Registration Dossier

Administrative data

Description of key information

n-BMA is a slight to moderate skin irritant.
n-BMA a slight eye irritant.
n-BMA vapour induced irritation of the respiratory tract at high concentrations.

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:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study well documented, guideline study
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Fa. Ivanovas, Kisslegg Allgäu
- Age at study initiation: no data
- Weight at study initiation: 2.5-2.6 kg
- Housing: "Asta" cage
- Diet (e.g. ad libitum): Standardisiertes Versuchstierfutter Altromin
- Water (e.g. ad libitum): tap water
- Acclimation period: 1 day

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 1
- Humidity (%): 50-60
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
other: occlusive and semi-occlusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.5 ml
Duration of treatment / exposure:
1 and 4 hour(s)
Observation period:
1, 24, 48 and 72 h, 7 and 14 days after exposure
Number of animals:
6
Details on study design:
TEST SITE
- Area of exposure: 3 x 3 cm, under a plaster with a thick dressing
- Type of wrap if used:
occlusive:
- plaster covered by rubberised tissue, adhesive film and Acrylastic circular wrap
semi-occlusive:
- plaster covered by single Acrylastic circular wrap
Irritation parameter:
erythema score
Remarks:
mean
Basis:
animal: #1, #2# #3, #4, #5, #6
Time point:
other: mean 24+48+72 h
Score:
1.11
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: 4-h semi-occlusive, reevaluated acc. DSD (overall mean).
Irritation parameter:
edema score
Remarks:
mean
Basis:
animal: #1, #2# #3, #4, #5, #6
Time point:
other: mean 24+48+72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: 4-h semi-occlusive, reevaluated acc. DSD (overall mean).
Irritation parameter:
erythema score
Basis:
animal #5
Time point:
other: mean 24+48+72 h
Score:
0.66
Max. score:
4
Reversibility:
fully reversible
Remarks:
7 days
Remarks on result:
other: 4-h semi-occlusive exposure, reevaluated acc. CLP criteria
Irritation parameter:
erythema score
Basis:
animal: #1, #2, #6
Time point:
other: mean 24+48+72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: 4-h semi-occlusive exposure, reevaluated acc. CLP criteria
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
other: mean 24+48+72 h
Score:
1.33
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: 4-h semi-occlusive exposure, reevaluated acc. CLP criteria
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
other: mean 24+48+72 h
Score:
1.66
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: 4-h semi-occlusive exposure, reevaluated acc. CLP criteria
Irritation parameter:
edema score
Remarks:
mean
Basis:
animal: #1, #2, #3, #4, #5, #6
Time point:
other: mean 24+48+72 h
Score:
0
Max. score:
4
Remarks on result:
other: 4-h semi-occlusive exposure, reevaluated acc. CLP criteria
Irritant / corrosive response data:
Occlusive exposure:
Erythema developed after 1 h and 4 h of exposure. The effects were not fully  reversible within 7 d, but after 14 d. Slight edema was observed in two animals after 4 h exposure, which disappeared after 72 h.

Semi-occlusive exposure:
After semi-occlusive exposure the observed effects were generally somewhat  less pronounced and fully reversible in 7 days.

Other effects:
No evidence of systemic effects.

Reevaluation according CLP criteria:

Application: occlusive, 1 h exposure:

Animal Nr.

Erythema

24 h

Erythema

48 h

Erythema

72h

Mean

Erythema

Edema

24 h

Edema

48 h

Edema

72 h

Mean

Edema

1

2

2

1

1.66

1

1

0

0.66

2

2

2

2

2

0

0

0

0

3

2

2

1

1.66

0

0

0

0

4

1

1

2

1.33

0

0

0

0

5

1

1

1

1

1

0

0

0.33

6

2

2

1

1.66

0

0

0

0

 

Reversibility: very slight erythema (score 1) in 3/6 animals (animal 1, 2 and 4) after 7 days. Fully reversible within 14 days.

