1,3-bis(1-isocyanato-1-methylethyl)benzene

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1981

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1981

Report date:

1981

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

1,3-bis(1-isocyanato-1-methylethyl)benzene

EC Number:

220-474-4

EC Name:

1,3-bis(1-isocyanato-1-methylethyl)benzene

Cas Number:

2778-42-9

Molecular formula:

C14H16N2O2

IUPAC Name:

1,3-bis(1-isocyanato-1-methylethyl)benzene

Details on test material:

- Name of test material (as cited in study report): 85,772
- Lot/batch No.: S-13708-76

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: New Zealand White, H.A.R.E. Rabbits For Research, Hewitt, N.J.
- Housing: Individually in wire mesh suspension cages
- Diet (e.g. ad libitum): Certified Rabbit Chow 5322, Ralston Purina Co., ad libitum
- Water (e.g. ad libitum): Potable water, ad libitum

ENVIRONMENTAL CONDITIONS
- Photoperiod (hrs dark / hrs light): 12 h dark/ 12 h fluorescent light

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: Left eye served as untreated control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL

Duration of treatment / exposure:

Single treatment

Observation period (in vivo):

14 d; eye irritation scored on Days 1, 2, 3, 4, 7, 10 and 13

Number of animals or in vitro replicates:

Nine

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Eyes in three rabbits rinsed with sterile water for 60 sec
- Time after start of exposure: 30 sec


SCORING SYSTEM: Draize method

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

24/48/72 h

Score:

15.1

Max. score:

110

Reversibility:

not fully reversible within: 13 d

Remarks on result:

other: with washout

Results 2

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

24/48/72 h

Score:

13.6

Max. score:

110

Reversibility:

not fully reversible within: 13 d

Remarks on result:

other: without washout

Results 3

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

Mean of 6 animals

Time point:

24/48/72 h

Score:

0

Reversibility:

not specified

Remarks on result:

other:

Remarks:

Without washout

Results 4

Irritation parameter:

iris score

Basis:

mean

Remarks:

mean of 6 animals

Time point:

24/48/72 h

Score:

0

Reversibility:

not specified

Remarks on result:

other:

Remarks:

Without washout

Results 5

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

mean of 6 animals

Time point:

24/48/72 h

Score:

0

Reversibility:

not specified

Remarks on result:

other:

Remarks:

With washout

Results 6

Irritation parameter:

iris score

Basis:

mean

Remarks:

Mean of 6 animals

Time point:

24/48/72 h

Score:

0

Reversibility:

not specified

Remarks on result:

other:

Remarks:

With washout

Results 7

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2.6

Reversibility:

not fully reversible within: 13 d

Remarks on result:

other:

Remarks:

Without washout

Results 8

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

2.3

Reversibility:

not fully reversible within: 13 d

Remarks on result:

other:

Remarks:

Without washout

Results 9

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1.67

Reversibility:

not fully reversible within: 13 d

Remarks on result:

other:

Remarks:

Without washout

Results 10

Irritation parameter:

conjunctivae score

Basis:

animal #4

Time point:

24/48/72 h

Score:

2.6

Reversibility:

not fully reversible within: 13 d

Remarks on result:

other:

Remarks:

Without washout

Results 11

Irritation parameter:

conjunctivae score

Basis:

animal #5

Time point:

24/48/72 h

Score:

2

Reversibility:

not fully reversible within: 13 d

Remarks on result:

other:

Remarks:

Without washout

Results 12

Irritation parameter:

conjunctivae score

Basis:

animal #6

Time point:

24/48/72 h

Score:

2.67

Reversibility:

not fully reversible within: 13 d

Remarks on result:

other:

Remarks:

Without washout

Results 13

Irritation parameter:

conjunctivae score

Basis:

animal: 7

Time point:

24/48/72 h

Score:

1.67

Reversibility:

not fully reversible within: 13 d

Remarks on result:

other:

Remarks:

With washout

Results 14

Irritation parameter:

conjunctivae score

Basis:

animal: 8

Time point:

24/48/72 h

Score:

2

Reversibility:

not fully reversible within: 13 d

Remarks on result:

other:

Remarks:

With washout

Results 15

Irritation parameter:

conjunctivae score

Basis:

animal: 9

Time point:

24/48/72 h

Score:

2

Reversibility:

not fully reversible within: 13 d

Remarks on result:

other:

Remarks:

