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Description of key information

Skin irritation study

The test item was not irritating to the skin of rabbits, under the test conditions chosen.

 

Eye irritation study

The test item was not irritating to the eyes of rabbits, under the test conditions chosen.

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:
From March 23, 2009 to October 5, 2009
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:
2002
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.2500 (Acute Dermal Irritation)
Version / remarks:
1998
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: MAFF in Japan, 12-Nousan-No. 8147, 2-1-4
Version / remarks:
2000
Deviations:
no
GLP compliance:
yes
Specific details on test material used for the study:
Batch no. 080722
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Minowa Breeding Center (Nagano, Japan) of Kitayama Labes Co., Ltd.
- Age at study initiation: 11 weeks
- Weight at study initiation: 2202 to 2494g
- Housing: Housed individually in an aluminum cage with wire-mesh floors (485 mm in width x 570 mm in depth x 360 mm in height). Cages were fixed into a stainless steel rack.
- Diet: Certified pellet diet LRC4 (Lot No. 081113, Oriental Yeast Co., Ltd., Tokyo, Japan), ad libitum
- Water: Tap water, ad libitum
- Acclimation period: 11 days

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 2°C
- Humidity: 50 ± 20 %
- Air changes (per hr): At least 10
- Photoperiod (hrs dark / hrs light): 12 hours of artificial light (0700 – 1900 GMT) in each 24-hour period

IN-LIFE DATES: From 07-April-2009 to 10-April-2009
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
yes
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.5 g moistened with 0.5 mL de-ionized water
Duration of treatment / exposure:
4 hours
Observation period:
72 hours
Number of animals:
3 female animals
Details on study design:
TEST SITE
- Area of exposure: Dorsolateral skin area
- Type of wrap: Cotton lint patches were held in place and wrapped with non-irritating adhesive tape

REMOVAL OF TEST SUBSTANCE
- Washing: De-ionized water
- Time after start of exposure: Yes, after the exposure for 4 hours

OBSERVATION TIME POINTS
1, 24, 48 and 72 hours

SCORING SYSTEM:
All animals were observed daily for signs of ill health or toxicity.

- Method of calculation:
Erythema / Eschar Formation Score
No erythema: 0
Very slight erythema (barely perceptible): 1
Well defined erythema: 2
Moderate to severe erythema: 3
Severe erythema (beef redness) to eschar formation preventing grading of erythema: 4

Edema Formation Score
No edema: 0
Very slight edema (barely perceptible): 1
Slight edema (edges of area well defined by definite raising): 2
Moderate edema (raised approximately l mm): 3
Severe edema (raised more than 1 mm and extending beyond area of exposure): 4
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Other effects:
Not specified
Interpretation of results:
GHS criteria not met
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:
From March 23, 2009 to October 5, 2009
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.2400 (Acute Eye Irritation)
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: JMAFF, No 12 Nosan No 8147
Deviations:
no
GLP compliance:
yes
Specific details on test material used for the study:
Batch no. 080722
Description: Pale yellow green powder
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Minowa Breeding Center (Nagano, Japan) of Kitayama Labes Co., Ltd.
- Age at study initiation: At least 10 weeks
- Weight at study initiation: 2168 to 2438 g
- Housing: Housed individually in aluminum cages with wire mesh floors.
- Diet: Certified pellet diet LRC4 (Lot No. 081113, Oriental Yeast Co., Ltd., Tokyo, Japan), ad libitum
- Water: Tap water, ad libitum
- Acclimation period: 11 days

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 2°C
- Humidity: 50 ± 20%
- Air changes (per hr): At least 10
- Photoperiod (hrs dark / hrs light): 12 hours of artificial light (07.00 – 19.00 GMT) in each 24-hour period

IN-LIFE DATES: From 07-Apr-2009 to 10-Apr-2009
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.1 g bulk volume


Duration of treatment / exposure:
24 hours
Observation period (in vivo):
maximum up to 28 days
Number of animals or in vitro replicates:
3 animals
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing: The main group’s eyes were not washed.

