Registration Dossier

Administrative data

Description of key information

Skin irritation: Not irritating (OECD 404, Rel.2, K)

Eye irritation: Not irritating (OECD 405, GLP, Rel. 1, K)

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:
1986
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study was performed according to OECD guideline 404 and GLP conditions not specified.
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to other study
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
1981
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Version / remarks:
Directive 84/449/EEC
Deviations:
no
Principles of method if other than guideline:
Not applicable
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: HOECHST AG, Kastengrund, conventional breed
- Age at study initiation: ca. 3 - 5 months
- Weight at study initiation: 3.1 - 3.4 kg
- Housing: Individually
- Diet: ad libitum Altromin 2123 rabbit diet
- Water: ad libitum deionized, chlorated water
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3
- Humidity (%): 50 ± 20
- Air changes (per hr): Fully airconditioned rooms
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: no data
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
physiological saline
Remarks:
0.9% NaCl solution
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.3 ml
- Concentration (if solution): 500 mg in 0.3 ml
Duration of treatment / exposure:
4 hours
Observation period:
Not specified
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: 2.5 x 2.5 cm
- Type of wrap if used: Approx. 24 hours prior to the start of the experiment 3 rabbits were depilated in the dorsal region of the trunk with an electric hair clipper on an area of approx. 25 cm2. Only animals with intact skin were used. Each animal was fixed on the prepared skin site with a wound plaster with 2.5 x 2.5 cm. The area was covered with a semi-occlusive dressing.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): remaining test substance removed with lukewarm tap water
- Time after start of exposure: 4 hours

SCORING SYSTEM: subjective numerical according to OECD Guideline 404 (Erythema and Eschar formation / Oedema formation). Maximum possible score: 4
Irritation parameter:
erythema score
Basis:
mean
Remarks:
all animals
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
mean
Remarks:
all animals
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
No irritant/corrosive response observed 30 min, 60 min, 24 h, 48h, 72h after removal of the patch.
Other effects:
None
Interpretation of results:
GHS criteria not met
Conclusions:
Under the test conditions, the test substance Tanfix AL is not classified according to the Regulation (EC) No. 1272/2008 (CLP) and to the GHS.
Executive summary:

A skin irritation study was performed according to OECD Guideline 404. 500 mg of test substance was applied to the clipped skin in 0.3 ml of physiological saline of three New Zealands White rabbits under a semi-occlusive cover. After a 4-hour exposure period, the remaining test substance was removed with lukewarm tap water. No reactions were observed.

Mean individual scores at 24, 48 and 72 h after exposure for the 3 animals were 0.0 / 0.0 /0.0 for erythema and 0.0 / 0.0 / 0.0 for edema.

Under the test conditions, the test substance Tanfix AL is not classified according to the Regulation (EC) No. 1272/2008 (CLP) and to the GHS.

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:
20 November 2001 - 30 November 2001
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
Test was conducted according to OECD Test Guideline No. 405, 1987, under GLP Standards, and QA.
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to other study
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
1987
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Version / remarks:
Directive 92/69/EEC
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.2400 (Acute Eye Irritation)
Version / remarks:
1998
Deviations:
no
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes
Remarks:
Statement of Compliance
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland GmbH
- Age at study initiation: no data
- Weight at study initiation: 2.9 - 3.2 kg
- Housing: in fully air-conditioned rooms in separate cages arranged in a battery
- Diet: ssniff K-H (V2333), ad libitum and hay (approx. 15 g daily)
- Water: water from automatic water dispensers, ad libitum
- Acclimation period: 1 week under study conditions

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3
- Humidity (%): 50 ± 20
- Air changes (per hr): fully air-conditioned
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: no data
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 g
Duration of treatment / exposure:
24 hours
Observation period (in vivo):
At 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): washed out thoroughly with isotonic saline at approx. 37 °C
- Time after start of exposure: 24 hours and at designated examination times at which discharge was observed or a corneal examination with fluorescein was performed

SCORING SYSTEM: subjective numerical according to OECD Guideline 405 (corneal (opacity and area), iridic and conjunctival irritation (redness/chemosis/discharge)).

