1,1'-(1,3-Phenylenedicarbonyl)diazepan-2-one

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

April 2007 - May 2007

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP-guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2007

Report date:

2007

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

1,1'-(1,3-Phenylenedicarbonyl)diazepan-2-one

EC Number:

616-020-3

Cas Number:

7381-13-7

Molecular formula:

C20H24N2O4

IUPAC Name:

1,1'-(1,3-Phenylenedicarbonyl)diazepan-2-one

Details on test material:

none

Test animals / tissue source

Species:

rabbit

Strain:

other: New Zealand

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Elevage de Gerome (Quartier Labaste - F40260 Linxe)
- Age at study initiation:
- Weight during the test: the animals weighed between 2.46 kg and 2.87 kg.
- Housing: in an individual box
- Acclimation period: 5-days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): between 18°C and 21 °C
- Humidity (%): between 40% and 68%
- Air changes (per hr): conventional air conditioned

Test system

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

0.1 g of the test item

Observation period (in vivo):

Ocular examinations were performedd on both right and left eyes 1 hour, 24, 48 and 72 hours following treatment.
If no reaction is observed 72 hours after instillation, the study is terminated.

Number of animals or in vitro replicates:

3 rabbits

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): test item remove with isotonic sodium chloride

SCORING SYSTEM:
CHEMOSIS (A)
• No swelling................................... ............ ....................................................................... .............. 0
• Slight swelling, including the nictitating membrane ...................................................................... 1
• Swelling with eversion ofthe eyelid............................................................................ .................. 2
• Swelling with eyelid half-closed...................................................................................... ........... ... 3
• Swelling with eyelid more than half-closed .................................................................... .... ........... 4

DISCHARGE (B)
• No discharge .................................................. ..................... .. ... ...................................................... 0
• Slight discharge (normal slight secrelions in the inner corner not to be
taken into account)....................................................................................................................... .. 1
• Discharge with moistening ofthe eyelids and neighbouring hairs ........ ............................ ............. 2
• Discharge with moistening of the eyelids and large areas around the eye ..................................... 3

REDNESS (C)
• Blood vessels normal. .................................................................................................................... 0
• Vessels significantly more prominent than normal........................................................................ 1
• Vessels individuaIly distinguishable with difficulty
Generalised red coloration........................................................................... ........ ..................... 2
Generalised deep red coloration .................................................. ................. ..... ................ .... ... 3

IRIS (D)
• Normal................... ................................................................................................................ ........ 0
• Iris significantly more wrinkled than normal, congeslion,
swelling ofthe iris which continues to react to light, even slowly................................................. 1
• No reaction to light, haemorrhage, significant damage
(any or all ofthese characteristics) ................................................................................................ 2

CORNEA: DEGREE OF OPACITY (E)
• No modification visible either directly or after
instillation of fluorescein (no 1055 of glint or polish) ...................... .......... ..................................... 0
• Translucent areas (diffuse or disseminated), iris details clearly visible .......... ............ .... ............... 1
• Easily identifiable translucent area, iris details slightly obscured.................................................. 2
• Opalescent area, no iris details visible, pupil outline scarcely distinguishable .............................. 3
• Total comeal opacity, completely obscuring the iris and pupil.............................................. ........ 4

CORNEA: EXTENT OF OPACITY (F)
• Opaque area present but covering one quarter or less .................................................................... 1
• Between one quarter and half.. ....................................................................................................... 2
• Between half and three quarters .. ......................................................... .......................................... 3
• Between three quarters and the entire surface.................................. .............................................. 4


TOOL USED TO ASSESS SCORE: hand-slit lamp / biomicroscope / fluorescein

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

conjunctivae score

Remarks:

CHEMOSIS

Basis:

animal: #1,#2,#3

Time point:

other: 24, 48 and 72 hours

Score:

0

Max. score:

4

Reversibility:

other: no effects

Results 2

Irritation parameter:

conjunctivae score

Remarks:

REDNESS

Basis:

animal: #1,#2,#3

Time point:

other: 24, 48 and 72 hours

Score:

0

Max. score:

3

Reversibility:

other: no effects

Results 3

Irritation parameter:

iris score

Remarks:

LESION

Basis:

animal: #1,#2,#3

Time point:

other: 24.48 and 72 hours

Score:

0

Max. score:

2

Reversibility:

other: no effects

Results 4

Irritation parameter:

cornea opacity score

Remarks:

OPACITY

Basis:

animal: #1,#2,#3

Time point:

other: 24, 48 and 72 hours

Score:

0

Max. score:

4

Reversibility:

other: no effects

Results 5

Irritation parameter:

conjunctivae score

Remarks:

DISCHARGE

Basis:

animal: #1,#2,#3

Time point:

other: 1 hour

Score:

2

Max. score:

3

Reversibility:

fully reversible

Results 6

Irritation parameter:

conjunctivae score

Remarks:

REDNESS

Basis:

animal: #1,#2,#3

Time point:

other: 1 hour

Score:

1

Max. score:

3

Reversibility:

fully reversible

Results 7

Irritation parameter:

conjunctivae score

Remarks:

CHEMOSIS

Basis:

animal: #2, #3

Time point:

other: 1 hour

Score:

1

Max. score:

4

Reversibility:

fully reversible

Irritant / corrosive response data:

- Raw data for each individual animal at each observation time up to removal of each animal from the test: data are given in above block of fields
'Irritation / corrosion results'.

Other effects:

none

Any other information on results incl. tables

The ocular conjunctivae reactions observed during the study have been slight and rapidly reversible in the three animals: a slight redness was noted only 1 hour after the test item instillation associated a slight chemosis in two animals only 1 hour after the test item instillation

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

not to be classified

Executive summary:

The test item was instilled as supplied, at the dose of 0.1 g, into the eye of one New Zealand rabbit (n=3).

The ocular conjunetivae reactions observed during the study have been slight and rapidly reversible in the three animals: a slight redness was noted only 1 hour after the test item instillation assoeiated a slight chemosis in !wo animals only 1 hour after the test item instillation.