[No public or meaningful name is available]

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

09-09-2013 to 19-09-2013

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

Guideline study performed under GLP. All relevant validity criteria were met.

Justification for type of information:

Information as to the availability of the in vivo study is provided in 'attached justification'.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2014

Report date:

2014

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

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2400 (Acute Eye Irritation)

Deviations:

no

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nousan, Notification No 8147, November 2000

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

inspected: March 2013 ; signature: May 2013

Test material

Test material information

Constituent 1

Reference substance name:

Reaction mass of (4RS,4aRS,8RS,8aRS)-4-ethyl-8-methyloctahydronaphthalen-1(2H)-one and (4RS,4aSR,8SR,8aRS)-4-ethyl-8-methyloctahydronaphthalen-1(2H)-one and (4RS,4aSR,8SR,8aSR)-4-ethyl-8-methyloctahydronaphthalen-1(2H)-one

Molecular formula:

C13H22O

IUPAC Name:

Reaction mass of (4RS,4aRS,8RS,8aRS)-4-ethyl-8-methyloctahydronaphthalen-1(2H)-one and (4RS,4aSR,8SR,8aRS)-4-ethyl-8-methyloctahydronaphthalen-1(2H)-one and (4RS,4aSR,8SR,8aSR)-4-ethyl-8-methyloctahydronaphthalen-1(2H)-one

Test material form:

liquid

Specific details on test material used for the study:

- Physical state: Liquid
- Storage condition of test material: In refrigerator (2-8°C) in the dark
- Other: clear colourless liquid

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Recognised Supplier
- Age at study initiation: 12 to 24 weeks
- Weight at study initiation: 2688 to 3164 g
- Housing: Individually housed in cages with perforated floors, with shelters and cage enrichment
- Diet (ad libitum): Global Diet 2030 (Recognised Supplier); provided ad libitum (approximately 100 g per day)
- Water (ad libitum): mains drinking water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.0 ± 3.0
- Humidity (%): 40 to 70 (Deviations from the minimum and maximum level of daily mean relative humidity occurred. Laboratory historical data do not indicate an effects resulting).
- Air changes (per hr): at least 15
- Photoperiod (hrs dark / hrs light): 12 h light / 12 h dark

IN-LIFE DATES: From: 09-09-2013 To: 19-09-2013

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: one eye remained untreated

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL.
- Concentration (if solution): undiluted

VEHICLE
- Amount(s) applied (volume or weight with unit): Not applicable.

Duration of treatment / exposure:

A volume of 0.1 mL of the test item, was placed into the conjunctival sac of the eye, formed by gently pulling the lower lid away from the eyeball. The upper and lower eyelids were held together for about one second immediately after treatment, to prevent loss of the test item, and then released. The other eye remained untreated and was used for control purposes. Irrigation of the eye with distilled water or saline, after 1 hour was deemed not necessary or was not reported during the study.

Observation period (in vivo):

Ocular assessment was conducted at approximately 1, 24, 48 and 72 hours after instillation of the test item, according to numerical evaluation.

Number of animals or in vitro replicates:

3 (male). Testing was conducted sequentially following testing with a sentinel.

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): none

SCORING SYSTEM:
The irritation was assessed according to Draize (1977) numerical scoring system. At each observation period, the highest scores given were recorded. Any other ocular effects were also noted.

TOOL USED TO ASSESS SCORE:
- Immediately after the 24-hour observation, a solution of 2% fluorescein in water (adjusted to pH 7.0) was instilled into both eyes of each animal to quantitatively determine corneal epithelial damage. This procedure was repeated to assess recovery.
- Examination of the eye was facilitated by the use of the light source from a standard ophthalmoscope.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

n = 3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 2

Irritation parameter:

iris score

Basis:

mean

Remarks:

n = 3

Time point:

24/48/72 h

Score:

0

Max. score:

2

Results 3

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

n = 3

Time point:

24/48/72 h

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 72 hours

Results 4

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

n = 3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 5

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 6

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

2

Results 7

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

3

Results 8

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 9

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 10

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

2

Results 11

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.7

Max. score:

3

Reversibility:

fully reversible within: 72 hours

Results 12

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 13

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 14

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

2

Results 15

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Results 16

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

No corneal effects were noted, all scores were zero.
No iridial effects were noted, all scores were zero.
Some conjunctival irritation (score = 2 or 1) was noted in all treated eyes 1 h and reduced (score =1) through 24h or 48 h after treatment. Chemosis was minimal (score = 1) at 1 hour to none (score = 0) at the 24 h through 72 h observation.
In all treated eyes and all effects had reversed (score = 0) at the 72 h observation.

Other effects:

All animals showed expected gain in bodyweight during the study.

Any other information on results incl. tables

Table 1.0: Individual and Mean Scores for Cornea, Iris and Conjunctivae

Number and Sex	Time After Treatment	Corneal Opacity		Iridial Inflammation	Conjunctival Redness	Conjunctival Chemosis
1# Male	24 Hours	0		0	0	0
	48 Hours	0	0		0	0
	72 Hours	0	0		0	0
Total		0		0	0	0
Mean		0.0		0.0	0.0 #	0.0 #
#2 Male	24 Hours	0		0	1	0
	48 Hours	0	0		1	0
	72 Hours	0	0		0	0
Total		0		0	2	0
Mean		0.0		0.0	0.7 #	0.0 #
#3 Male	24 Hours	0		0	1	0
	48 Hours	0	0		0	0
	72 Hours	0	0		0	0
Total		0		0	1	0
Mean		0.0	0.0		0.3 #	0.0 #

# All effects reversed by day 3

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of this study the test item is not considered irritating to the eye.

Executive summary:

The study was performed to OECD TG 405, EU Method B.5, US EPA OPPTS 870.2400 and Japan (JMAFF) 12 Nousan, Notification No 8147 guidelines under GLP to assess the irritancy potential of the test item to the eye following a single application in the New Zealand White rabbit. A volume of 0.1 ml of the test item was placed into the conjunctival sac of one eye of three rabbits. The other eye remained untreated and was used for control purposes. The test was conducted in a stepwise manner conducted singularly and then on a further two rabbits. Assessment of ocular damage/irritation was made approximately 1 hour and 24, 48 and 72 hours following treatment. A single application of the test item to the non-irrigated eye of three rabbits produced no corneal opacity, no iridial inflammation and conjunctival irritation (redness, score = 1) and no chemosis (score = 0) at 24 hours through 72 hours. All treated eyes appeared normal at the 72 hour observation (score = 0). Under the conditions of this study, the test item is not considered to be irritating to the eye.