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Description of key information

Skin irritation
Human data
Patch test study with volunteers: 18/20 showed erythema and dermatitis after exposure to 5% methyl methacrylate in paraffin or olive oil (Nyquist 1958). Although a clear distinction between sensitisation and irritation is difficult and the exposure period is far longer than usual in irritation testing the results suggest that MMA may have the potential for skin irritation in humans.
Animal data
in vivo, rabbit: low to moderate potential for skin irritation (Sterner 1977; Rohm & Haas 1982)


Eye irritation
Animal data
in vivo, rabbit, 0.1 mL, unwashed: no potential for eye irritation (Sterner 1978, Rohm and Haas 1982)
Irritation of the respiratory tract
Human data
Workplace exposure: acute and reversible irritation at concentration levels exceeding 100 ppm (ca. 0.410 mg/L; (Coleman, 1963, Roehm 1994, Muttray et al., 1997, Muttray et al., 2007)

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:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods
Qualifier:
according to guideline
Guideline:
other: "Appraisal of the safety of chemicals in foods, drugs and cosmetics"; Division of Pharmacology, FDA; according to the Draize Test, 1959
Principles of method if other than guideline:
Application: occlusive instead of semiocclusive
Exposute time: 24 hours instead of 4 hours
GLP compliance:
no
Specific details on test material used for the study:
- Provided by Röhm GmbH, Darmstadt
- Name of test material (as cited in study report): Methylmethacrylat
- Physical state: clear liquid
- Analytical purity: no data
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Mean weight at study initiation: 2.5 kg
- Housing: single
- Diet (ad libitum): Hoeing 222
- Water (ad libitum): not specified
- Acclimation period:


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20+-1
- Humidity (%): 50-60
- Photoperiod (hrs dark / hrs light): 12
Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
other: untreated areas on test animals served as control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied: 0.5 ml
Duration of treatment / exposure:
24 h
Observation period:
24 and 72 hrs
Number of animals:
6
Details on study design:
TEST SITE
- Area of exposure: 2.5*2.5 cm
- Type of wrap if used: rubberised cloth


REMOVAL OF TEST SUBSTANCE
- Washing: not performed
- Time after start of exposure: 24 h


SCORING SYSTEM: according to the OECD/Draize scoring system
Irritation parameter:
erythema score
Basis:
animal: #1, #2, #3, #4, #6
Time point:
other: mean 24/ 72 h
Score:
0
Max. score:
4
Reversibility:
other: no effcts
Remarks on result:
other: see table for details
Irritation parameter:
erythema score
Basis:
animal #5
Time point:
other: mean 24/72h
Score:
0.5
Max. score:
4
Reversibility:
fully reversible within: 72 h
Remarks on result:
other: see table for details
Irritation parameter:
edema score
Basis:
animal: #1; #2; #3; #4; #5; '6
Time point:
other: mean 24/72h
Score:
0
Max. score:
4
Reversibility:
other: no effects
Remarks on result:
other: see table for details
Exposition:  24 h occlusive, shaved skin    
Animal  Reading  Erythema Edema Symptoms
1 24 h 0 0  
2 24 h 0 0  
3 24 h 0 0  
4 24 h 0 0  
5 24 h 1 0  
6 24 h 0 0  
1 72 h 0 0  
2 72 h 0 0  
3 72 h 0 0  
4 72 h 0 0  
5 72 h 0 0  
6 72 h 0 0  
mean animal 1 24 - 72 h 0.00 0.00  
mean animal 2 24 - 72 h 0.00 0.00  
mean animal 3 24 - 72 h 0.00 0.00  
mean animal 4 24 - 72 h 0.00 0.00  
mean animal 5 24 - 72 h 0.50 0.00  
mean animal 6 24 - 72 h 0.00 0.00  
mean 24 - 72 h 0.08 0.00  

---

The mean erythema and edema scores of the 24 and 72 h readings of the scarified skin sites were 0.25 and 0.0, respectively. The slight erythema were fully reversible within 72 h.

Interpretation of results:
not irritating
Executive summary:

In an acute dermal irritation test acc. to Draize 1959 6 New Zealand White rabbits were exposed to methyl methacrylate under occlusive conditions for 24 hours on the shaved skin. Very slight erythema was observed in one animal which was fully reversible within 72 h.

