Amines, N-(C16-18 and C18-unsatd. alkyl)trimethylenedi-, diacetates

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

1997-03-28 to 1997-09-08

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

The assay was performed on a mixture containing 2-butoxyethanol (CAS 111-76-2) and no formal analytical certificate was available as the product was in phase of development at that time.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1997

Report date:

1997

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

Minor fluctuations of relative humidity recorded outside of the target ranges specified in the protocol were not considered to have an impact on the validity or integrity of the study.

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

yes

Remarks:

see above

GLP compliance:

yes

Test material

Test material information

1

Reference substance name:

Amines,N-(C16-18 and C18 unsaturated alkyl) trimethylenedi-,diacetates.

EC Number:

800-153-0

Cas Number:

1313206-64-2

Molecular formula:

R-NH2+ -(CH2)3-NH3+, (CH3 COO-)2 where R = C16-18 and C18-unsat alkyl

IUPAC Name:

Amines,N-(C16-18 and C18 unsaturated alkyl) trimethylenedi-,diacetates.

2

Reference substance name:

2-butoxyethanol

EC Number:

203-905-0

EC Name:

2-butoxyethanol

Cas Number:

111-76-2

Molecular formula:

C6H14O2

IUPAC Name:

2-butoxyethanol

3

Reference substance name:

Water

EC Number:

231-791-2

EC Name:

Water

Cas Number:

7732-18-5

Molecular formula:

H2O

IUPAC Name:

water

Test material form:

liquid

Details on test material:

Chemical registery number : 1313206-64-2
Chemical name : Amines, N-(C16-18 and C18-unsatd. alkyl)trimethylenedi-, diacetates

Based on the qualitative and quantitative information on the composition, the sample used are representative of the boundary composition shared and agreed by each registrant.

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Elevage Cunicole de Val de Selle, 80160 Prouzel, France
- Weight at study initiation: 2.4 +/- 0.2 kg.
- Housing: individually in polystyrene cages (35 cm x 55 cm x 32 cm or 48.2 cm x 58 cm x 36.5 cm)
- Diet (e.g. ad libitum): at libitum (112 C pelletet diet, UAR, Villemoisson-sur-Orge, France)
- Water (e.g. ad libitum): ad libitum drinking water filtered by F.G. Millipore membrane (0.22 micron)
- Acclimation period: at least five days before the beginning of the study

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 +/-3
- Humidity (%): 30 to 70%
- Air changes (per hr): 12 cycles/hour of filtered, non-recycled air.
- Photoperiod (hrs dark / hrs light): 12h/12h

IN-LIFE DATES: From: 01 April 1997 To: 15 April 1997

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

0.5 mL

Duration of treatment / exposure:

4 hours

Observation period:

1, 24, 48, 72h after patch removal; animals were observed daily for reversibility of irritating effects up to day 14

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: right flank of the animals
- % coverage: approximately 6 cm2
- Type of wrap if used: dry gauze pad held in contact by means of an adhesive hypoallergenic aerated semi-occlusive dressing and a restraining bandage.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no


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) to slight eschar formation (injuries in depth) ...... 4

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 millimetre)......................................... 3
. severe oedema (raised more than 1 millimetre and extending beyond area
of exposure)........................................................................................................... 4

Any other lesions was noted.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

not fully reversible within: 15 Days in 1/3 animals

Results 2

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

not fully reversible within: 15 Days in 1/3 animals

Irritant / corrosive response data:

On day 1, a well-defined erythema (grade 2) and a severe oedema (grade 4) were noted in all animals. A severe erythema (grade 4) and a severe oedema (grade 4) were observed in all animals from day 2 up to day 5. A very slight to severe erythema (grades 1 to 4) was then noted up to day 11 (one animal), 14 (one animal) or up to the end of the observation period (day 15, in the remaining animal). A severe oedema (grade 4) was observed in one animal from day 11 up to day 15.
Necrosis was recorded in all animals on days 2 and 3, then crusts were observed in all animals from day 4 up to day 9 or 10. Dryness of the skin was noted in two animals, from day 10 or 12 up to the end of the observation period (day 15).
Mean scores over 24, 48 and 72 hours for individual animal were 4.0, 4.0 and 4.0 for erythema and 4.0, 4.0 and 4.0 for oedema.

Applicant's summary and conclusion

Interpretation of results:

Category 2 (irritant) based on GHS criteria

Conclusions:

Amines,N-(C16-18 and C18 unsaturated alkyl) trimethylenedi-,diacetates is considered as a skin irritant cat. 2

Executive summary:

The potential of the test item (38% n-tallow alkyltrimethylene diamines, diacetates, mixed with 25% butyl glycol and 37% water) to induce skin irritation was evaluated in rabbits according to OECD (No. 404, 17th July 1992) and EC (92/69/EEC, B.4, 31st July 1992) guidelines. The study was conducted in compliance with the principles of Good Laboratory Practice Regulations.

 

The test item was applied for a period of 4 hours to three male New Zealand White rabbits at a dose-volume of 0.5 mL (undiluted) to the closely-clipped skin of one flank. The test item was held in contact with the skin by means of a semi-occlusive dressing.

 

Cutaneous reactions were observed approximately 1 hour, 24, 48 and 72 hours after removal of the dressing and then daily until the end of the observation period (day 15). The mean values of the scores for erythema and oedema were calculated for each animal. On day 1, a well-defined erythema (grade 2) and a severe oedema (grade 4) were noted in all animals. A severe erythema (grade 4) and a severe oedema (grade 4) were observed in all animals from day 2 up to day 5. A very slight to severe erythema (grades 1 to 4) was then noted up to day 11 (one animal), 14 (one animal) or up to the end of the observation period (day 15, in the remaining animal). A severe oedema (grade 4) was observed in one animal from day 11 up to day 15.Necrosis was recorded in all animals on days 2 and 3, then crusts were observed in all animals from day 4 up to day 9 or 10. Dryness of the skin was noted in two animals, from day 10 or 12 up to the end of the observation period (day 15).

Mean scores over 24, 48 and 72 hours for individual animals were 4.0, 4.0 and 4.0 for erythema and 4.0, 4.0 and 4.0 for oedema.

Under these experimental conditions, the test item is considered to be severely irritant for skin when applied topically to rabbits.