Registration Dossier

Administrative data

Description of key information

Skin irritation/corrosion: not irritating (OECD 404, GLP, K, rel. 1).

Eye irritation: not irritating (OECD 405, GLP, K, rel. 1).

Respiratory irritation: no information.

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 1999-05-05 to 1999-05-08
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
Study performed according to OECD test guideline No. 404 and in compliance with GLP.
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
1992
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
Principles of method if other than guideline:
not applicable
GLP compliance:
yes (incl. certificate)
Remarks:
UK GLP Compliance program (inspection date 1998-03-23)
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: David Percival Ltd, Moston, Sandbach, Cheshire, UK.
- Age at study initiation: 12-16 weeks old
- Weight at study initiation: 2.57-2.61 kg
- Housing: individually housed in suspended metal cages
- Diet (e.g. ad libitum): ad libitum ((STANRAB SQC Rabbit Diet, Special Diets Services Ltd, Witham, Essex, UK)
- Water (e.g. ad libitum): drinking water ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-23
- Humidity (%): 30-70
- Air changes (per hr): approximately 15 per hr
- Photoperiod: 12 hrs dark / 12 hrs light

IN-LIFE DATES: until 1999-05-12
Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
other: untreated skin served as control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL
Duration of treatment / exposure:
4 hours
Observation period:
1, 24, 48, and 72 hours after patch removal
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: dorsal flank area
- % coverage: 2.5 cm square (6.25 cm²)
- Type of wrap if used: cotton gauze patch secured in position with a strip of surgical adhesive tape
(BLENDERM: approximate size 2.5 cm x 4.0 cm). To prevent the animals interfering with the patches, the trunk of each rabbit was wrapped in an elasticated corset (TUBIGRIP).

REMOVAL OF TEST SUBSTANCE
- Washing (if done): gentle swabbing with cotton wool soaked in 74% IMS.
- Time after start of exposure: 4 hours

SCORING SYSTEM: Official Journal of the European Communities Annex V L383A/127 (Draize sclae).
Irritation parameter:
erythema score
Basis:
animal: #1, #2 and #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal: #1, #2 and #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
No evidence of skin irritation was noted during the study.
Other effects:
None

Table 7.3.1/1: Irritant/corrosive response data for the 3 animals at each observation time up to removal of animals from the test

 

Score at time point / Reversibility

Erythema

Max. score 4

Edema

Max. score 4

1 h

0/0/0

0/0/0

24 h

0/0/0

0/0/0

48 h

0/0/0

0/0/0

72 h

0/0/0

0/0/0

Average 24h, 48h, 72h

0/0/0

0/0/0

Reversibility*)

-

-

Average time (day) for reversion**

-

-

 *) Reversibility: c. = completely reversible; n.c. = not completely reversible; n. = not reversible

**): correspond to the last day for which skin irritation signs in the last animal were observed

Interpretation of results:
not irritating
Conclusions:
No evidence of skin irritation was noted during the study. The individual scores for each individual animal within 3 scoring times (24, 48 and 72 hours) were 0.0 for erythema and oedema.
Executive summary:

In a dermal irritation study performed according to the OECD guideline No. 404, and in compliance with GLP, 0.5 mL of undiluted ST 08 C 98 was dermally applied on the shaved skin of the dorsal flank area of 3 New Zealand White rabbits.Test sites were covered with a semi-occlusive dressing for 4 hours. Skin irritation was assessed and scored according to the Draize scale 1, 24, 48 and 72 hours after the removal of the patch.

No evidence of skin irritation was noted during the study. The individual scores for each individual animal within 3 scoring times (24, 48 and 72 hours) were 0.0 for erythema and oedema.

Therefore, ST 08 C 98 does not require a classification as irritant to the skin according to the Regulation (EC) No. 1272/2008 (CLP) and to the GHS.

This study is considered as acceptable and satisfies the requirement for skin irritation endpoint

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 1999-05-10 to 1999-05-16
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
Study performed according to OECD test guideline No. 405 and in compliance with GLP.
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
1987
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
Principles of method if other than guideline:
not applicable
GLP compliance:
yes (incl. certificate)
Remarks:
UK GLP Compliance program (inspection date 1998-03-23)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: David Percival Ltd, Moston, Sandbach, Cheshire, UK.
- Age at study initiation: 12-16 weeks old
- Weight at study initiation: 2.68 to 3.05 kg
- Housing: individually housed in suspended metal cages
- Diet (e.g. ad libitum): ad libitum ((STANRAB SQC Rabbit Diet, Special Diets Services Ltd, Witham, Essex, UK)
- Water (e.g. ad libitum): drinking water ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-23
- Humidity (%): 30-70
- Air changes (per hr): approximately 15 per hr
- Photoperiod: 12 hrs dark / 12 hrs light
Vehicle:
unchanged (no vehicle)
Controls:
other: Contralateral eye served as control.
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL
Duration of treatment / exposure:
The eye was not rinsed after the instillation of the test item.
Observation period (in vivo):
1, 24, 48 and 72 hours following instillation
Number of animals or in vitro replicates:
3
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): Not done
- Time after start of exposure: not applicable

