Amines, N-C12-18-alkyltrimethylenedi-

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2007-11-16 to 2008-04-04

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP-guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2008

Report date:

2008

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

Principles of method if other than guideline:

not applicable

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

Amines, N-C12-18-alkyltrimethylenedi-

EC Number:

268-957-9

EC Name:

Amines, N-C12-18-alkyltrimethylenedi-

Cas Number:

68155-37-3

Molecular formula:

R-NH-(CH2)3-NH2

IUPAC Name:

N-C12-18-alkyl-propane-1,3-diamine

Test material form:

liquid

Details on test material:

- Name of test material (as cited in study report): N-Coco-1,3-diaminopropane
- Physical state: liquid
- Composition of test material, percentage of components:

Total Primary amines: 8.3 %
Total Diamines: 91.7 %
Iodine number: 12 g I/100g
Water: 0.28 % (0-1 %)
C8 N Primary amine: 0.3 %
C10 N Primary amine: 0.5 %
C12 N Primary amine: 4.2 %
C14 N Primary amine: 1.6 %
C16 N Primary amine: 0.9 %
C18:1 N Primary amine: 0.6 %
C18:0 N Primary amine: 0.2 %
C8 Diamine: 4.0 %
C10 Diamine: 5.3 %
C12 Diamine: 45.5 %
C14 Diamine: 16.5 %
C16 Diamine: 9.5 %
C18:1 Diamine: 7.5 %
C18:0 Diamine: 3.6 %
Acrylnitrile: <4 ppm
Fatty acids: <1 %
Fatty alkyl nitriles: <1 %

- Purity test date: 2007-10-15
- Lot/batch No.: S000903
- Expiration date of the lot/batch: 2010-09-30
- Storage condition of test material: at RT

Test animals

Species:

rabbit

Strain:

other: New Zealand White HsdIf:NZW

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Winkelmann GmbH, Borchen, Germany
- Weight at study initiation: 2.4 to 2.5kg
- Housing: in ABS - plastic rabbit cages, floor 4200cm²
- Diet (e.g. ad libitum): free access to Altromin 2123 maintenance diets for rabbits, rich in crude fibre
- Water (e.g. ad libitum): free access to tap water (microbiologically controlled periodically)
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 +- 3°C
- Humidity (%): 55 +- 10%
- Air changes (per hr): at least 10x/h
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Type of coverage:

other: initial test: gauze patch was held in place with a semiocclusive dressing; additional test: patch was held manually in place

Preparation of test site:

other: clipping

Vehicle:

unchanged (no vehicle)

Controls:

other: untreated skin areas of the test animal served as control

Amount / concentration applied:

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

Duration of treatment / exposure:

initial test: 4h
additional test: 3min

Observation period:

1, 24, 48, 72h after patch removal (for both tests)

Number of animals:

1 animal for each both test

Details on study design:

TEST SITE
- Area of exposure: dorsal area of the trunk
- % coverage: small area of approximately 6cm²

REMOVAL OF TEST SUBSTANCE
initial test:
- Washing (if done): rinsed by using tap water
- Time after start of exposure: at the end of the exposure period

additional test:
Test substance was not rinsed.

SCORING SYSTEM:
according to guideline

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

other: PSI

Basis:

animal #1

Remarks:

initial test (exposure: 4h)

Time point:

other: average over 24/48/72h

Score:

8

Max. score:

4

Reversibility:

not reversible

Remarks:

within 72h

Remarks on result:

other: Necrosis covering the entire patch was observed at all times

Results 2

Irritation parameter:

other: PSI

Basis:

animal #2

Remarks:

additional test (exposure: 3min)

Time point:

other: average over 24/48/72h

Score:

8

Max. score:

4

Reversibility:

not reversible

Remarks:

within 72h

Remarks on result:

other: Black necrosis covering the entire patch area was observed at all times

Irritant / corrosive response data:

Dermal irritation was scored and recorded according to the grades stated in the guidelines. Due to the severe reactions and animal welfare the animals were euthanized shortly after the last observation.

Other effects:

Necrosis was observed, refer to Table 1.

Any other information on results incl. tables

Table 1: Dermal irritation of animal 1 and 2

	1h		24h		48h		72h
Animal number	Erythema	Oedema	Erythema	Oedema	Erythema	Oedema	Erythema	Oedema
1	4*	4	4*	4	4*	4	4*	4
2	1	2	4*	4	4*	4	4*	4

* necrosis covering the whole patch area

Applicant's summary and conclusion

Interpretation of results:

Category 1B (corrosive) based on GHS criteria

Remarks:

Migrated information

Conclusions:

According to the criteria of the Commission Directive 2001/59/EC, the test item N-Coco-1,3-diaminopropane has to be classified as corrosive.

Executive summary:

Acute dermal irritation/corrosion of N-Coco-1,3 -diaminopropane was investigated by administration of 0.5mL unchanged test substance. In the initial test, one female New Zealand White (NZW) rabbit was exposed 4h after removing fur from the dorsal area of the trunk. At the end of the exposure period, residual test substance was rinsed by using tap water. The animal was examined for signs of erythema and oedema at 1, 24, 48, 72h after patch removal. An additional test was requested by the sponsor. Therefore, another female NZW rabbit was exposed to the unchanged test substance for 3min. Residual test substance was not rinsed and the effects were also observed after 1, 24, 48 and 72h.

Calculation of Primary Irritation Scores (PIS) as an average value over 24h, 48h and 72h was calculated for each animal. This yielded a value of 8 for both tests. Necrosis covering the entire patch was observed at all times. These severely irritant effects were not reversible within 72h after patch removal. The animal of the initial test also showed weight loss during the observation period.

According to the EC criteria for classification and labelling requirements for dangerous substances and preparations (Guidelines in Commission Directive 2001/59/EC) the test item N-Coco-1,3-diamonipropane has to be classified as corrosive.

The test on acute dermal irritation/corrosion was performed under GLP and similar to guideline OECD Guideline 404, EU Method B.4 and EPA OPPTS 870.2500 without deviations.