Registration Dossier

Administrative data

Description of key information

Skin irritation/corrosion: not irritating (EU Method B.4, GLP, K, rel. 1)
Eye irritation: not irritating (EU Method B.5, GLP, K, rel. 1)

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 29 November to 7 December 1994
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Version / remarks:
Adopted 31st July 1992
Deviations:
no
Principles of method if other than guideline:
not applicable
GLP compliance:
yes (incl. certificate)
Specific details on test material used for the study:
Storage conditions: refrigerator in the dark
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Froxfield Farms (UK) Limited, Froxfield, Hampshire - U.K.
- Housing: The animals were individually housed in grid bottomed metal cages.
- Diet (e.g. ad libitum): ad libitum (antibiotic free rabbit diet (SQC standard rabbit pellets produced by Special Diet Services, Witham, Essex)
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-21
- Humidity (%): 47-62
- Air changes (per hr): air conditionned room
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL
Duration of treatment / exposure:
4 hours
Observation period:
7 days
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: 2.5 cm²
- Type of wrap if used: 0.5mL aliquot of the test article was placed evenly over a 2.5 cm square of surgical lint which was then applied to the skin site, on the flank and caudal to the last rib, so that the test article was in contact with the skin. This test patch was held in position by encircling the trunk of the animal with a length of 'Elastoplast' elastic adhesive bandage 7.5 cm wide.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): gently with cotton wool soaked in warm water
- Time after start of exposure: 4 hours

SCORING SYSTEM:

Erythema and eschar formation:
0 No erythema
1 Very slight erythema (barely perceptible)
2 Well definederythema
3 Moderate to severe erythema
4 Severe erythema (beet redness) to slight eschar formation (injuries in depth)

Oedema formation:
0 No oedema
1 Very slight oedema (barelyperceptible)
2 Slight oedema(edges of area well defined by definite raising)
3 Moderate oedema (raised approximately Imm)
4 Severe oedema (raised more than 1mm and extending beyond area of exposure)
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1.33
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 h
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritant / corrosive response data:
See "Illustration" for detailed results
Other effects:
none

Evaluation of Results

If significant inflammation but no full thickness destruction of skin tissue is caused and persists for 24 hours after the end of the exposure period, the test article would be classified as irritant and would attract the risk phrase "R38 Irritating to skin".

According to the criteria described in Commission Directive 93/21/EEC, inflammation is deemed to be significant when the test is completed in 3 rabbits if an individual mean score (calculated from the values recorded at the 24, 48 and 72 hour examinations) for either erythema or oedema of 2 or more is obtained in at least 2 of the 3 rabbits.

Skin inflammation would also be considered significant if it persists in at least 2 animals at the end of the observation time. Persistence of hyperplasia, desquamation, discoloration, fissures,escharformation or alopecia is taken into account in determining this.

If full thickness destruction of the skin occurs in at least one rabbit, the test article would be classified as corrosive and would attract the risk phrase "R34 Causes bums".

 

Results. The treated skin site on the animal used in the preliminary screen remained free from signs of irritation throughout the observation period. However, slight or well defined erythema was apparent at the treated site on the 2 remaining animals (No 134 and 135) from 24 hours after patch removal. In animal 134, thiserythematousresponse was accompanied by slight oedema.

Forty eight and 72 hours after patch removal, erythema persisted in both animals although the oedema previously noted at the treated site on animal 134 was no longer in evidence. At the final examination, 7 days after dosing, no signs of irritation were apparent at the treated site on any animal.

The individual mean scores, calculated as described before, were as follows:

 

Rabbit number

Erythema

Oedema

128

134

135

0.0

1.3

2.0

0.0

0.3

0.0

 

Interpretation of results:
GHS criteria not met
Conclusions:
Under the test conditions, the test material induced a slight irritation being reversible within 7 days of dosing and therefore does not require classification for skin irritation.
Executive summary:

Introduction.The purpose of this study was to assess the degree of irritation produced by the test article, ST 02 C 94, when applied to the intact skin of the albino rabbit. The procedures used were in accordance with the EU Method B.4, as described in Document L383 A, an annex to EEC Commission Directive 92/69/EEC of 31st July 1992 and with Classification and labelling requirements were determined in accordance with Commission Directive 93/21/EEC of 27th April 1993.

 

Methods. Initially, one animal only was dosed in a preliminary screen in order to estimate the potential irritancy of the test article. Twenty four hours after dosing, there was no irritation at the treated site on this first rabbit and 2 further animals were dosed, bringing the total number of rabbits used in the study to 3.

A 0.5 mL aliquot of the test article was applied over a previously clipped area of about 6 cm² of the intact dorsal skin of each rabbit. The test article was held in contact with the skin, under a semi-occlusive patch assembly, for a 4 hour period. The patches were then removed and the skin reaction assessed after one, 24, 48 and 72 hours. As an irritant response persisted in 2 animals 72 hours after patch removal, an additional examination was made 7 days after dosing.

Dermal application of the test article produced no signs of skin irritation in the animal used in the preliminary screen. In the remaining 2 animals, slight or moderate erythema was apparent at the treated site from 24 hours after dosing. Very slight oedema was also noted in one of these animals at this time. The erythema persisted in both animals at the 48 and 72 hour examinations but was no longer apparent at the final examination, 7 days after dosing.

The individual mean scores for erythema and oedema, calculated from the values recorded at the 24, 48 and 72 hour examinations are as follows:

 

Rabbit number

Erythema

Oedema

128

134

135

0.0

1.3

2.0

0.0

0.3

0.0

 

Since in 2 of the 3 rabbits the individual mean scores were less than 2.0, the inflammation produced by the test article is not deemed to be significant (as defined in Commission Directive 93/21/EEC).

