L-Aspartic acid, N,N'-1,2-ethanediylbis-

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:

weight of evidence

Study period:

26 to 29 May 1993

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Guideline study, to GLP; on related material

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1993

Report date:

1993

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:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OTS 798.4470 (Acute Dermal Irritation)

Deviations:

not specified

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

Trisodium EDDS

IUPAC Name:

Trisodium EDDS

Constituent 2

Reference substance name:

l-aspartic acid, N,N'-1,2-ethanediylbis-, trisodium salt

IUPAC Name:

l-aspartic acid, N,N'-1,2-ethanediylbis-, trisodium salt

Constituent 3

Reference substance name:

178949-82-1

EC Number:

605-842-8

Cas Number:

178949-82-1

IUPAC Name:

178949-82-1

Constituent 4

Reference substance name:

-

EC Number:

416-530-4

EC Name:

-

IUPAC Name:

416-530-4

Details on test material:

- Name of test material (as cited in study report): trisodium EDDS (under code)
- Molecular formula (if other than submission substance): C10-H13-N2-O8. 3Na
- Molecular weight (if other than submission substance): 358
- Smiles notation (if other than submission substance): [Na+].[Na+].[Na+].OC(=O)[C@H](CC([O-])=O)NCCNC(CC([O-])=O)C([O-])=O
- Substance type: technical product
- Physical state: white powder
- Purity test date: no data
- Lot/batch No.: 02
- Expiration date of the lot/batch: 1 January 1998
- Stability under test conditions: stable in water
- Storage condition of test material: dry conditions at room temperature in dark

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Dr Karl Thomae GmbH, Postfach 1755, D-7950 Biberach an der Riss, Germany
- Age at study initiation: 15 weeks
- Weight at study initiation: male, 2.8 kg; females 2.3-2.8 kg
- Housing: individually in stainless steel cages
- Diet (e.g. ad libitum): conventional, ad libitum
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: 4 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 3
- Humidity (%): 40-70
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Type of coverage:

semiocclusive

Preparation of test site:

other: clipped

Vehicle:

water

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 500 mg


VEHICLE
- Amount(s) applied (volume or weight with unit): "the test article was slightly moistened with tap water"

Duration of treatment / exposure:

4 h

Observation period:

1, 24, 48 and 72 h

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: back, 6 cm2
- % coverage: no data
- Type of wrap if used: surgical gauze covered with a semi-occlusive dressing wrapped around the abdomen and secured with an elastic bandage


REMOVAL OF TEST SUBSTANCE
- Washing (if done): with lukewarm tap water
- Time after start of exposure: 4 h then skin washed prior to the first reading with double-distilled water so any reactions would be clearly visible


SCORING SYSTEM: scored at 30 min after removal of the patches and at 24, 48 and 72 h for erythema and eschar formation and edema as follows:
No erythema 0
Very slight erythema 1
Well-defined erythema 2
Moderate to severe erythema 3
Severe erythema to slight eschar formation 4

No edema 0
Very slight edema 1
Slight edema 2
Moderate edema (raised about 1 mm) 3
Severe edema (raised more than 1 mm) 4

Results and discussion

In vivo

Results

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Time point:

other: 1, 24, 48 and 72 h

Score:

0

Max. score:

8

Reversibility:

other: not applicable

Irritant / corrosive response data:

No irritation response was seen in any of the three animals during the observation period

Other effects:

No mortaility or systemic effects were noted, and the body weight gain was within normal ranges. No staining of the treated area or corrosion was reported in any animal at any time point.

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

In a GLP study conducted according to OECD Guideline 404 and EU Method B.4, no evidence of irritation was observed when 0.5 g of trisodium EDDS was applied for 4 h (under a semi-occlusive dressing) to the intact skin of three rabbits.

Executive summary:

In a GLP study conducted according to OECD Guideline 404 and EU Method B.4, the ability of trisodium EDDS to induce skin irritation was assessed in a study in New Zealand White rabbits. The test substance, moistened slightly with water, was applied to the intact skin of the dorsal trunk region of three young rabbits (one male and two females) under a semi-occlusive dressing. The patch was removed after 4 h and the skin washed with lukewarm water and examined for erythema, eschar and edema after 1, 24, 48 and 72 h.

No signs of irritation (or corrosion or staining) were evident in any animal throughout the observation period.

In conclusion, no evidence of irritation was observed when 0.5 g of trisodium EDDS was applied for 4 h (under a semi-occlusive dressing) to the intact skin of three rabbits. According to EU CLP and DSD regulations, trisodium EDDS would not be classiffied as a skin irritant under the conditions of this test.

[Data on trisodium EDDS is considered relevant to use for understanding the skin irritation potential of EDDS acid, and is acceptable for using as read-across information.]