Amides, C12-18, N-[3-(dimethylamino)propyl]

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

15 to 16 December 2009

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

The study was generally compliant with OECD Guidelines and was conducted in accordance to GLP. Some deviations were noted in relation to pre-test determination of ph, acid reserve capacity and also in relation to evaluation of the results. The early termination of the sole rabbit exposed may have been premature for a realistic assessment of dermal reactions

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2010

Report date:

2010

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

Animal temperature room was lower than recommended in the guidelines.

Principles of method if other than guideline:

Not relevant

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

N-[3-(dimethylamino)propyl] C 12-C18 alkylamide

EC Number:

932-121-8

Cas Number:

1147459-12-8

Molecular formula:

UVCB substance not applicable

IUPAC Name:

N-[3-(dimethylamino)propyl] C 12-C18 alkylamide

Test material form:

solid

Details on test material:

- Name of test material (as cited in study report): Coco amidopropyldimethylamine
- Substance type: Amides, C12-18 (even numbered), N-[3-(dimethylamino)propyl]
- Physical state: Light brown, paste to solid
- Analytical purity: 99.1%
Free dimethyl amino propylamine 0.4%
Free fatty acid 0.5%
- Purity test date: 31 August 2009
- Lot/batch No.: S001824
- Expiration date of the lot/batch: 2nd July 2019
- Storage condition of test material: At room temperature, under nitrogen gas, in a dry and well-ventilated room
- Other: Kept in two transparent glass flasks.

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Grimaud Frères Sélection S.A.S., La Corbière, Roussay, France.
- Age at study initiation: 4 to 6 months old
- Weight at study initiation: 3.552kg
- Housing: The animal was housed individually in individual Pajon cages (50 cm x 57 cm x 75 cm).
- Diet (e.g. ad libitum): During the study, the animal had free access to 110C pelleted diet
- 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°C
- Humidity (%): 30 to 70%
- Air changes (per hr): approximately 12 cycles/hour of filtered, non-recycled air
- Photoperiod (hrs dark / hrs light): 12 h/12 h (7:00 - 19:00)

IN-LIFE DATES: From: 15 To:16 December 2009

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): 0.5ml

Duration of treatment / exposure:

Single exposure for 3 minutes

Observation period:

2 days

Number of animals:

one animal

Details on study design:

TEST SITE
- Area of exposure: Two areas on the anterior and posterior parts of each flank (approximately 3.5 x 5 cm).
- % coverage: No information provided
- Type of wrap if used: non-irritating semi-occlusive dressing and a restraining bandage.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Yes - any residual test item was wiped off by means of a moistened cotton pad.
- Time after start of exposure: Following removal of the dressing.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24 h

Score:

>= 4

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other: Due to the severe cutaneous reactions, the study was considered complete and was terminated on the second day.

Results 2

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24 h

Score:

>= 4

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other: Due to the severe cutaneous reactions, the study was considered complete and was terminated on the 2nd day.

Results 3

Irritation parameter:

other: Scabs

Basis:

animal #1

Time point:

24 h

Reversibility:

no data

Remarks on result:

other: Scabs were evident at the 24 hour time-point. Due to the severe cutaneous reactions observed, the study was considered complete and was terminated on the 2nd day.

Irritant / corrosive response data:

A very slight erythema (grade 1) was noted on day 1, 1 hour after removal of the dressing. On day 2, severe erythema and oedema (grade 4) and scabs were observed on the treated flank. Additionally, a brownish area was noted during the observation. As a result of the presence of these cutaneous reactions, the study was considered complete and the animal was sacrificed on day 2.

Other effects:

No additional effects.

Any other information on results incl. tables

Clinical examinations were made at least once daily for signs of mortality or moribundity. Body weight was weighed on the day of test item administration.

Dermal Irritation	Scores				Mean Irritation Score
	1 hour Day 1	24 hours Day 2	48 hours Day 3	72 hours Day 4
Erythema	1	4	-	-	4.0
Oedema	0	4	-	-	4.0
Other	*	A	-	-	-

* = none

A = scabs

- = animal sacrificed on Day 2 for ethical reasons.

Applicant's summary and conclusion

Interpretation of results:

corrosive

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

In vivo study of Coco amidopropyldimethylamine for skin corrosion showed that a 3 minute exposure to rabbit skin lead over the course of one day to the development to skin corrosion.

Executive summary:

Coco amidopropyldimethylamine was assessed for its ability to cause corrosion in a in vivo skin corrosion/irritation study in New Zealand White rabbits (OECD 40). The test item was applied undiluted at a concentration of 0.5 ml for period of 3 minutes to one male New Zealand White rabbit. The test item was held in contact with the skin by means of a semi-occlusive dressing. Cutaneous reactions were observed approximately 1 hour and 24 hours after removal of the dressing.

A very slight erythema was noted on day 1, 1 hour after removal of the dressing. On day 2, severe erythema and oedema and scabs were observed on the treated flank. Additionally, a brownish area was noted during the observation. According to these severe cutaneous reactions, the study was considered complete and the animal was prematurely sacrificed for ethical reasons on day 2.

Under the conditions of the study, the test substance, Coco amidopropyldimethylamine, was considered to be corrosive when topically applied to rabbits. In accordance with CLP Regulation 1272/2008, the test substance should be classified as Category 1 B corrosive substance with the signal word Danger and the hazard statement "H314: Causes severe skin burns and eye damage" associated with it.