Acetic acid, oxo-, sodium salt, reaction products with ethylenediamine and hydroxybenzenesulfonic acid monosodium salt, iron sodium salts

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

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

Adequacy of study:

key study

Study period:

2000-08-08 to 2000-08-13

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2000

Report date:

2000

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

other: EC Directive No. 92/69/EEC, B.4, 31st July 1992.

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

- Name of test material (as cited in study report): EDDHAS Fe, sel de K
- Molecular formula (if other than submission substance): C18H14FeN2O12S2(3K)
- Molecular weight (if other than submission substance): 687.3
- Smiles notation (if other than submission substance): O=C(O)C(NCCNC(C(=O)O)c1cc(ccc1(O))S(=O)(=O)O)c2cc(ccc2(O))S(=O)(=O)O
- InChl (if other than submission substance): InChI=1S/C18H20N2O12S2/c21-13-3-1-9(33(27,28)29)7-11(13)15(17(23)24)19-5-6-20-16(18(25)26)12-8-10(34(30,31)32)2-4-14(12)22/h1-4,7-8,15-16,19-22H,5-6H2,(H,23,24)(H,25,26)(H,27,28,29)(H,30,31,32)
- Substance type: Fe chelate
- Physical state: brownish/red powder
- Analytical purity: 55±2%
- Impurities (identity and concentrations): none
- Purity test date: 2000-10-24
- Expiration date of the lot/batch: 2001-01-24
- Stability under test conditions: at least 6 months from receipt (date of receipt: 24 July 2000)
- Storage condition of test material: at room temperature and protected from humidity
- Other:

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Elevage Cunicole de Val de Selle, 80160 Prouzel, France
- Age at study initiation: not reported
- Weight at study initiation: mean body weight of 3 animals 2.6 ± 0.2 kg
- Housing: individually in polystyrene cages (48.2 cm x 58 cm x 36.5 cm). Each cage was equipped with a food container and a water bottle.
- Diet (e.g. ad libitum): ad libitum. 110 pelleted diet (UAR, 91360 Villemoisson-sur-Orge, France).
- Water (e.g. ad libitum): Drinking water filtered by a FG Millipore membrane (0.22 micron) was provided ad libitum.
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 ±3
- Humidity (%): 30 to 70
- Air changes (per hr): 12
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Type of coverage:

semiocclusive

Preparation of test site:

other: clipped using electric clippers

Vehicle:

unchanged (no vehicle)

Remarks:

The untreated skin served as control

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 500 mg of the test substance were placed on a moistened gauze pad. Purified water (prepared at CIT by reverse osmosis) was used in order to moisten the test substance and ensure a good contact with the skin.

Duration of treatment / exposure:

3 min and 4 hours

Observation period:

The skin was examined approximately 1 hour, 24, 48 and 72 hours after removal of the dressing.

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: back
- % coverage: 6%
- Type of wrap if used: The test substance and the gauze pad were held in contact with the skin by means of an adhesive hypoallergenic aerated semi-occlusive dressing and a restraining bandage.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): any residual test substance was wiped off by means of a moistened gauze pad.
- Time after start of exposure: 3 min and 4 hours

SCORING SYSTEM:
Erythema and eschar formation:
- no erythema: 0
- very slight erythema (barely perceptible): 1
- well-defined erythema: 2
- moderate to severe erythema: 3
- severe erythema (beet redness) to slight eschar formation (injuries in depth): 4

Oedema formation
- no oedema: 0
- very slight oedema (barely perceptible): 1
- slight oedema (edges of area well-defined by definite raising): 2
- moderate oedema (raised approximately 1 millimetre): 3
- severe oedema (raised more than 1 millimetre and extending beyond area of exposure): 4
Any other lesions were noted.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

other: mean scores after 24, 48 and 72 hours

Score:

0

Max. score:

4

Reversibility:

other: no cutaneous reactions

Remarks on result:

other: A brown coloration of the skin, which could have masked a possible very slight erythema (grade 1), was noted at the 1-hour scoring only

Results 2

Irritation parameter:

edema score

Basis:

animal #1

Time point:

other: mean scores after 24, 48 and 72 hours

Score:

0

Max. score:

4

Reversibility:

other: no cutaneous reactions

Results 3

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

other: mean scores after 24, 48 and 72 hours

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Remarks on result:

other: a very slight or well-defined erythema (grade 1 or 2)

Results 4

Irritation parameter:

edema score

Basis:

animal #2

Time point:

other: mean scores after 24, 48 and 72 hours

Score:

0

Max. score:

4

Reversibility:

other: no cutaneous reactions

Results 5

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

other: mean scores after 24, 48 and 72 hours

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 72 hors

Remarks on result:

other: a very slight or well-defined erythema (grade 1 or 2)

Results 6

Irritation parameter:

edema score

Basis:

animal #3

Time point:

other: mean scores after 24, 48 and 72 hours

Score:

0

Max. score:

4

Reversibility:

other: no cutaneous reactions

Irritant / corrosive response data:

After a 3-minute exposure (one animal):
No cutaneous reactions were observed. A brown coloration of the skin, which could have masked a possible very slight erythema (grade 1), was noted at the 1-hour scoring only.
After a 4-hour exposure (three animals):
No cutaneous reactions were observed in 1/3 animals; a brown coloration of the skin, which could have masked a possible very slight erythema (grade 1), was noted at the 1-hour scoring only.
In both remaining animals, a very slight or well-defined erythema (grade 1 or 2) was noted from day 1 up to day 3.
Mean scores over 24, 48 and 72 hours for each animal were 0.0, 1.0 and 1.0 for erythema and 0.0, 0.0 and 0.0 for oedema.

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information according to the Regulation (EC) No. 1272/2008 Criteria used for interpretation of results: EU

Conclusions:

Under the experimental conditions, the test substance EDDHAS Fe 3K is slightly irritant when applied topically to rabbits. However, the average scores calculated for each of the three animals for three consecutive days (24, 48 and 72 hours) do not exceed cut-off-values defined in the CLP.

Executive summary:

The potential of the test substance Fe3KEDDHSA to induce skin irritation was evaluated in rabbits according to OECD (No. 404, 17th July 1992) and EC (92/69/EEC, B.4, 31st July 1992) guidelines. The test substance was applied for periods of 3 minutes and 4 hours to a single male New Zealand White rabbit. Since the test substance was not irritant on this first animal, it was then applied for 4 hours to two other animals. A single dose of 500 mg of the test substance in its original form was applied to the closely-clipped skin of one flank. The test substance was held in contact with the skin by means of a semi-occlusive dressing. Cutaneous reactions were observed approximately 1 hour, 24, 48 and 72 hours after removal of the dressing. The mean values of the scores for erythema and oedema were calculated for each animal. After a 3-minute exposure no cutaneous reactions were observed in the first animal. A brown coloration of the skin, which could have masked a possible very slight erythema, was noted at the 1-hour scoring only. After a 4-hour exposure no cutaneous reactions were observed in 1/3 animals; a brown coloration of the skin, which could have masked a possible very slight erythema, was noted at the 1 -hour scoring only. In both remaining animals, a very slight or well-defined erythema was noted from day 1 up to day 3. Mean scores over 24, 48 and 72 hours for each animal were 0.0, 1.0 and 1.0 for erythema and 0.0, 0.0 and 0.0 for oedema. Under the experimental conditions, the test substance Fe3KEDDHSA is slightly irritant when applied topically to rabbits.