2-Propenoic acid, 2-methyl-, C6-12-alkyl esters

Endpoint summary

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

Data on individual animals and total observation period not available.

Principles of method if other than guideline:

10 male albino rats/dose group; test material was administered as a 25 % (w/v) aqueous solution

GLP compliance:

not specified

Species:

rat

Strain:

not specified

Sex:

male

Route of administration:

oral: gavage

Vehicle:

water

No. of animals per sex per dose:

10 males per group

Sex:

male

Dose descriptor:

LD50

Effect level:

2 224 mg/kg bw

Remarks on result:

other: 2.18 ±0.05 ml/kg

Gross pathology:

Severe gastric irritation

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

In this study, Methacrylic acid is of low toxicity and has not to be classified in the current EU system. Under UN/OECD GHS the substance is Cat. 5 for acute oral toxicity.
Oral LD50 Males = 2224 mg/kg bw

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Remarks:

Summarized description of the method used and the results; brief summary, but sufficient for assessment purposes

Principles of method if other than guideline:

according to the Laboratory Protocol of Eastman Kodak Company, Health, Safety and Human Factors

GLP compliance:

no

Species:

rat

Strain:

not specified

Sex:

male

Route of administration:

oral: gavage

Vehicle:

corn oil

Remarks:

10% solution in corn oil

Doses:

200, 400, 800, 1600 and 3200 mg/kg body weight

No. of animals per sex per dose:

4 males per group

Details on study design:

Methacrylic acid was administered as a 10 % solution in corn oil  to groups of 4 male rats at 200, 400, 800, 1600 and 3200 mg/kg b.w..  Observation time: 14 days; no necropsies were conducted.

Sex:

male

Dose descriptor:

LD50

Effect level:

2 260 mg/kg bw

Clinical signs:

other: Clinical signs included weakness and rough haircoat.

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

In this study, Methacrylic acid is of low toxicity and has not to be classified in the current EU system. Under UN/OECD GHS the substance is Cat. 5 for acute oral toxicity.
Oral LD50 Males = 2260 mg/kg bw

Reference 3

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

Remarks:

As the substance was administered undiluted, it can be expected that the corrosive effects were manifested in the GI tract and the LD50 cannot be attributed solely to systemic toxicity. Very limited documentation of experimental details.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Principles of method if other than guideline:

Standard acute method: strain: Wistar; 8-10 male animals per group, 900-1750 mg/kg undiluted.

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

male

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Doses:

0.9, 1.00, 1.25, 1.50, 1.75 g/kg

No. of animals per sex per dose:

10 males per group at 0.9, 1.00, 1.25 g/kg; 8 males per group at 1.50, 1.75 g/kg

Details on study design:

Animals were observed for 10 days following adminstration of the substance.

Sex:

male

Dose descriptor:

LD50

Effect level:

1 320 mg/kg bw

Based on:

test mat.

Mortality:

Dose g/kg Mortality
0.9 0/10
1.00 2/10
1.25 4/10
1.50 6/8
1.75 8/8

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

Using a valid scientific method, the oral LD50 of undiluted MAA to male rats was 1320 mg/kg bw.

Executive summary:

Using a valid scientific method, the oral LD50 of undiluted MAA to male rats was 1320 mg/kg bw.

Reference 4

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Crj: CD(SD)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Japan Co. (Hino Breeding Center)
- Age at study initiation:
- Weight at receipt: 113-120g for males and 95-106 for females
- Fasting period before study: yes
- Housing: Stainless steel cage systems (W: 240 x D: 380 x H: 200mm) were used during quarantine and acclimatization, and 5 rats were housed in each cage. After dividing into groups, a rack of five stainless steel cages (W: 755 x D: 210 x H: 170mm) were used for individual housing.
- Diet (ad libitum): CRF-1, Oriental Yeast Co.
- Water (ad libitum): tap water
- Acclimation period: 12 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-23
- Humidity (%): 45-53
- Air changes (per hr): 12
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 0, 50, 100 or 200 mg/ml
- Amount of vehicle (if gavage): 5 ml/kg
- Justification for choice of vehicle: solubility

Doses:

0 (vehicle), 500, 1000, 2000 mg/kg/day

No. of animals per sex per dose:

five

Control animals:

yes

Details on study design:

Post dose observation period: 14 days
- Duration of observation period following administration: 14 days
- Frequency of observations: daily
- Weighing: Days 1, 3, 7, 10 and 14
- Necropsy of survivors performed: yes

Sex:

male/female

Dose descriptor:

LD0

Effect level:

> 2 000 mg/kg bw

Mortality:

There were no deaths in any group

Clinical signs:

other: Although soft faeces were observed in all treated groups, these effects were considered to be attributable to corn oil used as a vehicle.

