N-(butoxymethyl)acrylamide

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

26 June 2006 to 13 October 2006

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2006

Report date:

2006

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

the test material was applied to abraded as well as intact skin

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

N-(butoxymethyl)acrylamide

EC Number:

217-442-7

EC Name:

N-(butoxymethyl)acrylamide

Cas Number:

1852-16-0

Molecular formula:

C8H15NO2

IUPAC Name:

N-(butoxymethyl)prop-2-enamide

Test material form:

liquid

Details on test material:

- Physical state: Clear liquid
- Storage conditions of test material: Room temperature and humidity. Avoid prolonged storage above 100 °F.

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: The pre-test body weight range was 2.6 - 3.0 kg
- Age at study initiation: Approximately 14 weeks
- Housing: The animals were housed 1 per cage in suspended cages. Bedding was placed beneath the cages and changed at least three times per week.
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: Equilibrated for at least three days

ENVIRONMENTAL CONDITIONS
- Temperature: Not reported, the room was temperature controlled
- Photoperiod: 12 hour light / dark cycle

IN-LIFE DATES:
- From: 07 June 2006
- To: 03 July 2006

Test system

Type of coverage:

occlusive

Preparation of test site:

other: Rabbits were clipped and the substance applied to both intact and abraded skin

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied: 0.5 mL to two areas (one intact and one abraded) for a total dermal exposure dose of 1.0 mL

VEHICLE
The test material was used as received

OTHER
Rabbits were examined and found to be free of dermal irritation and skin abnormalities prior to the start of the test. The left side of each animal was abraded with a bent tip needle. Three abrasions approximately 2 - 3 cm apart, extending the length of the exposure site were made. The abrasions were sufficiently deep to penetrate the stratum corneum but not deep enough to produce bleeding. The right side of each animal remained intact.

Duration of treatment / exposure:

4 hours

Observation period:

7 days

Number of animals:

3 rabbits; one male and two female.

Details on study design:

TEST SITE
- Area of exposure: Back and sides of each animal.
- Type of wrap if used: 2.5 x 2.5 cm 4 ply surgical gauze patches which were secured with non-irritating adhesive tape. The torso was wrapped with plastic which was secured with non-irritating adhesive tape. In order to permit dermal observations during the 4-hour exposure period, the wrappings were fitted with a window which was opened to examine the test site. The sites were semi-occluded for 4 hours at which time the patches were removed.

REMOVAL OF TEST SUBSTANCE
- Washing: Not specified

OBSERVATION TIME POINTS
Animals were observed for skin reactions, including ulceration and necrosis, during the 4 hour exposure period at 3 minutes post-dose and at 1 and 4 hours post-dose. The test sites were scored again at 24, 48 and 72 hours and again on day 7. Erythema and eschar were scored according to the numerical Draize scale. Additional signs were described.
Bodyweights were recorded pre-test. The general health of each animal was monitored at each observation time. All animals were humanely sacrificed using CO2 following study termination.

SCORING SYSTEM:
Erythema and eschar formation:
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)

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

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Remarks:

G8728 Male

Time point:

24/48/72 h

Score:

1.67

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: Results from intact skin only.

Results 2

Irritation parameter:

erythema score

Basis:

animal #2

Remarks:

G8760 Female

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Remarks on result:

other: Results from intact skin only.

Results 3

Irritation parameter:

erythema score

Basis:

animal #3

Remarks:

G8761 Female

Time point:

24/48/72 h

Score:

0.67

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Remarks on result:

other: Results from intact skin only.

Results 4

Irritation parameter:

edema score

Basis:

animal #1

Remarks:

G8728 Male

Time point:

24/48/72 h

Score:

1.67

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: Results from intact skin only.

Results 5

Irritation parameter:

edema score

Basis:

animal #2

Remarks:

G8760 Female

Time point:

24/48/72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Remarks on result:

other: Results from intact skin only.

Results 6

Irritation parameter:

edema score

Basis:

animal #3

Remarks:

G8761 Female

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: Not applicable - No effects observed

Remarks on result:

other: Results from intact skin only

Irritant / corrosive response data:

Erythema was absent at three minutes after dosing, absent to very slight at one hour after dosing and very slight at four hours after dosing. Oedema was absent at three minutes and one hour after dosing and absent to slight at four hours after dosing.
At 24, 48 and 72 hours after patch removal, erythema was absent to well defined. Oedema was absent to very slight at 24 hours after patch removal and absent to well-defined at 48 and 72 hours.
Both erythema and oedema were absent by Day 7.

Other effects:

One instance of diarrhoea was the only abnormal physical sign noted during the observation period.

Any other information on results incl. tables

Table 1: Erythema and Eschar Formation

Test Condition	Rabbit No. / Sex	G8728/M	G8760/F	G8761/F
	Observation Time
Intact skin	3 minutes"	0	0	0
	1 hour"	0	0	0
	4 hours"	1	1	1
	24 hours**	1	1	1
	48 hours**	2	0	1
	72 hours**	2	0	0
	7 days**	0*	0*	0*
Abraded skin	3 minutes	0	0	0
	1 hour	1	0	0
	4 hours	1	1	1
	24 hours	2	1	0
	48 hours	2	0	0
	72 hours	2	0	0
	7 days	0*	0*	0*

" Post dose observation

* Reclipped

** Post-patch removal observation

Table 2: Oedema

Test Condition	Rabbit No. / Sex	G8728/M	G8760/F	G8761/F
	Observation Time
Intact skin	3 minutes	0	0	0
	1 hour	0	0	0
	4 hours	1	0	0
	24 hours	1	1	1
	48 hours	2	0	0
	72 hours	2	0	0
	7 days	0	0	0
Abraded skin	3 minutes	0	0	0
	1 hour	0	0	0
	4 hours	1	0	1
	24 hours	1	1	0
	48 hours	2	0	0
	72 hours	2	0	0
	7 days	0	0	0

Applicant's summary and conclusion

Interpretation of results:

other: Not classified in accordance with EU criteria

Conclusions:

The test material was not irritating to the skin.