tert-butyl methacrylate

Endpoint summary

Description of key information

Skin irritation: according to OECD TG 404, GLP compliant, K1, rabbit, irritating Cat. 2

Eye irritation: according to OECD TG 405, GLP compliant, K1, rabbit, irritating Cat. 2

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:

January 1994

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

1992

GLP compliance:

yes

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source (supplier): BASF AG
- Lot number of test material: LAB.J.NO. 387
- Purity: not specifed

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Refrigerator, exclusion of light
- Stability and homogeneity of the test material in the vehicle/solvent under test conditions and during storage: The stability of the test substance over the study period was proved by reanalysis. The result was reported in the form of an amendment (12 January 1995). According to the analytical determination, dated December 07, the test substance was stable over the study period. The sample appeared to be homogeneous.

FORM AS APPLIED IN THE TEST
- The test substance was applied in a single dose to the tact untreated skin. The test patch was secured in position with a semiocclusive dressing.

Species:

rabbit

Strain:

Vienna White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Gaukler, Offenbach/Main, D
- Age at study initiation: young adult, not further specified
- Weight at study initiation: 3.35 - 3.82 kg
- Housing: single
- Diet: Kliba Labordiaet 341, Klingenthalmuehle AG, Kauseraugst, Switzerland, about 130 g per animal per day
- Water: about 250 ml tap water per animal per day
- Acclimation period: at least 1 week

ENVIRONMENTAL CONDITIONS
- Temperature: 20-24°C
- Humidity: 30-70%
- Air changes (per hr): not specified
- Photoperiod (hrs dark / hrs light): 12 h/12 h (6.00 a.m.- 6.00 p.m./6.00 p.m.- 6.00 a.m.)

IN-LIFE DATES: not specified

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

other: Yes, untreated skin sites of the same animal

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): The test patch (2.5 cm x 2.5 cm) was moistened with a dose of 0.5 ml of the unchanged liquid test substance.

Duration of treatment / exposure:

4 h

Observation period:

15 d

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: upper third of the back or flanks
- % coverage: 2.5 x 2.5 cm
- Type of wrap if used: Idealbinde, Pfaelzische Verbandsstoff-Fabrik, Kaiserslautern, Germany and Fixomull stretch (adhesive fleece), Beiersdorf AG

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The test substance wa sremoved at the end of the exposure period with Lutrol (=Polyethylenglykol) pure and Lutrol/water 1:1
- Time after start of exposure: 4 h

SCORING SYSTEM: OECD Draize
- for detailed information please refer to section "Any other information on materials and methods incl. tables"

OBSERVATION TIME POINTS: 1 h, 24 h, 48 h, 72 h, 8 d and 15 d after removal of the patch

Irritation parameter:

erythema score

Basis:

animal #1

Remarks:

mean

Time point:

other: 24, 48, 72 h

Score:

3

Max. score:

4

Reversibility:

fully reversible within: 15 days

Remarks on result:

positive indication of irritation

Irritation parameter:

erythema score

Basis:

animal #2

Remarks:

mean

Time point:

other: 24, 48, 72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 15 d

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Basis:

animal #3

Remarks:

mean

Time point:

other: 24, 48, 72 h

Score:

2.3

Max. score:

4

Reversibility:

fully reversible within: 15 d

Remarks on result:

positive indication of irritation

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 24, 48, 72 h

Score:

2.43

Max. score:

4

Reversibility:

fully reversible within: 15 d

Remarks on result:

positive indication of irritation

Irritation parameter:

edema score

Basis:

animal #1

Remarks:

mean

Time point:

other: 24, 48, 72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 8 d

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal #2

Remarks:

mean

Time point:

other: 24, 48, 72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible within: 8 d

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal #3

Remarks:

mean

Time point:

other: 24, 48, 72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible within: 8 d

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 24, 48, 72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 8 d

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

The numerical scores awarded to the dermal reactions of each animal elicited by the test substance are given in Table 1 in section "Any other information on results incl. tables".

Table 1: Dermal reactions elicited by the test substance.

