Registration Dossier

Diss Factsheets

Administrative data

Description of key information

Skin irritation/corrosion: not irritating (OECD 404/EU Method B.4, GLP);

Eye irritation/corrosion: not irritating (OECD 405/EU Method B.5, GLP)

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:
1994-04-26 to 1994-04-29
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
1992-07-17
Deviations:
yes
Remarks:
body weight was not measured at the conclusion of the test; description of any other toxic effects besides skin reactions were not recorded.
GLP compliance:
yes (incl. QA statement)
Remarks:
signed 1994-03-16
Specific details on test material used for the study:
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: David Percival Ltd., Moston, Sandbach, Cheshire, U.K.
- Age at study initiation: twelve to sixteen weeks
- Weight at study initiation: 2.49 - 2.56 kg
- Housing: individually housed in suspended metal cages
- Diet (ad libitum): STANRAB SQC Rabbit Diet
- Water (ad libitum): mains drinking water
- Acclimation period: minimum of 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 18 - 23 °C
- Relative humidity: 51 - 59 %
- Air changes: approx. 15/hour
- Photoperiod (hrs dark / hrs light): 12:12

Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
other: distilled water
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g test material moistened with 0.5 mL of distilled water
Duration of treatment / exposure:
4 hours
Observation period:
72 hours
Number of animals:
3 male rabbits
Details on study design:
TEST SITE
- Area of exposure: skin area on the back was clipped
- Type of wrap if used: test item was introduced under a 2.5 cm x 2.5 cm gauze patch, which was secured with a strip of surgical adhesive tape (BLENDERM). Furthermore, each animal was wrapped in an elasticated corset (TUBIGRIP).

REMOVAL OF TEST SUBSTANCE
- Washing: test material removed by gently swabbing with cotton wool soaked in distilled water
- Time after start of exposure: 4 hours

OBSERVATION TIME POINTS
- approx. 1 hour as well as 24, 48 and 72 hours after removal of the test material

SCORING SYSTEM:
- Method of calculation: according to the Draize scale
Any other skin reactions were also recorded.

Irritation parameter:
erythema score
Basis:
mean
Remarks:
animal No. 1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
mean
Remarks:
animal No. 1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
erythema score
Basis:
mean
Remarks:
animal No. 2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
mean
Remarks:
animal No. 2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
erythema score
Basis:
mean
Remarks:
animal No. 3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
mean
Remarks:
animal No. 3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritant / corrosive response data:
No skin reactions were noted during the study.
Interpretation of results:
GHS criteria not met
Conclusions:
The substance is not irritating to the skin based on an in vivo study (OECD 404).
According to Regulation (EC) No 1272/2008 and subsequent adaptations, the substance does not require classification as skin irritant.
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2001-10-17 to 2001-10-27
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Version / remarks:
1992-07-31
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Remarks:
signed 2001-08-22
Specific details on test material used for the study:
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: kept dry and cool in the dark


Species:
rabbit
Strain:
other: albino
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Dr. Zimmermann, Schweizer Hof, D-73453 Untergröningen/Aalen
- Weight at study initiation: 3832, 3204 and 3617 g.
- Housing: separate housing in zinc-wire cages (area: 2450 cm²) without bedding material
- Diet (ad libitum): Raiffeisen Ringfutter Kaninchen Trockenfutter 52/P Raiffeisen Kraftfutter Kehl
- Water (ad libitum): tap water
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 20 - 23 °C
- Relative humidity: 30 - 70 %
- Photoperiod (hrs dark / hrs light): 12:12
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): 500 mg of the test substance moistened with water
Duration of treatment / exposure:
4 hours
Observation period:
6 days
Number of animals:
3 males
Details on study design:
TEST SITE
- Area of exposure: skin area (approx. 3 x 5 cm²) on the back was shaved the day before test item application
- Type of wrap if used: after the test item was applied, the treated area was covered with a patch (6 cm width) and fixed with an occlusive dressing (completely cellophaned). The bandage was fixed with adhesive ST-Tape (Wero-Medical).

REMOVAL OF TEST SUBSTANCE
- Washing: treated skin was washed with water
- Time after start of exposure: 4 hours

OBSERVATION TIME POINTS
- 1 hour as well as 1, 2, 3, 4, 5 days after removal of the test substance

SCORING SYSTEM:
- Method of calculation: Draize scale

OBSERVATIONS:
- mortality
- clincial signs
- body weight
- behaviour
- skin reaction
Irritation parameter:
erythema score
Basis:
mean
Remarks:
animal No. 1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
mean
Remarks:
animal No. 1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
erythema score
Basis:
mean
Remarks:
animal No. 2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
mean
Remarks:
animal No. 2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
erythema score
Basis:
mean
Remarks:
animal No. 3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
mean
Remarks:
animal No. 3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritant / corrosive response data:
No dermal irritation was observed in any of the rabbits during the study.
Other effects:
Observations:
- mortality: no mortality occured during the study
- clincial signs: no clincal signs were observed
- body weight: body weight gain was observed during the observation period.
- behaviour: animals were calm and alert
Interpretation of results:
GHS criteria not met
Conclusions:
The substance is not irritating to the skin based on an in vivo study (EU Method B.4).
According to Regulation (EC) No 1272/2008 and subsequent adaptations, the substance does not require classification as skin irritant.
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:
2001-10-17 to 2001-10-26
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Version / remarks:
1992-07-31
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Remarks:
signed 2001-08-22
Specific details on test material used for the study:
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: kept dry and cool in the dark
Species:
rabbit
Strain:
other: albino
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Dr. Zimmermann, Schweizer Hof, D-73453 Untergröningen/Aalen
- Weight at study initiation: 3277, 3828 and 3472 g.
- Housing: housed individually in zinc-wire cages (area: 2450 cm²) without bedding material
- Diet (ad libitum): Raiffeisen Ringfutter Kaninchen Trockenfutter 52/P Raiffeisen Kraftfutter Kehl
- Water (ad libitum): tap water
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 20 - 23 °C
- Relative humidity: 30 - 70 %
- Photoperiod (hrs dark / hrs light): 12/12
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 g of the test item
Duration of treatment / exposure:
24 hours
Observation period (in vivo):
immediately and 1 hour as well as 1, 2, 3, 4 and 5 days after treatment
Number of animals or in vitro replicates:
3 males
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): 0.9 % NaCl
- Time after start of exposure: 24 hours