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods with acceptable restrictions
Remarks:
Range-finding study, number of animals: 2.
Guideline:
other: not specified
Deviations:
yes
Remarks:
Range finding study: only 2 animals
Principles of method if other than guideline:
other: 0.5 ml, occluded, 4 hours
GLP compliance:
not specified
Specific details on test material used for the study:
Purity: 99.8% MMA
10 ppm Topanol A (12,4-Dimethyl-6-tert-butylphenol)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
not specified
Type of coverage:
occlusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
not specified
Amount / concentration applied:
0.5 ml
Duration of treatment / exposure:
4 hrs
Observation period:
0.5; 24 and 72 Hours and 7 days
Number of animals:
2
Details on study design:
After the 4 hours exposure the patches and cuffs were removed and the application sites were wiped gently
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: mean 24/72 h
Score:
0.5
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: mean 24/72 h
Score:
4
Max. score:
4
Reversibility:
not reversible
Remarks:
within 7 days
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: mean 24/72 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #2
Time point:
other: mean 24/72 h
Score:
2.5
Max. score:
0
Reversibility:
not fully reversible within: 7 days

Screening study with two animals. Only two animals: Effects in one animal were slight and fully reversibe, in the other animal a strong irritant response was observed but reversibility was not fully assessed (7 d)

WoE conclusion based on dermal tox. screening data: Fully reversible within 3 days at 0.2 mg/kg

2 rabbits received 0.2, 2 or 5 g/kg bw (occluded) for 24h. Moderate/severe irritation was observed at 24h. Complete recovery occurred at 0.2 g/kg (dose comparable to irritation guideline) but not at 2 or 5 g/kg.

Interpretation of results:
irritating
Remarks:
Migrated information after 4/24h occluded exposure Criteria used for interpretation of results: expert judgment
Conclusions:
WoE conclusion based on irritation and dermal toxicity screening data:

Irritation: 2 rabbits were exposed to MMA for 4 hrs. One animal showed very slight irritation, the other moderate to severe irritation. The screening study was terminated at 7 days and was of insufficient duration to demonstrate full reversibility in this animal.

Dermal Toxicity: Groups of 2 male rabbits were treated dermally with MMA at doses of 0.2, 2 or 5 g/kg bw under occluded conditions for 24 hours. Well-defined to severe erythema with blanching and moderate to severe oedema with pocketing were observed at 24 hours. The skin irritation was still present at day 14 in the animals treated at 2 or 5 g MMA/kg bw but was not present after day 3 in the animals treated at 0.2 g/kg bw. Eschar was observed at day 2 in animals treated at the 2 or 5 mg/kg bw dose levels and some eschar was observed to be sloughing off with new hair growth on the underlying skin at day 12 in animals dosed at 2 or 5 g/kg bw. This is consistent with reversible effects as a consequence of irritation and tissue recovery rather than skin corrosion and scaring. Desiccation was also observed after day 4 in animals treated at all 3 dose levels.

Although at 2 and 5 g/kg bw (after 24 h of exposure), reversal of tissue damage was not demonstrated by day 14 , the fact that is used a 24 hr contact period, and that reversibility was observed at 0.2 g/kg bw, correspond more closely to the applied dose used under a guideline skin irritation study (0.5 ml / 4 h ) the overall conclusion from these dermal irritation and toxicity studies is that MMA is irritant to the skin of rabbits.
Executive summary:

Based on screening data with two animals and 4 hours exposure of 0.5 ml of methyl methacrylate to New Zealand White rabbits, the substance is regaded as irritating to the skin.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Eye irritation

Link to relevant study records

Referenceopen allclose all

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods
Remarks:
Draize test
Qualifier:
according to guideline
Guideline:
other: "Appraisal of the safety of chemicals in foods, drugs and cosmetics" Division of Pharmacology, FDA. According to Draize, 1959
Principles of method if other than guideline:
Draize Test
GLP compliance:
no
Specific details on test material used for the study:
Supplier: Röhm GmbH, Darmstadt, Germany
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 2.4 - 2.6 kg
- Housing: single
- Diet (ad libitum): Hoeing 222
- Water (ad libitum): not specified


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18
- Humidity (%): 50-60
- Photoperiod (hrs dark / hrs light): 12:12
Vehicle:
unchanged (no vehicle)
Controls:
other: 1 eye untreated: control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied: 0.1 mL
Duration of treatment / exposure:
Single instillation of 0.1 ml into the left eye, eyes were left unwashed
Observation period (in vivo):
24, 48 and 72 hrs, 4, 5, 6, and 7 days
Number of animals or in vitro replicates:
6
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing: not performed

SCORING SYSTEM: according to the OECD/ Draize scoring system
Irritation parameter:
cornea opacity score
Basis:
animal: #1; #2; #3; #4; #5; #6
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: no effects
Irritation parameter:
iris score
Basis:
animal: #1; #2; #3; #4; #5; #6
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
other: no effects
Irritation parameter:
conjunctivae score
Basis:
animal: #1; #2; #3; #4; #5; #6
Time point:
24/48/72 h
Score:
0
Max. score:
3
Reversibility:
other: no effects
Remarks on result:
other: slight to moderate erythema was observed 1 to 8 h after application (before the relevant reading points).
Irritation parameter:
chemosis score
Basis:
animal: #1; #2; #3; #4; #5; #6
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: no effects
Remarks on result:
other: slight to moderate chemosis 1 to 8 h after application (before the relevant reading points).
Other effects:
Slight to moderate discharge was observed 1 to 8 h after application.