Application: occlusive, 4 h exposure:

Animal Nr.

Erythema

24 h

Erythema

48 h

Erythema

72h

Mean

Erythema

Edema

24 h

Edema

48 h

Edema

72 h

Mean

Edema

1

2

2

1

1.66

0

0

0

0

2

2

2

2

2

1

0

0

0.33

3

2

2

1

1.66

0

0

0

0

4

2

2

2

2

1

1

0

0.66

5

2

1

0

1

0

0

0

0

6

2

2

1

1.66

0

0

0

0

 

Reversibility: very slight erythema (score 1) in 2/6 ) animals (animal 2 and 4) after 7 days. Fully reversible within 14 days.


  

Application: semi-occlusive, 1 h exposure:

Animal Nr.

Erythema

24 h

Erythema

48 h

Erythema

72h

Mean

Erythema

Edema

24 h

Edema

48 h

Edema

72 h

Mean

Edema

1

2

1

1

1.33

0

0

0

0

2

1

1

1

1

0

0

0

0

3

2

1

1

1.33

0

0

0

0

4

1

1

1

1

0

0

0

0

5

1

1

0

0.66

0

0

0

0

6

1

1

1

1

0

0

0

0

 

Reversibility: Fully reversible within 7 days.

 

Application: semi-occlusive, 4 h exposure (used for evaluation of classification):

Animal Nr.

Erythema

24 h

Erythema

48 h

Erythema

72h

Mean

Erythema

Edema

24 h

Edema

48 h

Edema

72 h

Mean

Edema

1

1

1

1

1

0

0

0

0

2

1

1

1

1

0

0

0

0

3

2

1

1

1.33

0

0

0

0

4

1

2

2

1.66

0

0

0

0

5

1

1

0

0.66

0

0

0

0

6

1

1

1

1

0

0

0

0

 

Reversibility: Fully reversible within 7 days.

Reevaluation according DSD criteria:

 4 h Exposure, semi-occlusiv                  
  Erythema       Edema        
  24h 48h 72h 7d 24h 48h 72h 7d  
Animal 1 1 1 1 0 0 0 0 0  
Animal 2 1 1 1 0 0 0 0 0  
Animal 3 2 1 1 0 0 0 0 0  
Animal 4 1 2 2 0 0 0 0 0  
Animal 5 1 1 0 0 0 0 0 0  
Animal 6 1 1 1 0 0 0 0 0  
mean 1.166 1.166 1 0 0 0 0 0  
                   
Overall mean 1.11       0        
  Erythema       Edema        
                   
Fully reversible within 14 days                  
                   
Interpretation of results:
slightly irritating
Remarks:
Migrated information Criteria used for interpretation of results: other: CLP, EU GHS (Regulation (EC) No 1272/2008)
Executive summary:

In a study comparable to OECD 404, when 0.5 ml n-BMA was applied to the skin of rabbits under semi-occlusive and occlusive patch for one and 4 hours. Under occlusive conditions and one hour exposure mean erythema and edema scores were < 2.3. Very slight erythema were observed in 3/6 animals after 7 days which were fully reversible within 14 days. After 4 hours exposure mean scores were very slightly higher than after one hour exposure. Very slight erythema and edema were observed after 7 days but were fully reversible within 14 days.

Under semi-occlusive conditions after 1 hour and 4 hours exposure and and observation time point of 24, 48 and 72 h mean erythema scores were < 2.3 and no edema were observed. Erythema were fully reversible within 7 days. Reevaluated acc. DSD criteria and CLP criteria in this study n-Butyl methacrylate was considered slightly irritating.

