Registration Dossier

Administrative data

Description of key information

Non irritant for skin

Non irritant for eye

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:
other: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
1983
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
The test was conducted on a similar substance. The complete justification for the read across is attached at section 13.
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: Kleintierfarm Madoerin AG, CH-4414 Fuellinsdorf
- Age at study initiation: 12 - 14 weeks
- Weight at study initiation: 2 - 3 kgs
- Housing: Animals were housed individually in metal cages.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20± 3 °C
- Humidity (%): 30-70
- Air changes (per hr): 12 hours light/day
- Photoperiod (hrs dark / hrs light): approximately 15 air changes/h
Type of coverage:
open
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
not specified
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g
Duration of treatment / exposure:
4 hours
Observation period:
7 days
Number of animals:
3 animals
Details on study design:
TEST SITE
- Area of exposure: 6 sq. cm

SCORING SYSTEM: After removal of the dressings the skin reaction was assessed on the basis of an evaluation scheme (DRAIZE),
Irritation parameter:
erythema score
Basis:
animal: 19, 21
Time point:
other: 24, 48 and 72 hours
Score:
ca. 0
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
edema score
Basis:
animal: 19, 21
Time point:
other: 24, 48 and 72 hours
Score:
ca. 0
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
erythema score
Basis:
animal: 20
Time point:
other: 24, 48 and 72 hours
Score:
ca. 0.33
Max. score:
4
Reversibility:
fully reversible within: 24 h
Irritation parameter:
edema score
Basis:
animal: 20
Time point:
other: 24, 48 and 72 hours
Score:
ca. 0.33
Max. score:
4
Reversibility:
fully reversible within: 24 h
Interpretation of results:
other: Not classified according to the CLP Regulation
Conclusions:
The substance showed to be not irritant and not corrosive .
Executive summary:

The skin irritation study was conducted in rabbits according to OECD guideline 404.

Not less than 24 hours before treatment on the back of the experimental animal an area was shaven of at least 6 sq. cm, by means of an electric clipper. A gauze patch bearing 0.5 g of the test substance was applied to the skin and loosely held in place by adhesive but non irritating tape. The substance was water moistened before application. Exposure duration was 4 hours. After removal of the dressings the skin reaction was assessed on the basis of an evaluation scheme (Draize scoring system).

Under the conditions of the present experiment the substance was found to be not irritating when applied to the rabbit skin according to the CLP Regulation (EC n. 1272/2008).

Endpoint:
skin irritation: in vivo
Type of information:
other: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
From July 6, 1993 to July 13, 1993
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
The test was conducted on a similar substance. The complete justification for the read across is attached at section 13.
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
Principles of method if other than guideline:
Guidelines followed
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Broekman Institute, Someren, The Netherlands.
- Age at study initiation: Approx 12 weeks
- Weight at study initiation: 2374-2688 g
- Housing: Individually in labelled cages with perforated floors and equipped with an automatic drinking system (ITL, Bergen, The Netherlands).
- Diet: Standard laboratory rabbit diet (LKK-20, pellet diameter 4mm, Hope Farms, Woerden, The Netherlands) approximately 100 g/d.
- Water: Tap-water diluted with decalcified water, ad libitum
- Acclimation period: At least five d after veterinary examination.

ENVIRONMENTAL CONDITIONS
- Temperature: 21 °C
- Humidity: 55 %
- Air changes: Air-conditioned with 15 air changes/h
- Photoperiod: 12 h artificial fluorescent light/12 h dark

IN-LIFE DATES: From July 6, 1993 to July 13, 1993
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
other: the untreated flank of the same animal
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied: 500 mg
Duration of treatment / exposure:
4 h
Observation period:
7 d
Number of animals:
Three male animals
Details on study design:
TEST SITE
- Area of exposure: Approx 10x15 cm2
- Type of wrap if used: The test substance was applied using a moistened Scotchpak-non-woven patch mounted on Micropore tape. The dressing was wrapped around the abdomen and secured with an elastic bandage

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Removed at the end of the exposure period using a tissue moistened with tap-water and subsequently a dry tissue.
- Time after start of exposure: 4 h

