Amines, N-(C18-unsatd. alkyl)trimethylenedi-, ethoxylated

Endpoint summary

Description of key information

Corrosive properties are observed following exposures of 3 minutes and longer, with the skin destruction becoming visible after some delay.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

March 1999

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Well reported and carried out study according to guideline/standards

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes

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, Prouzel, France
- Age at study initiation: no info
- Weight at study initiation: 2.9 kg
- Housing: polystyrene cage
- Diet (e.g. ad libitum): ad lib
- Water (e.g. ad libitum): ad lib
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 ± 3
- Humidity (%): 30-70
- Air changes (per hr): ca. 12
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: 16 To: 18 March 1999

Type of coverage:

semiocclusive

Preparation of test site:

other: clipped

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit):0.5 ml
- Concentration (if solution): undiluted

Duration of treatment / exposure:

3 min on left flank, 4 h on right flank

Observation period:

2 days

Number of animals:

1

Details on study design:

TEST SITE
- Area of exposure: 6 cm2 gauze patch was used
- % coverage: no info
- Type of wrap if used: adhesive hypoallergenic aerated semi-occlusive dressing and a restraining bandage


REMOVAL OF TEST SUBSTANCE
- Washing (if done): after removal of the dressing of the 3-min exposure
- Time after start of exposure: 3 min


SCORING SYSTEM:
EVALUATION OF SKIN REACTIONS
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 mm) 3
Severe oedema (raised more than 1 mm and
extending beyond area of exposure) 4

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48 h

Score:

4

Max. score:

4

Reversibility:

other: animal killed after 2 days because of necrosis

Remarks on result:

other: Necrosis visible from 24 hrs

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48 h

Score:

4

Max. score:

4

Reversibility:

other: animal killed after 2 days because of necrosis

Remarks on result:

other: Necrosis visible from 24 hrs

Irritant / corrosive response data:

After a 3-minute exposure: No cutaneous reactions were observed at the 1-hour reading. A severe erythema (grade 4) and a severe oedema (grade 4), together with cutaneous necrosis, were noted on days 2 and 3.
After a 4-hour exposure: A well-defined erythema (grade 2) and a slight oedema (grade 2) were noted at the 1-hour reading. A
severe erythema (grade 4) and a severe oedema (grade 4), together with cutaneous necrosis, were observed on days 2 and 3.

Other effects:

As the substance showed corrosive properties the animal was killed for ethical reasons two days after application. The study was considered complete.

Interpretation of results:

Category 1B (corrosive) based on GHS criteria

Remarks:

Migrated information

Conclusions:

Because a 3-min exposure resulted in necrotic effects 1 and 2 days after application, but not at 1 h after application, the test material is considered corrosive to rabbit skin, and should be classified in Category 1B according to OECD-GHS.

Executive summary:

At the request of CECA S.A., Paris-la-Defense, France, the potential of the test substance DINORAMOX S3 (batch No. 96102808) to induce skin irritation was evaluated in rabbits according to OECD (No. 404, 17th July 1992) and EC (92169lEEC. B.4, 31st July 1992) guidelines. The study was conducted in compliance with the principles of Good Laboratory Practice Regulations. The study design was established according to available information on the test substance and the above guidelines. The test substance was applied in a first assay for a period of 3 minutes and 4 hours to one male New Zealand White rabbit. A single dose of 0.5 ml of the undiluted test substance was applied to the closely-clipped skin of one flank. The test substance was held in contact with the skin by means of a semi-occlusive dressing. Cutaneous reactions were observed approximately 1 hour, 24 and 48 hours after removal of the dressing. As the test substance showed corrosive properties in this first assay, the animal was killed for ethical reasons 2 days after application. The study was considered complete and the test substance was not evaluated on other animals. After a 3-min exposure: No cutaneous reactions were observed at the 1 -hour reading. A severe erythema and a severe oedema, together with cutaneous necrosis, were noted on days 2 and 3. After a 4 -hour exposure: A well-defined erythema and a slight oedema were observed at the 1-hour reading. A severe erythema and a severe oedema, together with cutaneous necrosis, were noted on days 2 and 3. Under these experimental conditions and according to the classification criteria laid down in OECD-GHS, the test substance DINORAMOX S3 (batch No. 96102808) should be considered as corrosive (Category 1B) when applied topically to rabbit skin.

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

Evaluation of dermal irritation/corrosion of Tris (2-hydroxyethyl) oleyl diaminopropane (recently redefined as Amines, N-(C18 unsaturated, alkyl) trimethylenedi-, ethoxylated (NLP), CAS 1268344-02-0), also referred to here as Oleyl-diamine3EO:

In order to limit animal testing with corrosive material, use is made ofread-across from the tallow-diamine3EO to Oleyl-diamine-3EO. This read-across is acceptable as these chemicals share the same structure and properties. The difference is a slightly lower alkyl chain for the tallow and a higher level of unsaturation of the oleyl. (See also separate document in support to read-across).

 

There is only one study available of high quality, in which Tallow-diamine3EO has been evaluated for acute dermal irritation/corrosion in rabbits according to OECD 404 and in compliance to GLP.

The test substance was applied in a first assay for a period of 3 minutes and 4 hours to one male New Zealand White rabbit. A single dose of 0.5 ml of the undiluted test substance was applied to the closely-clipped skin of one flank. The test substance was held in contact with the skin by means of a semi-occlusive dressing. Cutaneous reactions were observed approximately 1 hour, 24 and 48 hours after removal of the dressing. As the test substance showed corrosive properties in this first assay, the animal was killed for ethical reasons 2 days after application.

Results after a 3-min exposure: No cutaneous reactions were observed at the 1-hour reading. A severe erythema and a severe oedema, together with cutaneous necrosis, were noted on days 2 and 3. After a 4 -hour exposure: A well-defined erythema and a slight oedema were observed at the 1-hour reading. A severe erythema and a severe oedema, together with cutaneous necrosis, were noted on days 2 and 3. Based on the results of this study, Tallow-diamine3EO is considered to be severe corrosive to the skin.

 

Testing with Oleyl-diamine3EO can be expected to lead to similar results, and in order to limit unnecessary animal testing with corrosive substances, no further studies are considered.

Eye irritation:

Due to corrosive properties in de dermal irritation/corrosion studies with this substance testing in eyes would not be required.

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 classification Corrosive Category 1B is 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 below 0.0015 Pa at 20°C, the 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 classification STOT-SE Cat.3 for respiratory irritation is not required.