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:
other: Study meets minimum scientific standards for a dermal irritation study and provides sufficient information regarding the irritation potential of the test substance. Exposure longer (24 h) than current guideline standard (4 h).
Qualifier:
according to
Guideline:
other: Federal Hazardous Substances Labeling Act Regulations, Section 191.12, Federal Register: 29, 13009 (1964).
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
No data available
Type of coverage:
occlusive
Preparation of test site:
other: The fur was removed by clipping.  Half of the exposed area was abraded and the other half remained intact
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.5 ml
Duration of treatment / exposure:
24 hour(s)
Observation period:
24 and 72 h after exposure
Number of animals:
6
Details on study design:
Six NZ White rabbits were restrained in stocks and the fur removed by clipping.  Half of the exposed area was abraded and the other half remained intact. 0.5 ml (vol) of test compound was applied to the shaved intact and abraded skin sites and covered with surgical gauze. The area was then wrapped with impervious tape and a stockinette sleeve.  Test material remained in contact for 24 hrs and then removed.  Irritation scores were determined at 24 and 72 hours after patch removal.
Irritation parameter:
erythema score
Basis:
animal #5
Time point:
other: mean 24+72 h
Score:
1.5
Max. score:
4
Reversibility:
not fully reversible within: 72 h
Remarks on result:
other: 24 h exposure, intact skin; No data in respect to reversibility after > 72h exposure. Reevaluation acc. CLP criteria
Irritation parameter:
erythema score
Basis:
animal: #1, #4, #6
Time point:
other: mean 24+72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 72 h
Remarks on result:
other: 24 h exposure, intact skin; No data in respect to reversibility after > 72h exposure. Reevaluation acc. CLP criteria
Irritation parameter:
erythema score
Basis:
animal: #2, #3
Time point:
other: mean 24+72 h
Score:
2.5
Max. score:
4
Reversibility:
not fully reversible within: 72 h
Remarks on result:
other: 24 h exposure, intact skin; No data in respect to reversibility after > 72h exposure. Reevaluation acc. CLP criteria
Irritation parameter:
edema score
Basis:
animal #5
Time point:
other: mean 24+72 h
Score:
1
Max. score:
4
Reversibility:
not fully reversible within: 72 h
Remarks on result:
other: 24 h exposure, intact skin; No data in respect to reversibility after > 72h exposure. Reevaluation acc. CLP criteria
Irritation parameter:
edema score
Basis:
animal: #1, #3
Time point:
other: mean 24+72 h
Score:
1.5
Max. score:
4
Reversibility:
not fully reversible within: 72 h
Remarks on result:
other: 24 h exposure, intact skin; No data in respect to reversibility after > 72h exposure. Reevaluation acc. CLP criteria
Irritation parameter:
edema score
Basis:
animal #6
Time point:
other: mean 24+72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 72 h
Remarks on result:
other: 24 h exposure, intact skin; No data in respect to reversibility after > 72h exposure. Reevaluation acc. CLP criteria
Irritation parameter:
edema score
Basis:
animal #4
Time point:
other: mean 24+72 h
Score:
2.5
Max. score:
4
Reversibility:
not fully reversible within: 72 h
Remarks on result:
other: 24 h exposure, intact skin; No data in respect to reversibility after > 72h exposure. Reevaluation acc. CLP criteria
Irritation parameter:
edema score
Basis:
animal #2
Time point:
other: mean 24+72 h
Score:
3
Max. score:
4
Reversibility:
not fully reversible within: 72 h
Remarks on result:
other: 24 h exposure, intact skin; No data in respect to reversibility after > 72h exposure. Reevaluation acc. CLP criteria
Irritation parameter:
erythema score
Remarks:
mean
Basis:
animal: #1, #2# #3, #4, #5, #6
Time point:
other: mean 24+72 h
Score:
2.08
Max. score:
4
Reversibility:
not fully reversible within: 72 h
Remarks on result:
other: 24 h exposure, intact skin; No data in respect to reversibility after > 72h exposure. Reevaluation acc. DSD (overall mean).
Irritation parameter:
edema score
Remarks:
mean
Basis:
animal: #1, #2# #3, #4, #5, #6
Time point:
other: mean 24+72 h
Score:
1.83
Max. score:
4
Reversibility:
not fully reversible within: 72 h
Remarks on result:
other: 24 h exposure, intact skin; No data in respect to reversibility after > 72h exposure. Reevaluation acc. DSD (overall mean).
Irritant / corrosive response data:
Well-defined to moderate erythema and barely perceptible to moderate edema  were exhibited at the 24 h reading interval. Induration of the skin (2/6) were evident. Evidence of irritation persisted to 72 h in all case. Similar overall levels of response were recorded for both intact and abraded sites.