SCORING SYSTEM: Draize scoring system
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: 24, 48 and 72 h
Score:
0.67
Max. score:
4
Reversibility:
fully reversible within: 72 h
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: 24, 48 and 72 h
Score:
0
Max. score:
4
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: 24, 48 and 72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 7 d
Irritation parameter:
edema score
Basis:
animal #2
Time point:
other: 24, 48 and 72 h
Score:
0
Max. score:
4
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
other: 24, 48 and 72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 7 d
Irritation parameter:
edema score
Basis:
animal #3
Time point:
other: 24, 48 and 72 h
Score:
0
Max. score:
4
Irritant / corrosive response data:
Very slight erythema was observed in all three animals. The erythema had resolved within 72 h in one animal and within 7 days on other animals. Oedema was not observed in any of the animals during the observation period. Yellow staining of the treated skin by the test substance was observed in the three animals during the study. The body weights and variability in body weight gain of the animals were considered to be normal. No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred.
Other effects:
Except for yellow staining of the treated skin in all three animals, there were no signs of corrosion, body weight variability, toxicity or mortality in any animal during the observation period.
Interpretation of results:
other: Not classified according to the CLP Regulation
Conclusions:
Under the study conditions, the test substance was considered to be non-irritating to skin.
Executive summary:

A study was conducted to evaluate the skin irritation potential of the test substance in New Zealand White rabbits according to OECD Guideline 404 and EU Method B.4 in compliance with GLP.

500 mg of test substance was applied to a clipped skin area of 10 cm x 15 cm on one flank of each animal under a moistened 2 cm x 3 cm patch. The patch was held in contact with the skin for 4 h. Animals were scored for irritation reactions after 75 minutes, 24, 48 and 72 h, and then 7 d. Animals were monitored daily for viability, mortality and clinical signs. Body weights were recorded pre-test and at study termination.

No dermal reactions were observed throughout the observation period. No test substance-related effects on body weight gain, clinical signs or viability were observed.

Under the study conditions, the test substance was considered to be non-irritating to skin according to the CLP Regulation (EC n. 1272/2008).

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:
other: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
1983
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
The test was conducted on a similar substance. The complete justification for the read across is attached at section 13.
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Principles of method if other than guideline:
Guidelines followed
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Kleintierfarm Madoerin AG, CH-4414 Fuellinsdorf
- Age at study initiation: 12 - 14 weeks
- Weight at study initiation: 2 - 3 kgs
- Housing: Animals were housed individually in metal cages.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum):ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20±3 °C
- Humidity (%): 30-70
- Air changes (per hr): 15 air changes/h
- Photoperiod (hrs dark / hrs light): 12 hours light/day

Vehicle:
unchanged (no vehicle)
Controls:
other: The left eye remained untreated and served as a control.
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 g
Duration of treatment / exposure:
Single injection
Observation period (in vivo):
1, 24, 48, and 72 hours
Number of animals or in vitro replicates:
3 animals
Details on study design:
SCORING SYSTEM: The ocular irritation scores were evaluated according to the gradings mentioned in "Grades for ocular lesions"

Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
ca. 0
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
ca. 0
Max. score:
2
Reversibility:
fully reversible
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
ca. 0
Max. score:
3
Reversibility:
fully reversible
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
ca. 0
Max. score:
4
Reversibility:
fully reversible
Irritant / corrosive response data:
The substance showed to be slightly irritant and not corrosive
Interpretation of results:
other: Not classified according to the CLP Regulation
Conclusions:
The substance is not irritant and not corrosive.
Executive summary:

The purpose of the study was to find out the eye irritation potential of test item in rabbits. The study was conducted according to OECD guidelines 405.

The test substance was placed into the conjunctival sac of the right eye of each animal in the amount of 0.1 g after gently pulling away the lower lid from the eyeball. The lids were then held together for about one second in order to prevent loss of the test material. The left eye remained untreated and served as a control.

The eyes were examined at 1, 24, 48, and 72 hours after substance instillation.

Under the conditions of the present experiment the substance was found to be not irritant when applied to the rabbit eye mucosa according to the CLP Regulation (EC n. 1272/2008).

