Reaction products of cyclohexylamine and 4-alkylaniline and 1,1'-methanediylbis(4-isocyanatobenzene)

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 1992-07-27 to 1992-07-31

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

GLP study in accordance with recognised test guideline but: Lot/batch No.: not stated Expiration date of the lot/batch: not stated NOTE: study deemed acceptable because spectral data for A-3622 are available, covering approximately before and after the test period - see section 1.4 Analytical Information.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1992

Report date:

1992

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

1987

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

Annex V (84/449/EEC) of the Sixth Amendment (79/831/EEC) to the European Communities Council Directive 67/548/EEC

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Specific details on test material used for the study:

Physic State: off-white powder
Purity: approximately 100%
Storage Conditions: at ambient temperature, in the original container

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Rosemead Rabbits, Rosemead, Waltham Abbey, Essex, England

- Age at study initiation: approximately four to four and a half months old

- Weight at study initiation: bodyweights on the day of dosing were within the range 3.17 - 3.40 kg.

- Housing: individually in suspended stainless steel cages (Type RC10/L/TR6) mounted in mobile batteries (Modular Systems and Development Company Limited, London, England). The cages measured 61 x 76 x 46 cm high and were fitted with perforated counter-sunk floor panels. A tray beneath the floor was lined with absorbent paper which was changed regularly.

- Diet (e.g. ad libitum): free access to food hoppers containing standard pelleted rabbit diet, (S.Q.C. Rabbit Diet - Special Diets Services Limited, Witham, Essex, England). The diet contains no added antibiotic or other chemotherapeutic or prophylactic treatment.

- Water (e.g. ad libitum): free access to tap water taken from the public supply

- Acclimation period: The animals were held for a period of three weeks before administration of the test material.


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18°C (range 15-23°C)

- Humidity (%): 55% R.H. (range 40%-70% R.H.)

- Air changes (per hr): 15 complete air changes per hour without re-circulation.

- Photoperiod (hrs dark / hrs light): lighting cycle of 12 hours artificial light per day.


IN-LIFE DATES: From: 27 July 1992 To: 31 July 1992

Test system

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 100 mg
- Concentration (if solution): not applicable

Observation period (in vivo):

72 hours

Number of animals or in vitro replicates:

3

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): not done
- Time after start of exposure: not done


SCORING SYSTEM:

Darize, Refer to Attached Background Information for details of the scoring system used.


TOOL USED TO ASSESS SCORE: ophthalmoscope

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

other: for all three animal tested

Results 2

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

other: for all three animal tested

Results 3

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

>= 0 - <= 0.7

Max. score:

2

Reversibility:

fully reversible within: 72 hours

Remarks on result:

other: for all three animal tested

Results 4

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

other: for all three animal tested

Irritant / corrosive response data:

Injection of the conjunctival blood vessels was observed in two rabbits one hour following instillation of test item, and continued in one animal at the 24 hour examination. A crimson-red conjunctival appearance and very slight chemosis and discharge were observed in the remaining rabbit at the one hour examination; injection of the conjunctival blood vessels persisted in this animal to the 48 hour assessment.

Other effects:

Instillation of the test material caused practically no initial pain response.
The eyes of all rabbits were overtly normal by the 72 hour examination.

Any other information on results incl. tables

Mean values for ocular lesions 24, 48 and 72 hours after instillation. 

Animal number and sex	Corneal opacity	Iridial lesions	Redness of Conjunctiva	Chemosis
27TK 332M   27TK 338M   27TK 340M	0.0   0.0   0.0	0.0   0.0   0.0	0.7   0.3   0.0	0.0   0.0   0.0

Individual scores for ocular irritation response:

Animal No.	cornea opacity				iris				conjunctivae				chemosis
	1h	24h	48h	72h	1h	24h	48h	72h	1h	24h	48h	72h	1h	24h	48h	72h
27TK332M	0	0	0	0	0	0	0	0	2	1	1	0	1	0	0	0
27TK338M	0	0	0	0	0	0	0	0	1	1	0	0	0	0	0	0
27TK340M	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of this test, the test item was classified as 'non-irritant' to the eye.

Executive summary:

The potential of test item to cause damage to the conjunctiva, iris or cornea was assessed in three New Zealand White rabbits based on OECD 405, each subject to single ocular instillation of 100 mg of the test material. Ocular reactions were examined 1, 24, 48 and 72 hours after treatment. Injection of the conjunctival blood vessels was observed in two rabbits one and/or 24 hours following instillation. The third rabbit showed a crimson-red conjunctival appearance, slight chemosis and discharge at the one hour examination and injection of the conjunctival blood vessels up to the 48 hour assessment. The eyes of all rabbits were overtly normal by the 72 hour examination. Instillation of the test material caused practically no initial pain response. Under the conditions of this test, the test item was classified as 'non-irritant' to the eye.