Reevaluation acc. CLP criteria

Shaved skin

Animal Nr.

Erythema

24 h

Erythema

48 h

Erythema

72h

Mean

Erythema

Edema

24 h

Edema

48 h

Edema

72 h

Mean

Edema

1

3

-

1

2

2

-

1

1.5

2

3

-

2

2.5

3

-

3

3

3

3

-

2

2.5

2

-

1

1.5

4

2

-

2

2

3

-

2

2.5

5

2

-

1

1.5

1

-

1

1

6

2

-

2

2

2

-

2

2

 

Comparison with CLP criteria:

 Mean erythema and edema scores in 2 of 6 animals are > 2.3. Number of animals with irritation scores >2.3 are lower than criteria in CLP regulation. But compared with OECD guideline 404 exposure time was higher (24h instead of 4h) and observation time lower (only 72h) so that reversibility could not be demonstrated.

 

Shaved and abraded skin (not used for evaluation):

Animal Nr.

Erythema

24 h

Erythema

48 h

Erythema

72h

Mean

Erythema

Edema

24 h

Edema

48 h

Edema

72 h

Mean

Edema

1

3

-

1

2

2

-

1

1.5

2

3

-

2

2.5

3

-

3

3

3

3

-

1

2

1

-

1

1

4

2

-

2

2

3

-

2

2.5

5

2

-

1

1.5

1

-

1

1

6

2

-

2

2

1

-

1

1

 

Reevaluation acc. DSD criteria:

shaved skin

         
 24 h Exposure        
  Erythema   Edema  
  24h 72h 24h 72h
Animal 1 3 1 2 1
Animal 2 3 2 3 3
Animal 3 3 2 1 1
Animal 4 2 2 3 2
Animal 5 2 1 1 1
Animal 6 2 2 2 2
MW 2.5 1.66666667 2 1.66666667
         
Overall mean 2.08333333   1.83333333  
  Erythema   Edema  
Interpretation of results:
Category 2 (irritant)
Remarks:
Migrated information Criteria used for interpretation of results: other:
Conclusions:
In a valid guideline study the test substance was considered moderately irritating to rabbit skin.
Executive summary:

In a valid guideline study, six NZ White rabbits were restrained in stocks and the fur removed by clipping. Half of the exposed area was abraded and the other half remained intact. 0.5 ml (vol) of n-butyl methacrylate was applied to the shaved intact and abraded skin sites and covered with surgical gauze. The area was then wrapped with impervious tape and a stockinette sleeve. Test material remained in contact for 24 hrs and then removed. Irritation scores were determined at 24 and 72 hours after patch removal. Well-defined to moderate erythema and barely perceptible to moderate edema and induration of the skin (2/6) were evident. Reevaluated acc. DSD criteria mean scores for shaved skin over 24 and 72 hours was 2.08 and for erythema and 1.83 for edema. n-Butyl methacrylate was considered moderately irritating to rabbit skin acc. DSD criteria. Reevaluated acc. CLP criteria mean erythema and edema scores in 2/6 animal are > 2.3. As the most stringent result has to be used reevaluation acc. DSD criteria is the more stringet than CLP criteria. Erythema score is slightly above 2. Therefore n-Butyl methacrylate is considered moderately irritating.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
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
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Lippische Versuchstierzucht, Hagemall GmbH & Co. KG
- Age at study initiation: 8-10 W
- Weight at study initiation: no data
- Housing: individually
- Diet (e.g. ad libitum): mümmel z, ssniff/Soest
- Water (e.g. ad libitum): tap water
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 +/- 2
- Humidity (%): 40 - 50
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
Amount applied: 0.1 ml
Duration of treatment / exposure:
The test eyes were not washed out following the instillation
Observation period (in vivo):
1, 24, 48 and 72 hours as well as 8 days 
Number of animals or in vitro replicates:
3
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): no

