Registration Dossier

Administrative data

Description of key information

The test substance is not classified as irritating to skin or eyes

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:
13 January 1998 to 20 January 1998
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted to recent EU & OECD test guidance in compliance with GLP.
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland GmbH
- Weight at study initiation: 3.1 - 3.8 kg
- Housing: Full air-conditioned rooms in separate cages arranged in a battery
- Diet (e.g. ad libitum): ssniff K-H (V2333), ad libitum and hay (approx. 15 g daily)
- Water (e.g. ad libitum): water from automatic water dispensers, ad libitum
- Acclimation period: 1 week under study conditions

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20
- Humidity (%): 50
- Photoperiod (hrs dark / hrs light): 12 hours daily

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

VEHICLE
- Amount(s) applied (volume or weight with unit): 0.4ml
Duration of treatment / exposure:
Exposure 4 hours
Observation period:
7 days
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: 2.5cm x 2.5 cm
- Type of wrap if used: surgical plaster

REMOVAL OF TEST SUBSTANCE
- Washing (if done): warm tap water
- Time after start of exposure: 4 hours

SCORING SYSTEM: DRAIZE
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24, 48, 72 hours
Score:
1.7
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24, 48, 72 hours
Score:
0.3
Max. score:
1
Reversibility:
fully reversible within: 2 days
Irritant / corrosive response data:
30-60 minutes and 24 hours after removal of the plaster the animals showed moderate erythema. Very slight oedema were observed 24 hours after removal of the plaster. 48 and 72 hours after removal of the plaster the animals showed very slight up to well defined erythema. 7 days after removal of the plaster all irritations were reversible.

Based on the individual scores for erythema and oedema after 24, 48 and 72 hours, the following mean values were calculated: Erythema and eschar formation all animals : 1.7
animal 66 : 1.3
animal 67 : 2.0
animal 68 : 1.7

Oedema formation all animals : 0.3
animal 66 : 0.3
animal 67 : 0.3
animal 68 : 0.3

Based on the results of this study the substance is slightly irritating to skin.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
30-60 minutes and 24 hours after removal of the plaster the animals showed moderate erythema. Very slight oedema were observed 24 hours after removal of the plaster. 48 and 72 hours after removal of the plaster the animals showed very slight up to well defined erythema. 7 days after removal of the plaster all irritations were reversible.

Based on the individual scores for erythema and oedema after 24, 48 and 72 hours, the following mean values were calculated:

Erythema and eschar
formation all animals : 1.7
animal 66 : 1.3
animal 67 : 2.0
animal 68 : 1.7

Oedema
formation all animals : 0.3
animal 66 : 0.3
animal 67 : 0.3
animal 68 : 0.3

Based on the results of this study the substance is slightly irritating to skin. The substance does not meet the EU criteria for classification on the basis of the effects noted.
Executive summary:

Study conducted to EU test guidance 92/69/EEC part B4 and OECD guideline 404 in compliance with GLP.

30-60 minutes and 24 hours after removal of the plaster the animals showed moderate erythema. Very slight oedema were observed 24 hours after removal of the plaster. 48 and 72 hours after removal of the plaster the animals showed very slight up to well defined erythema. 7 days after removal of the plaster all irritations were reversible.

Based on the individual scores for erythema and oedema after 24, 48 and 72 hours, the following mean values were calculated: Erythema and eschar formation all animals : 1.7

animal 66 : 1.3

animal 67 : 2.0

animal 68 : 1.7

Oedema formation all animals : 0.3

animal 66 : 0.3

animal 67 : 0.3

animal 68 : 0.3

Based on the results of this study the substance is slightly irritating to skin. The substance does not meet the EU criteria for classification on the basis of the effects noted.

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 January 1998 to 06 February 1998
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted to recent EU & OECD test guidance in compliance with GLP.
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland GmbH
- Weight at study initiation: 2.5 - 3.5 kg
- Housing: in fully air-conditioned rooms in separate cages arranged in a battery
- Diet (e.g. ad libitum): ssniff® K-H (V2333), ad libitum and hay (approx. 15 g daily)
- Water (e.g. ad libitum): water from automatic water dispensers, ad libitum
- Acclimation period: 1 week under study conditions

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 (±3°C)
- Humidity (%): 50 (±20%)
- Photoperiod (hrs dark / hrs light): 12 hours daily
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 100 mg applied neat.
Duration of treatment / exposure:
Exposure 24 hours
Observation period (in vivo):
72 hours
Number of animals or in vitro replicates:
3
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): isotonic saline at approx. 37 °C
- Time after start of exposure: 24 hours

