Amines, N-tallow alkyltrimethylenedi-, propoxylated

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1987-03-04 to 1987-06-04

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Guideline study without detailed documentations (very few information on the tested substance reported)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1987

Report date:

1987

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

1-({3-[(2-hydroxypropyl)[(9E)-octadec-9-en-1-yl]amino]propyl}amino)propan-2-ol; 1-({3-[(2-hydroxypropyl)amino]propyl}(octadecyl)amino)propan-2-ol; 1-({3-[hexadecyl(2-hydroxypropyl)amino]propyl}amino)propan-2-ol

EC Number:

614-637-2

Cas Number:

68603-75-8

Molecular formula:

R-N(CH2CHOHCH3)xCH2CH2CH2N(CH2CHOHCH3)y with x+y=3 and where R = alkyl

IUPAC Name:

1-({3-[(2-hydroxypropyl)[(9E)-octadec-9-en-1-yl]amino]propyl}amino)propan-2-ol; 1-({3-[(2-hydroxypropyl)amino]propyl}(octadecyl)amino)propan-2-ol; 1-({3-[hexadecyl(2-hydroxypropyl)amino]propyl}amino)propan-2-ol

Details on test material:

- Name of test material (as cited in study report): DINORAM SL
- Physical state: Dark brown liquid
- Lot/batch No.: 96 01 267
No other data available

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Abbaye de Bellefontaine, Beggroles en Mauges, France
- Age at study initiation: no data
- Weight at study initiation: Mean weight: 2.6 +/- 0.1 kg
- Housing: The rabbits were individuall y housed in polystyrene cages
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 3° C
- Humidity (%): 50 +/-20%
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12 hours per day

Test system

Type of coverage:

semiocclusive

Preparation of test site:

other: clipped

Vehicle:

unchanged (no vehicle)

Controls:

other: each animal served as its own control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL
- Concentration (if solution): 100 %

VEHICLE
- no vehicle

Duration of treatment / exposure:

3 minutes for 3 animals and four hours for 3 other animals.

Observation period:

1hour, 24, 48 and 72 hours after patch removal then daily until day 14.

Number of animals:

6 males

Details on study design:

TEST SITE
- Area of exposure: flank, clipped 24 h before exposure and checked for healthy, intact skin before application
- % coverage: 6 cm²
- Type of wrap if used: dry gauze pad held in contact with the skin by means of a semi-occlusive dressing.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): any residual test substance was wiped off by means of a gauze saturated with sterile pyrogen-free water.
- Time after start of exposure: 3 minutes or 4 hours

SCORING SYSTEM:
Dermal irritation was evaluated for each animal according to OECD guideline 404 (draize scoring system)

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Remarks:

(for 3 minute- exposure)

Basis:

animal #1

Time point:

other: mean of the 24, 48 and 72-hour readings

Score:

1.7

Max. score:

4

Reversibility:

fully reversible within: 8 days

Results 2

Irritation parameter:

erythema score

Remarks:

(for 3-minute exposure)

Basis:

animal #2

Time point:

other: mean of the 24, 48 and 72-hour readings

Score:

3.7

Max. score:

4

Reversibility:

fully reversible within: 13 days

Results 3

Irritation parameter:

erythema score

Remarks:

(for 3-minute exposure)

Basis:

animal #3

Time point:

other: mean of the 24, 48 and 72-hour readings

Score:

3.7

Max. score:

4

Reversibility:

other: Dryness of the skin persisted at the end of the observation period.

Results 4

Irritation parameter:

edema score

Remarks:

( for 3-minute exposure)

Basis:

animal #1

Time point:

other: mean of the 24, 48 and 72-hour readings

Score:

1.7

Max. score:

4

Reversibility:

fully reversible within: 6 days

Results 5

Irritation parameter:

edema score

Remarks:

(for 3-minute exposure)

Basis:

animal #2

Time point:

other: mean of the 24, 48 and 72-hour readings

Score:

4

Max. score:

4

Reversibility:

fully reversible within: 9 days

Results 6

Irritation parameter:

edema score

Remarks:

(for 3-minute-exposure)

Basis:

animal #3

Time point:

other: mean of the 24, 48 and 72-hour readings

Score:

2.3

Max. score:

4

Reversibility:

fully reversible within: 7 days

Results 7

Irritation parameter:

erythema score

Remarks:

(for 4-hour exposure)

Basis:

animal #4

Time point:

other: mean of the 24, 48 and 72-hour readings

Score:

3.7

Max. score:

4

Reversibility:

other: Dryness of the skin persisted at the end of the observation period.

Results 8

Irritation parameter:

erythema score

Remarks:

(for 4-hour exposure)

Basis:

animal #5

Time point:

other: mean of the 24, 48 and 72-hour readings

Score:

4

Max. score:

4

Remarks on result:

other: necrosis from day 3 to 6 then crusts and dryness of the skin.

Results 9

Irritation parameter:

erythema score

Remarks:

(for 4-hour exposure)

Basis:

animal #6

Time point:

other: mean of the 24, 48 and 72-hour readings

Score:

4

Max. score:

4

Remarks on result:

other: necrosis from day 2 to 6 then crusts and dryness of the skin.

