Registration Dossier

Diss Factsheets

Administrative data

Description of key information

Skin irritation/corrosion
A skin irritation study (Parcell, 1997) is available which is key study. This study showed that the test substance is not irritating.
Eye irritation
An acute eye irritation study (Parcell, 1997) is available which is key study. This study showed that the test substance is moderately 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:
From 29 May to 1 June 1996
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study run to a method comparable with current guidelines and to GLP.
Qualifier:
according to guideline
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Harlan Interfauna UK Ltd., Huntingdon, Cambridgeshire, England
- Age at study initiation: 10-13 weeks of age
- Weight at study initiation: 2.4-2.8 kg
- Housing: Housed individually in metal cages with perforated floors
- Diet (e.g. ad libitum): A standard laboratory diet SDS Stanrab (P) Rabbit Diet
- Water (e.g. ad libitum): ad libitum
- Acclimation period: Yes

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Approximately 19℃
- Humidity (%): 30-70%
- Air changes (per hr): Approximately 19 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours of artificial light in each 24 hours period.

Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
water
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g
- Concentration (if solution):

VEHICLE
- Amount(s) applied (volume or weight with unit): 0.5 ml distilled water
- Concentration (if solution):
- Lot/batch no. (if required):
- Purity:
Duration of treatment / exposure:
4 hours
Observation period:
4 days
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: Approximately 100 mm * 100 mm
- % coverage:
- Type of wrap if used: Each treatment site was covered with "Elastoplast" elastic adhesive dressing

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The treatment sites was washed with warm water (30 to 40 ℃) to remove any residual test substance.
- Time after start of exposure: 4 hours
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: Mean of 24, 48 & 72 hours
Score:
0
Max. score:
0
Remarks on result:
other: No reactions
Irritation parameter:
edema score
Basis:
mean
Time point:
other: Mean of 24, 48 & 72 hours
Score:
0
Max. score:
0
Remarks on result:
other: No reactions
Irritant / corrosive response data:
No dermal response to treatment was observed in any animal throughout the observation period.

There were no signs of toxicity or ill health in any rabbit during the observation period.

Rabbit number and sex

E= Erythema

O= Oedema

Day

1*

2

3

4

2894 ♂

E

O

0

0

0

0

0

0

0

0

2895 ♂

E

O

0

0

0

0

0

0

0

0

2896 ♂

E

O

0

0

0

0

0

0

0

0

* Approximately 60 minutes after removal of the dressing.

 

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
A single semi-occlusive application of this substance to intact rabbit skin for four hours elicited no dermal irritation.
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:
From 3 to 24 June 1996
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study run to a method comparable with current guidelines and to GLP.
Qualifier:
according to guideline
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Harlan Interfauna UK Ltd, Huntingdon, Cambridgeshire, England
- Age at study initiation: Approximately 13 weeks of age
- Weight at study initiation: 3.2 kg
- Housing: Housed individually in metal cages with perforated floors
- Diet (e.g. ad libitum): A standard laboratory diet SDS Stanrab (P) Rabbit Diet
- Water (e.g. ad libitum): ad libitum
- Acclimation period: Yes

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Approximately 19℃
- Humidity (%): 30-70%
- Air changes (per hr): Approximately 19 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours of artificial light in each 24 hours period.
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): Approximately 84 mg
- Concentration (if solution):

Duration of treatment / exposure:
Single instillation without washing
Observation period (in vivo):
21 days
Number of animals or in vitro replicates:
1
Details on study design:
Due to the low pH of the test material (pH 1.98), one animal was treated in advance of others to ensure that if a severe response was produced, no further animals would be exposed. As a result of the severity of ocular reactions observed, no further animals were treated.
Approximately 84 mg of the test substance, the weight occupying a volume of 0.1 ml, it 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.
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
other: Mean of 24, 48 and 72 hours
Score:
3.33
Max. score:
4
Reversibility:
fully reversible within: 14 days
Irritation parameter:
iris score
Basis:
animal #1
Time point:
other: Mean of 24, 48 and 72 hours
Score:
0
Max. score:
0
Remarks on result:
other: No reactions
Irritation parameter:
conjunctivae score
Remarks:
Redness
Basis:
animal #1
Time point:
other: Mean of 24, 48 and 72 hours
Score:
2.67
Max. score:
3
Reversibility:
fully reversible within: 21 days
Remarks on result:
other: Blanching of nictating membrane
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
other: Mean of 24, 48 and 72 hours
Score:
2
Max. score:
2
Reversibility:
fully reversible within: 21 days
Irritant / corrosive response data:
Examination of the eye was made after 1 hour and 1, 2, 3, 4, 7, 14 and 21 days after instillation.
The numerical values given to the ocular reactions elicited by this substance are shown below. No iridial inflammation was observed. Corneal opacification (Grade 4) was noted within one hour of dosing.
A diffuse beefy red colouration of the conjunctivae was seen, accompanied by blanching of the nictating membrane and swelling with partial eversion of the eyelids. These responses gradually ameliorated and the eye was normal 21 days after instillation.

There were no signs of toxicity or ill health in any rabbit during the observation period.

Rabbit number and sex

Region of eye

One hour

Day after instillation

1

2

3

4

7

14

21

2885 ♂

Cornea

Density

4

4

3

3

3

1

0

0

Area

1

1

1

1

1

1

0

0

Iris

0

0

0

0

0

0

0

0

Conjunctiva

Redness

2a

2a

3a

3a

3a

2

2

0

Chemosis

2

2

2

2

2

2

1

0

Pilot animal

A Blanching of nictating membrane

 

Interpretation of results:
moderately irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Instillation of the substance into the rabbit eye elicited corneal opacification and moderate conjuntival irritation.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Additional information

Skin irritation/corrosion:

A skin irritation study (Parcell, 1997) was conducted according to EU Method B4 which is key study. This study showed that the test substance is not irritating.

Eye irritation:

An acute eye irritation study (Parcell, 1997) was conducted according to EU Method B5 which is key study. This study showed that the test substance is moderately irritating.


Justification for selection of skin irritation / corrosion endpoint:
Study run to a method comparable with current guidelines and to GLP.

Justification for selection of eye irritation endpoint:
Study run to a method comparable with current guidelines and to GLP.

Effects on eye irritation: moderately irritating

Justification for classification or non-classification

Skin irritation/corrosion: Mean scores at 24, 48 & 72 hours for erythema were < 2.3 (actual value 0), for oedema were < 2.3 (actual value 0).

Serious eye damage/eye irritation: Mean scores at 24, 48 & 72 hours for corneal opacity were > 1 (actual value 3.33), for iritis were < 1 (actual value 0), for conjunctival redness were > 2 (actual value 2.67) and for conjunctival oedema were > 1(actual value 2).

Therefore in accordance with Regulation (EC) No. 1272/2008 Tables 3.2.2 & 3.3.2 the substance is not classified for the skin corrosion/irritation and classified as "Category 1" for serious eye damage/eye irritation endpoint.