SCORING SYSTEM: See below

Cornea: degree of opacity (determined according to the most opaque area)
No ulceration or opacity: 0
Scattered or diffused opacity (different from the degree of cloudiness having ordinary luster); the details of the iris are clearly translucent: 1
There are some clear areas left, but nearly all of the iris is obscured: 2
Nacreous areas, no details of iris visible, size of pupil barely discernible: 3
Corneal opacity; iris not discernible through opaque areas: 4

Iris
Normal: 0
Clear and deep rugae, congestion, swelling, moderate hyperemia in the corneal periphery; any of these singly or in combination; the iris still reacts to light (reaction is slow and dull): 1
No reaction to light, haemorrhage, gross destruction (any or all of these): 2

Conjunctiva: Redness (refers to palpebral and bulbar conjunctiva)
Blood vessels normal: 0
Clear hyperemia in some blood vessels: 1
Diffuse crimson; individual blood vessels cannot be readily discerned: 2
Diffuse beefy red: 3

Edema (palpebral conjunctiva and/or nictitating membrane)
No swelling: 0
Greater than normal swelling (including nictitating membranes): 1
Obvious swelling accompanying ectropion of the eyelid: 2
Swelling such that the eyelid is less than half closed: 3
Swelling such that the eyelid is half or more closed: 4

Discharge
No discharge: 0
Any amount different from normal (does not include small amounts observed in inner canthus of normal animals): 1
Discharge with moistening of the lids and hairs just adjacent to lids: 2
Discharge with moistening of the lids and hairs, and considerable area around the eye: 3

In addition, other signs of eye irritation except for scoring reaction were recorded.
The typical eye irritation observed in animals was photographed.

TOOL USED TO ASSESS SCORE: Hand-slit lamp and fluorescein staining
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
3
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
3
Reversibility:
fully reversible within: 24 hours
Remarks on result:
other: after 1 hour redness of score 1 was observed
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
3
Reversibility:
fully reversible within: 24 hours
Remarks on result:
other: after 1 hour redness of score 1 was observed
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 24 hours
Remarks on result:
other: after 1 hour chemosis of score 1 was observed
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 24 hours
Remarks on result:
other: after 1 hour chemosis of score 1 was observed
Other effects:
No other effects were observed in this study.
Interpretation of results:
GHS criteria not met
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Key study: Skin irritation study_2009/1130544

In a primary dermal irritation study, three albino female New Zealand White rabbits were exposed by the dermal route to 0.5 g test substance for 4 hours. Neither erythema nor oedema was observed 1, 24, 48 or 72 hours after exposure.

Therefore, the test substance was not irritating to the skin of rabbits.

 

Key study: Eye irritation study_ 2009/1130543

In an eye irritation study, the eyes of six New Zealand White rabbits were exposed to 0.1 g of the test substance. The treated eyes in the main study (3 animals) were not rinsed. The eyes were then examined over the course of the following week(s) for signs of irritation.

Mean scores over 24, 48 and 72 hours for each animal were 0 for cornea opacity, iris lesions and conjunctiva edema. The 24, 48 and 72 hour mean score for conjunctiva redness was 0.9.

Therefore, the test substance was not irritating to the eye of rabbits.

Justification for classification or non-classification

Skin irritation

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. The mean score for erythema/ oedema over 24, 48, 72 hours for each animal was 0. As a result the substance is not considered to be classified for skin irritation under Regulation (EC) No 1272/2008, as amended for the eighth time in Regulation (EU) No 2016/918.

 

Eye irritation

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. Mean scores over 24, 48 and 72 hours for each animal were 0 for cornea opacity, iris lesions and conjunctiva redness/edema. As a result the substance is not considered to be classified for eye irritation under Regulation (EC) No 1272/2008, as amended for the eighth time in Regulation (EU) No 2016/918.