N,N-dimethyl-3-(octadecyloxy)propylamine

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From February 4th 2002 to February 7th 2002

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Remarks:

The test protocol followed the recommended procedure of the application for quasi-drugs in Japan.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2002

Report date:

2002

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: Q and A for application for quasi-drugs and cosmetics by Ministry of health, labour and welfare in Japan (Q14)

Version / remarks:

The test protocol followed the recommended procedure of the application for quasi-drugs in Japan.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

N,N-dimethyl-3-(octadecyloxy)propylamine

EC Number:

241-516-8

EC Name:

N,N-dimethyl-3-(octadecyloxy)propylamine

Cas Number:

17517-01-0

Molecular formula:

C23H49NO

IUPAC Name:

dimethyl[3-(octadecyloxy)propyl]amine

impurity 1

Reference substance name:

Octadecan-1-ol

EC Number:

204-017-6

EC Name:

Octadecan-1-ol

Cas Number:

112-92-5

Molecular formula:

C18H38O

IUPAC Name:

octadecan-1-ol

impurity 2

Reference substance name:

Unknown impurities

IUPAC Name:

Unknown impurities

Test material form:

liquid

Test animals

Species:

guinea pig

Strain:

Hartley

Details on test animals or test system and environmental conditions:

-Experimental animals
1) Species, strain, sex
Guinea pigs, Hartley strain, white, females
2) Breeder and Breeding style
Japan SLC, Inc. (3371-8, Koto-cho, Nishi-ku, Hamamatsu, Shizuoka), Clean, Closed colony
3) Study groups and the number of animals
Animals were used in groups of 5 for the study.
4) Age in weeks and body weights
Animals were obtained at 5 weeks of age, acclimatized to laboratory conditions for 6 days and quarantined during these days. Only well-grown animals in good physical condition were subjected to the study. The mean body weight was 407 g at the start of the study.

-Animal rearing management
1) Rearing environment
Animals were kept under the following conditions; room temperature: 23±2°C, relative humidity: 50±10%, ventilation frequency: 17 times/hour, lighting time: 12 hours (6:00 to 18:00)/day.
2) Rearing equipment and housing
Upon receipt, animals were housed 5 per cage in aluminum cages (W350XD400×H230 mm: Natsume Seisakusyo Co., Ltd.) placed on an automatic flush rack (Natsume Seisakusyo Co., Ltd.).
3) Feed and Drinking water
Animals were given free access to solid feed (RC4: Oriental Yeast Co., Ltd.) and municipal tap water filtered through a 5-μm cartridge filter.

Test system

Type of coverage:

occlusive

Preparation of test site:

other: clipped and shaved

Vehicle:

other: Ethanol

Controls:

yes, concurrent vehicle

yes, concurrent negative control

Amount / concentration applied:

-Amount
The fabric of which was impregnated with 0.1 mL of each solution was applied.

-Concentration
5% and 1% (as active ingredient)

Duration of treatment / exposure:

24-hour occlusive patch

Observation period:

3, 24, 48 h after the 24-hour occlusive patch removal

Number of animals:

5 animals/treatment

Details on study design:

-Study methods
1) Application methods
The application site was the left and right flank, and clipped and shaved. A tape for a patch test (small size: Torii Pharmaceutical Co., Ltd.), the fabric of which was impregnated with 0.1 mL of the test solution, was applied by a 24-hour occlusive patch test method. In addition, for securing dressings, the tape for a patch test was secured with adhesive sponge tape (Microfoam: 3M company) and elastic adhesive bandage (Silkytex, Alcare Co., Ltd). The application sites were varied among the animals so that the reaction might be averaged among the application sites.
 
2)
Skin reactions were judged using the Draize scoring criteria.

