Registration Dossier

Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
November 29, 2010 - February 17, 2011
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: This study has been performed according to OECD and/or EC guidelines and according to GLP principles.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2011
Report date:
2011

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
temporary deviations from the minimum level of relative humidity occurred (down to 33%)
Qualifier:
according to guideline
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
temporary deviations from the minimum level of relative humidity occurred (down to 33%)
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.2400 (Acute Eye Irritation)
Deviations:
yes
Remarks:
temporary deviations from the minimum level of relative humidity occurred (down to 33%)
Qualifier:
according to guideline
Guideline:
other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nousan, Notification No 8147, November 2000, including the most recent partial revisions.
Deviations:
yes
Remarks:
temporary deviations from the minimum level of relative humidity occurred (down to 33%)
GLP compliance:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
1-(2-ethylbutyl)cyclohexane-1-carboxylic acid
EC Number:
619-508-4
Cas Number:
381209-09-2
Molecular formula:
C13 H24 O2
IUPAC Name:
1-(2-ethylbutyl)cyclohexane-1-carboxylic acid
Details on test material:
- Name of test material (as cited in study report): CAT-Acid
- Stability under test conditions: stable
- Storage condition of test material: at room temperature in the dark
- Density: 0.98 g/mL
- pH (1% in water, indicative range): 5.4-5.2

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: animal no. 7 and 9: Harlan, Belton, Leics, England; animal no.8: Charles River France, L’Arbresle Cedex, France
- Age at study initiation: at least 6 weeks
- Weight at study initiation: at least 1.0 kg
- Housing: individually housed in labeled cages with perforated floors (Ebeco, Germany, dimensions 67 x 62 x 55 cm) and shelters (Ebeco, Germany, dimensions 40 x 32 x 23 cm)
- Diet (e.g. ad libitum): ad libitum; pelleted diet for rabbits (Global Diet 2030 from Harlan Teklad®, Mucedola, Milanese, Italy)
- Water (e.g. ad libitum): ad libitum; tap water
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18.6 – 20.0ºC
- Humidity (%): 33 - 50%; Temporary deviations from the minimum level of relative humidity occurred. As laboratory historical data do not indicate an effect of the deviations, the study integrity was not adversely affected.
- Air changes (per hr): approx. 15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours artificial fluorescent light and 12 hours darkness per day

Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: the untreated eye served as the reference control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL
Duration of treatment / exposure:
Not applicable (no washout)
Observation period (in vivo):
72 hours
Number of animals or in vitro replicates:
3 females
Details on study design:
REMOVAL OF TEST SUBSTANCE: Not applicable
SCORING SYSTEM: according to OECD 405
TOOL USED TO ASSESS SCORE:
- Where standard lighting was considered inadequate for observing minor effects, eye examinations were performed using an ophthalmic examination lamp.
- Immediately after the 24-hour observation, a solution of 2% fluorescein (Merck, Darmstadt, Germany) in water (adjusted to pH 7.0) was instilled into both eyes of each animal to quantitatively determine corneal epithelial damage. Any bright green stained area, indicating epithelial damage, was estimated as a percentage of the total corneal area.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
other: mean for animals #1, #2 and #3
Time point:
other: Mean value of score at 24, 48 and 72 h after installation
Score:
0
Max. score:
4
Remarks on result:
other: Individual mean scores: 0-0-0
Irritation parameter:
iris score
Basis:
other: mean for animals #1, #2 and #3
Time point:
other: Mean value of score at 24, 48 and 72 h after installation
Score:
0
Max. score:
2
Remarks on result:
other: Individual mean scores: 0-0-0
Irritation parameter:
conjunctivae score
Basis:
other: mean for animals #1, #2 and #3
Time point:
other: Mean value of score at 24, 48 and 72 h after installation
Score:
0.2
Max. score:
3
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: Individual mean scores: 0.3-0-0.3
Irritation parameter:
chemosis score
Basis:
other: mean for animals #1, #2 and #3
Time point:
other: Mean value of score at 24, 48 and 72 h after installation
Score:
0
Max. score:
4
Remarks on result:
other: Individual mean scores: 0-0-0
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritant / corrosive response data:
See the section "Any other information on results incl. tables"
Other effects:
- No staining of (peri) ocular tissues by the test substance was observed and no test substance remnants were seen.
- No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred.

Any other information on results incl. tables

 

Animal no.

 

Time after dosing

Cornea

 

Iris

Conjunctivae

Opacity

Area

Fluor area (%) (*)

Redness

Chemosis

Discharge

7

(sentinel)

1 hr

0

0

-

0

3

0

0

24 hrs

0

0

0

0

1

0

0

48 hrs

0

0

-

0

0

0

0

72 hrs

0

0

-

0

0

0

0

8

1 hr

0

0

-

0

2

0

0

24 hrs

0

0

0

0

0

0

0

48 hrs

0

0

-

0

0

0

0

72 hrs

0

0

-

0

0

0

0

9

1 hr

0

0

-

0

3

0

0

24 hrs

0

0

0

0

1

0

0

48 hrs

0

0

-

0

0

0

0

72 hrs

0

0

-

0

0

0

0

 (*)Green staining after fluorescein treatment (percentage of total corneal area)

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
In accordance with OECD 405 and GLP, an acute eye irritation study was conducted in 3 female rabbits. Instillation of 0.1 mL of the substance into one eye of each of three rabbits resulted in redness of the conjunctivae. The irritation had completely resolved within 24 hours in one animal and within 48 hours in the other two animals. No iridial irritation or corneal opacity was observed, and treatment of the eyes with 2% fluorescein 24 hours after test substance instillation revealed no corneal epithelial damage. Based on the results of this study, the substance does not need to be classified for eye irritation in accordance with the CLP Regulation.