SCORING SYSTEM: Draize scale

TOOL USED TO ASSESS SCORE: hand-slit lamp and fluorescein
Irritation parameter:
cornea opacity score
Basis:
animal: #1, #2, #3
Time point:
other: mean 24+48+72 h
Score:
0
Max. score:
4
Remarks on result:
other: Observation time: 8 days
Irritation parameter:
iris score
Basis:
animal: #1, #2, #3
Time point:
other: mean 24+48+72 h
Score:
0
Max. score:
2
Remarks on result:
other: Observation time: 8 days
Irritation parameter:
conjunctivae score
Basis:
animal: #1, #3
Time point:
other: mean 24+48+72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 h
Remarks on result:
other: Observation time: 8 days
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
other: mean 24+48+72 h
Score:
0
Max. score:
4
Remarks on result:
other: Observation time: 8 days
Irritation parameter:
chemosis score
Basis:
animal: #1, #2
Time point:
other: mean 24+48+72 h
Score:
0
Max. score:
4
Remarks on result:
other: Observation time: 8 days
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
other: mean 24+48+72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 h
Remarks on result:
other: Observation time: 8 days
Irritant / corrosive response data:
One hour after dosing, two animals exhibited slight conjunctival redness, chemosis and discharge, which persisted for 24 hours in one animal.  The second animal also exhibited conjunctival redness at 24 hours after dosing.  At 48 hours following dosing all signs of irritation had resolved.  The remaining animal showed no signs of irritation at any time during the test.

Classification of eye irritation studies according GHS-criteria

 

Substance:n-Butyl methacrylate                     CAS: 97-88-1

 

Source: UNTER 88-022

 

 

Animal No.

Corneal opacity/Hornhauttrübung[Scores]

 

Mean Draize score in 2 of 3 animals

Reversibility

[scores]

Hazard category

after 24 h

after 48 h

after 72 h

in 7 days

in 21 days

 

1

0

0

0

0

0

 

 

2

0

0

0

0

0

 

 

3

0

0

0

0

0

 

 

 

 

 

 

0

 

 

none

 

 

 

 

 

 

 

 

Animal No.

Iritis/Regenbogenhautentzündung[Scores]

 

Mean Draize score in 2 of 3 animals

Reversibility

[scores]

Hazard category

after 24 h

after 48 h

after 72 h

in 7 days

in 21 days

 

1

0

0

0

0

0

 

 

2

0

0

0

0

0

 

 

3

0

0

0

0

0

 

 

 

 

 

 

0

 

 

none

 

 

 

 

 

 

 

 

Animal No.

Conjunctiva redness (erythem) /Bindehautrötung[Scores]

 

Mean Draize score in 2 of 3 animals

Reversibility

[scores]

Hazard category

after 24 h

after 48 h

after 72 h

in 7 days

in 21 days

 

1

1

0

0

0.33

0

 

 

2

0

0

0

0

0

 

 

3

1

0

0

0.33

0

 

 

 

 

 

 

 

 

 

none


 

Animal No.