SCORING SYSTEM: Draize scale according to the OECD guideline No. 405

TOOL USED TO ASSESS SCORE: animals were examined under a light source from a standard ophthalmoscope.
Irritation parameter:
cornea opacity score
Basis:
animal: #1, #2 and #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal: #1, #2 and #3
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.33
Max. score:
3
Reversibility:
fully reversible within: 48h
Remarks on result:
probability of weak irritation
Irritation parameter:
conjunctivae score
Basis:
animal: #2 and #3
Time point:
24/48/72 h
Score:
0
Max. score:
3
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal: #1, #2 and #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
No corneal or iridial effects were noted during the study. Minimal conjunctival irritation was noted in all treated eyes one hour after treatment and persisted in one treated eye at the 24-hour observation. Two treated eyes appeared normal at the 24-hour observation and the remaining treated eye appeared normal at the 48-hour observation.
Other effects:
none

Table 7.3.2/1: Individual irritant/corrosive response data of the 3 animals at each observation time up to removal from the test

 

Score at time point / Reversibility

Cornea

Iris

(/2)

Conjunctivae

Opacity

(/4)

Area

(/4)

Redness

(/3)

Chemosis

(/4)

Discharge

(/3)

1 h

0/0/0

0/0/0

0/0/0

1/1/1

1/0/1

1/1/1

24 h

0/0/0

0/0/0

0/0/0

1/0/0

0/0/0

0/0/0

48 h

0/0/0

0/0/0

0/0/0

0/0/0

0/0/0

0/0/0

72 h

0/0/0

0/0/0

0/0/0

0/0/0

0/0/0

0/0/0

Mean 24-48-72

0/0/0

0/0/0

0/0/0

0.33/0/0

0/0/0

0/0/0

Reversibility*)

-

-

-

c

c

c

Average time (unit) for reversion

-

-

-

48 h

24 h

24 h

*) Reversibility: c. = completely reversible; n.c. = not completely reversible; n. = not reversible

Interpretation of results:
not irritating
Conclusions:
The individual score for each individual lesion for each individual animal within 3 scoring times (24, 48 and 72 hours ) were 0.00 for chemosis, discharge, iris and corneal lesions. A redness score of 0.33 was obtained in one animal, whereas the 2 others animals had scores of 0.00. Effects were fully reversible within 48 hours.
Executive summary:

In an eye irritation study performed according to the OECD guideline No. 405, and in compliance with GLP, 0.1 mL of undiluted ST 08 C 98 was instilled into the right eye of 3 New Zealand White Rabbit. The eyes were not rinsed after the instillation of ST 08 C 98. The left eye of each rabbit served as control. Animals were observed at 1, 24, 48 and 72 hours after dosing under a standard light source. The reactions in the conjunctiva (redness, chemosis and discharge), the iris and the cornea (opacity and area involved) were scored according to the Draize scale. 

No corneal or iridial effects were noted during the study. Minimal conjunctival irritation was noted in all treated eyes one hour after treatment and persisted in one treated eye at the 24-hour observation. Two treated eyes appeared normal at the 24-hour observation and the remaining treated eye appeared normal at the 48-hour observation.

 

 

The individual score for each individual lesion for each individual animal within 3 scoring times (24, 48 and 72 hours) were 0.00 for chemosis, discharge, iris and corneal lesions. A redness score of 0.33 was obtained in one animal, whereas the 2 others animals had scores of 0.00.

 

Under the test conditions, ST 08 C 98 is not classified as irritating to eyes according to the Regulation (EC) No. 1272/2008 (CLP) and to the GHS.

This study is considered as acceptable and satisfies the requirement for eye irritation endpoint.

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 (Safepharm, 1999, rel. 1). In this dermal irritation study performed according to the OECD guideline No. 404, and in compliance with GLP, undiluted ST 08 C 98 was applied on the skin of 3 rabbits. Test sites were covered with a semi-occlusive dressing for 4 hours.

No evidence of skin irritation was noted during the study. The individual scores for each animal within 3 scoring times (24, 48 and 72 hours) were 0.0 for erythema and oedema.

Therefore, ST 08 C 98 does not require a classification as irritant to the skin.

 

Eye irritation:

A key study was identified (Safepharm, 1999, rel. 1). In this eye irritation study performed according to the OECD guideline No. 405, and in compliance with GLP, undiluted ST 08 C 98 was instilled into the eye of 3 rabbits. The eyes were not rinsed after the instillation of the test item.

The individual score for each individual lesion for each animal within 3 scoring times (24, 48 and 72 hrs) were 0.00 for chemosis, discharge, iris and corneal lesions. A redness score of 0.33 was obtained in one animal, whereas the 2 others animals had scores of 0.00.

Therefore, ST 08 C 98 does not require classification as irritating to eye.

Justification for classification or non-classification

Harmonised classification:

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

Self classification:

Based on the available data no additional self-classification is proposed regarding both skin and eye irritation according to the CLP and to the GHS.

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.