Dipotassium dihydrogen ethylenediaminetetraacetate

Endpoint summary

Description of key information

No studies examining dermal or eye irritation/corrosion have been conducted with K2EDTA however studies conducted with edetic acid are available.

No skin irritation or corrosion could be observed in a skin irritation test on rabbits (BASF 1973).

No classifiable eye irritation could be observed in a test by BASF (1973). However, the test deviates from the OECD guideline in some details and as a result edetic acid has a mandatory classification in accordance with Regulation EC 1272/2008 as Eye irritant Cat. 2 H319. Given the read across aproach employed it would seem appropriate that this classification will be carried over to K2EDTA.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

Endpoint:

skin irritation: in vivo

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study meets generally accepted scientific principles

Justification for type of information:

Read across is based on a structurally similar material. An analogue justification is attached in section 13 of dataset.

Reason / purpose for cross-reference:

read-across source

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 and 15 minutes and 2 other animals for 20 h using occlusive conditions. An application site of 2.5 x 2.5 cm was covered with the liquid or powdered and moistened test substance. 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 8 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: 3.05; 3.31 kg

Type of coverage:

occlusive

Preparation of test site:

other: clipped

Vehicle:

water

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 2 ml
- Concentration (if solution): 50%

Duration of treatment / exposure:

20 h (2 additional animals for 1-15 min incubation)

Observation period:

8 days

Number of animals:

2

Details on study design:

TEST SITE
- Area of exposure: 2.5 x 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, 96 h, 7 d, 8 d 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

Max. score:

4

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 24 - 48 - 72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

- Additionally no irritation/ corrosive effects were observed in animals treated for up to 15 min

Other effects:

- Slight erythema (Draize Score 2) could be observed at the ear of both animals. The effects were fully reversible within 48 h

Interpretation of results:

not irritating

Remarks:

Migrated information

Reference 2

Endpoint:

skin irritation: in vitro / ex vivo

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

an in vitro skin irritation study does not need to be conducted because adequate data from an in vivo skin irritation study are available

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Reference 1

Endpoint:

eye irritation: in vitro / ex vivo

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

an in vitro eye irritation study does not need to be conducted because adequate data from an in vivo eye irritation study are available

Reference 2

Endpoint:

eye irritation: in vivo

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study meets generally accepted scientific principles

Justification for type of information:

Read across is based on a structurally similar material. An analogue justification is attached in section 13 of dataset.

Reason / purpose for cross-reference:

read-across source

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 50 µl or mg of the test substance were applied to the conjunctival sac of one eye of 2 animals. The non- or saline- treated eye served as control. 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: 3.2; 3.32 kg

Vehicle:

unchanged (no vehicle)

Controls:

other: talcum treated eye of the same animal

Amount / concentration applied:

TEST MATERIAL
- Amount applied: ca. 50 mg

Duration of treatment / exposure:

unspecified, 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
30 min, 1 h, 3 h, 24 h, 48 h, 5, 7 and 8 days after application

READING TIME POINTS USED FOR ASSESSMENT
24 and 48 h

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 h

Score:

1.5

Max. score:

4

Reversibility:

fully reversible within: 5 days

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

other: 24 - 48 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 5 days

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

other: 24 - 48 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 5 days

Irritation parameter:

iris score

Basis:

mean

Time point:

other: 24 - 48 h

Score:

0

Max. score:

2

Irritation parameter:

iris score

Basis:

animal #1

Time point:

other: 24 - 48 h

Score:

0

Max. score:

2

Irritation parameter:

iris score

Basis:

animal #2

Time point:

other: 24 - 48 h

Score:

0

Max. score:

2

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

other: 24 - 48 h

Score:

1.3

Max. score:

3

Reversibility:

fully reversible within: 8 days

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

other: 24 - 48 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 7 days

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

other: 24 - 48 h

Score:

1.5

Max. score:

3

Reversibility:

fully reversible within: 8 days

Irritation parameter:

chemosis score

Basis:

mean

Time point:

other: 24 - 48 h

Score:

0.5

Max. score:

4

Reversibility:

fully reversible within: 48 h

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

other: 24 - 48 h

Score:

0.5

Max. score:

4

Reversibility:

fully reversible within: 48 h

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

other: 24 - 48 h

Score:

0.5

Max. score:

4

Reversibility:

fully reversible within: 48 h

Other effects:

- Animal 2 had a smeary overlay of the substance treated eye which disappeared within 48 h.
- Bleeding was observed in both animals on the treatment day. It was reversible within 24 h (animal 1) or 48 h (animal 2).
- The talcum treated eye of the animals showed a conjunctivae score of one which was fully reversible within 48 h.

Interpretation of results:

irritating

Remarks:

Migrated information

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (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 50% aqueous solution of edetic acid. 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 8 days. No skin irritation was observed on the back of the animals at any exposure period tested. Solely a slight erythema could be observed on the ear of the animals which was fully reversible within 48 h.

In an eye irritation test performed by BASF (1973) 50 mg of solid edetic acid 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. The animals showed an average opacity grade 1.5, an average conjunctivae score of 1.3 and average chemiosis grade 0.5. All effects were fully reversible within 8 days.

Effects on eye irritation: irritating

Justification for classification or non-classification

Based on the results obtained in the toxicity studies and taking into account the provisions laid down in Council Directive 67/548/EEC and CLP, a classification as Xi, R36 and eye irritant cat 2, respectively, has to be done with respect to irritation or corrosion.