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

Endpoint summary

Description of key information

Corrosive properties are observed following exposures of 3 minutes and longer to the skin of rabbits, with skin destruction becoming visible the next day.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

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

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to other study

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

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

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.

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.

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.

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.

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.

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.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (corrosive)

Eye irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

In vitro Skin Irritation/Corrosion:

The potential corrosivity of Coco amidopropyldimethylamine was evaluated in an in vitro Reconstituted Human Epidermis Model (OECD 431). The EPISKIN model was used to distinguish between corrosive and non-corrosive chemicals. Duplicate tissues were treated with the test material for 3, 60 and 240 minutes. At the end of the exposure period, the test material was rinsed from each tissue before MTT-loading. Following this, a total biopsy of each epidermis was made and placed into micro tubes containing acidified isopropanol for extraction of formazon crystals out of MTT loaded tissues. Following extraction, each tube was mixed thoroughly and duplicate 200µl samples were transferred to the appropriate wells of a pre-labelled 96-well plate. Optical density was measured at 540 nm and data was presented in the form of percentage viability. Following the 3, 60 and 240 minutes exposure, the relative mean viability of the test material treated tissues were 88.7%, 74.8% and 93.1% respectively. Under the conditions of this study, the test material was considered to be non-corrosive.

However, available data obtained with cationic surfactants have shown that these RhE based tests do not provide reliable results, as proven with the available in vivo study on Coco amidopropyldimethylamine, and thus results from this study are not taken into consideration for classification.

 

In vivo Skin Irritation/Corrosion:

Coco amidopropyldimethylamine was assessed for its ability to cause corrosion in an in vivo skin corrosion/irritation study in New Zealand White rabbits (OECD 404). 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.

Justification for classification or non-classification

Available data indicate corrosive properties following exposures of 3 minutes and longer. Following exposure of 3 minutes, the skin destruction is observed at examination the next day, but not yet at the observation 1 hour after the exposure.Consequently, GHS classificationCorrosive Category 1Bis appropriate, with hazard statement H314: Causes severe skin burns and eye damage.

 

Due to corrosive properties demonstrated in the dermal irritation/corrosion study with this substance, testing in eyes is not justified. Under GHS with the hazard phrase ‘H314 Causes severe skin burns and eye damage’ additional classification for eyes is not necessary.

 

There is no information is available following exposure via inhalation. However, with a vapour pressure of 3.96 x 10-5 Pa at 25 °C (EpiWin), potential for inhalation of vapours is limited.Also the use of this substance will not result in aerosols, particles or droplets of an inhalable size, so exposure to humans via the inhalation route will be unlikely to occur.Consequently, despite the irritant nature of the substance, respiratory irritation is not expected, and classificationSTOT-SE Cat.3 for respiratory irritationis not required.