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Administrative data

Description of key information

Cyclohexylmethacrylate is nontoxic after single oral application (LD50 rat oral 12900 mg/kg) and after a single dermal application (LD50 rat dermal > 2000 mg/kg). A low acute inhalation toxicity is expected based on study results with the hydrolysis products cyclohexanol and methacrylic acid as well as the lower methacrylate ester methyl methacrylate (the LC50 rat inhalation is 29.8 mg/L).

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Principles of method if other than guideline:
According to "Appraisal of the safety of chemicals in foods, drugs and cosmetics" , by the staff of the Division of Pharmacology FDA, 1959
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Zucht Winkelmann (Paderborn)
- Fasting period before study: 16 hors before application
- Weight at study initiation: between 140 and 230 g
- Housing: group, 5 animals
- Diet: ad libitum
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22
- Humidity (%): 45 - 55
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Doses:
10, 12.6, 15.9, 20.0 mL/kg ( 9.94, 12.14, 15.32, 19.28 g/kg)
No. of animals per sex per dose:
5
Control animals:
no
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
12 900 mg/kg bw
Based on:
test mat.
Remarks on result:
other: Original data: 13.41 mL/kg
Mortality:
10 mL/kg: 1 female
12.6 mL/kg: 3 male and 2 female, day 5
15.9 mL/kg: 1 male after 48 h, 3 female day 5, 1 female day 7, 1 female day 8
20.00 mL/kg: 1 male and 2 female after 24 h, 2 female after 48 h, 4 male and 1 females day 5
Clinical signs:
20 mL/kg: Apathy
all Doses: depression, piloerection, anomaly position, coordination disturbance, reduced grasp and extremities tone
Symptoms were seen 20 min after application up to 24 hours. Normal behaviour was seen from 24 hours onwards.
Gross pathology:
In animals that were found dead inflamed mucosa of stomach and intestinal mucosa was observed. All sacrificed animals did not show any gross internal lesions.

Mortality

Dose (mL/kg)

No. of animals

Died within

24 h

48 h

5 days

7 days

8 days

14 days

10

5 male

0/5

0/5

0/5

0/5

0/5

0/5

 

5 female

0/5

0/5

1/5

1/5

1/5

1/5

12.6

5 male

0/5

0/5

3/5

3/5

3/5

3/5

 

5 female

0/5

0/5

2/5

2/5

2/5

2/5

15.9

5 male

0/5

1/5

1/5

1/5

1/5

1/5

 

5 female

0/5

0/5

3/5

4/5

5/5

5/5

20.0

5 male

1/5

1/5

5/5

5/5

5/5

5/5

 

5 female

2/5

4/5

5/5

5/5

5/5

5/5

Interpretation of results:
GHS criteria not met
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
12 900 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Principles of method if other than guideline:
Study to assess the acute inhalative toxicity of methyl methacrylate in rats after 4 h of exposure.
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Diet: Purina Laboratory Chow
- Water: tap water
- Acclimation period: at least one week
Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
75 liter glass dynamic chambers were used. The generation of the test atmosphere was previously described by Tansy et al., Environ. Res., 11:66, 1976.
Analytical verification of test atmosphere concentrations:
not specified
Duration of exposure:
4 h
Concentrations:
0 (sham exposed), 4750, 6146, 8044, 10209, 13479 ppm (corresponding to ca. 19.5, 25.2, 33.0, 41.9 and 55.3 mg/L)
No. of animals per sex per dose:
5
Control animals:
yes
Details on study design:
24 hour post-exposure observation period.
Statistics:
Interpolation of the linear regression of the log of the number of survivors against concentration of vapor. The LC50 was computed from responses of those groups where the mortality was greater than zero and less than 100%.
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
29.8 mg/L air
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
other: corresponding to 7093 ppm
Mortality:
19.5 mg/L (4750 ppm): 8/10 animals died
25.2 mg/L (6146 ppm): 6/10 animals died
33.0 mg/L (8044 ppm): 2/10 animals died
41.9 mg/L (10209 ppm): 0/10 animals died
55.3 mg/L (13479 ppm): 0/10 animals died
Clinical signs:
other: not reported
Body weight:
not reported
Gross pathology:
not reported
Interpretation of results:
GHS criteria not met
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC50
Value:
29 800 mg/m³

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
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 402 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes
Specific details on test material used for the study:
- Lot/batch No.: CHMA Verkaufstank 14 v.23.02.2010 PBG-Charge 010117eda0
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Wiga GmbH, Sulzfeld (Germany)
- Age at study initiation: young adult animals ( male animals approx. 8 weeks, female animals approx. 12 weeks)
- Weight at study initiation: animals of comparable weight ( +/- 20 % of the mean weight)
- Housing: single housing
- Diet: ad libitum ( VRF1(P); SDS Special Diets Services, Altrip, Germany)
- Water: ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 30 - 70
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: 40 cm²
- % coverage: 10 %
- Type of wrap if used: semi occlusive

REMOVAL OF TEST SUBSTANCE
- Washing: yes
- Time after start of exposure: 24 hours

Duration of exposure:
24 hours
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: weekly
- Other examinations performed: clinical signs
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred.
Clinical signs:
Systemic effects: No systemic clinical signs were observed during clinical examination.
Local effects: No local effects were observed.
Body weight:
The mean body weight of the animals increased throughout the study period within the normal range.
Gross pathology:
No macrosopic pathologic abnomalities were noted in the animals (5 males and 5 females) examined on the last day of observation.