Exposition:	4 h
Animal	Reading	Erythema	Edema	Symptoms
1	1 h	2	1
2	1 h	1	0
3	1 h	2	1
1	24 h	3	1
2	24 h	2	0
3	24 h	2	0
1	48 h	3	1
2	48 h	2	0
3	48 h	2	0
1	72 h	3	1
2	72 h	2	0
3	72 h	3	0
1	8 d	1	0	Scaling
2	8 d	1	0	Scaling
3	8 d	1	0	Scaling
1	15 d	0	0
2	15 d	0	0	Scaling
3	15 d	0	0
mean	24 - 72 h	2.44	0.33

Interpretation of results:

Category 2 (irritant) based on GHS criteria

Conclusions:

Under the test conditions chosen and considering the described findings the test substance gives indication of an irritant property to the skin.

Executive summary:

Acute dermal irritation or corrosion to skin was evaluated in a GLP compliant study according to the OECD TG 404. Thereby, test patches containing 0.5 ml of the test substance were applied by a single topical application to the intact skin of three white Vienna rabbits for 4 hours under semiocclusive dressing. The skin sites were evaluated for erythema/eschar and edema formation 1 h, 24 h, 48 h, 72 h, 8 d and 15 d following removal of the patches. The average score (24 to 72 hours) for irritation was calculated to be 2.4 for erythema and 0.3 for edema. Signs of skin irritation such as erythema and edema were reversible within 15 days after removal of the patches, while scaling was still present in one animal at study termination. Under the test conditions chosen and considering the described findings the test substance gives indication of an irritant property to the skin.

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

Study period:

1994-01-24 until 1994-02-07

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

1987

GLP compliance:

yes

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source (supplier): BASF
- LOT number of test material: LAB.-J.-NO. 387
- Purity: not specified

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Refrigerator, exclusion of light
- Stability and homogeneity of the test material in the vehicle/solvent under test conditions and during storage: The stability of the test substance over the study period was proved by reanalysis. The result was reported in the form of an amendment (12 January 1995). According to the analytical determination, dated December 07, the test substance was stable over the study period. The sample appeared to be homogeneous.

FORM AS APPLIED IN THE TEST
- The unchanged test substance was applicated once to the conjunctival sac of the right eyelid of the test animals.

Species:

rabbit

Strain:

Vienna White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Gaukler, Offenbach/Main, Germany
- Age at study initiation: young adult (not further specified)
- Weight at study initiation: 3.67 - 4.37 kg
- Housing: single housing
- Diet: Kliba Labordiaet 341, Klingenthalmuehle AG, Kauseraugst, Switzerland, about 130 g per animal per day
- Water: about 250 ml tap water per animal per day
- Acclimation period: at least 1 week

ENVIRONMENTAL CONDITIONS
- Temperature: 20-24°C
- Humidity: 30-70%
- Air changes (per hr): not specified
- Photoperiod:12 H/12 H (6.00 a.m.- 6.00 p.m./6.00 p.m. - 6.00 a.m.)

IN-LIFE DATES: not specified

Vehicle:

unchanged (no vehicle)

Controls:

other: untreated eye of each tested animal

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml

Duration of treatment / exposure:

unwashed

Observation period (in vivo):

8 days

Number of animals or in vitro replicates:

3

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing: The substance was not washed out.

SCORING SYSTEM: Draize scoring (for more details please refer to "Any other information on materials and methods incl. tables")

TOOL USED TO ASSESS SCORE: not specified

Irritation parameter:

cornea opacity score

Remarks:

mean

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

cornea opacity score

Remarks:

mean

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

cornea opacity score

Remarks:

mean

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Remarks:

mean

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Remarks:

mean

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Remarks:

mean

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Remarks:

mean

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

3

Reversibility:

fully reversible within: 8 days

Remarks on result:

positive indication of irritation

Irritation parameter:

conjunctivae score

Remarks:

mean

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

3

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Remarks:

mean

Basis:

animal #3

Time point:

24/48/72 h

Score:

2

Max. score:

3

Reversibility:

fully reversible within: 8 days

Remarks on result:

positive indication of irritation

Irritation parameter:

chemosis score

Remarks:

mean

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

chemosis score

Remarks:

mean

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

chemosis score

Remarks:

mean

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

The numerical scores awarded to the eye reactions elicited by the test substance are given in Table 1.

Table 1: TABULATION OF IRRITANT RESPONSE DATA FOR EACH INDIVIDUAL ANIMAL AT EACH OBSERVATION TIME AS WELL AS CALCULATION OF THE MEANS.

