Registration Dossier

Toxicological information

Eye irritation

Currently viewing:

Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 2013-03-18 to 2013-03-28
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study performed according to OECD test guideline No. 405 and in compliance with GLP.
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:
2013

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes (incl. certificate)
Remarks:
UK GLP Compliance Monitoring Programme (inspected on 2012-07-10)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: liquid
Details on test material:
- Name of test material (as cited in study report): Eucalyptus globulus oil
- Physical state: Extremely pale yellow liquid
- Storage condition of test material: At room temperature in the dark

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS: New Zealand White (Hsdlf:NZW) strain rabbit
- Source: Harlan Laboratories UK Ltd., Leicestershire, UK.
- Age at study initiation: twelve to twenty weeks old.
- Weight at study initiation: 2.38 to 2.95 kg.
- Housing: individually housed in suspended cages.
- Diet (e.g. ad libitum): free access to food (2930C Teklad Global Certified Rabbit diet supplied by Harlan Laboratories UK Ltd., Oxon, UK)
- Water (e.g. ad libitum): free access to drinking water.
The diet and drinking water were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study.
- Acclimation period: at least five days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-23
- Humidity (%): 30-70
Any occasional deviations from these targets were considered not to have affected the purpose or integrity of the study.
- Air changes (per hr): at least 15
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: the left eye of each rabbit served as control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL
Duration of treatment / exposure:
The eyes were not rinsed after administration of the test item.
Observation period (in vivo):
approximately 1 hour and 24, 48 and 72 hours following treatment
Number of animals or in vitro replicates:
3
Details on study design:
ANALGESIA
Sixty to seventy minutes prior to administration of the test item, buprenorphine 0.01 mg/kg was administered by subcutaneous injection (SC) to provide a therapeutic level of systemic analgesia.

LOCAL ANESTHESIC
Nineteen and five minutes prior to administration of the test item, a local anesthetic (0.5% tretracaine hydrochloride) was applied to each eye.

PAIN MANAGEMENT
Eight hours following the test item administration, buprenorphine 0.01 mg/kg SC and meloxicam 0.5 mg/kg SC was administered to provide a therapeutic level of systemic analgesia. The treated animals were checked for signs of pain and suffering approximately twelve hours later. No further analgesia was required.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The eyes were not rinsed after administration of the test item.

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: light source from a standard ophthalmoscope.

OTHER
Any clinical signs of toxicity, if present, were also recorded.
Individual bodyweights were recorded on Day 0 (the day of dosing) and at the end of the observation period.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
animal: #1, #2 & #3
Time point:
other: Mean 24-48-72 hours
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
animal: #1, #2 & #3
Time point:
other: Mean 24-48-72 hours
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Basis:
animal: #1 & #3
Time point:
other: Mean 24-48-72 hours
Score:
0.7
Max. score:
3
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
other: Mean 24-48-72 hours
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
chemosis score
Basis:
animal: #1, #2 & #3
Time point:
other: Mean 24-48-72 hours
Score:
0.7
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Irritant / corrosive response data:
No corneal or iridial effects were noted during the study. Moderate conjunctival irritation was noted in all treated eyes one hour after treatment with minimal conjunctival irritation noted at the 24 and 48-Hour observations. All treated eyes appeared normal at the 72-Hour observation.
Other effects:
One animal showed no gain in body weight and two animals showed expected gain in body weight during the study.

Any other information on results incl. tables

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

 

Score at time point / Reversibility

Cornea

Iris

(/2)

Conjunctivae

Opacity

(/4)

Area

(/4)

Redness

(/3)

Chemosis

(/4)

Discharge

(/3)

1 h

0 / 0 / 0

0 / 0 / 0

0 / 0 / 0

2 / 2 / 2

2 / 2 / 2

2 / 2 / 2

24 h

0 / 0 / 0

0 / 0 / 0

0 / 0 / 0

1 / 2 / 1

1 / 1 / 1

0 / 0 / 0

48 h

0 / 0 / 0

0 / 0 / 0

0 / 0 / 0

1 / 1 / 1

1 / 1 / 1

0 / 0 / 0

72 h

0 / 0 / 0

0 / 0 / 0

0 / 0 / 0

0 / 0 / 0

0 / 0 / 0

0 / 0 / 0

Average 24h, 48h, 72h

0 / 0 / 0

0 / 0 / 0

0 / 0 / 0

0.7 / 1 / 0.7

0.7 / 0.7 / 0.7

0 / 0 / 0

Reversibility*)

-

-

-

c.

c.

c.

Average time (unit) for reversion

-

-

-

72 h

72 h

24 h

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

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Mean scores calculated for each animal over 24, 48 and 72 hours were 0.0/0.0/0.0 for cornea opacity, 0.0/0.0/0.0 for iris lesions, 0.7/1.0/0.7 for redness of the conjunctivae and 0.7/0.7/0.7 for chemosis.
Executive summary:

In an eye irritation study performed according to the OECD guideline No. 405, and in compliance with GLP, 0.1 mL of undiluted Eucalyptus globulus oil was instilled initially into the right eye of a single New Zealand White rabbit. After consideration of the ocular responses produced in the first treated animal, two additional animals were treated. The eyes were not rinsed after administration of Eucalyptus globulus oil. The left eye of each rabbit served as control. Animals were observed 1, 24, 48 and 72 hours after dosing under a light source from a standard ophthalmoscope. The reactions in the conjunctiva (redness, chemosis and discharge), the iris and the cornea (opacity and area involved) were scored according to the Draize scale. 

No corneal or iridial effects were noted during the study. Moderate conjunctival irritation was noted in all treated eyes one hour after treatment with minimal conjunctival irritation noted at the 24 and 48-Hour observations. All treated eyes appeared normal at the 72-Hour observation.

One animal showed no gain in body weight and two animals showed expected gain in body weight during the study.

Mean scores calculated for each animal over 24, 48 and 72 hours were 0.0/0.0/0.0 for cornea opacity, 0.0/0.0/0.0 for iris lesions, 0.7/1.0/0.7 for redness of the conjunctivae and 0.7/0.7/0.7 for chemosis.

Under the test conditions, Eucaltus globulus oil is not classified as irritating to eyes according to the criteria of the Annex VI of the Regulation (EC) No. 1272/2008 (CLP) and of the Directive 67/548/EEC.

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