Disodium dihydrogen ethylenediaminetetraacetate

Endpoint summary

Description of key information

No classifiable skin or eye irritation could be observed in test on rabbits (BASF SE,1973).

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

Comparable to OECD 404 (1992) with acceptable restrictions [application time: 1, 5, 15 min and 20 h (OECD: 4 h); 2 animals used (OECD: 3); observation period 7 days (OECD: 14); dose 1 g (OECD: 0.5 mL)

Principles of method if other than guideline:

BASF-TEST: Before OECD guideline 404 was established, skin irritation was tested using an internal method. White Vienna rabbits were used. Usually, 2 animals were treated for 1, 5, 15 min and 20 h using occlusive conditions. An application site of 2.5 × 2.5 cm was covered with the liquid or powdered and moistened test substance. In addition, skin tissue from the ear was tested by wrapping the ear. These results from the ear, however, would not be taken into account for evaluation as they do not represent testing of the dorsal/lateral flank of the back. After the application time, the skin was washed with water which sometimes contained a mild detergent. The animals were observed 7 days and skin changes were recorded on working days.

GLP compliance:

no

Species:

rabbit

Strain:

Vienna White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 2.6 and 3.1 kg

Type of coverage:

occlusive

Preparation of test site:

other: clipped

Vehicle:

water

Controls:

other: untreated skin of the same animal

Amount / concentration applied:

- Amount applied: 2 mL of 50 % test substance in water

Duration of treatment / exposure:

Dorsal skin: 1, 5, 15 min
Dorsal skin: 20 h
Ear: 20 h

Observation period:

7 days

Number of animals:

2

Details on study design:

TEST SITE
- Area of exposure: 2.5 × 2.5 cm

REMOVAL OF TEST SUBSTANCE
- Washing: once with 100 % Lutrol and additionally with 50% Lutrol in water
- Time after start of exposure: 1, 5 or 15 minutes, the areas exposed for 20 h were not washed

READING TIME POINTS
24 h, 48 h, 72 h, 6 days, 7 days after application

READING TIME POINTS USED FOR ASSESSMENT
24, 48 and 72 h.

SCORING SYSTEM:
- For the evaluation the BASF scores given in the raw data were converted to Draize scores.

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 24 - 48 - 72 h

Score:

0.8

Max. score:

4

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

other: 24 - 48 - 72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 48 h

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

other: 24 - 48 - 72 h

Score:

1.3

Max. score:

4

Reversibility:

fully reversible within: 72 h

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 24 - 48 - 72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

- 20 h application: a very slight erythema was observable in one animal which was fully reversible within 24 h; a well defined erythema was observable in animal 2, which was fully reversible within 72 h.
- 1-15 min exposure did also cause no edema or erythema

Other effects:

- A well defined erythema was observed on the ear of both animals which was fully reversible within 48 h.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

Dose not exactly specified (OECD: volume of 0.1 mL); 2 animals are used (OECD: 3); examination using fluorescein (OECD: no use of fluorescein)

Principles of method if other than guideline:

BASF-TEST: Before OECD guideline 405 was established, eye irritation was tested using an internal method. White Vienna rabbits were used. Usually approximately 50 mg of the test substance were applied to the conjunctival sac of one eye of 2 animals. In studies with solids, talcum powder was used as control. The animals were observed several times on the treatment day and up to 8 days afterwards, and findings were recorded on working days.
The eyes were not washed out after 24 h as specified in OECD Guideline 405, which could be critical for solids which thus remained on the cornea for several days, causing mechanical damage. Probably, this would have been less severe if it had been washed out after 1 day.

GLP compliance:

no

Species:

rabbit

Strain:

Vienna White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 3.39; 3.15 kg

Vehicle:

unchanged (no vehicle)

Controls:

other: talcum treated eye of the same animal

Amount / concentration applied:

- Amount applied: a sharp spoon (probably approximately 50 mg)

Duration of treatment / exposure:

- substance was not washed out

Observation period (in vivo):

8 days

Number of animals or in vitro replicates:

2

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing: no washing was done

READING TIME POINTS
10 min, 1 h, 3 h, 24 h, 48 h, 72 h, 6 days and 8 days after application; however the data on the 48 h, 72 h and 6 days reading of animal 2 are not reported.

READING TIME POINTS USED FOR ASSESSMENT
24, 48 and 72 h for animal 1; 24 h for animal 2

SCORING SYSTEM:
For the evaluation the BASF scores given in the raw data were converted to Draize scores

TOOL USED TO ASSESS SCORE: fluorescein

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: 24 - 48 - 72 h

Score:

0

Max. score:

4

Irritation parameter:

iris score

Basis:

mean

Time point:

other: 24 - 48 - 72 h

Score:

0

Max. score:

2

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

other: 24 - 48 - 72 h for animal 1; 24 h for animal 2

Score:

0.5

Max. score:

3

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

other: 24 - 48 - 72 h

Score:

0.3

Max. score:

3

Reversibility:

fully reversible within: 48 h

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

other: 24 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 8 days

Irritation parameter:

chemosis score

Basis:

mean

Time point:

other: 24 - 48 - 72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

Both animals showed some redness of the conjunctivae (score 1), 24 h after application of the test susbtance. The same effect was observed in the talcum powder treated eye. This effect was fully reversible 48 h in animal 1 and at least within 8 days in animal 2.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Additional information

In a skin irritation study performed by BASF (1973), two rabbits were exposed occlusively for 1, 5 or 15 minutes on the back to a 5 0% aqueous solution of Na2EDTA. Two additional rabbits were exposed to the same solution for 20 h on the back and at the ear. The skin of the animals was observed for 7 days. Both animals developed a mild erythema 24 h after application (grad 1 or grade 2 respectively) which was fully reversible within 48 or 72 h. No edema was observed. A well-defined erythema was observed on the ear of both animals, which was fully reversible within 48 h.

In an eye irritation test performed by BASF (1973), 50 mg of solid Na2EDTA were instilled into the conjunctival sac of one eye of two animals. The other eye served as control and was treated with 50 mg talcum powder. The test substance was not washed out and the animals were observed for 8 days. A slight redness of the eye (scale 1) was observed in both animals, which was fully reversible within 8 days.

Justification for classification or non-classification

The available experimental test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. As a result the substance is not considered to be classified for skin irritation/corrosion or eye irritation under Regulation (EC) No 1272/2008, as amended for the tenth time in Regulation (EU) No 2017/776.