Conjunctiva chemosis /Bindehautödem[Scores]

 

Mean Draize score in 2 of 3 animals

Reversibility

[scores]

Hazard category

after 24 h

after 48 h

after 72 h

in 7 days

in 21 days

 

1

0

0

0

0

0

 

 

2

0

0

0

0

0

 

 

3

1

0

0

0.33

0

 

 

 

 

 

 

 

 

 

none

 

 

Classification:

Hazard Category

 

none

Interpretation of results:
slightly irritating
Remarks:
Migrated information not classified Criteria used for interpretation of results: other: REGULATION (EC) No 1272/2008 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL of 16 December 2008
Conclusions:
Classification: not irritating
Executive summary:

In an OECD 405 guideline study, n-butyl methacrylate (0.1 ml) was placed in the conjunctival sac of the right eye of three New Zealand White rabbits.   The lids were then gently held together for one second.   The test eyes were not washed out following the instillation.   The left eye remained untreated for control.   The eyes were examined at 1, 24, 48 and 72 hours as well as 8 days from beginning of test.   Eye irritation was scored for signs of corneal damage (density, area), iris reaction and lesions of the conjunctivae (erythema, chemosis, discharge).   Additionally, the cornea was examined with the aid of fluorescein after recording the observations at 24 hours. One hour after dosing, two animals exhibited slight conjunctival redness, chemosis and discharge, which persisted for 24 hours in one animal.   The second animal also exhibited conjunctival redness at 24 hours after dosing.   At 48 hours following dosing all signs of irritation had resolved.   The remaining animal showed no signs of irritation at any time during the test. n-Butyl methacrylate is considered as slightly irritating to eyes.

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Additional information

Skin irritation

In a study comparable to OECD 404, when 0.5 ml n-BMA was applied to the skin of rabbits under semi-occlusive and occlusive patch for one and 4 hours slight erythema was produced and for 4 hours slight oedema (4/6 animals) 1 hour after removal of the patch. Oedema regressed between day 1 and 3. Four out of 6 animals had fully recovered by day 7. The flank of 2/6 animals where n-BMA was applied under occlusive patch for 4 hours still showed a very slight erythema on day 7. After 14 days all signs of irritation had resolved. n-BMA was considered slightly irritant (Zechel, 1982).

In a valid guideline study Consultox/Poole (1980), six NZ White rabbits were restrained in stocks and the fur removed by clipping. Half of the exposed area was abraded and the other half remained intact. 0.5 ml (vol) of n-butyl methacrylate were applied to the shaved intact and abraded skin sites and covered with surgical gauze. The area was then wrapped with impervious tape and a stockinette sleeve. Test material remained in contact for 24 hrs and then removed. Irritation scores were determined at 24 and 72 hours after patch removal. Well-defined to moderate erythema and barely perceptible to moderate oedema and induration of the skin (2/6) were evident. Mean scores for shaved and abraded skin over 24 and 72 hours were 2.08 and 2.0 for erythema and 1.83 and 1.66 for oedema, respectively. n-Butyl methacrylate was considered moderately irritating to rabbit skin.

There are three further studies, that indicate similar effects (Sterner and Stiglic, 1977; Sarver, 1993).

In summary, there is a tendency towards stronger irritation with increasing contact time. Also, there is considerable variation in the irritation responses between studies and this possibly reflects differences in procedural conditions, e.g. occlusion. In some animals on some studies, namely the study of Consultox/Poole (1980), there is clear evidence of skin irritant potential. Consequently, on balance, n-BMA is considered as irritant to skin.

Eye irritation

In an OECD 405 guideline study, n-butyl methacrylate (0.1 ml) was placed in the conjunctival sac of the right eye of three New Zealand White rabbits (Schreiber and Wodtke, 1988). The lids were then gently held together for one second. The test eyes were not washed out following the instillation. The left eye remained untreated for control. The eyes were examined at 1, 24, 48 and 72 hours as well as 8 days from beginning of test. Eye irritation was scored for signs of corneal damage (density, area), iris reaction and lesions of the conjunctivae (erythema, chemosis, discharge). Additionally, the cornea was examined with the aid of fluorescein after recording the observations at 24 hours. One hour after dosing, two animals exhibited slight conjunctival redness, chemosis and discharge, which persisted for 24 hours in one animal. The second animal also exhibited conjunctival redness at 24 hours after dosing. At 48 hours following dosing all signs of irritation had resolved. The remaining animal showed no signs of irritation at any time during the test. n-Butyl methacrylate is considered as slightly irritating to eyes.

