Zinc methacrylate

Endpoint summary

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:

guideline study

Justification for type of information:

No justification could be found in the records.

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Principles of method if other than guideline:

Not applicable

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system 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:

24/48/72 h

Score:

ca. 2

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

edema score

Basis:

animal #1

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

ca. 1.3

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

erythema score

Basis:

animal #2

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

ca. 0

Max. score:

4

Reversibility:

other: not applicable

Irritation parameter:

edema score

Basis:

animal #2

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

ca. 0

Max. score:

4

Reversibility:

other: not applicable

Irritation parameter:

erythema score

Basis:

animal #3

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

ca. 0

Max. score:

4

Reversibility:

other: not applicable

Irritation parameter:

edema score

Basis:

animal #3

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

ca. 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:

GHS criteria not met

Conclusions:

Under the test conditions, Zinc Dimethacrylate is not classified as irritating to skin.

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 was not classified as irritating to skin (Bradshaw, 2012).

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:

supporting study

Study period:

15-22 June 1993

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

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

Qualifier:

according to guideline

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:

24/48/72 h

Score:

ca. 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:

24/48/72 h

Score:

ca. 1

Max. score:

2

Reversibility:

not reversible

Remarks:

within 7 days

Irritation parameter:

conjunctivae score

Basis:

animal #1

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

ca. 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:

24/48/72 h

Score:

ca. 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:

other: Category 1 (irreversible effects on the eye) based on EU CLP criteria

Conclusions:

Under the test conditions, test item showed irreversible signs of eye irritation (mis-shaped cornea and no reversible scores within 7 days).

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 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 showed irreversible signs of eye irritation (mis-shaped cornea and no reversible scores within 7 days) (Cerven, 1993).

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation

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 was not classified as irritating to skin (Bradshaw, 2012).

Eye irritation

In an eye irritation study conducted according to the OECD Guideline 405 and in compliance with GLP, 3 healthy female rabbits of the New Zealand White strain were exposed to 0.1 g of the read across substance zinc monomethacrylate in one eye while the another 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. Physiological rinse was done on Day 0 (at 1 h post-installation) to remove the remaining test item. The eyes were examined and the changes were observed at 1, 24, 48 and 72 h and Days 7, 14 and 21 after treatment and graded according to the method of OECD Guideline 405. Initially, a single animal was treated and after consideration of the responses produced on Day 7 in the first animal, two additional animals were treated. The ocular reactions observed during the study have been moderate to important and totally reversible. At the conjunctivae level, an important redness noted 24 h after the test item instillation and totally reversible between Days 7 and 14, associated with a moderate to important chemosis noted 24 h after the test item instillation and totally reversible on Day 7; at the iris level, a congestion, noted 24 h after the test item instillation, and totally reversible between Days 2 and 3; at the corneal level, a moderate corneal opacity, noted 24 h after the test item instillation, and totally reversible between Days 7 and 21. A corneal neovascularization was noted on Day 7 in one animal and on Day 14 in a second one. This reaction was totally reversible between Days 14 and 21. Mean individual scores at 24, 48 and 72 h after exposure for the 3 animals were 2.0, 2.0, 2.0 for cornea score; 0.7, 0.7, 0.3 for iris score; 2.3, 2.7, 2.7 for conjunctivae score and 1.3, 2.7, 2.3 for chemosis score. In this study, test item is an eye irritant on female rabbits. Under the study conditions, the test substance was found to be irritating to rabbit eyes (Colas, 2013).

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 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. Deviations were observed in this study according to the method of OECD Guideline 405. Therefore, the results of this study were not used for the purpose of classification. 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 showed irreversible signs of eye irritation (mis-shaped cornea and no reversible scores within 7 days) (Cerven, 1993). 

Justification for classification or non-classification

In an in vivo skin irritation study performed according 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 EU CLP Regulation (EC) No 1272/2008.

In an in vivo eye irritation study performed according to OECD guideline 405, the read across substance zinc monomethacrylate was irritating to rabbit eyes. Based on this study results, the registered substance warrants Eye Irritation Cat. 2 (H319: causes serious eye irritation) classification according to the EU CLP Regulation (EC) 1272-2008.