A mixture (1:2:1) of: bis(N-cyclohexyl-N'-phenyleneureido)methylene; bis(N-octadecyl-N'-phenyleneureido)methylene; bis(N-dicyclohexyl-N'-phenyleneureido)methylene

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

August 20, 1990 - August 23, 1990

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1990

Report date:

1990

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:

(1984)

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

A mixture (1:2:1) of: bis(N-cyclohexyl-N'-phenyleneureido)methylene; bis(N-octadecyl-N'-phenyleneureido)methylene; bis(N-dicyclohexyl-N'-phenyleneureido)methylene

EC Number:

406-550-1

EC Name:

A mixture (1:2:1) of: bis(N-cyclohexyl-N'-phenyleneureido)methylene; bis(N-octadecyl-N'-phenyleneureido)methylene; bis(N-dicyclohexyl-N'-phenyleneureido)methylene

IUPAC Name:

Reaction mass (1:2:1) of bis(N-cyclohexyl-N'-phenyleneureido)methylene and bis(N-octadecyl-N'-phenyleneureido)methylene and bis(N-dicyclohexyl-N'-phenyleneureido)methylene

Details on test material:

- Name of test material (as cited in study report): MDI/CHA/ODA/DCHA
- Description: White yellowish solid
- Storage condition of test material: At room temperature in the dark
- Density: 0.704 g/mL

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

- Source: Broekman Institute, Someren, The Netherlands
- Age at study initiation: Approx. 13-15 weeks
- Weight at study initiation: 2505 - 2762 g
- Housing: Individually housed in cages with perforated floors
- Diet: Standard laboratory rabbit diet (LKK-20, pellet diameter 4 mm, Hope Farms, Woerden, The Netherlands); approx. 100 g/day
- Water: Free access to tap water diluted with decalcified water
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 – 20
- Humidity (%): 60 - 72
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: August 20 to August 23, 1990

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: One eye of each animal remained untreated and served as the reference control.

Amount / concentration applied:

TEST MATERIAL
- Amounts applied: Approx. 70 mg (equivalent to 0.1 mL)/animal

Duration of treatment / exposure:

Single instillation on Day 1.

Observation period (in vivo):

The eyes of each animal were examined approximately 1, 24, 48 and 72 hours after instillation of the test substance

Number of animals or in vitro replicates:

3 females

Details on study design:

TREATMENT
- The test substance was instilled 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 the test substance. The other eye remained untreated and served as the reference control.
- Immediately after the 24 hours observation, a solution of 2% fluorescein in water (adjusted to pH 7.0) was applied to both eyes of each animal to quantitatively examine the potential for corneal injury. Any bright green stained area, indicating epithelial damage, was estimated as a percentage of the total corneal area.

REMOVAL OF TEST SUBSTANCE
-Washing (if done): No

OBSERVATIONS
- Mortality/Viability: Daily
- Toxicity: Daily
- Body Weight: Day 1
- Necropsy: No
- Irritation:
The eyes of each animal were examined approximately 1, 24, 48 and 72 hours after instillation of the test substance.
The irritation scores and a description of all other (local) effects were recorded.The irritation was assessed according to OECD 405.

Where standard lighting was considered inadequate for observing minor effects, eye examinations were performed using a pocket flash light. In cases of equivocal results when comparing the treated and untreated eyes, the illustrated guide from the Consumer Product Safety Commission, Washington, D.C. 20207 was used for additional control purposes.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 2

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

2

Results 3

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.67

Max. score:

3

Reversibility:

fully reversible within: 72 hours

Results 4

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 5

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 6

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

2

Results 7

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

3

Results 8

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 9

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 10

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

2

Results 11

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.67

Max. score:

3

Reversibility:

fully reversible within: 72 hours

Results 12

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

- Instillation of the test substance affected the conjunctivae of all 3 animals. The effects were reversible within 24 hours in 1 animal and within 72 hours in the other 2 animals
- Chemosis was observed in 2 animals at 1 hour
- Treatment with fluorescin did not reveal corneal epithelial damage in any of the animals
- No corrosive effects were observed

Other effects:

- Lacrimation was observed in 2 animals at 1 hour
- No staining of the test substance was observed
- No clinical signs of toxicity were observed and no mortality occurred

Applicant's summary and conclusion

Interpretation of results:

other: Not irritating

Remarks:

According to Regulation (EC) No. 1272/2008.

Conclusions:

Based on a performed in vivo eye irritation study, the substance does not need to be classified as irritating/corrosive to eyes in accordance with the CLP Regulation.

Executive summary:

An in vivo eye irritation study was performed with the substance in accordance with OECD 405 (1987) and according to GLP principles. An amount of approximately 70 mg of MDI/CHA/ODA/DCHA was instilled in one of the eyes of 3 rabbits, followed by an observation period of 72 hours. Instillation of the test substance affected the conjunctivae of all 3 animals. The effects were reversible within 24 hours in 1 animal and within 72 hours in the other 2 animals. No corrosive effects and no clinical signs of toxicity were observed. Based on the results of the study, the substance does not need to be classified as irritating/corrosive to eyes in accordance with the CLP Regulation.