0: No erythema
1: Very slight erythema (barely perceptible)
2: Well-defined erythema
3: Moderate to severe erythema
4: Severe erythema (beet redness) to slight eschar formation (injuries in depth)

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

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

mean

Time point:

48 h

Score:

3.8

Max. score:

4

Reversibility:

not specified

Remarks on result:

other: 5% solution

Results 2

Irritation parameter:

edema score

Basis:

mean

Time point:

48 h

Score:

3.4

Max. score:

4

Reversibility:

not specified

Remarks on result:

other: 5 % solution

Results 3

Irritation parameter:

erythema score

Basis:

mean

Time point:

48 h

Score:

2.8

Max. score:

4

Reversibility:

not specified

Remarks on result:

other: 1% solution

Results 4

Irritation parameter:

edema score

Basis:

mean

Time point:

48 h

Score:

0.8

Max. score:

4

Reversibility:

not specified

Remarks on result:

other: 1% solution

Irritant / corrosive response data:

-Findings

1) 5% solution of N,N-dimethyl octadecyloxy propylamine (Lot. EA-3) (vehicle: ethanol)
Well-defined erythema was observed, accompanied with only mild edema in 4 of 5 animals from 3 hours after removal. The lesion progressed to eschar formation and mild edema 24 hours after removal and then, further progressed to eschar formation and severe edema 48 hours after removal. As for the rest of one animal, well-defined erythema was observed from 3 hours after removal. The lesion progressed to moderate to severe erythema, accompanied with only mild edema 24 hours after removal and persisted until 48 hours after removal.

2) 1% solution of N,N-dimethyl octadecyloxy propylamine (Lot. EA-3)(vehicle: ethanol)
Only mild erythema was observed in all of the animals from 3 hours after removal. The lesion progressed to moderate to severe erythema, accompanied with only mild edema in 2 of 5 animals 24 hours after removal and further progressed to eschar formation and mild edema 48 hours after removal. In addition, the lesion progressed to well-defined erythema in 3 animals 24 hours after removal and persisted until 48 hours after removal.

3) Ethanol (vehicle control)
No irritation reactions were observed at any time point.

4) Distilled water (negative control)
No irritation reactions were observed at any time point.

Other effects:

During the study period, no abnormalities in clinical signs were noted.

Applicant's summary and conclusion

Interpretation of results:

other: The study cannot be used for classification directly because the diluted test solution was used. However the irritation/corrosive potential of test substance was evaluated based on this study for classification.

Conclusions:

5% solution of N,N-dimethyl octadecyloxy propylamine (Lot. EA-3) (vehicle: ethanol):
Well-defined erythema was observed, accompanied with only mild edema in 4 of 5 animals from 3 hours after removal. The lesion progressed to eschar formation and mild edema 24 hours after removal and then, further progressed to eschar formation and severe edema 48 hours after removal. As for the rest of one animal, well-defined erythema was observed from 3 hours after removal. The lesion progressed to moderate to severe erythema, accompanied with only mild edema 24 hours after removal and persisted until 48 hours after removal.

Executive summary:

The primary skin irritation of N,N-dimethyl octadecyloxy propylamine (Lot. EA-3) were evaluated in guinea pigs. Animals were used in groups of 5 for the study. The application site was the left and right flanks of animals. The lint fabric of a tape for a patch test was impregnated with 0.1 mL of the test solution, and a 24 -hour occlusive-patch test was performed.

As a result, no abnormalities in clinical signs were noted. The mean scores of skin reactions are shown as follows.

(Based of the avarage score of 5 animals. Highest score: 4)

Test solution	Concentration* (%)	Vehicle	Time after removal
			3 hr (erythema /edema)	24 hr (erythema /edema)	48 hr (erythema /edema)
N,N-dimethyl octadecyloxy propylamine (Lot.EA-3)	5	Ethanol	2 / 0.8	3.8 / 1.8	3.8 / 3.4
N,N-dimethyl octadecyloxy propylamine (Lot.EA-3)	1	Ethanol	1 / 0	2.4 / 0.4	2.8 / 0.8
Ethanol (vehicle control)	-	-	0 / 0	0 / 0	0 / 0
Distilled water (negative control)	-	-	0 / 0	0 / 0	0 / 0

*Concentrations as “N,N-dimethyl octadecyloxy propylamine”