N-methylacetamide

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1999

Report date:

1999

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

N-methylacetamide

EC Number:

201-182-6

EC Name:

N-methylacetamide

Cas Number:

79-16-3

Molecular formula:

C3H7NO

IUPAC Name:

N-methylacetamide

Details on test material:

- Name of test material (as cited in study report): N-METHYLACETAMIDE, 98/392-1
- Physical state: Colorless solid
- Analytical purity: 99.82% (GC)
- Lot/batch No.: Tank 143
- Date of manufacturing: September 24, 1998
- Stability: Reanalysis: stable until January 1999.
- Storage condition of test material: at room temperature (approx. 20°C) away from direct
sunlight.

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Elevage Scientifique des Dombes F-0 1400 Chatillon sur Chalaronne
- Number of animals: 1 male, 2 females
- Age at study initiation: 15 weeks
- Weight at study initiation: male: 2.605 kg, females: 2.817 and 2.794 kg
- Housing: Individually in stainless steel cages with an automatic cleaning system equipped with feed hoppers, drinking water bowls, with haysticks and wood for gnawing.
- Diet (e.g. ad libitum): Pelleted standard Kliba 3410 rabbit maintenance diet ad libitum (batch no. 62/98). Provimi Kliba AG, 4303 Kaiseraugst, Switzerland.
- Water (e.g. ad libitum): Community tap water from Itingen, ad libitum, provided by water bowls.
- Acclimatization period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ±3
- Humidity (%): 40-70
- Air changes (per hr): 10-15 air changes per hour,
- Photoperiod (hrs dark / hrs light): 12 hour Iight/dark cycle.

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: The right eye remained untreated and served as the reference control.

Duration of treatment / exposure:

24 hours

Observation period (in vivo):

21 days

Number of animals or in vitro replicates:

3

Details on study design:

TREATMENT
On the day of treatment, the test article (undiluted) was placed in the conjunctival sac of the left eye of each animal after gently pulling the lower lid away from the eyeball. The lids were then gently held together for about one second to prevent loss of test article.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The treated eyes were rinsed gently with bidistilled water.
- Time after start of exposure: approximately 24 hours after administration.

SCORING SYSTEM: The ocular reaction was assessed according to the numerical scoring system listed in the EEC Commission Directive 92/69/EEC, July 31, 1992 at approximately 1, 24, 48 and 72 hours and 7, 14 and 21 days after administration.

TOOL USED TO ASSESS SCORE: Varta Cliptrix diagnostic-lamp (A. Riegger, Basel, Switzerland).

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: 24, 48, 72 h

Score:

0

Max. score:

4

Reversibility:

other: no effects

Results 2

Irritation parameter:

iris score

Basis:

mean

Time point:

other: 24, 48, 72 h

Score:

0

Max. score:

2

Reversibility:

other: no effects

Results 3

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

other: 24, 48, 72 h

Score:

1.11

Max. score:

3

Reversibility:

fully reversible within: 14 days

Remarks on result:

other: for details see table below

Results 4

Irritation parameter:

chemosis score

Basis:

mean

Time point:

other: 24, 48, 72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 h

Remarks on result:

other: for details see table below

Any other information on results incl. tables

Exposition: Single application to the conjunctival sac of the eyelid; the substance was washed out after 24 h
Animal	Reading	Cornea Opacity	Iris	Conjunctiva		Additional findings
				Redness	Chemosis
1	1 h	0	0	2	1	nictitating membrane swollen, moderate watery discharge, sclera: blood vessels hyperemic.
2	1 h	0	0	2	1	nictitating membrane swollen, moderate watery discharge; sclera: blood vessels hyperemic.
3	1 h	0	0	2	1	nictitating membrane swollen, moderate watery discharge; sclera: blood vessels hyperemic.
1	24 h	0	0	1	1	slight swelling, blood vessels hyperemic.
2	24 h	0	0	2	1	nictitating membrane swollen, moderate watery discharge; sclera: blood vessels hyperemic.
3	24 h	0	0	2	1	nictitating membrane swollen, moderate watery discharge; sclera: blood vessels hyperemic.
1	48 h	0	0	1	0	-
2	48 h	0	0	1	0	-
3	48 h	0	0	1	0	sclera: blood vessels hyperemic.
1	72 h	0	0	1	0	-
2	72 h	0	0	0	0	-
3	72 h	0	0	1	0	sclera: blood vessels hyperemic.
1	7 d	0	0	1	0	-
2	7 d	0	0	0	0	-
3	7 d	0	0	1	0	sclera: blood vessels hyperemic.
1	14 d	0	0	0	0	-
2	14 d	0	0	0	0	-
3	14 d	0	0	0	0	sclera: blood vessels hyperemic.-
1	21 d	0	0	0	0
2	21 d	0	0	0	0
3	21 d	0	0	0	0	sclera: blood vessels hyperemic.
mean animal 1	24 - 72 h	0.00	0.00	1.00	0.33
mean animal 2	24 - 72 h	0.00	0.00	1.00	0.33
mean animal 3	24 - 72 h	0.00	0.00	1.33	0.33
mean	24 - 72 h total	0.00	0.00	1.11	0.33

Applicant's summary and conclusion

Interpretation of results:

Category 2A (irritating to eyes) based on GHS criteria

Conclusions:

Due to irreversibility of the hyperemia of the scleral blood vessels in one animal and according to the conditions of the test, the test substance has to be classified as irritating to the eye following the GHS (Category 2 (A)) requirements.