out using several dose levels; in 1957 no guideline was available.

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

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

Details on test material:

- Name of test material (as cited in study report): 24.7 % of CaNa2EDTA

Test animals

Species:

rat

Strain:

not specified

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 191-216 gms
- Fasting period before study: 16-20 hrs
- Housing: rats were housed in indiviual cages
- Diet ( ad libitum): Nutritionally adequate diet
- Water ( ad libitum): Tap water

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

Not specified in the report

Doses:

1.01 gm/kg bw, 2.02 gm/kg bw, 4.05 gm/kg bw, 5.72 gm/kg bw, 8.10 gm/kg bw, 9.63 gm/kg, 11.44 gm/kg bw, 16.20 gm/kg bw

No. of animals per sex per dose:

1.01 gm/kg bw - 4
2.02 gm/kg bw - 10
4.05 gm/kg bw - 10
5.72 gm/kg bw - 20
8.10 gm/kg bw - 20
9.63 gm/kg bw - 20
11.44 gm/kg bw - 20
16.20 gm/kg bw - 10

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The rats were observed carefully at frequent intervals through 2 days and daily thereafter for two weeks.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, and Gross pathology

Statistics:

Not specified in the report

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

10 000 mg/kg bw

Mortality:

1.01 gm/kg bw - 0 %
2.02 gm/kg bw - 0 %
4.05 gm/kg bw - 20 %
5.72 gm/kg bw - 0 %
8.10 gm/kg bw - 25 %
9.63 gm/kg bw - 45 %
11.44 gm/kg bw - 70 %
16.20 gm/kg bw - 100 %

Clinical signs:

other: The abnormal symptoms were observed were abdominal discomfort or pain, excessive laxation, urinary incontinence, nasal irritation, prostration.No signs of intoxication was observed in dose levels of 1.01 gm/kg bw and 2.02 gm/kg bw.

Gross pathology:

At the end of the test period all survivors were sacrificed. The rats that died and those that survived at the higher dosage levels and were subsequently sacrificed were necropsied.Histopathological examinations were made of the livers and kidneys of rats from the critical groupsi.e.two rats of each sex in a group in which all rats survived, groups containing some rats died and some survived, groups containing all the rats died.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Based on the results of this study the acute oral estimated LD50 for rats of CaNa2EDTA is approximately 10 gm/kg bw.

Executive summary:

One hundred and fourteen young albino male and female rats weighing between 200 -225 gms served as experimental subjects. They were fasted 16 -20 hours before intragastric administration of the test sample i.e.24.7 % CaNa2EDTA in doses graded in proportion to body weight.

In preliminary trials, pairs of rats were given doses of approximately 1,2,4,8 and 16 gm CaNa2EDTA per kilogram of body weight. On the basis of responses observed, the groups in the range of the LD50 were increased to ten rats each. When the critical range was confirmed, the size of the groups at 4 dose levels was increased to 20 rats.

Following the dosage the rats were returned to individual cages and supplied with nutritionally adequate diet and fresh tap water adlibitum. The rats were observed carefully at frequent intervals through the first 2 days and daily thereafter for two weeks, records being made body weights, abnormal symptoms, mortality, gross pathology and histopathology.

At the end of the test period all survivors were sacrificed. The rats that died and those that survived at the higher dosage levels and were subsequently sacrificed were necropsied.Histopathological examinations were made of the livers and kidneys of rats from the critical groupsi.e.two rats of each sex in a group in which all rats survived, groups containing some rats died and some survived, groups containing all the rats died.

l rats that survived following the dosage gained weight during the period of two weeks. The abnormal symptoms were observed were abdominal discomfort or pain, excessive laxation, urinary incontinence, nasal irritation, prostration. No signs of intoxication was observed in dose levels of 1.01 gm/kg bw and 2.02 gm/kg bw.

Upon gross autopsy examination, the principal abnormalities seen were hemorrhagic lungs, hypermic and hemorrhagic gastric mucosa and anemic kidneys. The major histopathological findings in the kidneys and liver were osmotic nephrosis and slight, fine vacuolation of the hepatic cells respectively.

Based on the results of this study the acute oral estimated LD50 for rats of CaNa2EDTA is approximately 10 gm/kg bw.