Sodium calcium edetate

Endpoint summary

Description of key information

The LD50 value in rats was ca. 10 g/kg bw; the LD50 value in rabbits was ca. 7 g/kg bw and the LD50 in dogs ca. 12 g/kg bw, the 7-h LC50 value was in excess of 1.13 mg/L (nominal). Non-physiological routes of exposure (iv and ip) also showed low acute toxicity.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

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.

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

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

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

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.

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.

 

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Quality of whole database:

Although the key and supporting studies were conducted prior to GLP and guidelines, these studies are well documented and sufficient data is available for the interpretation of study results.

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1976

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: This study was conducted prior to GLP but sufficient data is available for the interpretation of study results together with results of inhalation studies with other metal chelates.

Qualifier:

no guideline followed

Principles of method if other than guideline:

A limit test was carried out.

GLP compliance:

no

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

not specified

Sex:

not specified

Details on test animals or test system and environmental conditions:

Not specified in the report

Route of administration:

inhalation: dust

Type of inhalation exposure:

not specified

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

Not specified in the report

Analytical verification of test atmosphere concentrations:

not specified

Duration of exposure:

7 h

Concentrations:

Nominal concentration 1.13 mg/L

No. of animals per sex per dose:

4 albino rats

Control animals:

not specified

Details on study design:

The exposure of 4 albino rats to the dust atmosphere (nominal concentration 1.13 mg/L) for 7 hours

Statistics:

Not specified in the report

Sex:

not specified

Dose descriptor:

LC50

Effect level:

> 1.13 mg/L air (nominal)

Based on:

test mat.

Exp. duration:

7 h

Remarks on result:

other: 100% survival

Mortality:

All animals survived

Clinical signs:

other: Not specified in the report

Body weight:

Not specified in the report

Gross pathology:

Not specified in the report

Other findings:

Not specified in the report

Interpretation of results:

practically nontoxic

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Based on the results of this study this test material is practically nontoxic as per EU classification when tested on albino rats via dust inhalation.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Quality of whole database:

OLd study, pre-GLP, and only nominal concentration reported. However, other studies with metal-chelates of EDTA (EDTA-MnNa2, EDTA-FeNa, EDTA-CuNa2) also showed very limited acute toxicity (4-h LC50 > 5 mg/L). In addition, a study with Ca-DTPA showed a 2-h LC50 > 1.15 mg/L.

Acute toxicity: via dermal route

Endpoint conclusion

Quality of whole database:

Studies with two other metal chelates were available both showing LD50 values in excess of 2000 mg/kg bw.

Additional information

The oral and inhalation route for the endpoint acute toxicity are already covered. A third route is not required by Regulation 1907/2006. In addition, the absorption via the skin is expected to be very low (EU RAR, 2004). Acute dermal studies with two other metal chelates showed LD50 values in excess of 2000 mg/kg bw.

Justification for selection of acute toxicity – oral endpoint
Study in rats, comparable to OECD guideline 401.

Justification for selection of acute toxicity – inhalation endpoint
One inhalation toxicity study was available for EDTA-CaNa2.

Justification for classification or non-classification

Based on the very low toxicity of EDTA-CaNa2 via the inhalation and oral route, and the expected very low dermal absorption, no classification is needed for acute toxicity.