2,2-dimethylpropane-1,3-diyl cyclohex-4-ene-1,2-dicarboxylate

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2011

Report date:

2011

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

1,2,3,6-Tetrahydrophthalic anhydride, oligomeric reaction products with 2,2-dimethylpropane-1,3-diol

EC Number:

500-091-1

EC Name:

1,2,3,6-Tetrahydrophthalic anhydride, oligomeric reaction products with 2,2-dimethylpropane-1,3-diol

Cas Number:

36621-20-2

Molecular formula:

(C8H8O3.C5H12O2)x

IUPAC Name:

1,2,3,6-Tetrahydrophthalic anhydride, oligomeric reaction products with 2,2-dimethylpropane-1,3-diol

Constituent 2

Reference substance name:

1,3-Isobenzofurandione, 3a,4,7,7a-tetrahydro-, polymer with 2,2-dimethyl-1,3-propanediol

IUPAC Name:

1,3-Isobenzofurandione, 3a,4,7,7a-tetrahydro-, polymer with 2,2-dimethyl-1,3-propanediol

Details on test material:

As per IUCLID Sections 1.1. 1.2. and 4.1.

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

The animals were acquired from Myrtle’s Rabbitry; Thompsons Station, Wills Point, TX and weighted 2.525-3.400 kg upon reciept. Each animal was housed in a suspended, wire bottom, stainless steel cage. The animal room maintained a 12-hour light/dark cycle, 10-12 air changes/hour
a temperature range of 18-25°C and relative humidity of 24-92%. The animals were offered PMI Feeds, Inc.TM Lab Rabbit Diet #532 1, ~8 oz. daily and Municipal water supply analyzed by TCEQ Water Utilities Division available ad libitum from automatic water system.

Test system

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

0.1 mL

Duration of treatment / exposure:

24 hr

Observation period (in vivo):

17 days, one animal only.

Number of animals or in vitro replicates:

3

Details on study design:

On Day 0, a dose of 0.1 mL of the undiluted test substance was placed into the conjunctival sac of the right eye of each animal by gently pulling the lower lid away from the eyeball to form a cup into which the test substance was dropped. The lids were gently held together for one second to prevent loss of material. The untreated left eyes served as comparative controls.

The grades of ocular reaction were recorded at 1, 24, 48 and 72 hours, at 4 and 7 days (all animals), as well as 10, 14 and 17 days (initial animal only) after treatment. The corneas of all treated eyes were examined immediately after the 24-hour observation with a fluorescein sodium ophthalmic solution. Any of the corneas that exhibited fluorescein staining at the 24-hour observation were re-examined with the fluorescein sodium ophthalmic solution at each consecutive observation until fluorescein staining of the cornea no longer occurred. All treated eyes were washed with room temperature DI water for one minute immediately after recording the 24-hour observation.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

24/48/72 h

Score:

ca. 37

Reversibility:

fully reversible within: 17 days.

Results 2

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.3

Reversibility:

not reversible

Remarks on result:

probability of moderate irritation

Results 3

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.6

Reversibility:

fully reversible

Results 4

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Reversibility:

fully reversible

Results 5

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

10

Reversibility:

not reversible

Remarks on result:

probability of moderate irritation

Results 6

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

10

Results 7

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

10

Results 8

Irritation parameter:

iris score

Basis:

animal #4

Time point:

24/48/72 h

Score:

0

Max. score:

10

Results 9

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

3

Reversibility:

fully reversible

Results 10

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

2

Max. score:

3

Reversibility:

fully reversible

Results 11

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.66

Max. score:

3

Reversibility:

fully reversible

Results 12

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

3

Max. score:

4

Reversibility:

fully reversible

Results 13

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1.3

Max. score:

4

Reversibility:

fully reversible

Results 14

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible

Irritant / corrosive response data:

One animal had corneal opacity scores of 2-4 from days 7-14. This animal also exhibited Conjuntivae Chemosis and Discharge scores of 3 beginning at 24 hr and extending out to day 7. A second animal exhibited corneal opacity from 24 hr to day 4 with complete clearing by day 7. This animal also had Conjunctivae Redness scores of 2 ay 24-72 hr. The third animal exhibited some corneal opacity at 24-72 hr.

Applicant's summary and conclusion

Interpretation of results:

moderately irritating

Remarks:

Migrated information Criteria used for interpretation of results: expert judgment

Conclusions:

The test substance is a moderate eye irritant and requires Classification and Labeling in the EU.

Executive summary:

The test substance, 1,2,3,6-Tetrahydrophthalic anhydride, oligomeric reaction products with 2,2-dimethylpropane-1,3-diol, was evaluated for eye irritation potential in rabbits in an O.E.C.D. test guideline 405 study. Based upon the study results the test substance is judged to be a moderate eye irritant and requires Classification and Labeling in the EU.