Registration Dossier

Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Between 27 October 1997 and 01 November 1997
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted according to OECD/EU guideline under GLP conditions.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1997
Report Date:
2000

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
The values for temperature and humidity were recorded as 13 - 25.5°C and 25 - 73% respectively. These were outside the ranges as stated in the protocol. These deviations are not considered to affect the validity of the study.
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
The values for temperature and humidity were recorded as 13 - 25.5°C and 25 - 73% respectively. These were outside the ranges as stated in the protocol. These deviations are not considered to affect the validity of the study.
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: colourless liquid
Details on test material:
Identity: 97-204-01
Commercial name: Montaverdi
Appearance: Clear colourless liquid
Storage conditions: Room temperature in the dark

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
Animals for this study were selected from a stock supply of healthy adult rabbits of the New Zealand White strain, obtained from Charles River UK Ltd., Margate, Kent, England.
The animals were in the weight range of 3.0 to 3.5 kg and approximately 13 to 15 weeks of age, prior to treatment (Day 1). All rabbits were acclimatised to the experimental environment.
The rabbits were selected without conscious bias for the study. They were housed individually in metal cages with perforated floors in Building R14 Room 5.
A standard laboratory diet SDS Stanrab (P) SQC Rabbit Diet and drinking water were provided ad libitum
The batch of diet used for the study was analysed for nutrients, contaminants or micro-organisms.
Results of routine physical and chemical examination of drinking water as conducted by the supplier, are made available to Huntingdon Life Sciences Ltd as quarterly summaries.
Animal room temperature was maintained at l3 to 25.5°C and relative humidity at 25 - 73%. These environmental parameters were recorded daily. Air exchange was maintained at approximately 19 air changes per hour and lighting was controlled by means of a time switch to give 12 hours of artificial light (0700 - 1900 hours) in each 24 hours period.
Each animal was identified by a numbered aluminium tag placed through the edge of one ear. This number was unique within the Huntingdon Life Sciences Acute Toxicology Department throughout the duration of the study. Each cage, was identified by a coloured label displaying the study schedule number, animal number and initials of the Study Director and Home Office licensee.

Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: The contralateral eye remained untreated.
Amount / concentration applied:
0.1 ml of the test substance
Duration of treatment / exposure:
Up to 1 hour
Observation period (in vivo):
Examination of the eyes was made after 1 hour and 1, 2, 3 days (equivalent to 24, 48 and 72 hours) after instillation.
Number of animals or in vitro replicates:
3 animals were tested in total. One animal was treated in advance of the others, to ensure that if a severe response was produced, no further animals would be exposed.
Details on study design:
TREATMENT PROCEDURE
The eyes of each animal were examined prior to instillation of the test substance to ensure that there was no pre-existing corneal damage, iridial or conjunctival inflammation.
One animal was treated in advance of the others, to ensure that if a severe response was produced, no further animals would be exposed (pilot animal).
A volume of 0.1 ml of the test substance was placed into the lower everted lid of one eye of each animal.
The eyelid was then gently held together for one second before releasing. The contralateral eye remained untreated.

OBSERVATIONS
Clinical signs
All animals were observed daily for signs of ill health or toxicity.
Ocular responses
Examination of the eyes was made after 1 hour and 1, 2, 3 days (equivalent to 24, 48 and 72 hours) after instillation. Observation of the eyes was aided by the use of a handheld light.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
animal: 2452 Female
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
4
Reversibility:
other: No effects observed
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
animal: 2453 Female
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
4
Reversibility:
other: No effects observed
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
animal: 2454 Female
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
4
Reversibility:
other: No effects observed
Irritation parameter:
iris score
Basis:
mean
Remarks:
animal: 2452 Female
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
2
Reversibility:
other: No effects observed
Irritation parameter:
iris score
Basis:
mean
Remarks:
animal: 2453 Female
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
2
Reversibility:
other: No effects observed
Irritation parameter:
iris score
Basis:
mean
Remarks:
animal: 2454 Female
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
2
Reversibility:
other: No effects observed
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
animal: 2452 Female
Time point:
other: 24, 48 and 72 hours
Score:
0.33
Max. score:
3
Reversibility:
fully reversible within: 24 hours
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
animal: 2453 Female
Time point:
other: 24, 48 and 72 hours
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
animal: 2454 Female
Time point:
other: 24, 48 and 72 hours
Score:
0.33
Max. score:
3
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
animal: 2452 Female
Time point:
other: 24, 48 and 72
Score:
0
Max. score:
4
Reversibility:
other: No effects observed
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
animal: 2453 Female
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
4
Reversibility:
other: no effects observed
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
animal: 2454 Female
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
4
Reversibility:
other: no effects observed
Irritant / corrosive response data:
No corneal damage or iridial inflammation was observed.
A diffuse crimson colouration of the conjunctivae was seen in two rabbits accompanied by slight swelling of the eyelids. Transient hyperaemia of blood vessels of the conjunctivae was seen in the remaining animal.
All reactions had resolved completely by two or three 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 1                       Ocular Reactions

 

Rabbit no. and sex

Region of eye

One hour

Day after instillation

1

2

3

2452 Female*

Cornea

Density

0

0

0

0

Area

0

0

0

0

Iris

0

0

0

0

Conjunctiva

Redness

1

1

0

0

Chemosis

0

0

0

0

2453 Female

Cornea

Density

0

0

0

0

Area

0

0

0

0

Iris

0

0

0

0

Conjunctiva

Redness

2

2

1

0

Chemosis

1

0

0

0

2454 Female

Cornea

Density

0

0

0

0

Area

0

0

0

0

Iris

0

0

0

0

Conjunctiva

Redness

2

1

0

0

Chemosis

1

0

0

0

 

* - Pilot animal

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Instillation of 97-204-01 into the rabbit eye elicited transient very slight to well-defined conjunctival irritation but not sufficient to warrant classification.
Executive summary:

An in vivo study was performed to assess the eye irritation potential of Montaverdi to the rabbit. The method followed was that described in:

EEC Methods for the determination of toxicity, Annex to Directive 92/69/EEC (01 No. L383A, 29.12.92), Part B, Method B.5. Acute toxicity (eye irritation) or OECD Guideline for Testing of Chemicals No. 405, "Acute Eye Irritation/Corrosion". Adopted: 24 February 1987. Three rabbits were each administered a single ocular dose of a volume of 0.1 ml of the test substance and observed for three days after instillation. A single instillation of Montaverdi into the eye of the rabbit elicited transient very slight to well-defined conjunctival irritation. The scores obtained however do not lead to classification according to the criteria set out in the DSD 67/548/EC or the CLP Regulation (EC) 1272/2008.