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Administrative data

Description of key information

No signs of irritation leading to classification in an in vivo skin irritation study on rabbits.
Irreversible signs of eye irritation found in an in vivo eye irritation study on rabbits.

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:
22 May - 10 June 2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP study conducted in compliance with OECD Guideline 404 without any deviation.
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Laboratories UK Ltd., Leicestershire, UK.
- Age at study initiation: 12-20 weeks
- Weight at study initiation: 2.59-2.64 kg
- Housing: Animals were individually housed in suspended cages.
- Diet: Food (2930C Teklad Global Rabbit diet supplied by Harlan Laboratories UK Ltd., Oxon, UK), ad libitum
- Water: Mains drinking water, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 17-23 °C
- Humidity: 30-70 %
- Air changes: 15 changes/h
- Photoperiod: 12 h dark / 12 h light
Type of coverage:
semiocclusive
Preparation of test site:
other: clipped
Vehicle:
other: 0.5 g of the test item, moistened sufficiently with 0.5 ml of distilled water to achieve paste consistency
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (weight with unit): 0.5 g
Duration of treatment / exposure:
4 h
Observation period:
7 days for first animal and 72 h for remaining two animals.
Number of animals:
3 males
Details on study design:
TEST SITE
- Area of exposure: Dorsal/flank area
- Type of wrap if used: Test item was applied to the skin under a 2.5 cm x 2.5 cm cotton gauze patch. The patch was secured in position with a strip of surgical adhesive tape. To prevent the animal interfering with the patch, the trunk of the rabbit was wrapped in an elasticated corset and the animal was returned to its cage for the duration of the 4 hour exposure period.

REMOVAL OF TEST SUBSTANCE
- After removal of the dressing, any residual test item removed by gentle swabbing with cotton wool soaked in distilled water.
- Time after start of exposure: 4 h

SCORING SYSTEM: According to OECD Guideline 404
Irritation parameter:
erythema score
Basis:
animal #1
Remarks:
mean individual score
Time point:
other: 24, 48 and 72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
edema score
Basis:
animal #1
Remarks:
mean individual score
Time point:
other: 24, 48 and 72 h
Score:
1.3
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
erythema score
Basis:
animal #2
Remarks:
mean individual score
Time point:
other: 24, 48 and 72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
edema score
Basis:
animal #2
Remarks:
mean individual score
Time point:
other: 24, 48 and 72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
erythema score
Basis:
animal #3
Remarks:
mean individual score
Time point:
other: 24, 48 and 72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
edema score
Basis:
animal #3
Remarks:
mean individual score
Time point:
other: 24, 48 and 72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritant / corrosive response data:
- Very slight erythema and very slight oedema were noted at one treated skin site immediately after patch removal with well-defined erythema and slight oedema noted at 1 and 24 h after patch removal. Well-defined erythema and very slight oedema were noted at this treated skin site at the 48 and 72 h observations. Light brown discolouration of the epidermis and loss of skin elasticity were noted at this treated skin site at the 24, 48 and 72 h observations with slight desquamation noted at the 7-Day observation.
- No evidence of skin irritation was noted at two treated skin sites during the study.
Other effects:
All animals showed expected bodyweight gain during the study.

Table 7.3.1/1: Individual Skin Reactions

Skin Reaction

Observation Time

(following patch

removal)

Individual Scores – Rabbit Number and Sex

72042 Male

72101 Male

72102 Male

Erythema/Eschar

Formation

Immediately

1

0

0

1 h

2

0

0

24 h

2 BrLe

0

0

48 h

2 BrLe

0

0

72 h

2 BrLe

0

0

7 days

0D

-

-

Mean (24, 48 and 72 h)

2

0

0

Oedema

Formation

Immediately

1

0

0

1 h

2

0

0

24 h

2

0

0

48 h

1

0

0

72 h

1

0

0

7 days

0

-

-

Mean (24, 48 and 72 h)

