Allyl methacrylate

Endpoint summary

Description of key information

Acute oral toxicity:
- oral: rat (males): LD50 = 470 mg/kg
- inhalative, rat (males/females): LC50 = 1.47 mg/L (according to EU, OECD and EPA OTS 798.1150 (Acute inhalation toxicity))
- dermal, rat (males): LD50 = 467 mg/kg

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

Study period:

1975

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Equivalent or similar to OECD guideline, non GLP.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

not specified

Principles of method if other than guideline:

After 24 hours of fasting groups of 10 male albino (CF Nelson) rats were dosed with a 10% (w/v) corn oil dispersion of the product at each of four concentrations: 157, 313, 625, and 1250 mg/kg. Animals were observed for signs of intoxication and mortality at dosing, 6 and 24 hours post-dosing, and daily thereafter for 14 days. Necropsies were performed on all survivors.

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

other: CF Nelson (albino)

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Fasting period before study: 24 h

Route of administration:

oral: unspecified

Vehicle:

corn oil

Remarks:

10% (w/v) dispersion

Details on oral exposure:

Animals were dosed with a 10.0 % (w/v) corn oil dispersion of the product.

Doses:

157, 313, 625 and 1250 mg/kg

No. of animals per sex per dose:

10 male animals

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed for signs of intoxication and mortality at dosing, 6 and 24 hours post-dosing, and daily thereafter for 14 days.
- Necropsy of survivors performed: yes

Statistics:

no data

Preliminary study:

no data

Sex:

male

Dose descriptor:

LD50

Effect level:

470 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 350-640 mg/kg bw

Mortality:

157 mg/kg: 0/10;
313 mg/kg: 2/10;
625 mg/kg: 7/10;
1250 mg/kg: 10/10;

Clinical signs:

other: Lacrimation noted in animals at the 1250 mg/kg dose group and piloerection was noted in animals at 1250, 625 and 313 mg/kg dose groups.

Gross pathology:

Necropsy findings noted in the survivors included: irregular dark yellow liver lesions, all animals had adhesions of the stomach (primarily) and/or liver to peritoneum.

In a standard acute oral toxicity test equivalent to OECD 401 10 mal CF Nelson (albino rats) were exposed to 157, 313, 625 and 1250 mg/kg Oral LD50 was 470 mg/kg. Necropsy findings noted in the survivors included: irregular dark yellow liver lesions, all animals had adhesions of the stomach (primarily) and/or liver to peritoneum.

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.

 

Interpretation of results:

Toxicity Category IV

Remarks:

Migrated information Criteria used for interpretation of results: other: CLP, EU GHS (Regulation (EC) No 1272/2008)

Conclusions:

Under the conditions of the study the oral LD50 was 470 mg/kg for Allyl Methacrylate.

Executive summary:

In a standard acute oral toxicity test equivalent to OECD 401 10 mal CF Nelson (albino rats) were exposed to 157, 313, 625 and 1250 mg/kg Oral LD50 was 470 mg/kg. Necropsy findings noted in the survivors included: irregular dark yellow liver lesions, all animals had adhesions of the stomach (primarily) and/or liver to peritoneum.

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.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

470 mg/kg bw

Quality of whole database:

OECD equivalent study. At year of study GLP was not established.

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2000

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP and guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1300 (Acute inhalation toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River UK Limited, England
- Age at study initiation: approximately 7 and 8 weeks old, respectively
- Housing: by sex in groups of 5
- Diet: free access to a measured excess amount of food (SDS rat and mouse diet (RMI))
- Water: free access to tap water
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.5 - 22.5
- Humidity (%): 36 - 64
- Air changes (per hr): 15

Route of administration:

inhalation: vapour

Type of inhalation exposure:

nose only

Vehicle:

air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus / Method of holding animals in test chamber: The snout-only exposure chambers used for the exposures were of cylindrical form. The internal surfaces of the chamber have a chemically resistant coating. The rats were held for exposure in moulded polycarbonate restraining tubes, which were attached at evenly spaced ports in the cylindrical section of the chamber and were designed to allow only the snout to project into the chamber: Each rat was restrained in a forward position by an adjustable toamed plastic stopper which also provided a seal for the tube. The conditioned test atmosphere entered through a port at the top centre of the chamber and passed out through a port below the level of rats. Each chamber was positioned in a large cabinet equipped with an exhausting through an absolute filter.
- Source and rate of air: A pre-heated supply of clean dried air was connected to the vapour generator and the supply pressure was adjusted to give a flow rate of 12 litres/min - measured at the generator outlet tube.
- Method of conditioning air: The resultant test vapour was passed through a glass column containing glass wool in order to remove any condensate.
- System of generating particulates/aerosols: by evaporation of the test substance from a fritted glass disc with a countercurrent of air; the air supply to the vaporiser was warmed by passage through a stainless steel coil immersed in water maintained at 35 - 40°C in a water bath, as an aid to evaporation; the test substance was supplied to the generator from a syringe driven at a constant rate by a syringe pump; the compressed air supply to the generator was dried, filtered and oil free;
- Temperature, humidity, pressure in air chamber: The chamber exhaust was calibrated at the point of attachment to the exposure chamber and was adjusted to produce a slightly negative chamber pressure. The temperature and humidity were recorded at the start of exposure and then at 30-minute intervals during the 4-hour exposure: mean temperature: 20.1 - 20.8°C; mean humiditiy: 33 - 38%; the mean relative humidity of test atmospheres was marginally lower than the control valve and was considered not to have affected the outcome of the study. The mean chamber air temperature was similar for the control and test atmospheres;

