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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:
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.
Body weight:
All rats that survived following the dosage gained weight during the period of two weeks.
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.