reaction mass of 1-[2-(2-aminobutoxy)ethoxy]but-2-ylamine and 1-({[2-(2-aminobutoxy)ethoxy]methyl}propoxy)but-2-ylamine

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2003-03 - 2003-04

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2003

Report date:

2003

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 OPPTS 870.2500 (Acute Dermal Irritation)

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Test material form:

liquid

Details on test material:

- Batch: 8191-34
- Purity: 97.8% (expressed as primary amine, % of total)

Specific details on test material used for the study:

- Name of test material (as cited in study report): XTJ 568
- Physical state: Clear colourless liquid
- Analytical purity: 97.8%
- Impurities (identity and concentrations): No data
- Purity test date: No data
- Lot/batch No.: 8191-34
- Expiration date of the lot/batch: 01-01-2004
- Stability under test conditions: no data
- Storage condition of test material: at room temperature in the dark
- Other: specific gravity: 0.94 g/cm3

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland, Kisslegg, Germany
- Age at study initiation: at least 6 weeks old
- Weight at study initiation: at least 1.0 kg
- Housing: Animals were housed in controlled environment. Individually in labelled cages with perforated floors (Scanbur, Denmark, dimensions 56 x 44 x 37.5 cm)
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days before start of treatment under laboratory conditions

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17.9 - 21.7 °C
- Humidity (%): 49-76%
- Air changes (per hr): 15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 / 12
- Cleaning procedures in the room might have caused the temporary fluctuations above the optimal level of 70% for relative humidity. Based on laboratory historical data these conditions were considered not to have affected the study integrity

Test system

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL

Duration of treatment / exposure:

3 min and 1 h

Observation period:

In the initially treated animal, the skin reactions of all visible treated sites were assessed immediately after removal of a dressing. The skin reactions on the 3-minute treated skin area were also assessed approximately 1 hour after exposure.

Number of animals:

1 male

Details on study design:

TEST SITE
- Area of exposure: clipped skin of the flanks
- % coverage: 150 cm2 (10 x 15 cm2)
- Type of wrap if used: Metalline patch of 2 x 3 cm; the patch was mounted on Micropore tape, which was wrapped around the abdomen and secured with Coban elastic bandage.

REMOVAL OF TEST SUBSTANCE
- The dressing was removed 3 minutes and 1 hour after application. The treated skin was cleaned with water.

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)*: 4
*: Where signs of necrosis or corrosion (injuries in depth) prevent erythema scoring, the maximum grade for erythema (=4) is given.

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 millimeter): 3
Severe oedema (raised more than 1 millimeter and extending beyond the area of exposure: 4

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Remarks:

3 min exposure

Time point:

other: immediately after removal bandage

Score:

1

Results 2

Irritation parameter:

erythema score

Basis:

animal #1

Remarks:

3 min exposure

Time point:

other: 1 h after removal bandage

Score:

2

Results 3

Irritation parameter:

edema score

Basis:

animal #1

Remarks:

3 min exposure

Time point:

other: immediately and 1 h after removal of dressing

Score:

0

Results 4

Irritation parameter:

erythema score

Basis:

animal #1

Remarks:

1 h exposure (2 test sites)

Time point:

other: immediately after removal of dressing

Score:

4

Remarks on result:

other: Wound with serious exudate, grey discolouration, sign of necrosis

Results 5

Irritation parameter:

edema score

Basis:

animal #1

Remarks:

1 h exposure (2 test sites)

Time point:

other: immediately after removal bandage

Score:

2

Irritant / corrosive response data:

1-hour and intended 4-hours treatment site: wound with serious exudate
A 3-minute exposure to 0.5 mL of XTJ 568 resulted in well defined erythema in the treated skin-area. A 1-hour exposure resulted in severe erythema and slight oedema. In addition, gray discolouration of the treated skin (signs of necrosis) and a wound with serious exudate were seen on the 1-hour treated skin sites.

Colouring:
No staining of the treated skin by the test substance was observed

Other effects:

Toxicity/Mortality:
No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred.

Applicant's summary and conclusion

Interpretation of results:

Category 1B (corrosive) based on GHS criteria

Conclusions:

Evidence of full thickness destruction of the skin (wounds and gray discolouration of the skin) was observed immediately after a 1-hour exposure period, indicating that corrosion of the skin had occurred by dermal application of the substance to the intact rabbit skin. The substance is considered classified as corrosive to the skin (category 1B) according to CLP criteria.