TEST ATMOSPHERE
- Brief description of analytical method used: At least five air samples were taken from the chamber during each exposure in order to detemine the concentration of the test substance in air (analyzed by HPLC). Samples were obtained following equilibration and then approximately at hourly intervals. An additional sample was taken during the exposure of Group 2 (Sample 2) in order to ensure satisfactory generation of the test atmosphere.

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

Mean chamber concentration: 0, 1.02 and 2.13 mg/L (198 and 414 ppm); the nominal concentrations were 3.18 and 1.49 mg/L; the mean chamber concentrations of allyl methacrylate were approximately 67 % and 68 % of the nominal concentrations; such differences are considered likely to be associated with condensation of the test substance in the exposure system;

No. of animals per sex per dose:

5

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, food consumption, water consumption, the lungs (including the Iarynx and trachea) were removed, dissected clear of surrounding tissue, weighed and the weights recorded;

Statistics:

no data

Preliminary study:

no data

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

1.47 mg/L air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

other: LC50 (4- hour) for allyl methacrylate is between 1.02 and 2.13 mg/L (198 and 414 ppm) in air and may be considered equivalent to 1.47 mg/L (278 ppm), the geometric mean of these two concentrations.

Mortality:

Group 1 (control): 0/5 (males), 0/5 (females);
Group 2 (2.13 mg/L): 5/5 (males), 5/5 (females);
Group 3 (1.02 mg/L): 0/5 (males), 0/5 (females);

All deaths occurred within 1 day of exposure.

Clinical signs:

other: During exposure: Exaggerated breathing was first noted in test rats at 15 and 30 minutes into exposure for Groups 2 and 3, respectively. A decreased breathing rate was evident in all Group 3 test rats from 2 hours into exposure. Observation period: Gaspin

Body weight:

Bodyweight losses were recorded for all Group 2 decedents prior to necropsy. A mean bodyweight loss was evident for Group 3 rats during the 4-day period following exposure. Thereafter, a general bodyweight gain was evident for Group 3 rats for Days 4 to 7 of the observation period. The mean bodyweight gain of Group 3 rats during the second week of the observation period was similar to or greater than control values for males and females respectively.

Gross pathology:

Decedents (Group 2): The lungs of a proportion of decedents were minimally/moderately congested. A clear or white frothy discharge from the trachea was evident in a proportion of decedents. Gas-filled stomachs and intestines were noted in all decedents and a decedent male respectively. External findings noted prior to necropsy included crusty brown staining around snout and jaws, clear discharge from snout, wet fur (snout/jaws) and fur soiled with excreta.
Rats surviving the 14-day observation period: There were no treatment-related findings.
Lung weights:
Decedents (Group 2): The lung weights of female decedents were higher than similarly treated rats surviving the 14-day observation period.
Rats surviving the 14-day observation period: There were no treatment-related effects.
External findings of fur soiled with excreta and matted fur in the urino-genital region were noted for a Group 3 female prior to necropsy.

Other findings:

A reduction in the food consumption of Group 3 rats was evident during the first week following exposure. There were no treatment-related effects in water consumption.

The 'mortality curve' (mortality plotted against chamber concentration) in this investigation was relatively steep, with no unscheduled deaths following exposure at 1.02 mg/l and 100% mortality at 2.13 mg/l. Exposure of further groups was therefore considered unnecessary.

Interpretation of results:

Toxicity Category II

Remarks:

Migrated information Criteria used for interpretation of results: other: CLP, EU GHS (Regulation (EC) No 1272/2008)

Conclusions:

The 4 hour LC50 value for allyl methacrylates in rats (male and female) was 1,47 mg/l air.

Executive summary:

In an acute inhalation toxicity study according to OECD 403 the LC50 (4-hour) for allyl methacrylate is between 1.02 and 2.13 mg/l (198 and 414 ppm) in air and may be considered equivalent to 1.47 mg/l (278 ppm), the geometric mean of these two concentrations.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LC50

Value:

1 470 mg/m³ air

Quality of whole database:

GLP and guideline study

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

Study period:

1969

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Basic data given (comparable to standards). Equivalent or similar to OECD guideline. Non GLP

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

not specified

Principles of method if other than guideline:

Penetration of rabbit skin is estimated by a technique closely akin to the one-day cuff method of Draize, using groups of four male albino New Zealand rabbits. The fur is removed from the entire trunk by clipping, and the dose is retained beneath an impervious plastic film. The animals are immobilized during the 24-hour contact period, after which the film is removed, the rabbits are caged for the subsequent 14-day observation period and the LD50 is determined.