TOOL USED TO ASSESS SCORE: fluorescein
Irritation parameter:
cornea opacity score
Remarks:
opacity
Basis:
mean
Remarks:
all animals
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
mean
Remarks:
all animals
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
other: not applicable
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
mean
Remarks:
all animals
Time point:
24/48/72 h
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 72 hours
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
all animals
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 24 hours
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
One hour up to 48 hours after administration the conjunctivae of all animals showed definitely injected blood vessels up to diffuse crimson color, so that individual vessels were not easily discernible. Swelling with lids about half closed was observed in all animals one hour after administration. In addition, serious-colorless eye discharge was noted. 72 hours after administration all signs of irritation had completely disappeared.
Other effects:
None

Table 7.3.2 Individual scores

 

1h

24h

48h

72h

Mean 24/48/72h

Corneal opacity

0 / 0 / 0

0 / 0 / 0

0 / 0 / 0

0 / 0 / 0

0 / 0 / 0

Iris

0 / 0 / 0

0 / 0 / 0

0 / 0 / 0

0 / 0 / 0

0 / 0 / 0

Redness

2 / 2 / 2

2 / 2 / 2

1 / 1 / 1

0 / 0 / 0

1 / 1 / 1

Chemosis

3 / 3 / 3

0 / 0 / 0

0 / 0 / 0

0 / 0 / 0

0 / 0 / 0

Discharge

2 / 2 / 2

0 / 0 / 0

0 / 0 / 0

0 / 0 / 0

0 / 0 / 0

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

An eye irritation study was performed according to OECD Guideline 405 and in compliance with GLP. One eye of three rabbits each was exposed to 0.1g of the test substance for 24 hours. Observation occurred at 1, 24, 48 and 72 hours. One hour up to 48 hours after administration the conjunctivae of all animals showed definitely injected blood vessels up to diffuse crimson color, so that individual vessels were not easily discernible. Swelling with lids about half closed was observed in all animals one hour after administration. In addition, serous-colorless eye discharge was noted. 72 hours after administration all signs of irritation had completely disappeared.

Mean individual scores at 24, 48 and 72 h after exposure for the 3 animals were 0.0 / 0.0 / 0.0 for cornea score; 0.0 / 0.0 / 0.0 for iris score; 1.0 / 1.0 / 1.0 for conjunctivae score and 0.0 / 0.0 / 0.0 for chemosis score.

Under the test conditions, the test material Locron P is not classified according to the Regulation (EC) No. 1272/2008 (CLP) and to the GHS.

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation

A key study was identified (Hofmann, 1986). In this skin irritation study performed according to OECD Guideline 404, 500 mg of test substance in 0.3 ml of physiological saline was applied to the clipped skin of three New Zealands White rabbits under a semi-occlusive cover. After a 4 -hour exposure period, the remaining test substance was removed with lukewarm tap water. No reactions were observed.

Eye irritation

A key study was identified (Kauffmann, 2001). In this eye irritation study was performed according to OECD Guideline 405 and in compliance with GLP. One eye of three rabbits each was exposed to 100 mg of the test substance for 24 hours. One hour up to 48 hours after administration the conjunctivae of all animals showed definitely injected blood vessels up to diffuse crimson color, so that individual vessels were not easily discernible. Swelling with lids about half closed was observed in all animals one hour after administration. In addition, serous-colorless eye discharge was noted. 72 hours after administration all signs of irritation had completely disappeared.

Justification for classification or non-classification

Harmonized classification:

The substance has no harmonized classification for skin or eye irritation according to the Regulation (EC) No. 1272/2008.

Self classification:

Skin irritation

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

Eye irritation

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

Respiratory irritation

No data was available.