SCORING SYSTEM: Scale for scoring ocular reactions

TOOL USED TO ASSESS SCORE: fluorescein-sodium solution
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
of all 3 animals
Time point:
other: Overall after 24, 48 & 72 hours
Score:
0
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
iris score
Basis:
mean
Remarks:
of all 3 animals
Time point:
other: overall after 24, 48 & 72 hours
Score:
0
Max. score:
2
Reversibility:
fully reversible
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: overall after 25, 48 & 72 hours
Score:
0.55
Max. score:
3
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
of all 3 animals
Time point:
other: overall after 24, 48 & 72 hours
Score:
0.11
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Irritant / corrosive response data:
One and 24 hours after administration the conjunctivae of the animals showed definetely injected blood vessels up to a difuse crimson red color and sporadically very slight up to obvious swellings. Additionally, clear from the substance colored eye discharge was noted. 48 hours after administration the conjunctivae of one animal showed definetely injected blood vessels. 72 hours after administration all signs of irritation were reversible.

Based on the individual scores after 24, 48 and 72 hours, the following mean values were calculated:

Opacity of cornea all animals : 0.00
animal 63 : 0.00
animal 64 : 0.00
animal 82 : 0.00

Ins all animals : 0.00
animal 63 : 0.00
animal 64 : 0.00
animal 82 : 0.00

Redness of
conjunctiva all animals : 0.55
animal 63 : 0.33
animal 64 : 0.33
animal 82 : 1.00

Chemosis of
conjunctiva all animals : 0.11
animal 63 : 0.00
animal 64 : 0.00
animal 82 : 0.33

Testing of the substance for primary eye irritation in the rabbit showed, that the substance is not irritating to eye.
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
One and 24 hours after administration the conjunctivae of the animals showed definetely injected blood vessels up to a difuse crimson red color and sporadically very slight up to obvious swellings. Additionally, clear from the substance colored eye discharge was noted. 48 hours after administration the conjunctivae of one animal showed definetely injected blood vessels. 72 hours after administration all signs of irritation were reversible.

Based on the individual scores after 24, 48 and 72 hours, the following mean values were calculated:

Opacity of cornea all animals : 0.00
animal 63 : 0.00
animal 64 : 0.00
animal 82 : 0.00

Ins all animals : 0.00
animal 63 : 0.00
animal 64 : 0.00
animal 82 : 0.00

Redness of
conjunctiva all animals : 0.55
animal 63 : 0.33
animal 64 : 0.33
animal 82 : 1.00

Chemosis of
conjunctiva all animals : 0.11
animal 63 : 0.00
animal 64 : 0.00
animal 82 : 0.33

Testing of the substance for primary eye irritation in the rabbit showed, that the substance is not irritating to eye.
Executive summary:

Study conducted to EU test guidance 92/69/EEC part B5 and to OECD test guideline 405 in compliance with GLP.

One and 24 hours after administration the conjunctivae of the animals showed definitely injected blood vessels up to a difusse crimson red colour and sporadically very slight up to obvious swellings. Additionally, clear from the substance coloured eye discharge was noted. 48 hours after administration the conjunctivae of one animal showed definitely injected blood vessels. 72 hours after administration all signs of irritation were reversible.

Testing of the substance for primary eye irritation in the rabbit showed, that the substance is not irritating to eye.

 

 

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

Respiratory irritation

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

Additional information

Skin irritation / Corrosion.

A single study was evaluated on this endpoint. In these the substance was tested for primary dermal irritation and corrosiveness. Results indicate that has a potential for slight dermal irritation, although effects were reversible within 7 days. It is not a dermal irritant or corrosive. No risk phrase or classification is required.

Eye irritation.

A single study was evaluated on this endpoint. In these the substance was tested for acute irritation and was found not to be an irritant to the rabbit eye. Effects were noted in all animals assessed; however these were fully reversible within 72 hours. No classification is applicable.

Respiratory irritation

Respiratory irritation was not assessed; however no effects on the animals were noted in any associated studies.

Justification for classification or non-classification

The above studies have all been ranked reliability 1 according to the Klimish et al system. This ranking was deemed appropriate because the studies were conducted to GLP an in compliance with agreed protocols. Sufficient dose ranges and numbers are detailed; hence it is appropriate for use based on reliability and animal welfare grounds.

The above results triggered no classification under the Dangerous Substance Directive (67/548/EEC) and the CLP Regulation (EC No 1272/2008). No classification for irritation effects is therefore required.