Registration Dossier

Administrative data

Description of key 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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: according to information in OECD SIDS (2002)
Principles of method if other than guideline:
Skin irritation was tested using an internal standard method (BASF test). White Vienna rabbits were used. 2 animals were treated for 1, 5 and 15 minutes and for 20 hours usually using occlusive conditions. An application site of 2.5 X 2.5 cm was covered with the moistened test substance using cotton patches of this size.
GLP compliance:
no
Species:
rabbit
Strain:
Vienna White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Gaukler (breeder)
- Weight at study initiation: 3.14kg and 3.3 kg


ENVIRONMENTAL CONDITIONS
not reported
Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
water
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): ca. 1 mL (80% aqueous solution) administered using cotton patches of 2.5 x 2.5 cm size.
Duration of treatment / exposure:
Experiment 1: 1, 5, or 15 minutes
Experiment 2: 20 h
Observation period:
8 days (observations at 1, 3, 4, 7 and 8 days post patch removal)
Number of animals:
2
Details on study design:
TEST SITE
- Area of exposure:
An application site of 2.5 X 2.5 cm was covered with the aqueous solution of the test substance (37°C; approx. 1 ml) using a cotton pad of this size.

REMOVAL OF TEST SUBSTANCE

Experiment 1:
Washing of the treated skin in the 1 min, 5 min and 15 min test immediately after the respective treatment period. Concentrated Lutrol (a mild detergent) and a 50% aqueous solution therof was used for washing.

Experiment 2: No washing was done after the 20 h treatment period.

SCORING SYSTEM:
Descriptive grading in the raw data: no effect / questionable / slight / strong / very strong.
In addition, indication of the type of finding as appropriate: erythema / edema / scale formation / necrosis / scar.
The descriptive scores in the raw data were converted into OECD/ Draize scores.

Irritation parameter:
erythema score
Remarks:
after 20 h treatment period
Basis:
animal #1
Time point:
24 h
Score:
0.5
Max. score:
4
Reversibility:
fully reversible within: 72 h
Remarks on result:
other: Treated skin was not washed after the 20 h treatment period. Skin irritation was evaluated after 24 h and 72 h but not after 48 h.
Irritation parameter:
erythema score
Remarks:
after 20 h treatment period
Basis:
animal #2
Time point:
24 h
Score:
0.5
Max. score:
4
Reversibility:
fully reversible within: 72 h
Remarks on result:
other: Treated skin was not washed after the 20 h treatment period. Skin irritation was evaluated after 24 h and 72 h but not after 48 h.
Irritation parameter:
edema score
Remarks:
after 20 h treatment period
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: Treated skin was not washed after the 20 h treatment period
Irritation parameter:
edema score
Remarks:
after 20 h treatment period
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: Treated skin was washed after the 20 h treatment period
Other effects:
No other effects were evident.
Interpretation of results:
other: not irritating according to EU regulation
Conclusions:
Based on the results of the present study, the test substance has not to be classified as skin irritant following EU CLP requirements. At 48 h post patch removal, skin irritation was not recorded. Nevertheless, in view of only minimal findings at 24 h and the absence of findings at 72 h post patch removal, the study result is fully conclusive regarding classification and labelling according to EU regulations.
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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: according to information in OECD SIDS (2002)
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
; 50 mg instead of 100 mg test substance instilled
GLP compliance:
no
Species:
rabbit
Strain:
Vienna White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Gaukler (breeder)
- Weight at study initiation: 2.98 and 3.09 kg


ENVIRONMENTAL CONDITIONS
not reported
Vehicle:
unchanged (no vehicle)
Controls:
other: 50 mg talcum into the other eye
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit):
50 mg into the conjunctival sac of one eye per rabbit. The contralateral eye received 50 mg talcum to serve as a control.
Duration of treatment / exposure:
Once. There was no mentioning in the raw data or report that eyes were rinsed after treatment. Consequently the treatment/exposure period was equivalent to the entire observation period following administration, which was 8 days, or lasted until removal of the test material by physiological mechanisms, whichever happened sooner.
Observation period (in vivo):
8 days (observations at 10 min, 1 h, 3h, 1, 2, 3, 4, 7 and 8 days post instillation)
Number of animals or in vitro replicates:
2
Details on study design:
SCORING SYSTEM:
Descriptive grading in the raw data: no effect / questionable / slight / strong / very strong.
In addition, indication of the type of finding as appropriate: erythema / edema / scale formation / necrosis / opacity / scar.
The descriptive scores in the raw data were converted into OECD/ Draize scores.

FLUORESCEIN:
On day 8 staining with fluorescein to support eye evaluation.
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.67
Max. score:
3
Reversibility:
fully reversible within: 48 h
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.67
Max. score:
3
Reversibility:
fully reversible within: 48 h
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Other effects:
Secretion was noted in one animal at 10 min post instillation in the other animal at 1 h post instillation, but was no longer seen thereafter.

 

Animal 

Reading 

Opacity

Iritis

Redness

Chemosis

Comment

1

 1 h

0

0

1

0

Secretion

2

 1 h

0

0

1

0

1

24 h

0

0

0

0

 

2

24 h

0

0

0

0

 

1

48 h

0

0

1

0

 

2

48 h

0

0

1

0

 

1

72 h

0

0

1

0

 

2

72 h

0

0

1

0

 

1

4 d

0

0

1

0

 

2

4 d

0

0

1

0

 

1

7 d

0

0

1

0

 

2

7 d

0

0

1

0

 

1

8 d

0

0

1

0

score before application of fluorescein

2

8 d

0

0

0

0

score before application of fluorescein

1

8 d

0

0

0

0

score after application of fluorescein

2

8 d

0

0

0

0

score after application of fluorescein

mean

24 - 72 h

0.00

0.00

0.67

0.00

 

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Since irritation data have been recommended for a 4 h treatment period of skin, results of the available 20 h and the 15 minute treatment periods served as approximation. At 48 h post patch removal, skin irritation was not recorded. Nevertheless, in view of only minimal irritation findings at 24 h and no findings at 72 h post patch removal, the study result is fully conclusive regarding classification and labelling according to EU regulations.

Descriptive eye irritation scores in the raw data were converted to OECD/Draize scores for the robust study summary. In deviation to the OECD 405 test guideline, only 50 mg instead of 100 mg of THEIC were instilled per treated eye. In view, of only very minor ocular findings (conjunctival redness, confined to Draize grade 1 in degree and transient secretion), the eye irritation study was fully adequate and conclusive regarding classification and labelling according to EU regulations.

Justification for classification or non-classification

The Draize scores derived from the skin and eye irritation studies in rabbits were very low and, in general, all findings were reversible. In the eye irritation study, effects in THEIC treated eyes were rather less than those in the talcum treated control eyes. At the end of the observation period (8 days post instillation), both talcum and THEIC resulted in slight conjunctival redness in one animal the other animal showing no reactions on this day.

According to EU classification rules [REGULATION (EC) 1272/2008] these minor findings in the skin and eye irritation studies do not require any classification and labelling regarding skin and eye irritation.