With washout

Results 16

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

3.3

Reversibility:

not fully reversible within: 13 d

Remarks on result:

other:

Remarks:

Without washout

Results 17

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

3.3

Reversibility:

not fully reversible within: 13 d

Remarks on result:

other:

Remarks:

Without washout

Results 18

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

3.3

Reversibility:

not fully reversible within: 13 d

Remarks on result:

other:

Remarks:

Without washout

Results 19

Irritation parameter:

chemosis score

Basis:

animal #4

Time point:

24/48/72 h

Score:

3

Reversibility:

not fully reversible within: 13 d

Remarks on result:

other:

Remarks:

Without washout

Results 20

Irritation parameter:

chemosis score

Basis:

animal #5

Time point:

24/48/72 h

Score:

3

Reversibility:

not fully reversible within: 13 d

Remarks on result:

other:

Remarks:

Without washout

Results 21

Irritation parameter:

chemosis score

Basis:

animal #6

Time point:

24/48/72 h

Score:

3.67

Reversibility:

not fully reversible within: 13 d

Remarks on result:

other:

Remarks:

Without washout

Results 22

Irritation parameter:

chemosis score

Basis:

animal: 7

Time point:

24/48/72 h

Score:

2.67

Reversibility:

not fully reversible within: 13 d

Remarks on result:

other:

Remarks:

With washout

Results 23

Irritation parameter:

chemosis score

Basis:

animal: 8

Time point:

24/48/72 h

Score:

2

Reversibility:

not fully reversible within: 13 d

Remarks on result:

other:

Remarks:

With washout

Results 24

Irritation parameter:

chemosis score

Basis:

animal: 9

Time point:

24/48/72 h

Score:

3.67

Reversibility:

not fully reversible within: 13 d

Remarks on result:

other:

Remarks:

With washout

Irritant / corrosive response data:

Irritation to the conjunctivae appeared to dissipate but still persisted at the termination of the study.
For details, see 'table 1' and 'table 2'

Other effects:

- No corneal damage at any time
- All treated eyes responded to light and no iridal score was observed in any rabbit
- Discharge, chemosis and redness of the conjunctivae were observed in all animals
- Rinsing appeared to lessen the irritation

Any other information on results incl. tables

Table 1. Ocular irritation (Draize) scores (mean)

Group	No	Washed	1	2	3	4	7	10	13
1	6	No	18.0	15.3	12.0	13.0	13.3	13.0	11.7
2	3	Yes	15.3	13.3	12.0	13.3	12.7	12.0	10.7

Table 2: Mean ocular irritation scores observed at 24, 48 and 72 h

Animal No.	Corneal opacity	Iritis	Conjunctivae	Chemosis
1	0	0	2.6	3.3
2	0	0	2.3	3.3
3	0	0	1.67	3.3
4	0	0	2.6	3
5	0	0	2	3
6	0	0	2.67	3.67
7*	0	0	1.67	2.67
8*	0	0	2	2
9*	0	0	2	3.67

* Eyes in three rabbits rinsed with sterile water for 60 sec

Applicant's summary and conclusion

Interpretation of results:

Category 2A (irritating to eyes)

Conclusions:

Under the test conditions, the test material was considered to be irritating to eyes in rabbit.

Executive summary:

A study was conducted to evaluate the ocular toxicity of the test substance in rabbits. The study was performed similar to the OECD Guideline 405. 0.1 mL of the test substance was instilled into the right eye of nine rabbits; the left eye served as an untreated control. One group of six rabbits received no further treatment. In the second group of three rabbits, eyes were rinsed 30 sec post-instillation for 60 sec. Irritation was scored by Draize scoring system at 1, 2, 3, 4, 7, 10 and 13 d post-instillation. Mean irritation scores at 24, 48 and 72 h for animals in group 1 (eyes without washing) were 0/0/2.6/3.3; 0/0/2.3/3.3; 0/0/1.67/3.3; 0/0/2.6/3.0; 0/0/2/3.0 and 0/0/2.67/3.67. Mean irritation scores at 24, 48 and 72 h for animals in group 2 (eyes with washing) were 0/0/1.67/2.67; 0/0/2/2 and 0/0/2/3.67. Irritation to the conjunctivae appeared to dissipate but still persisted at the termination of the study. Mean overall irritation score for 24, 48 and 72 h was 15.1/110 and 13.6/110 in the washed and unwashed eyes, respectively (Chow, 1981).