Reaction mass of 1,1'-(2,2,4-trimethylhexane-1,6-diyl)bis-1H-pyrrole-2,5-dione and 1H-Pyrrole-2,5-dione, 1,1'-(2,4,4-trimethyl-1,6-hexanediyl)bis-

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1989-11-2 to 1989-11-27

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1989

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:

adopted 24 Feb 1987

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

Version: March 1984

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Reaction mass of 1,1'-(2,2,4-trimethylhexane-1,6-diyl)bis-1H-pyrrole-2,5-dione and 1,1'-(2,4,4-trimethylhexane-1,6-diyl)bis-1H-pyrrole-2,5-dione

EC Number:

915-671-3

Molecular formula:

C17H22N2O4

IUPAC Name:

Reaction mass of 1,1'-(2,2,4-trimethylhexane-1,6-diyl)bis-1H-pyrrole-2,5-dione and 1,1'-(2,4,4-trimethylhexane-1,6-diyl)bis-1H-pyrrole-2,5-dione

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Biological Research Laboratories Ltd., Fuellinsdorf, Switzerland
- Age at start of treatment: 14 weeks (males) and 15 weeks (females)
- Weight at study initiation: 2.6 - 2.7 kg (males) and 2.0 kg (females)
- Housing: individually in stainless steel cages
- Diet: pelleted standard Kliba 341 rabbit maintainance diet (Kliba, Klingentalmuehle AG, Kaiseraugst, Switzerland) ad libitum
- Water: community tap water, ad libitum
- Acclimation period: 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20°C ± 3
- Humidity (%): 40-70
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 02 Nov 1989 To: 27 Nov 1989

Test system

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

0.1 g / animal

Duration of treatment / exposure:

Single exposure, no washing

Observation period (in vivo):

21 days
Reading time points: 1, 24, 48 and 72 h, 7, 14 and 21 days

Number of animals or in vitro replicates:

3

Details on study design:

SCORING SYSTEM: Draize scoring system

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2.67

Max. score:

4

Reversibility:

not fully reversible within: 21 days

Results 2

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

2.67

Max. score:

4

Reversibility:

not fully reversible within: 21 days

Results 3

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

2.67

Max. score:

4

Reversibility:

not fully reversible within: 21 days

Results 4

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

2

Reversibility:

fully reversible within: 21 days

Results 5

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.67

Max. score:

2

Reversibility:

fully reversible within: 21 days

Results 6

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

2

Reversibility:

fully reversible within: 21 days

Results 7

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

3

Reversibility:

not fully reversible within: 21 days

Results 8

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

2.67

Max. score:

3

Reversibility:

not fully reversible within: 21 days

Results 9

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

2

Max. score:

3

Reversibility:

not fully reversible within: 21 days

Results 10

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

3

Max. score:

4

Reversibility:

not fully reversible within: 21 days

Results 11

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

3.33

Max. score:

4

Reversibility:

not fully reversible within: 21 days

Results 12

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

3

Max. score:

4

Reversibility:

fully reversible within: 21 days

Irritant / corrosive response data:

Corneal opacity of grade 1 was noted in 2/3 rabbits 1 h following administration, which increased to grade 2 in all rabbits within 24 h and to grade 3 at the 48 and 72 h reading time point. Corneal opacity of grade 4 was observed in all animals up to 7 days after test item instillation. In 2/3 animals the effects remained unchanged at grade 4 until study termination, whereas in 1/3 rabbits a corneal opacity score of grade 2 was observed at the 14 and 21 day reading time point.
Iris reactions of grade 1 were observed in 2/3 rabbits from 24 h after test item instillation onwards and in 1/3 rabbits 48 h after test item instillation. 7 days after test item instillation, all 3 rabbits showed iris reactions of grade 2. At the 14 day reading time point the iris reaction score was of grade 1 in all 3 rabbits and fully reversible until study termination on Day 21.
Conjunctiva redness of score 2 was noted in 2/3 rabbits from 1 h after test item instillation until study Day 14 and decreased to score 1 until study termination on Day 21. In the third rabbit, conjunctival redness was of score 2 at the 1 and 24 h reading time point, increased to grade 3 on reading time points 48 h, 72 h and 7 days and decreased to a score of grade 2 on study Day 14 and to a score of grade 1 at study termination on Day 21.
Conjunctival chemosis was observed at grade 3 to 4 in all rabbits until 72 h post-test item instillation. At 7 days after instillation, all rabbits had a chemosis score of grade 2, which remained of grade 2 until study Day 14 in 2/3 rabbits and declined to grade 1 in the third rabbit. At study termination, 2/3 rabbits had a chemosis score of grade 1, whereas the finding of conjunctival chemosis was fully reversible until study Day 21 in the third rabbit.
Partly corrosion of the conjunctivae was observed in all animals from 24 h to 7 days after treatment.

Other effects:

No staining of the cornea and conjunctivae of the treated eyes by pigment or coloring of the test article was observed.
The body weight development of the animals was not affected by treatment.

Any other information on results incl. tables

Table 1: Eye irritation scores for individual animals

Animal Number		1 h	24 h	48 h	72 h	7 days	14 days	21 days	Individual mean 24-48-72 h
Cornea Opacity	75 male	1	2	3	3	4	4	4	2.67
	76 male	0	2	3	3	4	2	2	2.67
	77 female	1	2	3	3	4	4	4	2.67
Iris	75 male	0	1	1	1	2	1	0	1.00
	76 male	0	0	1	1	2	1	0	0.67
	77 female	0	1	1	1	2	1	0	1.00
Conjunctiva Redness	75 male	2	2	2	2	2	2	1	2.00
	76 male	2	2	3	3	3	2	1	2.67
	77 female	2	2	2	2	2	2	1	2.00
Conjunctiva Chemosis	75 male	3	3	3	3	2	2	1	3.00
	76 male	4	4	3	3	2	2	1	3.33
	77 female	3	3	3	3	2	1	0	3.00

Applicant's summary and conclusion

Interpretation of results:

Category 1 (irreversible effects on the eye) based on GHS criteria

Conclusions:

The test item caused irreversible damage to the eyes of all animals, evident as corneal opacity, iritis, conjunctival redness and conjunctival chemosis which were not fully reversible within 21 days of observation.
CLP: Eye Damage 1, H318 according to Regulation (EC) No. 1272/2008