Results 10

Irritation parameter:

edema score

Remarks:

(for 4-hour exposure)

Basis:

animal #4

Time point:

other: mean of the 24, 48 and 72-hour readings

Score:

3

Max. score:

4

Reversibility:

fully reversible within: 7 days

Results 11

Irritation parameter:

edema score

Remarks:

( for 4-hour exposure)

Basis:

animal #5

Time point:

other: mean of the 24, 48 and 72-hour readings

Score:

4

Max. score:

4

Reversibility:

fully reversible within: day 7

Results 12

Irritation parameter:

edema score

Remarks:

(for 4-hour exposure)

Basis:

animal #6

Time point:

other: mean of the 24, 48 and 72-hour readings

Score:

4

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritant / corrosive response data:

- Application for 3 minutes :
Slight to severe erythema and oedema were observed in all animals. These reactions regressed slowly. They were totally reversible in 8 and 13 days in 2 rabbits. Dryness of the skin was still present at the end of the observation period in the remaining one (See tables 1 and 2 in results and discussion free-text for details).

_ Application for 4 hours:
Moderate to severe erythema and oedema were observed in all animals. Erythema regressed slowly and was no more visible on Day 14 in 1 animal. Dryness of the skin or crusts were still present at the end of the observation period in the 2 others. Oedema disappeared on Day 7 in all rabbit.
24 and 48 hours after application, necrosis were noted in 2 rabbits and persisted until day 6 . Crusts were then observed until day 11 for one animal and till the end of the observation period for the remaining one (See tables 3 and 4 in results and discussion free-text for details).

Any other information on results incl. tables

Table 1: Erythema scores after a 3- minute exposure

Animal	1 hour (D1)	24 hours (D2)	48 hours (D3)	72 hours  (D4)	D5	D6	D7	D8	D9	D10	D11	D12	D13	D14
1	0	2	2	1	1	1/S	0/S	0	-	-	-	-	-	-
2	0	3	4	4	4	4/S	3	2/S	1/S	1/S	0/S	0/S	0	-
3	0	3	4	4	4	4/S	0/S	0/S	0/S	0/S	0/S	0/S	0/S	0/S

Grading scale according to OECD 404 guidelines

Table 2: Oedema scores after a 3 -minute exposure

Animal	1 hour (D1)	24 hours (D2)	48 hours (D3)	72 hours  (D4)	D5	D6	D7	D8	D9	D10	D11	D12	D13	D14
1	0	2	2	1	1	0	0	0	-	-	-	-	-	-
2	0	4	4	4	4	4	2	1	0	0	0	0	0	-
3	0	3	2	2	2	2	0	0	0	0	0	0	0	0

Grading scale according to OECD 404 guideline

Table 3: Erythema scores after a 4- hour exposure

Animal

1 hour (D1)

24 hours (D2)

48 hours (D3)

72 hours  (D4)

D5

D6

D7

D8

D9

D10

D11

D12

D13

D14

4

1

3

4

4

4

4/S

4/S

C/S

C/S

C/S

0/S

0/S

0/S

0/S

5

2

4

N

N

N

N

C/S

C/S

C/S

C/S

C/S

0/S

0/S

0

6

2

N

N

N

N

N

C/S

C/S

C/S

C/S

C/S

C/S

C

C

Grading scale according to OECD 404 guideline

Table 4: Oedema scores after a 4 -hour exposure

Animal	1 hour (D1)	24 hours (D2)	48 hours (D3)	72 hours  (D4)	D5	D6	D7	D8	D9	D10	D11	D12	D13	D14
4	1	3	3	3	3	3	0	0	0	0	0	0	0	0
5	2	4	4	4	4	4	0	0	0	0	0	0	0	0
6	2	4	4	4	4	4	0	0	0	0	0	0	0	0

Grading scale according to OECD 404 guideline

C = crusts, N= necrosis, S= dryness of the skin

Applicant's summary and conclusion

Interpretation of results:

corrosive

Remarks:

Migrated information Criteria used for interpretation of results: other: CLP (Reg. 1272/2008/EC) and Directive 67/548/EEC

Conclusions:

Under the experimental conditions of this study and according to the criteria laid down in CLP (Reg 1272/2008/EC) and directive 67/548/EEC, the test material is classified Skin corrosive category 1 C, H314 and Corrosive R34 respectively.

Executive summary:

The potential of the test substance to induce skin irritation was assessed in 6 rabbits according to the OECD 404 guideline in compliance with the

principles of Good Laboratory Practice regulations.

A single dose of 0.5 ml of the test substance was applied to the skin of 3 rabbits under a semi-occlusive dressing for a 3 -minute exposure period. 3 other rabbits received the test substance under the same protocol but for an exposure period of 4 hours . Skin reactions were observed 1, 24, 48, 72 hours after removal of the dressing and then daily until day 14 in order to observe their reversibility. The mean values of the scores for erythema and oedema were calculated for each animal.

After 3 minutes of exposure, the mean scores over 24, 48 and 72 hours for individual animals were 1.7, 3.7 and 3.7 for erythema and 1.7, 4.0 and 2.3 for oedema. Slight to severe erythema and oedema were observed in all animals. These reactions regressed slowly. They were totally reversible in 8 and 13 days in 2 rabbits. Dryness of the skin was still present at the end of the observation period in the remaining one.

After 4 hours of exposure, the mean scores over 24, 48 and 72 hours for individual animals were 3.7 for erythema in one rabbit, the scores of the 2 others were not calculable due to necrosis. Indeed, 24 and 48 hours after application, necrosis were noted in 2 rabbits and persisted until day 6 . Crusts were then observed until day 11 for one animal and till the end of the observation period for the remaining one. For the third rabbit, erythema regressed slowly and was no more visible on Day 14.

Mean scores over 24, 48 and 72 hours for individual animals were 3.0, 4.0 and 4.0 for oedema . Oedema disappeared on Day 7 in all rabbits.

Under these experimental conditions, the test substance was considered to be corrosive to the rabbit skin after 4 hours of exposure.