Registration Dossier

Administrative data

Description of key information

Skin irritation (in vitro): non irritating (OECDTG 404)
Eye irritation (in vitro): non irritating (OECD TG 405)
Respiratory irritation: not irritating

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Between 24th and 29th January 1995
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted according to OECD guidelines and in compliance with GLP.
Reference:
Composition 0
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test material information:
Composition 1
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
Three healthy adult rabbits of the New Zealand White strain were obtained from Froxfield (U .K.) Ltd., Petersfield, Hampshire, England .
They were in the weight range of 2.1 to 3.2 kg and approximately 9 to 14 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 plastic cages with perforated floors in Building R 14 Room 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 usually weekly by the supplier, are made available to Huntingdon Research Centre Ltd. as quarterly summarIes.
The mean minimum and maximum animal room temperature was 19.5°C and 20.5°C and relative humidity 55 % and 61 % . 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 license.
Type of coverage:
semiocclusive
Preparation of test site:
other: clipped
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
0.5 ml
Duration of treatment / exposure:
4 hours
Observation period:
5 days
Number of animals:
3
Details on study design:
TREATMENT PROCEDURE
Approximately 24 hours prior to application of the test substance, hair was removed with electric clippers from the dorso-lumbar region of each rabbit exposing an area of skin approximately 100 mm x 100 mm.
A 0.5 ml amount of the test substance was applied under a 25 mm x 25 mm gauze pad to one intact skin site on each animal.
Each treatment site was covered with "Elastoplast" elastic adhesive dressing for four hours. The animals were not restrained during the exposure period and were returned to their cages immediately after treatment.
At the end of the exposure period, the semi-occlusive dressing and gauze pad were removed and the treatment site was washed with warm water (30° to 40°C) to remove any residual test substance. The treated area was blotted dry with absorbent paper.

OBSERVATIONS
Clinical signs
All animals were observed daily for signs of ill health or toxicity.
Dermal responses
Examination of the treated skin was made on Day 1 (i.e. approximately 60 minutes after removal of the dressings) and on Days 2, 3 and 4 (equivalent to 24, 48 and 72 hours after exposure). Additional observations were made on Days 5 and 6.
Irritation parameter:
erythema score
Basis:
animal: 383 female
Time point:
other: mean score at 24, 48 and 72 hours
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 6 days
Irritation parameter:
erythema score
Basis:
animal: 297 male
Time point:
other: mean score at 24, 48 and 72 hours
Score:
1.67
Max. score:
4
Reversibility:
fully reversible within: 5 days
Irritation parameter:
erythema score
Basis:
animal: 410 female
Time point:
other: mean score at 24, 48 and 72 hours
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 1 day
Irritation parameter:
edema score
Basis:
animal: 383 female
Time point:
other: mean score at 24, 48 and 72 hours
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 5 days
Irritation parameter:
edema score
Basis:
animal: 297 male
Time point:
other: mean score at 24, 48 and 72 hours
Score:
0.67
Max. score:
4
Reversibility:
fully reversible within: 4 days
Irritation parameter:
edema score
Basis:
animal: 410 female
Time point:
other: mean score at 24, 48 and 72 hours
Score:
0
Max. score:
4
Reversibility:
other: No effects seen
Irritant / corrosive response data:
The numerical values given to the dermal reactions elicited by Salicynalva are shown in Table 1 (please see any other information on results section).
Well-defined erythema with very slight oedema was seen in two rabbits.
Very slight erythema alone was seen in the third animal.
The application sites were normal on days 2, 5 or 6.
Other effects:
There were no signs of ill health in any rabbit during the observation period. There were very slight to well-defined dermal reactions found within the study however this was not enough to trigger classification for this endpoint.

TABLE 1

Dermal reactions observed after application of Salicynalva

Rabbit number and sex

E = Erythema

O = Oedema

Day

1*

2

3

4

5

6

383 female

E

O

2

1

2

1

2

1

2

1

1

0

0

0

297 male

E

O

2

1

2

1

2

1

1

0

0

0

 

410 female

E

O

1

0

0

0

0

0

0

0

 

 

* Approximately 60 minutes after removal of the dressing
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
A single semi-occlusive application of Salicynalva to intact rabbit skin for four hours elicited very slight to well-defined dermal reactions which completely resoved in all animals by Day 6. The reactions had resolved by Day 2, 5 or 6. Salicynalva does not require labelling with the risk phrase R38 "Irritating to skin" in accordance with EEC Council Directive 79/831/EEC, Annex VI, Part II(D) as described in Commission Directive 93 /21/EEC.
Executive summary:

This study was performed to assess the skin irritation potential of Salicynalva to the rabbit according to EEC Methods for the determination of toxicity, Annex to Directive 92/69/EEC (01 No. L383A, 29.12. 92), Part B, Method B.4. Acute toxicity (skin irritation) and OECD Guideline for Testing of Chemicals No. 404 "Acute Dermal Irritation/Corrosion". Adopted: 17 July 1992.

Three rabbits were each administered a single dermal dose of 0. 5 ml of the test substance and observed for a maximum of six days. A single semi-occlusive application of Salicynalva to intact rabbit skin for four hours elicited very slight to well-defined dermal reactions. The reactions had resolved by Day 2, 5 or 6.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records
Reference
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.
Reference:
Composition 0
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 information:
Composition 1
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.
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.
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.

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

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.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Additional information

Skin irritation: This study was performed to assess the skin irritation potential of Salicynalva to the rabbit according to EEC Methods for the determination of toxicity, Annex to Directive 92/69/EEC (01 No. L383A, 29.12. 92), Part B, Method B.4. Acute toxicity (skin irritation) and OECD Guideline for Testing of Chemicals No. 404 "Acute Dermal Irritation/Corrosion". Adopted: 17 July 1992. Three rabbits were each administered a single dermal dose of 0. 5 ml of the test substance and observed for a maximum of six days. A single semi-occlusive application of Salicynalva to intact rabbit skin for four hours elicited very slight to well-defined dermal reactions. The reactions had resolved by Day 2, 5 or 6.

Eye irritation: 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.

Respiratory irritation: For respiratory irritation mostly human data are used for the assessment because no suitable in vitro or in vivo tests are available that can identify respiratory irritation (REACH guidance R.7.2.3). There are no human data such as indicated in R7.2.3 the ECHA guidance that indicate respiratory reactions of the substance e. g. from consumer experience or occupational exposure. The substance is not a skin and eye irritant which minimizes the respiratory irritation hazard (REACH guidance: 7.2.1.2). Also the substance has a low vapour pressure (6.4 Pa) which minimises the exposure via the inhalation route.


Justification for selection of skin irritation / corrosion endpoint:
The one in vivo study available is adequate to cover the skin irritation and corrosion potential.

Justification for selection of eye irritation endpoint:
The one in vivo study available is adequate to cover the skin irritation and corrosion potential.

Justification for classification or non-classification

The substance need not be classified as irritating to the skin, eyes and respiratory irritation in accordance with the criteria outlined in Annex VI of 67/548/EEC (DSD) and Annex I of 1272/2008/EC (CLP).