Gross pathology:

No treatment related macroscopic abnormality was observed.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: other: REGULATION (EC) No 1272/2008

Conclusions:

The LD0 value was more than 2000 mg/kg for males and females.

Executive summary:

The Acute oral toxicity of 2-ethylhexyl methacrylate was evaluated in male and female Crj: CD(SD) rats according to OECD N°401 guideline and in compliance with principles of Good Laboratory Practices. Animals were treated by gavage at the dose level of 2000 mg/kg and then observed for 14 days for mortality, clinical signs and effect on body weight. No mortality was recorded in the 14 day-observation period. Although soft faeces were observed in all treated groups, these effects were considered to be attributable to corn oil used as a vehicle. A tendency of the depression of body weight gain was observed on the second day in both sexes. No treatment related macroscopic abnormality was observed. Under these experimental conditions, the oral LD₀of 2-ethylhexyl methacrylate is higher than 2000 mg/kg in female/male rats.

Reference 5

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1973

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: OSHA toxicity screening test. Limited documentation of the study.

Guideline:

other: OSHA Toxicity Screening Test

GLP compliance:

no

Test type:

other: single dose

Limit test:

yes

Species:

rat

Strain:

other: Albino

Sex:

male

Route of administration:

oral: unspecified

Vehicle:

unchanged (no vehicle)

Doses:

Dosage: 5000 mg/kg

No. of animals per sex per dose:

6

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations:
after 1h; 2h; 3h; 4h; 1d; 2d; 3d; 4d; 5d; 6d; 7d; 14d
- Necropsy of survivors performed: yes

- Other examinations performed: clinical signs, body weight

Sex:

male

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

no (0/6)

Clinical signs:

other: After one hour: ruffled fur and hypoactivity After one day: diarrhea All animals had recovered on day 2

Gross pathology:

No gross pathologic alterations were noted.

Other findings:

not reported

Animal no.	Body weight on day 0	Body weight on day 14
1	171	327
2	171	319
3	173	329
4	162	300
5	164	304
6	174	332

 

Interpretation of results:

practically nontoxic

Remarks:

Migrated information

Conclusions:

In an OSHA toxicity screening test in male Albino rats on acute oral toxicity with Isodecyl methacrylate, the test substance was administered undiluted with a dosage of 5000 mg/kg. b.w. Some mild signs of intoxication as ruffled fur, hypoactivity and diarrhea were reversible within 2 days.
The determined LD50 was > 5000 mg/kg.

Executive summary:

In an OSHA toxicity screening test in male Albino rats on acute oral toxicity with Isodecyl methacrylate, the test substance was administered undiluted with a dosage of 5000 mg/kg. b.w. Some mild signs of intoxication as ruffled fur, hypoactivity and diarrhea were reversible within 2 days.

The determined LD50 was > 5000 mg/kg.

NOTE: Any of data in this dataset are disseminated by the European Union on a right-to-know basis and this is not a publication in the same sense as a book or an article in a journal. The right of ownership in any part of this information is reserved by the data owner(s). The use of this information for any other, e.g. commercial purpose is strictly reserved to the data owners and those persons or legal entities having paid the respective access fee for the intended purpose.

Reference 6

Endpoint:

acute toxicity: oral

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

supporting study

Study period:

25-10-1988 - 08-11-1988

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study OECD 401, GLP.

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Wistar rats (strain: BOR: WISW (SPF TNO)), F. Winkelmann GmbH & Co KG, Borchen, Germany
- Age at study initiation: 9 weeks
- Weight at study initiation: Males: 202 - 205 ± 7-9 g; Females: 186 - 187 ± 5-7g
- Fasting period before study: overnight before test begin
- Housing: Groups of 5 in Makrolon cages
- Diet: ad libitum, Ssniff R food
- Water: ad libitum drinking water
- Acclimation period: One week under laboratory conditions


ENVIRONMENTAL CONDITIONS
- Temperature (°C): no data
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12 hr light/ 12 hr dark period.

Route of administration:

oral: gavage

Vehicle:

water

Doses:

5000 mg/kg b.w. and a gavage volume of 10 mL/kg b.w.

No. of animals per sex per dose:

5 males, 5 females per dose group
Total number of animals: 15 males, 15 females

Control animals:

yes

Details on study design:

- Test article preparation: immediately prior to dosing
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: After administration of the test substance the rats are weighted again and held in single macrolon cages. Clinical examination was made twice a day during the length of the acute period of the intoxication, thereafter once a day.
- Necropsy of survivors performed: all animals were necropsied.
- Other examinations performed: clinical signs and symptoms, body weight, mortality, macroscopic findings
The tissues of all rats are weighted: lung, livers, kidneys, spleens, adrenals and testes; all pathological changes were recorded.

