nickel(2+) disodium 2,2',2'',2'''-(ethane-1,2-diyldinitrilo)tetraacetate

Endpoint summary

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

Endpoint:

skin irritation: in vivo

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Justification for type of information:

The substance EDTA-NiNa2 consists of the organic moiety edetic acid and the metal ions nickel(2+) and sodium(+). Sodium ions are known to be non irritating on skin. Nickel salts are prooved to be non-irritating to eyes by the European Union Risk Assessment Report for nickel and nickel salts. Thus skin irritating properties can be excluded. Furthermore this report summarizes studies on skin irritation of nickel(2+) salts and states that only slight irritation or no irritation occured after contact of nickel salts with the skin. The complexation of the nickel(II) salt in this substance will lower the already minor irritating effect so the test material does neither have to be tested on skin irritating properties nor a classification as skin irritating has to be considered. The irritating properties of edetic acid are assessed in a seperate study.

Reference 2

Endpoint:

skin corrosion: in vitro / ex vivo

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Reference 3

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:

guideline study with acceptable restrictions

Justification for type of information:

The complex EDTA-NiNa2 consist of the organic moiety EDTA, the central atom Ni2+ and the sodium ions. As the Na+ ions are known to be non-irritant only the EDTA-Ni complex must be regarded as dangerous. In general, the complex with the chelated Ni2+ ion should be less irritant than the free Ni2+ ion. Based on that and that the complex EDTA-Ni has an average stability, a worst-case assessment where the EDTA-NiNa2 complex dissociate in its components can be done and so a read-across is possible to free EDTA and other Ni2+ compounds. For the tests disodium dihydrogen ethylenediaminetetraacetate was used.

Reason / purpose for cross-reference:

read-across source

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.

Interpretation of results:

GHS criteria not met

Conclusions:

The test substance disodium dihydrogen ethylenediaminetetraacetate has not to be classified according to the regulation (EC) No 1272/2008.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Reference 1

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:

data from handbook or collection of data

Justification for type of information:

The substance EDTA-NiNa2 consists of the organic moiety edetic acid and the metal ions nickel(2+) and sodium(+). Sodium ions are known to be non irritating on eyes. The irritating properties of edetic acid are assessed in a seperate study. This report is used for the assessment of the eye irritating properties of the nickel moiety.

Reason / purpose for cross-reference:

read-across source

Qualifier:

no guideline required

Principles of method if other than guideline:

This reports evaluates the eye irritating properties of metallic nickel and several widely used nickel salts. It collects all available information on toxicological properties of those substances, was written and reviewed by experts and thus can be seen as a reliable data source.

GLP compliance:

not specified

Specific details on test material used for the study:

The report refers to studies on metallic nickel and several metal salts, e.g. nickel sulphate.

Irritation parameter:

other: evaluation of the parameters of several studies

Basis:

mean

Time point:

other: not stated

Score:

0

Interpretation of results:

GHS criteria not met

Conclusions:

The report concludes that neither nickel nor the evaluated nickel(2+) salts are eye irritating due to their chemical properties. For metallic nickel powder a mechanical eye irritation has to be considered which does not apply for this substance.

Reference 2

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 3

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.

Interpretation of results:

GHS criteria not met

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

The test material consists of three moieties that are regarded seperately for their irritating/corrosive potential on skin and eye. The substance EDTA-NiNa2 consists of the organic moiety edetic acid and the metal ions nickel(2+) and sodium(+).

Sodium ions are known to be neither irritating on eyes nor on skin.

The European Union Risk Assessment Report for nickel and nickel salts reviews the important, relevant studies on the skin and eye irritating potential of several widely used nickel(II) salts. It concludes that nickel salts are not eye irritating and only have minor skin irritating potential. The complexation of the nickel(II) salt in the test material will lower this already minor irritating effect so the nickel moiety can be considered as neither eye nor skin irritating.

Furthermore, it could be shown, that sodium EDTA does not act as skin irritant but as an useful reagent which inhibit allergic/irritating skin reaction by complexation of the metall 2+. In an additional study it could complementary be shown, that EDTA-Na2 is non-irritant and has not to be classified according to the regulation (EC) No 1272/2008 (CLP-regulation).

In regards to the eye-irritating properties it could be shown, that EDTA-Na2 is not classified as eye irritant.

But furthermore, it has to be consider, that EDTA has a harmonised classification as substance which causes serious eye irritation (H319) according to Annex VI of the regulation (EC) No 1272/2008 (CLP Regulation).

To conclude the test substance EDTA-NiNa2 should be classified as not skin irritating based on the study results of the single moieties but as eye irritating based on the harmonised classification of EDTA. The study results would not cause a classification as eye irritating.