Registration Dossier

Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 18 to 26 December 1991
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study.
Cross-referenceopen allclose all
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1992
Report Date:
1992

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Principles of method if other than guideline:
Not applicable.
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): 1-(2-tert-butyl cyclohexyloxy)-2-butanol cited as P#620

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Froxfield Ltd., Petersfield, Hampshire, UK
- Age at study initiation: 12 weeks
- Weight at study initiation: 2.8 to 3.0 kg
- Housing: housed individually in metal cages with perforated floors
- Diet (e.g. ad libitum): standard diet SDS Stanrab (P), ad libitum
- Water (e.g. ad libitum): drinking water, ad libitum
- Acclimation period: yes

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19°C
- Humidity (%): 30-70%
- Air changes (per hr): 19 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hrs dark, 12 hrs light

IN-LIFE DATES: From: To: no data

Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: the contralateral eye remained untreated
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL
- Concentration (if solution): not applicable

VEHICLE
Not applicable
Duration of treatment / exposure:
The eye was not rinsed after the instillation of the test item.
Observation period (in vivo):
Examination of the eyes was made after 1 hour and then 24, 48 and 72 hrs, 4 and 7 days after instillation.
Number of animals or in vitro replicates:
3
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): not applicable
- Time after start of exposure: not applicable

SCORING SYSTEM: Draize scale according to the OECD guideline No. 405

TOOL USED TO ASSESS SCORE: handheld lamp

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
animal #1
Remarks:
mean individual score
Time point:
other: overall at 24, 48 and 72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: day 4
Irritation parameter:
cornea opacity score
Basis:
animal #2
Remarks:
mean individual score
Time point:
other: overall at 24, 48 and 72 h
Score:
1.66
Max. score:
4
Reversibility:
fully reversible within: day 7
Irritation parameter:
cornea opacity score
Basis:
animal #3
Remarks:
mean individual score
Time point:
other: overall at 24, 48 and 72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: day 7
Irritation parameter:
iris score
Basis:
animal #1
Remarks:
mean individual score
Time point:
other: overall at 24, 48 and 72 h
Score:
0
Max. score:
2
Irritation parameter:
iris score
Basis:
animal #2
Remarks:
mean individual score
Time point:
other: overall at 24, 48 and 72 h
Score:
0
Max. score:
2
Irritation parameter:
iris score
Basis:
animal #3
Remarks:
mean individual score
Time point:
other: overall at 24, 48 and 72 h
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
animal #1
Remarks:
mean individual score
Time point:
other: overall at 24, 48 and 72 h
Score:
1.33
Max. score:
3
Reversibility:
fully reversible within: day 4
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
animal #2
Remarks:
mean individual score
Time point:
other: overall at 24, 48 and 72 h
Score:
1
Max. score:
3
Reversibility:
fully reversible within: day 4
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
animal #3
Remarks:
mean individual score
Time point:
other: overall at 24, 48 and 72 h
Score:
1
Max. score:
3
Reversibility:
fully reversible within: day 4
Irritation parameter:
chemosis score
Basis:
animal #1
Remarks:
mean individual score
Time point:
other: overall at 24, 48 and 72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: day 2
Irritation parameter:
chemosis score
Basis:
animal #2
Remarks:
mean individual score
Time point:
other: overall at 24, 48 and 72 h
Score:
0.66
Max. score:
4
Reversibility:
fully reversible within: day 4
Irritation parameter:
chemosis score
Basis:
animal #3
Remarks:
mean individual score
Time point:
other: overall at 24, 48 and 72 h
Score:
0
Max. score:
4
Irritant / corrosive response data:
Dulling of the cornea was observed in all three animals one hour after instillation. By the following day corneal opacities had developed which were present 4 days after instillation in 2 animals but has resolved 7 days after instillation.
No iridial inflammation was observed.
Injection of the bood vessels to diffuse crimson colour of the conjunctivae with or without slight swelling was seen in all three animals. Conjunctival irritation had resolved four days after instillation.
Other effects:
There were no signs of toxicity or ill health in any rabbit during the observation period.

Any other information on results incl. tables

Table 7.3.2/1:Irritant/corrosive response data for each animal at each observation time up to removal of each animal from the test

Score at time point / Reversibility

Cornea

Iris

Conjunctivae

Chemosis

Max. score: 4

Max. score: 2

Max. score: 3

Max. score: 4

60 min

D/D/D

0/0/0

2/2/2

1/1/1

24 h

1/1/1

0/0/0

2/1/1

1/0/0

48 h

1/2/1

0/0/0

1/1/1

0/1/0

72 h

1/2/1

0/0/0

1/1/1

0/1/0

Average 24h, 48h, 72h

1/1.7/1

0.0/0.0/0.0

1.3/1/1

0.3/0.7/0

Reversibility*)

c

-

c

c

Average time (day) for reversion**)

7

-

4

4

 *) Reversibility: c. = completely reversible; n.c. = not completely reversible; n. = not reversible

**): correspond to the last day for which eye irritation signs in the last animal were observed

D: Dulling of the cornea

Applicant's summary and conclusion

Interpretation of results:
irritating
Remarks:
Migrated information Category 2 Criteria used for interpretation of results: EU
Conclusions:
Under the test conditions, the test item 1-(2-tert-butyl cyclohexyloxy)-2-butanol (P#620) induced a reversible eye irritation, with a mean score for cornea opacity ≥1 for at least 2/3 animals. The test item is therefore classified as irritating to eyes in Category 2 (H319, Causes serious eye irritation) according to the criteria of the Annex VI of the Regulation (EC) No 1272/2008 (CLP) but is not classified for eye irritation according to the criteria of the Annex VI of the Directive 67/548/EEC.
Executive summary:

In an eye irritation study performed according to the OECD No. 405, and in compliance with the GLP, 0.1 mL of undiluted 1-(2-tert-butyl cyclohexyloxy)-2-butanol (P#620) (purity of 89.01%) was instilled into the lower evertid lid of one eye of 3 male New Zealand White Rabbit. After the instillation the substance was not remained. Animals were then observed for 7 days for eye edema (chemosis) and erythema (conjunctivae) of the conjunctive, corneal opacity and iris lesion. 

Eye irritation was assessed and scored according to the Draize scale at 1, 24, 48 and 72 hrs after the instillation of the substance. The mean individual scores were calculated within 3 scoring times (24, 48 and 72 hrs).

The mean individual scores were 0.3/0.7/0.0 for chemosis, 1.3/1/1 for conjunctival erythema, 1/1.7/1 for corneal opacity and 0.0/0.0/0.0 for iris lesion. These observed effects were all reversible within 7 days.

Under the test conditions, the test item 1-(2-tert-butyl cyclohexyloxy)-2-butanol (P#620) induced a reversible eye irritation, with a mean individual score for cornea opacity ≥1 for at least 2/3 animals. The test item is therefore classified as irritating to eyes in Category 2 (H319, Causes serious eye irritation) according to the criteria of the Annex VI of the Regulation (EC) No 1272/2008 (CLP) but is not classified for eye irritation according to the criteria of the Annex VI of the Directive 67/548/EEC.

This study is considered as acceptable and satisfies the requirement for eye irritation endpoint.