Registration Dossier

Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Between 30 January 1995 and 13 February 1995
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted according to OECD guidelines and in compliance with GLP.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1996
Report Date:
1996

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
GLP compliance:
yes (incl. certificate)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: liquid
Details on test material:
Identity: Salicynalva
Chemical name: 2- Phenylhexanenitrile
Appearance: Light yellow liquid
Storage conditions: Room temperature in the dark
Date received: 28 September 1994

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
Three healthy adult rabbits of the New Zealand White strain were obtained from Froxfield (UK) Ltd., Petersfield, Hampshire, England and Interfauna U.K. Ltd., Huntingdon, Cambridgeshire, England.
The animals were in the weight range of 2.6 to 2.9 kg and approximately 11 to 12 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 and plastic cages with perforated floors in Building R 14 Room 5 and 1.
A standard laboratory diet SDS Stanrab (P) Rabbit Diet and drinking water were provided ad libitum. The batch of diet used for the study was not analysed for nutrients, contaminants or micro-organisms.
Results of routine physical and chemical examination of drinking water at source as conducted by the supplier, are made available to Huntingdon Research Centre Ltd. as quarterly summaries.
The mean minimum and maximum animal room temperature was 19°C and 20°C and relative humidity 50% and 59%. 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 HRC Industrial 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 left eye remained untreated and was used for control purposes.
Amount / concentration applied:
0.1 ml
Duration of treatment / exposure:
Up to 1 hour
Observation period (in vivo):
7 days
Number of animals or in vitro replicates:
3
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 see Table 1).
Approximately 0.1 ml of the test substance was placed into the lower everted lid of one eye of each animal.
The eyelids were 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 (equivalent to 24, 48 and 72 hours after instillation), 4 and 7 days 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:
animal: 380 Female
Time point:
other: mean score for 24, 48 and 72 hours after treatment
Score:
0
Max. score:
4
Reversibility:
other: No effects observed
Irritation parameter:
cornea opacity score
Basis:
animal: 484 Male
Time point:
other: mean score for 24, 48 and 72 hours after treatment
Score:
0
Max. score:
4
Reversibility:
not specified
Remarks:
No effects observed
Remarks on result:
other: Dulling
Irritation parameter:
cornea opacity score
Basis:
animal: 485 Male
Time point:
other: mean score for 24, 48 and 72 hours after treatment
Score:
0
Max. score:
4
Reversibility:
other: No effects observed
Remarks on result:
other: Dulling
Irritation parameter:
iris score
Basis:
animal: 380 Female
Time point:
other: mean score for 24, 48 and 72 hours after treatment
Score:
0
Max. score:
2
Reversibility:
other: No effects observed
Irritation parameter:
iris score
Basis:
animal: 484 Male
Time point:
other: mean score for 24, 48 and 72 hours after treatment
Score:
0
Max. score:
2
Reversibility:
other: No effects observed
Irritation parameter:
iris score
Basis:
animal: 485 Male
Time point:
other: mean score for 24, 48 and 72 hours after treatment
Score:
0
Max. score:
2
Reversibility:
other: No effects observed
Irritation parameter:
other: redness
Basis:
animal: 380 Female
Time point:
other: mean score for 24, 48 and 72 hours after treatment
Score:
0
Max. score:
3
Reversibility:
fully reversible within: 24 hour
Irritation parameter:
other: redness
Basis:
animal: 484 Male
Time point:
other: mean score for 24, 48 and 72 hours after treatment
Score:
0
Max. score:
3
Reversibility:
fully reversible within: 24 hour
Irritation parameter:
other: redness
Basis:
animal: 485 Male
Time point:
other: mean score for 24, 48 and 72 hours after treatment
Score:
0
Max. score:
3
Reversibility:
fully reversible within: 24 hour
Irritation parameter:
chemosis score
Basis:
animal: 380 Female
Time point:
other: mean score for 24, 48 and 72 hours after treatment
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 24 hour
Irritation parameter:
chemosis score
Basis:
animal: 484 Male
Time point:
other: mean score for 24, 48 and 72 hours after treatment
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 24 hour
Irritation parameter:
chemosis score
Basis:
animal: 485 Male
Time point:
other: mean score for 24, 48 and 72 hours after treatment
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 24 hour
Irritant / corrosive response data:
The numerical values given to the ocular reactions elicited by Salicynalva are shown in Table 1 (please see the any other information on results section).
Dulling of the normal lustre of the cornea was seen in two animals one hour after instillation.
No iridial inflammation was observed.
Hyperaemia or diffuse crimson colouration of the palpebral and bulbar conjunctivae with slight swelling or partial eversion of the eyelids was seen in all three animals one hour after treatment.
The eyes were normal one day 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 observed after instillation of Salicynalva

 

Rabbit number and sex

Region of Eye

One hour

Day after instillation

1

2

3

4

7

380

Female*

Cornea

0

0

0

0

0

0

Iris

0

0

0

0

0

0

Conjunctiva

Redness

0

0

0

0

0

0

Chemosis

0

0

0

0

0

0

484

Male

Cornea

D

0

0

0

0

0

Iris

0

0

0

0

0

0

Conjunctiva

Redness

0

0

0

0

0

0

Chemosis

0

0

0

0

0

0

485

Male

Cornea

D

0

0

0

0

0

Iris

0

0

0

0

0

0

Conjunctiva

Redness

0

0

0

0

0

0

Chemosis

0

0

0

0

0

0

 

*    Pilot animal

D  Dulling

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Instillation of Salicynalva into the rabbit eye elicited transient dulling effects on cornea in 2/3 animals at 1 hour.
Executive summary:

A study was performed to assess the eye irritation potential of Salicynalva 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). 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 0.1 ml of the test substance and observed for seven days after instillation. A single instillation of Salicynalva into the eye of the rabbit elicited transient dulling effect on the cornea of 2/3 animals after 1 hour. All reactions had resolved one day after instillation.