2-(2-oxopyrrolidin-1-yl)butyramide

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2003

Reliability:

1 (reliable without restriction)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2003

Report date:

2003

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2400 (Acute Eye Irritation)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Reference

Name:

Unnamed

Type:

Constituent

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

Batch: C02421 -1620
Purity: 98.6%

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-01400 Chatillon sur Chalaronne / France
- Age at study initiation: 11 weeks
- Number of animals per test: 1 male, 2 female
- Housing: Standard Laboratory Conditions Air-conditioned with target ranges for room temperature 17-23 “C, relative humidity 30-70 Y. and approximately 10-15 air changes per hour. Room temperature and humidity were monitored continuously and values outside of these ranges may have occasionally occurred, usually following room cleaning. These transient variations are considered not to have any influence on the study and, therefore, these data are not reported but are retained at RCC. The animals were provided with an automatically controlled light cycle of 12 hours light and 12 hours dark. Music was played during the daytime light period.
- Diet : Pelleted standard Provimi Kliba 3418 rabbit maintenance diet ad /ibitum (batch no. 28/03) provided by Provimi Kliba AG, CH-4303 Kaiseraugst. Results of analysis for contaminants are archived at RCC Ltd, Itingen.
- Water :Community tap water from Fuliinsdorf, ad Iibitum. Results of bacteriological, chemical and contaminant analyses are archived at RCC Ltd, Itingen.
- Acclimatization:Under laboratory conditions after health examination. Only animals without any visual signs of illness were used for the study.

Test system

Vehicle:

unchanged (no vehicle)

Amount / concentration applied:

0.1g

Observation period (in vivo):

72h

Number of animals or in vitro replicates:

3

Details on study design:

The eyes of the animals were examined one day prior to test item administration.Animals with overt signs of ocular injury or irritation which may have interfered with the interpretation of the results were not used in the test. On the day of treatment, 0.1 g of ucb 6474 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 item. The right eye remained untreated and served as the reference control. The treated eyes were not rinsed after instillation.

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 after instillation. When present, corrosion and/or staining of conjunctival, sclerae and cornea by the test item were recorded and reported. Eye examinations were made with a Varta Cliptrix diagnostic-lamp (Roth AG, CH-4153 Reinach/Switzerland).

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #1

Remarks:

(mean score 1)

Time point:

other: overall at 24, 48 and 72 h

Score:

1

Results 2

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #2

Remarks:

(mean score 2)

Time point:

other: overall at 24, 48 and 72 h

Score:

1

Results 3

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #3

Remarks:

(mean score 3)

Time point:

other: overall at 24, 48 and 72 h

Score:

0.67

Results 4

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Max. score:

2

Remarks on result:

other: Max. duration: 24 h; Max. value at end of observation period: 0 (related to all animals)

Results 5

Irritation parameter:

chemosis score

Basis:

animal #1

Remarks:

(mean score 1)

Time point:

other: overall at 24, 48 and 72 h

Score:

0

Results 6

Irritation parameter:

chemosis score

Basis:

animal #2

Remarks:

(mean score 2)

Time point:

other: overall at 24, 48 and 72 h

Score:

0

Results 7

Irritation parameter:

chemosis score

Basis:

animal #3

Remarks:

(mean score 3)

Time point:

other: overall at 24, 48 and 72 h

Score:

0

Results 8

Irritation parameter:

chemosis score

Max. score:

2

Remarks on result:

other: Max. duration: 1 h; Max. value at end of observation period: 0 (related to all animals)

Results 9

Irritation parameter:

cornea opacity score

Basis:

animal #1

Remarks:

(mean score 1)

Time point:

other: overall at 24, 48 and 72 h

Score:

0

Results 10

Irritation parameter:

cornea opacity score

Basis:

animal #2

Remarks:

(mean score 2)

Time point:

other: overall at 24, 48 and 72 h

Score:

0

Results 11

Irritation parameter:

cornea opacity score

Basis:

animal #3

Remarks:

(mean score 3)

Time point:

other: overall at 24, 48 and 72 h

Score:

0

Results 12

Irritation parameter:

cornea opacity score

Max. score:

0

Remarks on result:

other: Max. duration: h; Max. value at end of observation period: 0 (related to all animals)

Results 13

Irritation parameter:

iris score

Basis:

animal #1

Remarks:

(mean score 1)

Time point:

other: overall at 24, 48 and 72 h

Score:

0

Results 14

Irritation parameter:

iris score

Basis:

animal #2

Remarks:

(mean score 2)

Time point:

other: overall at 24, 48 and 72 h

Score:

0

Results 15

Irritation parameter:

iris score

Basis:

animal #3

Remarks:

(mean score 3)

Time point:

other: overall at 24, 48 and 72 h

Score:

0

Results 16

Irritation parameter:

iris score

Max. score:

0

Remarks on result:

other: Max. duration: h; Max. value at end of observation period: 0 (related to all animals)

Irritant / corrosive response data:

The mean score was calculated across 3 scoring times (24, 48 and 72 hours after instillation) for each animal for corneal opacity, iris, redness and chemosis of the conjunctival, separately. The individual mean scores for corneal opacity and iris were 0.00 for all three animals. The individual mean scores for the conjunctival were 1.00, 1.00 and 0.67 for reddening and 0.00 for chemosis for all three animals. No abnormal findings were observed in the cornea or iris of any animal at any of the measurement intervals. Moderate reddening of the conjunctival was observed in all animals at the 1-hour reading. Slight to moderate reddening of the conjunctival was noted in all animals 24 hours after treatment and slight reddening was still present in all animals at thr 48-hour examination. Slight to moderate swelling (chemosis) of the conjunctival was present in all animals at the 1-hour reading.
Moderate reddening of the sclerae was observed in all animals at the 1-hour reading. Slight to moderate reddening of the sclerae was noted in all animals 24 hours after treatment and slight reddening was still evident in one animal at the 48-hour examination. Slight ocular discharge was apparent in all animals 1 hour after treatment. No abnormal findings were observed in the treated eye of any animal 72 hours after treatment, the end of the observation period for all animals.

Other effects:

No clinical signs of systemic toxicity were observed in the animals during the study and no mortality occurred.
No staining of the treated eyes produced by the test item was observed.
No corrosion of the cornea was observed at any of the reading times.

Any other information on results incl. tables

No necropsy was performed on the animals sacrificed at termination of observation.

The body weights of all rabbits were considered to be within the normal range of variability.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Based upon the referred classification criteria (Commission Directive 2001/59/EC of August 06,2001 ), ucb 6474 is considered to be “not irritating” to the rabbit eye.

Executive summary:

The instillation of ucb 6474 into the eye resulted in mild, early-onset and transient ocular changes, such as reddening of the conjunctival and sclerae, discharge and chemosis. These effects were reversible and were no longer evident 72 hours after treatment, the end of the observation period for all animals. No abnormal findings were observed in the cornea or iris of any animal at any of the examinations. No corrosion was observed at any of the measuring intervals. No staining of the treated eyes by the test item was observed and no other clinical signs of test item related effects were observed. Thus, the test item did not induce significant or irreversible damage to the rabbit eye.