In addition, in an FDA Draize test, 0.1 ml undiluted n-BMA were applied into the conjunctival sac of one eye of six New-Zealand white rabbits, the ocular reactions were observed at 24, 48 and 72 hours after the instillation. Slight towell defined redness of the conjunctivae was observed in four out of six animals. Mean scores over 24, 48 and 72 hours were 0.77, 0.27, 0 and 0 for erythema, chemosis, iris and cornea, respectively (1980).

In summary, n-BMA causes only light irritation and is rated as non-irritant.

Respiratory irritation

In accordance with the vapour pressure of n-BMA, exposures at concentrations above approx. 2,000 ppm (11.6 mg/L) would have been to a mixture of vapour and aerosol. Results from single (Kelly, 1993) and repeated exposure ( Hagan et al., 1993) inhalation studies demonstrate that n-BMA is irritant to the respiratory tract, when the animals have been exposed to a vapour/aerosol mixture or at high vapour concentrations.

Exposure of groups of five male and five female Crl:CDBR rats to 0, 13.8, 18.2, 23.9, 26.6, 28.6 or 36 mg/l (0, 2332, 3079, 4044, 4500, 48839 and 6091 ppm) n-BMA for 4 hours (Kelly, 1993) produced clinical symptoms consistent with marked irritation to the respiratory tract (nasal discharge, gasping, irregular respiration, lung noise) and eyes (corneal opacity, one rat at 6091 ppm).

In a 4-week vapour inhalation study in CrI:CDBR rats exposed to 0, 310, 952 and 1891 ppm n-BMA, clinical symptoms consistent with irritancy to the respiratory tract such as laboured breathing were seen during the first day of exposure to 1891 ppm n-BMA (Hagan et al,1993; Section Acute toxicity: inhalation). After 4 weeks, the NOAEL for respiratory tract irritation was 310 ppm.

In an inhalation study (Jones, 2002, Section Acute toxicity: inhalation) in F344 rats, using specialist histopathology techniques to study the nasal tissues, n-butyl methacrylate did not produce lesions in the olfactory region of the nasal cavity following exposure at 200 ppm for 6 hrs.

In summary, n-BMA is rated as irritating to the respiratory tract.

Corrosion

nBMA is not corrosive to skin or eyes. Since the primary acid metabolite, MAA, is corrosive to skin and eyes and this hazard is not observed in the irritation studies with the parent C1-C8 methacrylate esters, localised metabolism and associated local effects due to high concentrations of the MAA metabolite are not of concern for irritation effects.


Effects on skin irritation/corrosion: irritating

Effects on eye irritation: slightly irritating

Effects on respiratory irritation: irritating

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 pronounced effects in single animals. Hence, n-butyl methacrylate is classified as a skin irritant (R38/H315 and skin irritation Cat. 2 according to 67/548/EEC and CLP / UN-GHS criteria, respectively).

Eye irritation

It is considered, that n-butyl methacrylate possess the potential for maximum slight irritation effects on the rabbit eye, which were below the criteria for classification according to 67/548/EEC and CLP / UN-GHS criteria, respectively. No classification. Please note: While the data support no classification, the CLP Annex VI entries still specify n-BMA as eye irritant, category 2.

Irritation of the respiratory tract

Based on results of studies n-butyl methacrylate has to be classified as irritant to the respiratory tract (R37/H335 and STOT single exposure Cat. 3 according to 67/548/EEC and CLP/UN-GHS criteria, respectively).