Animal  Reading  Opacity Cornea area Iritis Redness Chemosis Discharge Symptoms
1 1 h 0 0 0 2 2 1  
2 1 h 0 0 0 2 1 1  
3 1 h 0 0 0 1 0 0  
4 1 h 0 0 0 2 2 1  
5 1 h 0 0 0 2 2 1  
6 1 h 0 0 0 2 2 1  
1 2 h 0 0 0 2 2 1  
2 2 h 0 0 0 2 1 2  
3 2 h 0 0 0 1 0 0  
4 2 h 0 0 0 2 2 1  
5 2 h 0 0 0 2 1 2  
6 2 h 0 0 0 2 2 2  
1 8 h 0 0 0 2 1 2  
2 8 h 0 0 0 2 1 2  
3 8 h 0 0 0 1 0 0  
4 8 h 0 0 0 2 2 2  
5 8 h 0 0 0 2 2 2  
6 8 h 0 0 0 2 2 2  
1 24 h 0 0 0 0 0 0  
2 24 h 0 0 0 0 0 0  
3 24 h 0 0 0 0 0 0  
4 24 h 0 0 0 0 0 0  
5 24 h 0 0 0 0 0 0  
6 24 h 0 0 0 0 0 0  
1 48 h 0 0 0 0 0 0  
2 48 h 0 0 0 0 0 0  
3 48 h 0 0 0 0 0 0  
4 48 h 0 0 0 0 0 0  
5 48 h 0 0 0 0 0 0  
6 48 h 0 0 0 0 0 0  
1 72 h 0 0 0 0 0 0  
2 72 h 0 0 0 0 0 0  
3 72 h 0 0 0 0 0 0  
4 72 h 0 0 0 0 0 0  
5 72 h 0 0 0 0 0 0  
6 72 h 0 0 0 0 0 0  
1 4 d 0 0 0 0 0 0  
2 4 d 0 0 0 0 0 0  
3 4 d 0 0 0 0 0 0  
4 4 d 0 0 0 0 0 0  
5 4 d 0 0 0 0 0 0  
6 4 d 0 0 0 0 0 0  
1 5 d 0 0 0 0 0 0  
2 5 d 0 0 0 0 0 0  
3 5 d 0 0 0 0 0 0  
4 5 d 0 0 0 0 0 0  
5 5 d 0 0 0 0 0 0  
6 5 d 0 0 0 0 0 0  
1 6 d 0 0 0 0 0 0  
2 6 d 0 0 0 0 0 0  
3 6 d 0 0 0 0 0 0  
4 6 d 0 0 0 0 0 0  
5 6 d 0 0 0 0 0 0  
6 6 d 0 0 0 0 0 0  
1 24 - 72 h 0.00   0.00 0.00 0.00    
2 24 - 72 h 0.00   0.00 0.00 0.00    
3 24 - 72 h 0.00   0.00 0.00 0.00    
4 24 - 72 h 0.00   0.00 0.00 0.00    
5 24 - 72 h 0.00   0.00 0.00 0.00    
6 24 - 72 h 0.00   0.00 0.00 0.00    
mean  24 - 72 h 0.00   0.00 0.00 0.00    
Interpretation of results:
GHS criteria not met
Conclusions:
Methyl methacrylate was not irriating in an eye irritation test according to Draize (1959)
Executive summary:

In an acute eye irritation test according the appraisal of the safety of chemicals in foods, drugs and cosmetics (1959), 6 New Zealand White rabbits were tested. No irritation was observed in all animals.

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Range-finding study, number of animals: 2.
Guideline:
other: range finding study
Principles of method if other than guideline:
only 2 animals
GLP compliance:
not specified
Specific details on test material used for the study:
Purity: 99.8% MMA
10 ppm Topanol A (12,4-Dimethyl-6-tert-butylphenol)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
males
Vehicle:
unchanged (no vehicle)
Controls:
other: other eye on same animal
Amount / concentration applied:
0.1 ml of the test substance, as received, was applied onto the cornea
Duration of treatment / exposure:
unwashed
Observation period (in vivo):
7d
Number of animals or in vitro replicates:
2
Irritation parameter:
cornea opacity score
Basis:
animal: #1; #2
Remarks:
only 2 animals testd
Time point:
24/48/72 h
Score:
0
Irritation parameter:
iris score
Basis:
animal: #1; #2
Remarks:
only 2 animals tested
Time point:
24/48/72 h
Score:
0
Irritation parameter:
conjunctivae score
Basis:
animal: #1; #2
Remarks:
only 2 animals tested
Time point:
24/48/72 h
Score:
0.66
Reversibility:
fully reversible within: 48 h
Irritant / corrosive response data:
Based on the duration and nature of the ocular effects alone, this test substance is considered to be "slightly irritating" to the eyes of rabbits (i.e. conjunctival effects only, and reversible within 48 hr but not 24 hr).