1.3

0

0

Br = Light brown discolouration of the epidermis

Le = Loss of skin elasticity

D = Slight desquamation

- = Not applicable

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the test conditions, Zinc Dimethacrylate is not classified as irritating to skin according to the criteria of Annex VI to the Directive 67/548/EEC and CLP Regulation (EC) N° (1272-2008).
Executive summary:

In a primary dermal irritation study performed according to OECD Guideline 404 and in compliance with GLP, three male New Zealand White rabbits were dermally exposed to 0.5 g of Zinc Dimethacrylate under a semi-occlusive dressing. The test item was first evaluated on a single animal and the duration of exposure was 4 h on the dorsal/flank area. After consideration of the skin reactions produced in the first animal, two additional animals were similarly treated. After removal of the residual test item, irritation was scored as outlined in the OECD Guideline 404 at 1, 24, 48 and 72 h and 7 days after exposure.

Very slight erythema and very slight oedema were noted at one treated skin site immediately after patch removal with well-defined erythema and slight oedema noted at 1 and 24 h after patch removal. Well-defined erythema and very slight oedema were noted at this treated skin site at the 48 and 72 h observations. Light brown discolouration of the epidermis and loss of skin elasticity were noted at this treated skin site at the 24, 48 and 72 h observations with slight desquamation noted at the 7-Day observation. No evidence of skin irritation was noted at two treated skin sites during the study. Mean individual scores at 24, 48 and 72 h after exposure for the 3 animals were 2, 0, 0 for erythema and 1.3, 0, 0 for oedema score, respectively. In this study, Zinc Dimethacrylate is not a skin irritant on male rabbits.

Under the test conditions, Zinc Dimethacrylate is not classified as irritating to skin according to the criteria of Annex VI to the Directive 67/548/EEC and CLP Regulation (EC) N° (1272-2008).

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:
15-22 June 1993
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP study conducted in compliance with OECD Guideline 405 with deviations: temperature and humidity of animal room was not reported; animals were not observed for 21 days to study the reversibility; purity of test item not reported
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
temperature and humidity of animal room was not reported; animals were not observed for 21 days to study the reversibility; purity of test item not reported
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 3.3 kg
- Housing: Animals were housed individually in a suspended wire cage.
- Diet: Fresh Purina Rabbit Chow (Diet #5321), ad libitum
- Water: Water, ad libitum

ENVIRONMENTAL CONDITIONS
- Photoperiod: 12 h dark / 12 h light
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL
- Concentration (if solution): Used as received
Duration of treatment / exposure:
No washing was done
Observation period (in vivo):
7 days (1 h after administration, Days 1, 2, 3 and 7)
Number of animals or in vitro replicates:
One female
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing: No

SCORING SYSTEM: According to OECD Guideline 405

TOOL USED TO ASSESS SCORE: A hand held source of illumination was used to aid in scoring.
Irritation parameter:
cornea opacity score
Basis:
animal #1
Remarks:
mean individual score
Time point:
other: 24, 48 and 72 h
Score:
2.3
Max. score:
4
Reversibility:
not reversible
Remarks:
within 7 days
Irritation parameter:
iris score
Basis:
animal #1
Remarks:
mean individual score
Time point:
other: 24, 48 and 72 h
Score:
1
Max. score:
2
Reversibility:
not reversible
Remarks:
within 7 days
Irritation parameter:
conjunctivae score
Basis:
animal #1
Remarks:
mean individual score
Time point:
other: 24, 48 and 72 h
Score:
2.7
Max. score:
3
Reversibility:
not reversible
Remarks:
within 7 days
Irritation parameter:
chemosis score
Basis:
animal #1
Remarks:
mean individual score
Time point:
other: 24, 48 and 72 h
Score:
3
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritant / corrosive response data:
- Corneal opacity, iritis and moderate conjunctival irritation persisted through Day 7 with apparition of mis-shaped cornea and no sign of reversibility. There were no abnormal physical signs noted during the observation period.
Other effects:
None