SCORING SYSTEM: Draize scale

OBSERVATIONS:
- mortality
- clincial signs
- body weight
- behaviour
- eye reaction
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
mean
Remarks:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
3
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
mean
Remarks:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
3
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
mean
Remarks:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
3
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritant / corrosive response data:
At the 1 hour observation, slight conjunctival redness (score: 1 of 3) with serious exudation was observed in all treated eyes. No effects were observed in the untreated control eyes.
Other effects:
- mortality: no mortality occured during the study
- clincial signs: no clinical signs were observed during the study
- body weight: body weight gain was observed during the observation period
- behaviour: animals were calm and alert

Interpretation of results:
GHS criteria not met
Conclusions:
The substance is not irritating to the eyes.
According to Regulation (EC) No 1272/2008 and subsequent adaptations, the substance does not require classification as eye irritant.
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1994-05-03 to 1994-05-08
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
1987-02-24
Deviations:
yes
Remarks:
slightly modified Draize scale
GLP compliance:
yes (incl. QA statement)
Remarks:
signed 1994-03-16
Specific details on test material used for the study:
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: David Percival Ltd., Moston, Sandbach, Cheshire, U.K.
- Age at study initiation: approx. 12 - 16 weeks old
- Weight at study initiation: 2.56 - 2.80 kg
- Housing: individually housed in suspended metal cages
- Diet (ad libitum): STANRAB SQC Rabbit Diet
- Water (ad libitum): mains drinking water
- Acclimation period: minimum of 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 18 - 23 °C
- Relative humidity: 55 - 67 %
- Air changes: approx. 15/hour
- Photoperiod (hrs dark / hrs light): 12/12
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL of the test substance (approx. 78 mg)
Duration of treatment / exposure:
not applicable
Observation period (in vivo):
approx. 1 hour and 24, 48, and 72 hours following treatment
Number of animals or in vitro replicates:
2 male rabbits / 1 female rabbit
Details on study design:
INITIAL AND CONFIRMATORY TEST
One rabbit was initially treated. After consideration of te ocular responses produced in the first treated animal, two additional animals were treated.

USAGE OF ANAESTHETICS AND SYSTEMIC ANALGESICS
In order to minimise pain on instillation of the test material, one drop of local anaesthetic ("Ophthaine", 0.5 % proxymetacaine hydrochloride) was instilled into both eyes of one animal 1 - 2 minutes before treatment.

SCORING SYSTEM: modified Draize scale
Any other adverse ocular effects were also noted.
Immediately after administration of the test material, an assessment of the initial pain reaction was made.

TOOL USED TO ASSESS SCORE: standard ophthalmoscope
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
mean
Remarks:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
animal #1
Time point:
24/48/72 h
Score:
0.3
Max. score:
3
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
mean
Remarks:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
animal #2
Time point:
24/48/72 h
Score:
0.3
Max. score:
3
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
animal #2
Time point:
24/48/72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
mean
Remarks:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
animal #3
Time point:
24/48/72 h
Score:
0.3
Max. score:
3
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritant / corrosive response data:
- residual test material was noted around the treated eye of all animals at the one hour observation.
- dulling of the normal lustre of the cornea was noted in all treated eyes at the one hour observation. No other corneal effects were noted.
- transient iridial inflammation was noted in all treated eyes at the one hour observation
- moderate conjunctival irritation was noted in all treated eyes at the one hour observation with minimal conjunctival irritation persisting at the 24-hour observation
- all treated eyes appeared normal at the 48-hour observation

Interpretation of results:
GHS criteria not met
Conclusions:
The substance is not irritating to the eyes.
According to Regulation (EC) No 1272/2008 and subsequent adaptations, the substance does not require classification as eye irritant.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Additional information

Skin irritation

The substance was not observed to be irritating to the skin in two reliable in vivo skin irritation studies according to OECD 404 and EU method B.4, respectively.

Eye irritation

The substance was not observed to be irritating to the eyes in two reliable in vivo skin irritation studies according to OECD 405 and EU method B.5, respectively.

Justification for classification or non-classification

Skin irritation

The substance does not possess a skin irritating potential based on two in vivo skin irritation studies based on either OECD 404 (1992) or EU Method B.4 (1992). The substance does not require classification as skin irritating according to Regulation (EC) No 1272/2008 and its subsequent adaptations.

Eye irritation

The substance does not possess an eye irritating potential based on two in vivo eye irritation studies based on either OECD 405 (1987) or EU Method B.5 (1992). The following findings were made during the study, but these did not lead to a classification:

Allen (1994): at the one hour observation dulling of the normal lustre of the cornea, transient iridial inflammation, and moderate conjunctival irritation were observed in all animals. At the 24 hour observation minimal conjunctival irritation was observed in all animals. All treated eyes appeared normal at the 48 hour observation.

Bücher (2001): at the 1 hour observation, slight conjunctival redness with serious exudation was observed in all treated eyes. No further effects were observed.

The substance does not require classification as eye irritating according to Regulation (EC) No 1272/2008 and its subsequent adaptations.