Time

Structure

Animal 1

Animal 2

Mean

24 h

Cornea

Iris

Conjunctivae

0

0

2

0

0

2

0

0

2

48 h

Cornea

Iris

Conjunctivae

0

0

0

0

0

0

0

0

0

72 h

Cornea

Iris

Conjunctivae

0

0

0

0

0

0

0

0

0

7 d

Cornea

Iris

Conjunctivae

0

0

0

0

0

0

0

0

0

Interpretation of results:
GHS criteria not met
Conclusions:
Classification: not irritating
Executive summary:

Based on the duration and nature of the ocular effects alone, this test substance is considered to be "slightly irritating" to the eyes of rabbits (i.e. conjunctival effects only, and reversible within 72 hr but not 24 hr).

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Additional information

There was valid in vivo information available to assess the potential for skin and eye irritation of methyl methacrylate.

Skin irritation

Human data

Nyquist et al.(1958) reported erythema and eczematous dermatitis in 18/20 human volunteers to methyl methacrylate (5% in paraffin or olive oil). Although a clear distinction between sensitisation and irritation was not made by the author and the exposure period is far longer than usual in irritation testing the results suggest that MMA may have the potential for skin irritation in humans.

Animal data

The results of the reliable studies varied. In the most reliable study (standardized test protocol according to the Draize test, 0.5 mL of the unchanged test substance were applied to shaved skin sites of six New Zealand White rabbits under occlusive conditions for 24 hours), only slight erythema were observed in 1/6 animals in the 24 h reading; no further effects were observed. The mean erythema and oedema scores were 0.08 and 0.00 for all animals and readings, respectively (Sterner 1977). On the other hand, Rohm and Haas (1982) reported moderate skin irritation after application of 0.5 mL of the test substance to the rabbit skin under occlusive conditions for 4/24 hours. In an overall view it is considered that methyl methacrylate possess the potential for skin irritation.

 

Eye irritation

Animal data

Here, the results of the reliable studies produced a clear pattern. In the most reliable study, 0.1 mL of the unchanged test substance was applied to the eyes of six New Zealand White rabbits and the treated eyes were not washed out (Sterner 1978). In the relevant reading period between 24 h and 72 h after application there were no irritation effects observed on cornea, iris and conjunctivae (redness and chemosis). The respective scores were 0.0 for all parametersm and all animals. Slight to moderate conjunctivae redness, chemosis and discharge was observed in the readings 1 h to 8 h after application, which were not relevant for classification.In addition, slight, transient effects were described in a study of Rohm & Haas (1982). Overall it is considered that methyl methacrylate possess the potential for, at most, slight irritation effects on the rabbit eye.

 

Irritation of the respiratory tract

Human data

Reversible irritation reactions have been observed after short-term peak exposures to humans at concentration levels exceeding 100 ppm (Coleman, 1963, Roehm 1994). No damage to olfactory function was reported in a cross-sectional smell test in workers exposed to MMA up to 50 ppm during the past 6 years and up to 100 ppm the time before (mean duration of exposure 9.6 years) (Muttray et al., 1997). No effects were seen after single exposures to 50 ppm in a study with human volunteers investigating changes in cytokine levels indicative of subclinical, irritating effects (Muttray et al., 2007)



Justification for classification or non-classification

Skin irritation

The results of the reliable animal studies varied between slight and moderate, reversible irritation effects on the rabbit skin. There are also indications of irritation in human patch tests with prolonged exposure. Hence, methyl methacrylate is classified as skin irritation Cat. 2 according to Regulation (EC) 1272/2008 requirements and UN-GHS criteria, respectively.

Eye irritation

It is considered that methyl methacrylate possess the potential for maximum slight irritation effects on the rabbit eye, which were below the criteria for classification according to Regulation (EC) 1272/2008 requirements. No classification.

Irritation of the respiratory tract

Based on results of studies in humans and animals methyl methacrylate has to be classified as irritant to the respiratory tract according to Regulation (EC) 1272/2008 requirementsand UN-GHS criteria, respectively).