Dimethyl(octyl)amine

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1996

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1996

Report date:

1996

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

1992

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Dimethyl(octyl)amine

EC Number:

230-939-3

EC Name:

Dimethyl(octyl)amine

Cas Number:

7378-99-6

Molecular formula:

C10H23N

IUPAC Name:

dimethyl(octyl)amine

Details on test material:

Name: AD 1
Chemical Name: N, N-Dimethyloctylamine
CAS No.: 7378-99-6
Batch No.: 13602808
Expiry Date: not applicable
Physical State at Room Temperature: liquid
Colour: clear
Volatility: volatile
Density: 0.765
Molecular Weight: 157.3
Active Components: > 95%
Structure Formula of
Active Component: C8H17-N-(CH3)2
Storage Conditions: at room temperature

Specific details on test material used for the study:

A consignment of 300 g (net) Famin DM08P, a clear, colourless liquid, was received from the Sponsor on 21 November 1995. The test material was further identified by the Lot No. 1318. It was kept at ambient temperature, in the original container. The identity, strength and purity of the test material received, and its stability under the storage conditions above, were the responsibility of the Sponsor.

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

The animals were housed in a lagomorph room within a limited-access building. The room was kept at slight positive pressure relative to the outside and had its own filtered air supply giving at least 10 complete air changes per hour without re-circulation. Target values for temperature and humidity were 18°C (range 15°-23°C) and 55% R.H. (range 40%-70% R.H.), respectively. The achieved values were monitored daily. Electric time-switches operated a lighting cycle of 12 hours of artificial light per day. An emergency generator was available to maintain the electricity supply in the event of a power failure.
Each animal was inspected on arrival, and unsuitable individuals were rejected. Individual bodyweight was recorded on the day of arrival and at least weekly intervals thereafter. All animals were identified by a uniquely numbered eartag. During the acclimatization period, the health status of each animal was monitored and a record kept. This record was consulted before an animal was allocated to study.
On the day before dosing, the dorsum between the limb girdles was clipped (chemical depilatories were not used). Each animal was examined for abnormality or irritation of the dermal test site before allocation to study.

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Amount / concentration applied:

0.5 mL AD-1 at 100% concentration (as received) applied over approximate 3 x 2 cm area

Duration of treatment / exposure:

The dressings were removed after four hours exposure; the treatment sites were gently washed with warm water and dried with paper tissues to remove excess test material adhering to the skin.

Observation period:

Assessment of skin irritation responses at the control and treated test sites. were made 1, 24, 48 and.72 hours after removal of the bandages. Additional observations of persistent effects of treatment were made on Days 7, 10, 13 and 16. Reactions of the test sites were assessed according to the criteria of Draize (1959) below. Reactions not included below were described as appropriate.

Criteria for assessment of skin irritation responses
Erythema and eschar formation Value
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 4
formation (injury in depth)

Oedema formation Value
No oedema 0
Very slight oedema (barely perceptible) 1
Slight oedema (edges of area well-defined by 2
definite raising)
Moderate oedema (raised approximately 1 mm) 3
Severe oedema (raised more than 1 mm and extending 4
beyond the area of exposure)

Number of animals:

3 (sex not specified)

Details on study design:

Each rabbit was securely restrained by a technician. Two test areas (6 x 6 cm) were marked on either side of the clipped area of dorsum. A · single dose was applied directly to the skin (3 x 2 cm) and covered by an unmedicated gauze patch (3 x 2 cm) which was held in place on the left test site by strips of Blendenn (Community Care Products, 3M Health Care, Loughborough, England). The right test site, acting as a control, was covered by a similar semi-occlusive dressing but otherwise remained untreated. Pads of cotton wool and elasticated bandage were used to protect the patches and ensure good contact between the skin and the test material during the four-hour exposure period. The elasticated bandage was held in place by thin strips of waterproof plaster ('Blenderm') at both edges.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

4

Reversibility:

not fully reversible within: 16 days.

Remarks:

At termination on Day 16, the test site of the animal has suffered a loss of elasticity, eschar formation and exfoliation was observed.

Remarks on result:

positive indication of irritation

Results 2

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

4

Reversibility:

not fully reversible within: 16 days

Remarks:

At termination on Day 16, the test site of the animal has suffered eschar formation.

Remarks on result:

positive indication of irritation

Results 3

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

4

Reversibility:

not fully reversible within: 16 days

Remarks:

At termination on Day 16, the test site of the animal has suffered a loss of elasticity, eschar formation and become solid. Erythema extended beyond test site was observed.

Remarks on result:

positive indication of irritation

Results 4

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1.3

Reversibility:

fully reversible within: 16 days

Remarks on result:

positive indication of irritation

Results 5

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1.7

Reversibility:

fully reversible within: 16 days

Remarks on result:

positive indication of irritation

Results 6

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1.7

Reversibility:

fully reversible within: 16 days

Remarks on result:

positive indication of irritation

Irritant / corrosive response data:

Moderate erythema and oedema were observed on the test sites of all animals one hour after bandage removal. Severe erythema, extending beyond the test site, and very slight to severe oedema were seen from the 24 hour examination to Day 13; loss of elasticity, eschar fonnation, darkened skin and a solid test site were also apparent during this time. At termination on Day 16, the test site of one animal was solid,
eschar fonnation was seen on another rabbit and eschar formation, loss of elasticity and exfoliation were seen on the third animal.
Because of the significant reactions seen at the end of the observation period, the animals were killed following this examination and the test sites were excised and examined in cross section. This examination revealed thickened skin in both animals, but not full thickness destruction of the skin.
The control sites did not show any response to the control procedure.
The mean values for erythema and oedema recorded 24, 48 and 72 hours after treatment exceeded the EEC limit values considered to indicate a significant inflammatory response to treatment. However, macroscopic examination of the test sites did not reveal full thickness destruction and the test material was not, therefore, considered to be corrosive.

Applicant's summary and conclusion

Interpretation of results:

Category 1B (corrosive) based on GHS criteria

Conclusions:

Under the conditions of this test and the criteria of the EEC, Farmin DM08P was classified as 'corrosive' to skin (Category 1B based on GHS criteria).

Executive summary:

The potential of Farmin DM08P to cause inflammatory or corrosive changes upon first contact with skin was assessed by semi-occluded application of 0.5 ml of the test material to the closely-clipped dorsa of three New Zealand White rabbits for four hours. Denna) reactions were assessed 1, 24, 48 and 72 hours after removal of the dressings and on Days 7, 10, 13 and 16.

Moderate erythema and oedema were observed on the test sites of all animals one hour after bandage removal. Severe erythema, extending beyond the test site, and very slight to severe oedema were seen from the 24 hour examination to Day 13; loss of elasticity, eschar formation, darkened skin and a solid test ·site were also apparent during this time. At termination on Day 16, the test site of one animal was solid, eschar formation was seen on another rabbit and eschar formation, loss of elasticity and exfoliation were seen on the third animal. Because of the significant reactions seen at the end of the observation period, two of the animals were killed following this examination and the test sites were excised and examined in cross section. This examination revealed thickened skin in both animals, but not full thickness destruction of the skin.

Under the conditions of this test and the criteria of the EEC, Farmin DM08P was classified as 'corrosive' to skin (Category 1B based on GHS criteria).