Reaction mass of sodium 3-{[3-(diethylamino)propyl]carbamoyl}-2-(dodecylamino)propanoate and sodium 3-{[3-(diethylamino)propyl]carbamoyl}-3-(dodecylamino)propanoate

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

02 March – 04 April 2006

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP study conducted in compliance with OECD Guideline 404 without any deviation.

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2006

Report date:

2006

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Principles of method if other than guideline:

Not applicable

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Reaction mass of sodium 3-{[3-(diethylamino)propyl]carbamoyl}-2-(dodecylamino)propanoate and sodium 3-{[3-(diethylamino)propyl]carbamoyl}-3-(dodecylamino)propanoate

EC Number:

939-579-8

Molecular formula:

Empirical Formula : C11H21N3O3Na C2nH4n+1 (n=4 – 9), C11H21N3O3NaC18H35, C11H21N3O3NaC18H33 Molecular formula of the two main constituents : C23H46N3O3Na

IUPAC Name:

Reaction mass of sodium 3-{[3-(diethylamino)propyl]carbamoyl}-2-(dodecylamino)propanoate and sodium 3-{[3-(diethylamino)propyl]carbamoyl}-3-(dodecylamino)propanoate

Details on test material:

- Name of test material (as cited in study report): CHIMEXANE HB
- Physical state: Yellowish thick gel
- Analytical purity: 55.9 %
- Lot/batch No.: 0126344
- pH of undiluted test item: 11.21
- Date of receipt: 21 February 2006
- Expiration date of the lot/batch: March 2007
- Storage condition of test material: At room temperature

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Grimaud frères selection S.A.S., La Corbière, France
- Age at study initiation: 2-4 months
- Weight at study initiation: 2.5 ± 0.1 kg
- Housing: Individually housed in Pajon cages
- Diet: 110 pelleted diet (SAFE, Epinay-sur-Orge, France), ad libitum
- Water: Drinking water filtered by a FG Millipore membrane (0.22 µm), ad libitum
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 18 ± 3 °C
- Humidity: 30-70 %
- Air changes: Approximately 12 cycles/h of filtered, non-recycled air
- Photoperiod: 12 h dark / 12 h light

Test system

Type of coverage:

semiocclusive

Preparation of test site:

other: clipped

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (weight with unit): 0.5 mL
- Concentration (if solution): Undiluted test item

Duration of treatment / exposure:

4 h

Observation period:

14 d

Number of animals:

3 males

Details on study design:

TEST SITE
- Area of exposure: Area of approximately 6 cm2 of the anterior left flank (application for 3 min), the anterior right flank (application for 1 h) or the posterior right flank (application for 4 h) of the animals.
- Type of wrap if used: Test item (0.5 mL) was applied to the clipped skin under a dry gauze pad. The gauze pad was held in contact with the skin by means of an adhesive hypoallergenic aerated semi-occlusive dressing and a restraining bandage.

REMOVAL OF TEST SUBSTANCE
- After removal of the dressing, any residual test item was wiped off by means of a dry cotton pad.

SCORING SYSTEM: According to OECD Guideline 404

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

3

Max. score:

4

Reversibility:

not fully reversible within: 14 days

Results 2

Irritation parameter:

edema score

Basis:

animal #1

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 7 days

Results 3

Irritation parameter:

erythema score

Basis:

animal #2

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 13 days

Results 4

Irritation parameter:

edema score

Basis:

animal #2

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 5 days

Results 5

Irritation parameter:

erythema score

Basis:

animal #3

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

3

Max. score:

4

Reversibility:

not fully reversible within: 14 days

Results 6

Irritation parameter:

edema score

Basis:

animal #3

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

1.3

Max. score:

4

Reversibility:

fully reversible within: 5 days

Irritant / corrosive response data:

After a 3 min exposure period (one animal only):
- No cutaneous reactions were observed.

After a 1 h exposure period (one animal only):
- A very slight to moderate erythema (grades 1 to 3) was noted from Day 1 up to Day 15 (end of the observation period).
- A very slight edema (grade 1) was noted from Day 2 up to Day 5.
- A brownish area was observed from Day 4 up to Day 6.
- A dryness of the skin was noted from Day 6 up to Day 15 (end of the observation period).

After a 4 h exposure period (three animals):
- A very slight to moderate erythema (grades 1 to 3) was noted in all animals from Day 1 up to Day 13 in 1/3 animals or Day 15 in 2/3 animals (end of the observation period).
- A very slight or slight edema (grade 1 or 2) was observed in all animals from Day 2 up to Day 5 (2/3 animals) or Day 7 (1/3 animals).
- A brownish area was observed in 1/3 animals from Day 3 up to Day 6.
- A dryness of the skin was observed in 1/3 animals from Day 4, in 1/3 animals from Day 5 and 1/3 animals from Day 6, up to Day 15 (end of the observation period).
- Crusts were noted in 1/3 animals between Days 4 and 11.

Other effects:

None

Any other information on results incl. tables

Table 7.3.1/1: Individual skin reactions

 

Rabbits No.		Animal 1	Animal 2	Animal 3
Erythema	1 h	2	2	2
	24 h	3	2	3
	48 h	3	2	3
	72 h	3	2	3
Mean (24, 48 and 72 h)		3	2	3
Oedema	1 h	0	0	0
	24 h	2	1	2
	48 h	2	1	1
	72 h	2	1	1
Mean (24, 48 and 72 h)		2	1	1.3

Applicant's summary and conclusion

Interpretation of results:

Category 2 (irritant)

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the test conditions, CHIMEXANE HB is classified as ‘R38 Irritating to skin’ according to the criteria of Annex VI to the Directive 67/548/EEC and ‘Category 2: Irritant’ according to CLP Regulation (EC) N° (1272-2008).

Executive summary:

In a primary dermal irritation study performed according to OECD Guideline 404 and in compliance with GLP, three male New Zealand White rabbits were dermally exposed to 0.5 mL of undiluted CHIMEXANE HB under a semi-occlusive dressing. The test item was first evaluated on a single animal and the duration of exposure was 3 min on the anterior left flank, 1 h on the anterior right flank and 4 h on the posterior right flank. Since the test item was not severely irritant on this first animal, it was then applied for 4 h to two other animals. After removal of the residual test item, irritation was scored as outlined in the OECD Guideline 404 at 1, 24, 48 and 72 h after removal of the dressing and then daily until the end of the observation period (Day 15).

 

After a 3 min exposure period, no cutaneous reactions were observed. After a 1 h exposure period, a very slight to moderate erythema was noted up to Day 15 and a very slight edema was noted up to Day 5. After a 4 h exposure period, a very slight to moderate erythema was noted in all animals up to Day 13 in 1/3 animals or Day 15 in 2/3 animals. A very slight or slight edema was observed in all animals up to Day 5 (2/3 animals) or Day 7 (1/3 animals). Mean individual scores for the 3 animals at 24, 48 and 72 h post patch removal were 3, 2, 3 for erythema and 2, 1, 1.3 for oedema score, respectively. In this study, CHIMEXANE HB is a skin irritant on male rabbits.

 

Under the test conditions, CHIMEXANE HB is classified as ‘R38 Irritating to skin’ according to the criteria of Annex VI to the Directive 67/548/EEC and ‘Category 2: Irritant’ according to CLP Regulation (EC) N° (1272-2008).