Amides, coco, N-[3-(dimethylamino)propyl], N-oxides

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From October 26, 1999 to November 16, 1999

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: OECD guideline 404 and EU guideline B.4. GLP study.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2000

Report date:

2000

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

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

Amides, coco, N-[3-(dimethylamino)propyl], N-oxides

EC Number:

268-938-5

EC Name:

Amides, coco, N-[3-(dimethylamino)propyl], N-oxides

Cas Number:

68155-09-9

Molecular formula:

Unspecified

IUPAC Name:

Amides, coco, N-[3-(dimethylamino)propyl], N-oxides

Details on test material:

- Purity: approximately 79%
- Lot/batch No.: 876 TK
- Physical state: off white paste
- Storage condition of test material: room temperature, in the dark

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: David Percival Ltd, Moston, Sandbach, Cheshire, UK
- Age at study initiation: 12 to 16 weeks old
- Weight at study initiation: 2.48 to 3.09 kg
- Housing: The animals were individually housed in suspended metal cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: a minimum of five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-23 ºC
- Humidity (%): 30 to 70 %
- Air changes (per hr): the rate was approximately fifteen changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours continuous light and 12 hours of darkness.

Test system

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 of the test material.

Duration of treatment / exposure:

4 hour

Observation period:

14 days

Number of animals:

3 animals

Details on study design:

TEST SITE
- Area of exposure: 2.5 x 2.5 cm
- Type of wrap if used: the trunk of the rabbit was wrapped in an elasticated corset (TUBIGRIP)

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Any residual test material was removed by gentle swabbing with cotton wool soaked in 74% Industrial Methylated Spirits.
- Time after start of exposure: 4 hours after application (when the patch was removed).

SCORING SYSTEM:
according to the OECD guideline nº 404.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24 h

Score:

0

Results 2

Irritation parameter:

edema score

Basis:

animal #1

Time point:

48 h

Score:

0

Results 3

Irritation parameter:

edema score

Basis:

animal #1

Time point:

72 h

Score:

0

Results 4

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24 h

Score:

0

Results 5

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

48 h

Score:

0

Results 6

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

72 h

Score:

0

Results 7

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24 h

Score:

1

Max. score:

1

Reversibility:

fully reversible within: 7 days

Results 8

Irritation parameter:

edema score

Basis:

animal #2

Time point:

48 h

Score:

1

Max. score:

1

Reversibility:

fully reversible within: 7days

Results 9

Irritation parameter:

edema score

Basis:

animal #2

Time point:

72 h

Score:

1

Max. score:

1

Reversibility:

fully reversible within: 7 days

Results 10

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24 h

Score:

2

Max. score:

2

Reversibility:

fully reversible within: 7 days

Results 11

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

48 h

Score:

2

Max. score:

2

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: Loss of skin elasticity.

Results 12

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

72 h

Score:

2

Max. score:

2

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: Loss of skin elasticity and loss of skin flexibility. At day 7, crust formation was observed. At day 14, slight desquamation was observed.

Results 13

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24 h

Score:

2

Max. score:

2

Reversibility:

fully reversible within: 7 days

Results 14

Irritation parameter:

edema score

Basis:

animal #3

Time point:

48 h

Score:

2

Max. score:

2

Reversibility:

fully reversible within: 7 days

Results 15

Irritation parameter:

edema score

Basis:

animal #3

Time point:

72 h

Score:

2

Max. score:

2

Reversibility:

fully reversible within: 7 days

Results 16

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24 h

Score:

2

Max. score:

2

Reversibility:

fully reversible within: 7 days

Results 17

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

72 h

Score:

2

Max. score:

2

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: Loss of skin elasticity and loss of skin flexibility. At day 7, crust formation was observed. At day 14, slight desquamation was observed.

Results 18

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

48 h

Score:

2

Max. score:

2

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: Loss of skin elasticity

Irritant / corrosive response data:

No corrosive effects were noted.

Any other information on results incl. tables

Individual skin reactions following 4-hours exposure period

 

Skin Reaction	Observation Time	Individual Scores -Rabbit Number and Sex (Bodyweight kg)			Total
Erythema/Eschar Formation		1Male (3.09)	198 Male (2.74)	200 Female (2.48)
	1 Hour	0	2	2	( 4 )
	24 Hours	0	2	2	4
	48 Hours	0	2Le	2le	( 4 )
	72 Hours	0	2LeLf	2LeLf	4
	7 Days	-	OCf	OCf	( 0 )
	1 4 Days	-	OD	OD	( 0 )
Oedema Formation	1Hour	0	2	2	( 4 )
	24 Hours	0	1	2	3
	48 Hours	0	1	2	( 3 )
	72Hours	0	1	1	2
	7 Days	-	0	0	( 0 )
	14 Days	-	0	0	( 0 )
Sum of 24 and 72-hour Readings (S)                 13
Primary Irritation Index                               13/6 - 2.2

( ): total values not used for calculation of the primary index

Cf: crust formation

D: slight desquamation

Le: loss of skin elasticity

Lf: loss of skin flexibility

- : observation not required

 

Individual daily and mean scores for dermal irritation following 4-hour exposure

 

Skin Reaction	Reading (Hours)	Individual Scores - Rabbit Number and Sex (Bodyweight kg)
		1Male (3.09)	198Male (2.48)	200Female (2.74)
Erythema/Eschar Formation	24	0	2	2
	48	0	2	2
	72	0	2	2
total		0	6	6
Mean Score		0.0	2.2	2.0
Oedema Formation	24	0	1	2
	48	0	1	2
	72	0	1	1
Total		0	3	5
Mean Score		0.0	1.0	1.7

 

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Well-defined erythema was noted at two treated skin sites one hour after patch removal and at the 24, 48 and 72-hour observations. Slight oedema was noted at two treated skin sites one hour after patch removal. Very slight oedema was noted at two treated skin sites at the 72-hour observation. Mean values (all animals mean of 24/48/72h) are 0.9 oedema and 1.3 for erythema. One treated skin site appeared normal throughout the study. Crust formation was noted at two treated skin sites at the 7-day observation with slight desquamation at these two treated skin sites at the 14-day observation. Hence the substance was not classified for irritation according to GHS, EU.

Executive summary:

The Acute Dermal Irritation/corrosion assay for the test substance was performed in New Zealand rabbits. 0.5 mL of the test material was applied to a site of about 2.5 x 2.5 cm of intact skin of 3 rabbits and covered by semi-occlusive dressing. The administration of the test substance was performed in a sequential manner. The first animal was exposed to the test substance stepwise at three sites of the skin: site 1 for three minutes, site 2 for 1 hour and site 3 for 4 hours. Any residual test substance was removed by swabbing with cotton wool soaked in 74% Industrial Methylated Spirits. After considerations of the skin reactions produced on the first animal, the remaining two animals were exposed to the test substance for 4 hours. The treated areas of the animals were examine for erythema/eschar and oedema as well as other local skin alterations approximately 1, 24, 48, and 72 hours after patch removal. Additional observations were made on days 7 and 14 to assess the reversibility of skin reactions. Dermal alterations were scored according to OECD guideline nº 404. Well-defined erythema was noted at two treated skin sites one hour after patch removal and at the 24, 48 and 72-hour observations. Slight oedema was noted at two treated skin sites one hour after patch removal. Very slight oedema was noted at two treated skin sites at the 72-hour observation.One treated skin site appeared normal throughout the study.Crust formation was noted at two treated skin sites at the 7-day observation with slight desquamation at these two treated skin sites at the 14-day observation. No corrosive effects were noted.