Mortality

Dose (mg/kg bw):

2000

2000

Sex:

Male

Female

Administration:

1

1

No. of animals:

5

5

Mortality (animals):

No mortality

No mortality

 

Interpretation of results:
GHS criteria not met
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw

Additional information

Acute oral toxicity

In an acute oral toxicity study, groups of fasted young Wistar rats (5/sex) were given a single oral dose of the test substance at doses of 10, 12.6, 15.9, 20.0 mL/kg (9.94, 12.14, 15.32, 19.28 g/kg). Animals were observed for 14 days (Evonik, 1978).

All animals died in the highest dosing group. At the lowest dosing group one female was found dead on day 5. At 12.6 mL/kg three males and two females were found dead on day 5. All females and one male died at 15.9 mL/kg. In all dosing groups depression, piloerection, anomaly position, coordination disturbance, reduced grasp and extremities tone was observed 20 min after application. Normal behaviour was seen from 24 hours onwards. At the highest dosing group the animals showed apathy. In animals that were found dead inflamed mucosa of stomach and intestinal mucosa was observed. All sacrificed animals did not show any gross internal lesions.

Based on the results of this study an LD50 of 13.41 mL/kg was determined corresponding to 12900 mg/kg bw.

Acute dermal toxicity

In an acute dermal toxicity study according to OECD guideline 402, groups of young adult Wistar rats (5/sex) were dermally exposed to the unchanged test substance at a limit concentration of 2000 mg/kg bw for 24 hours (BASF SE, 2010). Animals were then observed for 14 days.

No mortality was observed. The test substance did not lead to any systemic or local clinical effects. Body increased in a normal range throughout the study period. No gross internal lesions were observed during necropsy.

Based on these findings an LD50 of above 2000 mg/kg bw was determined.

Acute inhalation toxicity

Studies of acute inhalative toxicity of cyclohexylmethacrylate are not available. Reliable studies of the hydrolysis products methacrylic acid and cyclohexanol as well as methyl methacrylate were used to assess the potential of cyclohexylmethacrylate for acute inhalation.

Results of a publication of Tansy et al. (1980) indicate a very low acute toxic potential of methyl methacrylate in rats after inhalative exposure. Sprague Dawley rats were whole body exposed to vapour concentrations of 4750, 6146, 8044, 10209, 13479 ppm (corresponding to 19.5, 25.2, 33.0, 41.9 and 55.3 mg/L) for four hours. The lowest valid LC50 value is 29.8 mg/L in rats after 4 hours of exposure.

In an acute inhalation toxicity study (comparable to OECD guideline 403, limit test) 20 Sprague-Dawley rats/dose (10/sex) were exposed head and nose only by the inhalation route to aerosols of cyclohexanol (no data on purity) in air for 4 hours at a saturated air concentration of 3.6 mg/L (BASF AG, 1979). Animals were then observed for 14 days. No mortality was observed within the 14 day observation period. Ruffled fur coat was the only clinical sign of toxicity manifested by the rats. No gross pathological findings were noted.

Crl:CD BR rats were exposed nose only to an aerosol vapor mixture of methacrylic acid (MAA) at concentrations of 4.3, 5.9, 7.3, 8.2 mg/L for four hours. Death occurred at 5.9 mg/L and higher. Following exposure, typical clinical observations at 5.9 mg/L were discharge, gasping, lethargy, lung noise, stained fur, and weakness. Sores and alopecia on the nose, corneal opacity (one rat), hunched posture, and irregular respiration developed during the recovery period. At higher doses corneal opacity, gasping, irregular respiration, lethargy, lung noise, stained and wet fur, and nasal, ocular, and vaginal discharge were observed. Mortality is clearly associated with exposure to aerosol. Exposure to (saturated) vapour was the same at all concentration levels. Exposure to vapour alone was not associated with mortality, while exposure to aerosol increased in parallel, led to an increase in mortality. The 4 hour LC50 of MAA to male and female rats was 7.1 mg/L (1983 ppm; vapour/aerosol mix).

The above studies show a very low acute toxic potential for the degradations products and the lower methacrylate ester. The highest toxic potential can be observed for methacrylic acid. As this substance is highly irritating, the above observed signs of toxicity might be related to the corrosive nature of this acid. Cyclohexanol did not cause any severe clinical signs when tested as saturated vapour. The inhalation of methyl methacrylate vapour for four hours also led to an LC50 value that does not trigger classification. It is therefore concluded that the test substance does not include any acute toxic properties.

Justification for classification or non-classification

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

The available data are reliable and suitable for classification purposes under Regulation 1272/2008. The acute oral LD50 value was determined to be 129000 mg/kg bw and dermal LD50 value was determined to be > 2000 mg/kg bw. The acute inhalation LC50 for a read-across substance was determined to be 29800 mg/m^3. As a result the substance is not considered to be classified for acute toxicity via oral, dermal or inhalation route under Regulation (EC) No 1272/2008, as amended for the tenth time in Regulation (EU) No 2017/776.