Statistics:

The t-test was the adequate statistical value for comparison the results between the experimental and control groups.

Preliminary study:

The limit dose of 5000 mg/kg b.w. were applied to the rats as a range finding dose.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Mortality:

Mortality was neigther observed in the experimental group nor in the controls during the observation period of 14 days.

Clinical signs:

other: The clinical appearance and behavior of the male and female rats did not differ from the controls for the whole experimental period, except of oily fouled skin in the rectum region of all experimental rats at the first day, and rough hair for the first tw

Gross pathology:

At necropsy substance-related signs of toxicity were not clearly obvious in comparison to the controls. The only observations were similar
incidences of red and white foci on the lung surface of the experimental and control rats. But in 2/5 male and 1/5 female rats slightly swollen liver
margins were observed for the experimental group only.
The results of the mean tissue weights show no differences between the experimental and control groups.

Interpretation of results:

practically nontoxic

Remarks:

Migrated information Criteria used for interpretation of results: OECD GHS

Conclusions:

According to the test result: LD50(14days): > 5000 mg/kg bw the test substance Dodecylmethacrylate has to be classified as practically nontoxic in
rats in respect of its acute oral toxicity.

Executive summary:

In an acute oral toxicity study according to OECD guidline 401 (Limit test) with GLP, groups of fasted male and female SPF Wistar rats were given a single oral dose of Dodecylmethacrylate (purity: 97%) at a dose of 5000 mg/kg bw and observed for 14 days.

 

Oral LD₅₀ Combined = > 5000 mg/kg bw

   

Dodecylmethacrylate is oral practically nontoxic in SPF Wistar rats (OECD GHS no category) based on this LD₅₀ test in males and females.

Reference 7

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline study; no data regarding GLP

Qualifier:

according to guideline

Guideline:

other: Appraisal of the safety of chemicals in foods, drugs and cosmetics", Staff of the Division of Pharmacology, FDA (1959)

Deviations:

not specified

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source:
- Age at study initiation:
- Weight at study initiation: 140-180g
- Fasting period before study:
- Housing:
- Diet (e.g. ad libitum): Ssniff, Intermast
- Water (e.g. ad libitum): tap water
- Acclimation period:


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22
- Humidity (%): 45-55
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: To:

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 20 ml/kg

Doses:

10.0, 12.6, 15.9, and 20.0 ml/kg

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, 10 min, 1, 3, 24 hours, 7 and 14 days after administration
- Weighing: on day 0 and 14
- Necropsy of survivors performed: yes

Sex:

male/female

Dose descriptor:

LD50

Effect level:

18.5 mL/kg bw

95% CL:

14.8 - 23.13

Remarks on result:

other: 16465 mg/kg bw

Mortality:

Dose 24h 14 days
10 ml/kg 0/10 1/10
12.6 ml/kg 0/10 1/10
15.9 ml/kg 1/10 3/10
20.0 ml/kg 3/10 6/10

Clinical signs:

other: Reduced activity, impairment of coordination, exophthalmos, piloerection;

Gross pathology:

Reddening of mucous membranes in the stomach and the intestine.

Conclusions:

In a valid guideline study, the acute oral LD50 in rats was 16465 mg/kg bw.

Executive summary:

The Acute oral toxicity of 2-ethylhexyl methacrylate was evaluated in male and female Wistar rats according to FDA (1959) guideline. Animals were treated by gavage at the dose level of 10.0, 12.6, 15.9, and 20.0 ml/kg and then observed for 14 days for mortality, clinical signs and effect on body weight. Mortality was observed in 1/10, 1/10, 3/10 and 6/10 rats in the 14 day-observation period, respectively. Reduced activity, impairment of coordination, exophthalmos and piloerection were observed up to 24 hours after treatment. At the end of the observation period, the body weight of the animals were in a normal range. Reddening of mucous membranes was observed in the stomach and the intestine. Under these experimental conditions, the oral LD50 of 2-ethylhexyl methacrylate was 18.5 ml/kg bw (16465 mg/kg bw).

In a valid guideline study, the acute oral LD50 in rats was 16465 mg/kg bw.

Reference 8

Endpoint:

acute toxicity: oral

Type of information:

migrated information: read-across based on grouping of substances (category approach)

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study well documented, meets generally accepted scientific principles, acceptable for assessment.

