5,7-di-tert-butyl-3-[4-(2-hydroxyethoxy)phenyl]-1-heteropolycycl-2(3H)-one

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

19 November 2012 to 25 December 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study conducted to GLP in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2013

Report date:

2013

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

- Physical state: off white powder

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Age at study initiation: 12 - 20 weeks old
- Weight at study initiation: 2.48 or 2.58 kg
- Housing: individually housed in suspended cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days
The animals were provided with environmental enrichment items which were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 - 23 °C
- Humidity (%): 30 - 70 %
- Air changes (per hr): at least 15
- Photoperiod (hrs dark / hrs light): controlled by a time switch to give twelve hours continuous light (06:00 to 18:00) and twelve hours darkness

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: the left eye of each animal remained untreated and was used for control purposes

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL, weighing approximately 59 mg (as measured by gently compacting the required volume into an adapted syringe)

Duration of treatment / exposure:

Single exposure

Observation period (in vivo):

21 days

Number of animals or in vitro replicates:

2

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): None
- Time after start of exposure: Not applicable

SCORING SYSTEM: Draize J H (1977) "Dermal and Eye Toxicity Tests" In: Principles and Procedures for Evaluating the Toxicity of Household Substances, National Academy of Sciences, Washington DC p.48 to 49

TOOL USED TO ASSESS SCORE: standard opthalmoscope

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Results 2

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.67

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Results 3

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

2

Reversibility:

fully reversible within: 7 days

Results 4

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

2

Reversibility:

fully reversible within: 7 days

Results 5

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

3

Reversibility:

fully reversible within: 14 days

Results 6

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

2

Max. score:

3

Reversibility:

fully reversible within: 21 days

Results 7

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 14 days

Results 8

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 21 days

Irritant / corrosive response data:

Scattered or diffuse corneal opacity was noted in both treated eyes at the 24 and 48-Hour observations and in one treated eye at the 72-Hour observation.
lridial inflammation was noted in both treated eyes one hour after treatment and at the 24, 48 and 72-Hour observations.
Moderate conjunctival irritation was noted in both treated eyes one hour after treatment. Severe conjunctival irritation was noted in one treated eye with moderate conjunctival irritation noted in the other treated eye at the 24-Hour observation. Moderate conjunctival irritation was noted in both treated eyes at the 48 and 72-Hour observations. Moderate conjunctival irritation persisted in one treated eye with minimal conjunctival irritation noted in the other treated eye at the 7-Day observation. Minimal conjunctival irritation was noted in one treated eye at the 14-Day observation.
One treated eye appeared normal at the 14-Day observation and the other treated eye appeared normal at the 21-Day observation.

Other effects:

Both animals showed expected gain in bodyweight during the study.

Any other information on results incl. tables

Table 1: Individual Scores and Individual Total Scores for Ocular Irritation

Rabbit Number and Sex	72696 Male						72767 Male
	IPR = 2						IPR = 2
Time After Treatment	1 hr	24 hr	48 hr	72 hr	7 days	14 days	1 hr	24 hr	48 hr	72 hr	7 days	14 days	21 days
CORNEA E = Degree of Opacity   F = Area of Opacity	0   0	1   2	1   2	1   1	0   0	0   0	0   0	1   1	1   1	0   0	0   0	0   0	0   0
Score (E x F) x 5	0	10	10	5	0	0	0	5	5	0	0	0	0
IRIS D	1	1	1	1	0	0	1	1	1	1	0	0	0
Score (D x 5)	5	5	5	5	0	0	5	5	5	5	0	0	0
CONJUNCTIVAE A = Redness B = Chemosis C = Discharge	2 3 2	2 3 3	2 2 1	2 1 1	1 1 1	0 0 0	2 2 3	2 2 3	2 2 1	2 2 1	1 2 1	1 1 0	0 0 0
Score (A + B + C) x 2	14	16	10	8	6	0	14	14	10	10	8	4	0
Total Score	19	31	25	18	6	0	19	24	20	15	8	4	0

 

Key: hr = hour(s)             IPR = initial pain reaction              

Applicant's summary and conclusion

Interpretation of results:

Category II

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of the test, the test material was determined to be irritating to the eye based on iritis, conjunctival redness and chemosis.

Executive summary:

An in vivo study was performed under GLP conditions to assess the irritancy potential of the test item to the eye of the New Zealand White rabbit. The method was designed to be compatible with OECD Guideline 405 and EU Test Method B.5.

A single application of the test item to the non-irrigated eye of two rabbits produced scattered or diffuse corneal opacity, iridial inflammation and moderate to severe conjunctival irritation. One treated eye appeared normal at the 14-Day observation and the other treated eye appeared normal at the 21-Day observation.

Under the conditions of the test, the test material was determined to be irritating to the eye based on iritis, conjunctival redness and chemosis.

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