Butyl methacrylate

Endpoint summary

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

Reference

Reference 1

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

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system 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.

Reference 2

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

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 or test system 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

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

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).