Qualifier:

according to guideline

Guideline:

other: "Appraisal of the safety of chemicals in foods , drugs and cosmetics, FDA"

Principles of method if other than guideline:

Method: according to Appraisal of the safety of chemicals in foods, drugs and cosmetics; FDA (1959)

GLP compliance:

no

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: SPF Wistar rats, Zucht Winkelmann, Paderborn, Germany
- Age at study initiation: no data
- Weight at study initiation: 160 - 180 g
- Fasting period before study: 16 hours
- Housing: single housing
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: no data


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C
- Humidity (%): 45 - 55 %
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12 hrs dark / 12 hrs light

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

- Maximum dose volume applied: 3.6 ml
- Rationale for the selection of the starting dose: preliminary study for range finding

Doses:

20.0 ml/kg

No. of animals per sex per dose:

5f/5m per dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighting: 20 min, 1h, 3h, 24h, 7d, 14d
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, organ weights, histopathology, other: reflexes, emotions, consciousness, central
symptoms, autonomous functions, tone

Preliminary study:

No further information mentioned in the study report.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 17 500 mg/kg bw

Remarks on result:

other: 14 days LD50

Mortality:

No mortality was observed in both test groups during the observation time of 14 days.

Clinical signs:

other: Methacrylic acid ester 12.6 caused decresed activity, disturbance in coordination, diuresis and piloreaction. These symptoms were seen 30 minutes after application of the test substance and persisted for approximately 3 hours. After that time all animals

Gross pathology:

No pathological effects during the test period and observation time of 14 days.

Weight development:

 

group/ number of animals	mean initial weight	mean weight after 14 -days
I 5m/5f	168.0 g	248.0 g
II 5m/5f	173.0 g	194.5 g

Interpretation of results:

study cannot be used for classification

Remarks:

Migrated information

Conclusions:

According to the test result: LD50(14days) > 17500 mg/kg bw the test substance Methacrylic acid ester 12.6 has to be classified as nontoxic in
respect of its acute oral toxicity.

Executive summary:

In an acute oral toxicity study, groups of fasted male and female SPF Wistar rats were given a single oral dose of Methacrylic acid ester 12.6 at a dose of  20.0 ml/kg/bw and observed for 14days.

 

Oral LD₅₀Combined = > 20.0 ml/kg bw equals > 17500 mg/kg bw (95% C.I. not available)

GHS Category 5 ranges from 2000 -5000 mg/kg bw and represents the lowest hazard category for classifying the acute oral toxicity of a chemical substance. ("Criteria for hazard Category 5 are intended to enable the identification of the test substancese which are of relatively low acute toxicity hazard but which, under certain circumstances may present a danger to vulnerable populations". (OECD guideline 425 annex 4)).

    

Methacrylic acid ester 12.6 is practically nontoxicity after oral administration based on this LD₅₀test in males and females.

NOTE: Any of data in this dataset are disseminated by the European Union on a right-to-know basis and this is not a publication in the same sense as a book or an article in a journal. The right of ownership in any part of this information is reserved by the data owner(s). The use of this information for any other, e.g. commercial purpose is strictly reserved to the data owners and those persons or legal entities having paid the respective access fee for the intended purpose.

Reference 9

Endpoint:

acute toxicity: oral

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Justification for type of information:

REPORTING FORMAT FOR THE ANALOGUE APPROACH
Further information is included as attachment. Please also see attached justification.

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
The constituents of the UVCB substance NUMA (Nonyl-Undecyl methacrylate) are structurally related mono alkyl methacrylate esters differing only in the respective alcoholic moieties. The main proportion of these esters are of the n-type the minor proportion of the iso type. Considering the small amount of iso-types and the negligible differences in (eco-) toxicological properties between the n- and iso types, in this assessment both types of one ester with one specific chain length are assessed together as a whole.
Further information is included as attachment. Please also see attached justification Chapter 1

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
Further information is included as attachment. Please also see attached justification Chapter 1.

3. ANALOGUE APPROACH JUSTIFICATION
Please see attached justification Chapter 1 and 3.

4. DATA MATRIX
Please see attached justification Chapter 1.

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Sex:

not specified

Dose descriptor:

LD50

Effect level:

>= 5 000 mg/kg bw

Based on:

test mat.

Conclusions:

Therefore, the LD50 for NUMA and its constituents is predicted to be also above 5000 mg/kg bodyweight.

Executive summary:

The outcome of the tested substances with LD50 values above the general limit values for acute toxicity testing does not enable interpolation. Therefore, the LD50 for NUMA and its constituents is predicted to be also above 5000 mg/kg bodyweight. This read across is conducted with high confidence.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 000 mg/kg bw

Additional information

The outcome of the tested substances with LD50 values above the general limit values for acute toxicity testing does not enable interpolation. Therefore, the LD50 for NUMA and its constituents is predicted to be also above 5000 mg/kg bodyweight. This read across is conducted with high confidence.