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Administrative data

Description of key information

Cyclohexylmethacrylate is not irritating to the skin, and does not cause any risk of serious damage to the eyes. In inhalation studies local degeneration of the olfactory epithelia was observed in acute to chronic studies with marked degeneration at 400 ppm and above with the hydrolysis product methacrylic acid and the lower methacrylate ester methyl methacrylate.

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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
according to
Guideline:
other: "Appraisal of the safety of chemicals in foods, drugs and cosmetics"; Division of Pharmacology, FDA; according to the Draize Test, 1959
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: mean 2.5 kg
- Housing: single
- Diet: ad libitum
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20
- Humidity (%): 45 - 55
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
other: other flank of the same animal
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL
Duration of treatment / exposure:
24 hours
Observation period:
72 hours
Number of animals:
6
Details on study design:
TEST SITE
- Area of exposure: 2.5 x 2.5 cm
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24h - 72h
Score:
0.42
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24h - 72h
Score:
0.25
Max. score:
4
Reversibility:
fully reversible

Raw data

 

No. of Animals

24 h

72 h

Erythema

1

0

0

 

2

0

0

 

3

2

1

 

4

1

0

 

5

1

0

 

6

0

0

Edema

1

0

0

 

2

0

0

 

3

0

0

 

4

1

0

 

5

1

0

 

6

1

0

Interpretation of results:
GHS criteria not met
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Qualifier:
according to
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
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:
mean
Remarks:
6 animals
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: no effects
Irritation parameter:
iris score
Basis:
mean
Remarks:
6 animals
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
other: no effects
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
6 animals
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:
mean
Remarks:
6 animals
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.

Raw data

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
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 primary dermal irritation study according to Draize et al. (1959), six New Zealand White rabbits were dermally exposed to 0.5 mL of undiluted cyclohexyl methacrylate for 24 hours under an occlusive dressing (Evonik Roehm, 1978). Animals were then observed for 72 hours. Irritation was scored by the method of Draize et al (1959).

Three animals showed slight to moderate erythema and slight edema after 24 hours. All other animals did not show any irritating skin reactions. Erythema and edema were fully reversible within 72 hours. One animal out of six still showed very slight erythema after 72 hours. According to the results the substance was not regarded as skin irritating.

Eye irritation

An in vitro study with fresh bovine cornea was conducted according to EU method B.47 to investigate the eye irritation properties of the Cyclohexyl methacrylate (BASF SE, 2010). After a first opacity measurement of the fresh bovine cornea, the undiluted test substance, the positive and the negative controls were applied to cornea and incubated for 10 min at 32 °C. After the incubation phase the substances were rinsed from the cornea. The cornea were incubated for 2 h at 32 °C in incubation medium, and opacity was measured a second time. After the opacity measurements permeability of the cornea was determined by measuring spectrophotometrically the transfer of sodium fluorescein after incubation in a horizontal position for 90 minutes at 32 °C. The positive control showed opacity and permeability of the cornea (mean IVIS = 158.4). Relative to the negative control, the test substance did not cause an increase of the corneal opacity or permeability. The calculated mean IVIS was 7.7 (threshold for serious eye damage: IVIS > 65). According to test guideline the test item is not identified as corrosive or severe irritant.

In addition the structural analog methyl methacrylate possesses the potential for max slight irritation effects on the rabbit eye, which were below the criteria for classification according to UN-GHS criteria.

The results of the reliable studies with methyl methacrylate 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 (Evonik Roehm, 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 mean scores were 0.0 for all parameters. Slight to moderate conjunctivae redness, chemosis and discharge was observed in the readings 1 h to 8 h after application. They were regarded as 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 possesses the potential for, at most, slight irritation effects on the rabbit eye.

Based on the in vitro and in vivo results it is concluded that Cyclohexyl methacrylate does not show any irritating effects to the eyes.

Respiratory irritation

In inhalation studies local degeneration of the olfactory epithelia was observed in acute (6hrs) at 100 ppm, through to chronic (2-yr) studies at 100 ppm (LOEL) with marked degeneration at 400 ppm and above with the hydrolysis product methacrylic acid and the lower methacrylate ester methyl methacrylate. Therefore respiratory irritation cannot be excluded based on the available data with the analogue substances.

Justification for classification or non-classification

Harmonised Annex VI classification according to Regulation CLP of group entry for monoalkyl or monoaryl or monoalkyaryl ester of methacrylic acid:

- Skin corrosion/irritation: Category 2

- Serious eye damage/eye irritation: Category 2A

- Specific target organ toxicity, Single exposure: Category 3 (May cause respiratory irritation)

The toxicological results of the above studies with cyclohexyl methacrylate and methyl methacrylate would not trigger the above classification for skin and eye irritation. Based on other findings with methacrylic acid and methyl methacrylate, respiratory irritation cannot be excluded.