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Toxicological information

Eye irritation

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Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
26 June - 04 July 2000
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
/ GLP guideline study with minor deviations (no information about animal age, body weight determined only once)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2000
Report date:
2000

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
02 Oct 2012
Deviations:
yes
Remarks:
/ GLP guideline study with minor deviations (no information about animal age, body weight determined only once)
Qualifier:
according to guideline
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Version / remarks:
30 May 2008
Deviations:
yes
Remarks:
/ GLP guideline study with minor deviations (no information about animal age, body weight determined only once)
GLP compliance:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
(R)-6-(isopropyl)-3-methylcyclohex-2-en-1-one
EC Number:
224-957-0
EC Name:
(R)-6-(isopropyl)-3-methylcyclohex-2-en-1-one
Cas Number:
4573-50-6
Molecular formula:
C10H16O
IUPAC Name:
(6R)-3-methyl-6-(propan-2-yl)cyclohex-2-en-1-one

Test animals / tissue source

Species:
rabbit
Strain:
other: SPF albino rabbits, Chbb:HM(SPF) - Littlerussian
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: BI Pharma KG, Biberach, Germany
- Weight at study initiation: 1.5 - 1.7 kg (females)
- Housing: individual in PPO cages with perforated floor
- Diet : pelleted diet Altromin 2123 (Altromin, Lage, Lippe Germany), ad libitum
- Water: water (acidified with hydrochloric acid, pH 2,5), ad libitum (analysis was performed)
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3
- Humidity (%): 55 ± 15
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/ 12

IN-LIFE DATES: From: 26 June To: 04 July 2000

Test system

Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL of the test article were applied into one eye of the rabbits.
Duration of treatment / exposure:
single application without washing
Observation period (in vivo):
7 days
Reading time points: 1, 24, 48, 72 h and 7 days after the treatment
Number of animals or in vitro replicates:
4 females
Details on study design:
SCORING SYSTEM: Draize scoring system

TOOL USED TO ASSESS SCORE: fluorescein

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Remarks:
before fluorescein application
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
cornea opacity score
Remarks:
before fluorescein application
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.7
Max. score:
4
Reversibility:
fully reversible within: 3 days
Irritation parameter:
cornea opacity score
Remarks:
before fluorescein application
Basis:
animal #3
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
cornea opacity score
Basis:
animal #4
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.7
Max. score:
2
Reversibility:
fully reversible within: 3 days
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.7
Max. score:
2
Reversibility:
fully reversible within: 3 days
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 7 days
Irritation parameter:
iris score
Basis:
animal #4
Time point:
24/48/72 h
Score:
0.7
Max. score:
2
Reversibility:
fully reversible within: 3 days
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1.7
Max. score:
3
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1.3
Max. score:
3
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
2
Max. score:
3
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Basis:
animal #4
Time point:
24/48/72 h
Score:
1.3
Max. score:
3
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1.3
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1.3
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
animal #4
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritant / corrosive response data:
Based on the readings before fluorescein application, all 4 animals showed a cornea opacity (scored with 1) after 1h , which was reversible within 72 h in 1/4 animals. All animals showed an Iris score of 1 after 1 h, which was reversible within 72h in 2/4 animals. Conjunctivae was observed in all animals after 1 h (scored with 3 in 1 animal and with 2 in the other 3 animals). After 24 h all animals showed a conjunctivae scored with 2. After 48 h or 72 h the scoring decreased to 1 (in 2 or 1 animal, respectively). The fourth animal showed a consistent scoring of 2 within the 72 h. Chemosis was observed in all animals after 1 h (scored with 2). 2/2 animals showed a decrease in scoring to 1 after 24 h, the other 2 animals after 48 h.
7 days after application of the test article all four animals were free of any signs of eye irritation.

Any other information on results incl. tables

Table 1: Individual scores of eye irritation

Rabbit #

Time [h]

conjunctivae

iris

cornea

cornea (after Fluorescein)

redness

chemosis (swelling)

1

1

3

2

1

1

-

24

2

2

1

1

1

48

2

1

1

1

1

72

1

1

0

1

1

mean

1.7

1.3

0.7

1.0

1.0

2

1

2

2

1

1

-

24

2

1

1

1

1

48

1

1

1

1

1

72

1

1

0

0

1

mean

1.3

1.0

0.7

0.7

1.0

3

1

2

2

1

1

-

24

2

2

1

1

1

48

2

1

1

1

1

72

2

1

1

1

0

mean

2.0

1.3

1.0

1.0

0.7

4

1

2

2

1

1

-

24

2

1

1

1

1

48

1

1

1

1

1

72

1

1

0

1

1

mean

1.3

1.0

0.7

1.0

1.0

Iris: 0 - 2 numerical scores, Redness: 0 - 3 numerical scores, Chemosis and Cornea opacity score : 0 - 4 numerical scores

 

Only the scores from the readings after 24, 48 and 72 hours are included in the calculation of the individual mean scores.

Applicant's summary and conclusion

Interpretation of results:
Category 2 (irritating to eyes) based on GHS criteria
Conclusions:
CLP: Eye irrit 2, H319
Executive summary:

The eye irritation potential of the test substance was determined by an in vivo eye irritation test according to OECD Guideline 405 and in compliance with GLP (2016).Application of the test substance to the rabbit eye resulted in a mean corneal opacity score of 1 in 3/4 animals, which was reversible within maximum 7 days. Thus, the test substance is considered to be irritant to the eye.