 

Conclusions. The test article, ST 02 C 94, does not require labelling according to the Regulation (EEC) No 1272/2008 (CLP).

Endpoint:
skin irritation: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro skin irritation study does not need to be conducted because adequate data from an in vivo skin irritation study are available
Justification for type of information:
In accordance with section 1.1 (Use of existing data) of Annex XI to the REACH Regulation, the in-vitro skin irritation study (required in section 8.1) does not need to be conducted as a reliable in-vivo study is available and provides sound conclusive evidence that the substance is non-irritating.
Reason / purpose:
data waiving: supporting information
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Referenceopen allclose all

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 13 to 17 December 1994
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
equivalent or similar to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Version / remarks:
Adopted 31st July 1992
Deviations:
no
Principles of method if other than guideline:
not applicable
GLP compliance:
yes (incl. certificate)
Specific details on test material used for the study:
Storage conditions: refrigerator in the dark
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Froxfield Farms (UK) Limited, Froxfield, Hampshire - U.K.
- Housing: The animals were individually housed in grid bottomed metal cages.
- Diet (e.g. ad libitum): ad libitum (antibiotic free rabbit diet (SQC staudardrabbit pellets produced by Special Diet Services, Witham, Essex)
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-21
- Humidity (%): 44-61
- Air changes (per hr): air conditionned room
- Photoperiod (hrs dark / hrs light): 12/12
Vehicle:
unchanged (no vehicle)
Controls:
other: left eye of rabbits
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL/eye
Duration of treatment / exposure:
72 hours
Observation period (in vivo):
Directly after instillation and after 1, 24, 48 and 72 hours
Number of animals or in vitro replicates:
3
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): none

SCORING SYSTEM & TOOL USED TO ASSESS SCORE: treated eyes were examined under a standard light source designed to comply with the requirements of BS 950 Part I (Artificial Daylight for the Assessment of Colour) , see "Attached background material"
Irritation parameter:
cornea opacity score
Basis:
animal: #1 & #2 & #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
animal: #1 & #2 & #3
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Basis:
animal: #1 & #2 & #3
Time point:
24/48/72 h
Score:
0
Max. score:
3
Irritation parameter:
chemosis score
Basis:
animal: #1 & #2 & #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritant / corrosive response data:
See "Illustration" for detailed results
Other effects:
none

none

Interpretation of results:
GHS criteria not met
Conclusions:
Under the test conditions, the test material is not classified as irritating to eyes according to the criteria of the Regulation (EC) No 1272/2008 (CLP).
Executive summary:

Introduction. The purpose of this study was to assess the degree of ocular irritation produced when the test article, ST 02 C 94, was introduced into the eye of the albino rabbit. The study was conducted in accordance with the EU Method B.5, as described in OJ L 383 A of 29th December 1992, an annex to Commission Directive 92/69/EEC of 31st July 1992. Classification and labelling requirements were determined in accordance with Commission Directive 93/21/EEC of 27th April 1993.

Methods. Initially, one animal only was dosed in a preliminary screen to assess the potential irritancy of the test article.

Twenty four hours after dosing, there were no signs of irritation in the treated eye of this first animal and a further 2 animals were dosed, bringing the total number of rabbits used in the study to 3.

A 0.1 ml aliquot of the pure test article was instilled into the right eye of each rabbit and the resulting reaction to treatment was assessed one, 24, 48 and 72 hours after treatment.

One hour after dosing, very slight conjunctival hyperaemia was noted in the treated eye of all 3 rabbits. However, no signs of ocular irritation were apparent in any animal at all subsequent examinations.

No severe ocular lesions were detected in the treated eye of any animal and the irritation produced by the test article would not be deemed to be significant according to the criteria described in the Annex VI of the Directive 67/548/EEC and of the Regulation (EC) No 1272/2008 (CLP).

Conclusion. Under the test conditions, the test material is not classified as irritating to eyes according to the Annex VI of the Regulation (EC) No 1272/2008 (CLP).

Endpoint:
eye irritation: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro eye irritation study does not need to be conducted because adequate data from an in vivo eye irritation study are available
Justification for type of information:
In accordance with section 1.1 (Use of existing data) of Annex XI to the REACH Regulation, the in-vitro eye irritation study (required in section 8.2) does not need to be conducted as a reliable in-vivo study is available and provides sound conclusive evidence that the substance is non-irritating.
Reason / purpose:
data waiving: supporting information
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation/Corrosion

A key study was identified (Toxicol, 1994, rel. 1). This dermal irritation study was performed according to the EU Method B.4, and in compliance with GLP. The mean scores calculated over the three rabbits tested within 3 scoring times (24, 48 and 72 h) were 0.0/1.33/2.0 for erythema and 0.0/0.33/0.0 for edema. Seven days after dosing, erythema and oedema were no longer apparent in any animal. The test material does not require classification for skin irritation.

Eye irritation:

A key study was identified (Toxicol, 1994, rel. 1). This eye irritation study was performed according to the Eu Method B.5, and in compliance with GLP. One hour after dosing, very slight conjunctival hyperaemia was noted in the treated eye of all 3 rabbits. However, no signs of ocular irritation were apparent in any animal at all subsequent examinations. The calculated mean score for each individual lesion for each animal within 3 scoring times (24, 48 and 72 h) were 0.00 for chemosis, redness, discharge, iris and corneal lesions. The test material does not require classification for eye irritation.

Justification for classification or non-classification

Harmonized classification:

The substance has no harmonized classification according to the Regulation (EC) No. 1272/2008.

Self-classification:

Based on the available data no additional self-classification is proposed regarding both skin and eye irritation according to the Regulation (EC) No. 1272/2008 (CLP).

No data was available regarding respiratory irritation, however the substance not being classified for skin and eye irritation, no classification is expected for respiratory irritation.