See attached Document for Tables of Results

Interpretation of results:
Category 1 (irreversible effects on the eye)
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the test conditions, test item, SR-365C showed irreversible signs of eye irritation (mis-shaped cornea and no reversible scores within 7 days) therefore the test item is classified as “R41 Risk of serious damage to eyes”, according to the Annex VI of the Directive 67/548/EEC and ‘Category 1’ according to the CLP Regulation (EC) N° 1272-2008.
Executive summary:

In an eye irritation study conducted according to the OECD Guideline 405 and in compliance with GLP, one healthy female rabbit of the New Zealand White strain was exposed to 0.1 mL of undiluted test item SR-365C in their left eye while the right eye remained untreated and served as control. The eyelids were then gently held together for about one second to avoid any loss of test item. The eyes were examined and the changes were observed at 1 h and Days 1, 2, 3 and 7 after treatment and graded according to the method of OECD Guideline 405.

Corneal opacity, iritis and moderate conjunctival irritation persisted through Day 7 with apparition of mis-shaped cornea and no sign of reversibility. There were no abnormal physical signs noted during the observation period. Mean individual scores at 24, 48 and 72 h after exposure for one animal was 2.3, 1.0, 2.7 and 3.0 for cornea, iris, conjunctivae and chemosis, respectively. In this study, test item, SR-365C is considered to show irreversible signs of eye irritation on female rabbit.

Under the test conditions, test item, SR-365C showed irreversible signs of eye irritation (mis-shaped cornea and no reversible scores within 7 days) therefore the test item is classified as “R41 Risk of serious damage to eyes”, according to the Annex VI of the Directive 67/548/EEC and ‘Category 1’ according to the CLP Regulation (EC) N° 1272-2008.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

In a primary dermal irritation study performed according to OECD Guideline 404 and in compliance with GLP, very slight erythema and very slight oedema were noted at one treated skin site immediately after patch removal with well-defined erythema and slight oedema noted at 1 and 24 h after patch removal. Well-defined erythema and very slight oedema were noted at this treated skin site at the 48 and 72 h observations. Light brown discolouration of the epidermis and loss of skin elasticity were noted at this treated skin site at the 24, 48 and 72 h observations with slight desquamation noted at the 7-Day observation. No evidence of skin irritation was noted at two treated skin sites during the study. Mean individual scores at 24, 48 and 72 h after exposure for the 3 animals were 2, 0, 0 for erythema and 1.3, 0, 0 for oedema score, respectively.

In an eye irritation study conducted according to the OECD Guideline 405 and in compliance with GLP, one healthy female rabbit of the New Zealand White strain, corneal opacity, iritis and moderate conjunctival irritation persisted through Day 7 with apparition of mis-shaped cornea and no sign of reversibility. There were no abnormal physical signs noted during the observation period. Mean individual scores at 24, 48 and 72 h after exposure for one animal was 2.3, 1.0, 2.7 and 3.0 for cornea, iris, conjunctivae and chemosis, respectively. In this study, test item is considered to show irreversible signs of eye irritation on female rabbit.


Justification for selection of skin irritation / corrosion endpoint:
Only one study available

Justification for selection of eye irritation endpoint:
Only one study available

Effects on eye irritation: corrosive

Justification for classification or non-classification

In an in vivo skin irritation study performed accoring to OECD guideline 404, zinc methacrylate showed only slight reversible signs of skin irritation not sufficient to lead to classification. Therefore, zinc methacrylate does not need to be classified for skin irritation according to the Annex VI to the Directive 67/548/EEC and to the CLP Regulation (EC) No 1272/2008.

In an in vivo eye irritation study performed accoring to OECD guideline 405, zinc methacrylate showed irreversible signs of eye irritation (mis-shaped cornea and no reversible scores within 7 days) therefore it is classified as “R41 Risk of serious damage to eyes”, according to the Annex VI of the Directive 67/548/EEC and ‘Category 1’ according to the CLP Regulation (EC) N° 1272-2008.