N-(1,1-dimethyl-3-oxobutyl)acrylamide

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2005

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study with GLP.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2004

Report date:

2004

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

N-(1,1-dimethyl-3-oxobutyl)acrylamide

EC Number:

220-713-2

EC Name:

N-(1,1-dimethyl-3-oxobutyl)acrylamide

Cas Number:

2873-97-4

Molecular formula:

C9H15NO2

IUPAC Name:

N-(1,1-dimethyl-3-oxobutyl)acrylamide

Constituent 2

Reference substance name:

diacetone acrylamide

IUPAC Name:

diacetone acrylamide

Details on test material:

Appearance: White powder. Batch No.: SSHD 044Conditions of storage: In the dark, may be used under light. Stability in aqueous solution: Stable.The pH of a 1 % aqueous solution is 6.49

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

Supplier: Charles River Deutschland GmbH, D-97633 Sulzfeld.Number and sex: 3 females.Body weights (at the start and at the termination of the study): 2.0-2.6 and 2.2-2.7 Hygiene: Optimal hygienic conditions.Room temperature: Average of 19.5 °C (continuous control and recording).Relative humidity: Average of 66.8 % (continuous control and recording).Light: Artificial light from 6 a.m. to 6 p.m.Cages: Individual caging in metal wire cages, Ehret GmbH, D-79312 Emmendingen, type KK 016R, 79 cm x 59 cm bottom area, 38 cm height.Feed: Altromin 2123 maintenance diet for rabbits, rich in crude fibre, ad libitum. Analysis of the feed for ingredients and contaminants is performed randomly by Altromin, D-32791 Lage, Germany.Hay-briquettes (supplied by SSNIFF, D-59494 Soest) are offered additionally as a dietary supplement.Water: Tap water from an automatic watering system, ad libitum.Environmental Enrichment: Wooden rest shelves.Acclimatisation: 5 days (1 animal) and 12 days (2 animals).Identification: Individual labelling with felt-tipped pen on an ear pinna and cage labels.

Test system

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

The weighed amounts of the individual doses were 55, 71 and 70 mg.

Duration of treatment / exposure:

The approximate equivalent of 0.1 mL of the test substance was administered per animal into the conjunctival sacs of the right eyes by gently pulling the lower lids away from the eyeballs for instillation. The eyes were held closed for about one second to prevent a loss of test substance.The left eyes remained untreated and served as a control.

Observation period (in vivo):

Both eyes of the animals were examined within 24 hours before the instillation and approximately 1, 24, 48 and 72 hours p.a. Animal 1 was also observed 6 d p.a.

Number of animals or in vitro replicates:

3

Details on study design:

Firstly, the test substance was given to one animal. As no evidence for a serious damage to the eye of this animal was found during the initial 72 hour observation period (no corrosive effect), the test substance was administered to the other two animals subsequently.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

other: 1, 24, 48 and 72 h p.a. and 6 d p.a.

Score:

0 - 1

Max. score:

1

Reversibility:

fully reversible within: 72 h

Remarks on result:

other: Score at 24 and 48 h p.a.: 1, 1/4 of the cornea was affected. Score at 0 and 72 h and at 6 d p.a.: 0

Results 2

Irritation parameter:

cornea opacity score

Basis:

animal: 2 and 3

Time point:

other: 1, 24, 48 and 72 h p.a.

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Results 3

Irritation parameter:

iris score

Basis:

animal: each

Time point:

other: 1, 24, 48 and 72 h p.a.

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Results 4

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

other: 1, 24, 48 and 72 hours and 6 d p.a.

Score:

0 - 1

Max. score:

1

Reversibility:

fully reversible within: 6 d

Remarks on result:

other: Score at 1 to 72 h p.a.: 1; score at 6d p.a.; 0

Results 5

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

other: 1, 24, 48 and 72 h p.a.

Score:

0 - 1

Max. score:

1

Reversibility:

fully reversible within: 72 h

Remarks on result:

other: Score at 24 and 48 h p.a.: 1; Score at 1 and 72 h p.a.: 0

Results 6

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

other: 1, 24, 48 and 72 h p.a.

Score:

0 - 1

Max. score:

1

Reversibility:

fully reversible within: 72 h p.a.

Remarks on result:

other: Score 1, 24 and 48 h p.a.: 1; Score at 72 h p.a.: 0

Results 7

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

other: 1, 24, 48 and 72 h p.a. and 6 d p.a.

Score:

0 - 4

Max. score:

4

Reversibility:

fully reversible within: 72 h

Remarks on result:

other: Score at 1 h: 4; Score at 24 h: 2; Score at 48 h: 1; Score at 72 h and 6 d p.a.: 0

Results 8

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

other: 1, 24, 48 and 72 h p.a.

Score:

0 - 2

Max. score:

2

Reversibility:

fully reversible within: 72 h p.a.

Remarks on result:

other: Score at 1 h: 2; Score at 24 h: 2; Score at 48 h: 1; Score at 72 h: 0

Results 9

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

other: 1, 24, 48 and 72 h p.a.

Score:

0 - 2

Max. score:

2

Reversibility:

fully reversible within: 48 h p.a.

Remarks on result:

other: Score at 1 h: 2; Score at 24 h: 1; Score at 48 h: 0; Score at 72 h: 0

Other effects:

No signs of systemic toxicity were observed in the animals during the test period and no mortality occurred.

Any other information on results incl. tables

The untreated eyes ("control eyes") were normal at each observation time. The eyes, treated with the test substance ("test eyes") were normal before the instillation.

The following mean scores were calculated for the examinations at 24, 48 and 72 h p.a.:

	Mean Scores for Animal No.:
	1	2	3
Corneae	0.7	0.0	0.0
Irises	0.0	0.0	0.0
Conjunctivae, redness	1.0	0.7	0.7
Conjunctivae, chemosis	1.0	1.0	0.3

Ocular lesions were reversible in all animals within 6 d p.a.

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Diacetone acrylamide is not irritating to skin.

Executive summary:

The possible irritation by the test substance following a single application to the intact eyes of rabbits was determined applying the EU-methods. Results:

- Corneae: Diffuse areas of opacity (score of "1", 25 % of the cornea affected) were observed in 2/3 animals from 1 h or 24 h onwards until a maximum of 48 h p.a.

- Irises: Not affected.

- Conjunctivae, redness: In all animals some injected blood vessels (score of "1") were observed from 1 h or 24 h onwards until a maximum of 72 h p.a.

- Conjunctivae, chemosis: Severe or obvious swelling (scores of "4" or "2"), decreasing afterwards, was seen in all animals from 1 h onwards until a maximum of 48 h p.a.

Diacetone acrylamide is not irritating to skin according to the EC classification scheme of Directive 2001/59/EC.