Animal	Reading	Opacity	Iritis	Redness	Chemosis	Symptoms
1	1 h	0	0	2	1	discharge score 3; small retractions of the eye lids
2	1 h	0	0	0	0
3	1 h	0	0	1	0	discharge score 1
1	24 h	0	0	2	0	small retractions of the eye lids
2	24 h	0	0	0	0
3	24 h	0	0	2	1	discharge score 1
1	48 h	0	0	2	0	small retractions of the eye lids
2	48 h	0	0	0	0
3	48 h	0	0	2	0	discharge score 1
1	72 h	0	0	2	0	small retractions of the eye lids
2	72 h	0	0	0	0
3	72 h	0	0	2	0	discharge score 1
1	8 d	0	0	0	0
2	8 d	0	0	0	0
3	8 d	0	0	0	0
mean	24 - 72 h	0.00	0.00	1.33	0.11

Interpretation of results:

Category 2 (irritating to eyes) based on GHS criteria

Conclusions:

Under the test conditions chosen and considering the described findings the test substance does give indication of an irritant property to the eye.

Executive summary:

The potential of the test substance to cause damage to the conjunctiva, iris or cornea was assessed according to a OECD TG 405 conform and GLP compliant study. The unchanged test substance was applicated once to the conjunctival sac of the right eyelid of three white Vienna rabbits. Exposure to the test susbstance produced conjunctival redness in 2/3 animals by all scoring intervals (24, 48 and 72 hours). One animal showed chemosis by the 24-hour scoring interval. The findings were reversible in all animals within 8 days after application. Under the test conditions chosen and considering the described findings the test substance does give indication of an irritant property to the eye.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Additional information

Skin irritation

 

Key study: Acute dermal irritation or corrosion to skin was evaluated in a GLP compliant study according to the OECD TG 404. Thereby, test patches containing 0.5 ml of the test substance were applied by a single topical application to the intact skin of three white Vienna rabbits for 4 hours under semiocclusive dressing. The skin sites were evaluated for erythema/eschar and edema formation 1 h, 24 h, 48 h, 72 h, 8 d and 15 d following removal of the patches. The average score (24 to 72 hours) for irritation was calculated to be 2.4 for erythema and 0.3 for edema. Signs of skin irritation such as erythema and edema were reversible within 15 days after removal of the patches, while scaling was still present in one animal at study termination. Under the test conditions chosen and considering the described findings the test substance gives indication of an irritant property to the skin.

 

Supporting study: Acute dermal irritation or corrosion to skin was evaluated in a GLP compliant study similar to the OECD TG 404. Thereby, test patches containing 0.5 ml of the test substance were applied by a single topical occlusive application for 24 h. Immediately prior to application of the test substance, an area of skin approximately 2.5 cm square on the right side of the spine was abraded using the tip of a blade scalpel incisions through the stratum corneum. These were not deep enough to disturb the dermis or cause bleeding. A similar site on the left side remained intact. The skin sites were evaluated for erythema/eschar and edema formation 24 and 72 h following removal of the patches. Under the test conditions chosen and considering the described findings the test substance gives not indication of an irritant property to the skin.

 

Eye irritation

Key study: The potential of the test substance to cause damage to the conjunctiva, iris or cornea was assessed according to a OECD TG 405 conform and GLP compliant study. The unchanged test substance was applicated once to the conjunctival sac of the right eyelid of threewhite Vienna rabbits. Exposure to the test susbstance produced conjunctival redness in 2/3 animals by all scoring intervals (24, 48 and 72 hours). One animal showed chemosis by the 24-hour scoring interval. The findings were reversible in all animals within 8 days after application. Under the test conditions chosen and considering the described findings the test substance is regarded as eye irritant.

 

 

 

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. A GLP-compliant OECD 404 study is available for skin irritation. A GLP-compliant OECD 405 study is available for eye irritation. Based on the results of both in vivo studies the test substance is classified for skin and eye irritation Cat. 2 under Regulation (EC) No. 1272/2008, as amended for the fourteenth time in Regulation (EC) No. 2020/217.

 

Based on the signs of respiratoy tract irritation observed in the acute inhalation toxicity test with a structural analoque substance and based on a harmonised classification - Annex VI of Regulation (EC) No 1272/2008 (CLP) (chemical group: monoalkyl or monoaryl or monoalkyaryl esters of methacrylid acid with the exception of those specified elsewhere in this Annex, Index 607-134-00-4) the test item is classified as STOT SE3 (H335: specific concentration limit C >= 10%) according to Regulation (EC) No 1272/2008 (CLP).