Endpoint:
eye irritation: in vivo
Type of information:
other: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
From 12 July, 1993 to 19 July, 1993
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
The test was conducted on a similar substance. The complete justification for the read across is attached at section 13.
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
Principles of method if other than guideline:
Guidelines followed
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Broekman Institute, Someren, The Netherlands.
- Age at study initiation: Approximately 12 weeks
- Weight at study initiation: 2233-2539 g
- Housing: Individually in labelled cages with perforated floors and equipped with an automatic drinking system (ITL, Bergen, The Netherlands).
- Diet (e.g. ad libitum): Standard laboratory rabbit diet (LKK-20, pellet diameter 4 mm, Hope Farms, Woerden, The Netherlands) approximately 100 g/d
- Water (e.g. ad libitum): Tap-water diluted with decalcified water, ad libitum
- Acclimation period: At least 5 d after veterinary examination.

ENVIRONMENTAL CONDITIONS
- Temperature: 21 °C
- Humidity: 55%
- Air changes: Air-conditioned with 15 air changes/h
- Photoperiod: 12 h artificial fluorescent light/12 h dark.

IN-LIFE DATES: From July 12, 1993 to July 19, 1993
Vehicle:
unchanged (no vehicle)
Controls:
other: untreated eye
Amount / concentration applied:
TEST MATERIAL
- Amount applied (weight with unit): 87 ± 1 mg/animal
Duration of treatment / exposure:
Single exposure
Observation period (in vivo):
Up to 7 d (The eyes of each animal were examined for irritation for approx. 1, 24, 48 and 72 h and 7 d after instillation of the test substance)
Number of animals or in vitro replicates:
3 males
Details on study design:
Prior to test substance instillation, the animals were physically examined to ensure normal ocular surface integrity.

SCORING SYSTEM: Draize scoring system

TOOL USED TO ASSESS SCORE: Fluorescein
Irritation parameter:
cornea opacity score
Basis:
animal: 1491, 1492, 1493
Time point:
other: 24, 48 and 72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
iris score
Basis:
animal: 1491, 1492, 1493
Time point:
other: 24, 48 and 72 h
Score:
0
Max. score:
2
Reversibility:
fully reversible
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
animal: 1491, 1492, 1493
Time point:
other: 24, 48 and 72 h
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 7 d
Irritation parameter:
chemosis score
Basis:
animal: 1491, 1492, 1493
Time point:
other: 24, 48 and 72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible
Other effects:
There were no signs of periocular tissue staining, body weight variability, toxicity or mortality in any animal during the observation period.
Interpretation of results:
other: not classified according to the CLP Regulation
Conclusions:
Under the study conditions, the test substance produced mild conjunctival reactions which were reversible within 7 d.
Executive summary:

A study was conducted to assess the eye irritancy potential of the test substance in New Zeland White rabbits according to OECD Guideline 405 and EU Method B.5 in compliance with GLP.

A single ocular dose of 87±1 mg of test substance was applied into the lower eye lid of one eye of each animal. The eyelids were then gently held together for one second before releasing. The untreated eye served as control. Without washing, eyes were scored for irritation reactions at 1, 24, 48, and 72 h and 7 d post-instillation.

Slight conjunctival irritation was observed, which resolved within 7 d of instillation. Ocular corrosion was not observed in any of the rabbits. Also, no signs of systemic intoxication were seen.

The substance is considered as not irritating according to the CLP Regulation (EC n. 1272/2008)

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for classification or non-classification

Skin Irritation

According to the CLP Regulation (EC 1272/2008), 3.2 Skin corrosion/irritation section, skin Irritation means the production of reversible damage to the skin following the application of a test substance for up to 4 hours.

The key study shows a very low interaction between the substance and the skin rabbit, the values of erythema and oedema are below the trigger values for classification, therefore no classification is warranted according to the CLP Regulation (EC n. 1272/2008).

Eye Irritation

According to the CLP Regulation (EC n. 1272/2008) eye irritation means the production of changes in the eye following the application of test substance to the anterior surface of the eye, which are fully reversible within 21 days of application.

The substance is not capable to produce serious eye irritations signs and after 72 hours of observation period all effects are fully recovered or below the trigger value for classification; therefore no classification is warranted according to the CLP Regulation (EC n. 1272/2008).