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rabbit

Strain:

other: albino New Zealand rabbits

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 2.5 - 3.5 kg

Type of coverage:

occlusive

Vehicle:

not specified

Details on dermal exposure:

REMOVAL OF TEST SUBSTANCE
- Washing: yes (not further specified)
- Time after start of exposure: 24 hours

Duration of exposure:

24 h

Doses:

no data

No. of animals per sex per dose:

4 male animals

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days

Statistics:

no data

Preliminary study:

no data

Sex:

male

Dose descriptor:

LD50

Effect level:

467 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 345 - 635 mg/kg bw (= 0.5 mL/kg and 0.37 - 0.68 mL/kg, respectively)

Mortality:

no data

Clinical signs:

other: no data

Gross pathology:

no data

Interpretation of results:

Toxicity Category III

Remarks:

Migrated information Criteria used for interpretation of results: other: CLP, EU GHS (Regulation (EC) No 1272/2008)

Conclusions:

In a standard acute dermal toxicity test the LD50 of Allyl methacrylate was reported to be 467 mg/kg.

Executive summary:

In a standard acute dermal toxicity test reported in 1969 with 4 male Albino New Zealand rabbits for 24 hours exposure under occlusive conditions the LD50 of Allyl methacrylate was reported to be 467 mg/kg.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

467 mg/kg bw

Quality of whole database:

OECD equivalent study. At year of study GLP was not established.

Additional information

There are reliable data available to assess the acute toxicity of allyl methacrylate.

Oral:

A study from the Rohm and Haas Company (1975) which was cited in the OECD SIDS IUCLID data set (2009) resulted in a LD50 of 470 mg/kg bw. In this study CF Nelson male rats (10/dose) were administered allyl methacrylate via gavage at 157, 313, 625 and 1250 mg/kg bw in 10% (w/v) corn oil suspension and observed for 14 days. The mortality was 0/10, 2/10, 7/10 and 10/10 at 157, 313, 625 and 1250 mg/kg bw, respectively. The clinical signs included lacrimation at the high-dose and piloerection at 313, 625 and 1250 mg/kg bw. Necropsy findings in the survivors included: irregular dark yellow liver lesions and adhesions of the stomach (primarily) and/or liver to peritoneum.

Additionally, single oral dose toxicity was estimated by the gastric intubation of groups of five non-fasted, Carworth-Wistar male rats. A LD50 value of 401 mg/kg bw was established (Smyth, 1969)

Both studies were performed before GLP and OECD guidelines were established and therefore only basic data were available. Although females were not included in the study, there is no indications in studies with other methacrylates in general that toxicity is greater in females than males.

Inhalative:

In a acute inhalation study (Huntington, 2000), Sprague-Dawley rats (5/sex/concentration) were exposed (via nose-only) to allyl methacrylate vapor at 0, 1.02 and 2.13 mg/L for 4 hours and were observed for 14 days following the exposure. The study was conducted in compliance with GLP and according to OECD 403. Mortality was 0/10, 0/10 and 10/10 at 0, 1.02 and 2.13 mg/L, respectively. Clinical signs during exposure included initial exaggerated breathing for approximately 2 hours followed by a decreased breathing rate. In decedents, gasping, noisy and exaggerated breathing or slow breathing rate persisted until death. In addition, partially closed eyes, lethargy and whole body cold to touch (high concentration only), wet fur (snout/jaws) and peripheral vasodilation (characterized by 'red feet') were noted post-exposure. At the low concentration, brown staining on the head and whole body and around the snout/jaws was noted from 1 day post-exposure and persisting in females until day 6. Poor grooming was also noted in rats at the low concentration. Food consumption was lower at the high concentration during the first week. Although body weights were decreased during the first week, animals showed normal weight gain during the second weight. In decedents, congestion of lungs, higher lung weights and gas filled stomachs and intestines were seen at necropsy. No treatment-related findings were noted at necropsy of surviving rats. The 4-hour inhalation LC50 was 1.47 mg/L (the geometric mean of the two concentrations).

In a second study, Sprague-Dawley rats (5/sex/concentration) were exposed (via whole body) to allyl methacrylate vapor at measured concentrations of 1200, 1500, or 1800 ppm (6.18, 7.73 and 9.27 mg/L, respectively) for 1 hour and at 0 (sham), 210, 300, and 350 ppm (0, 1.08, 1.55 and 1.60 mg/L, respectively) for 4 hours (in compliance with GLP, according to EPA OTS 798.1150). Animals were observed for 14 days following the exposure. Combined male and female mortality following the 1-hour exposure was 2/10, 4/10 and 8/10, respectively at 6.18, 7.73 and 9.27 mg/L. Following the 4-hour exposure, the combined mortality was 0/10, 4/10 and 8/10 at 1.08, 1.55 and 1.60 mg/L, respectively. Clinical signs of treatment observed during and following exposures included secretory responses (chromodacryorrhea, nasal discharge, excessive lacrimation, and excessive salivation) and respiratory responses (labored breathing, gasping and moist rales). These signs were transient and mostly disappeared in surviving animals during the second week post exposure. Body weight loss was observed for males and reduced body weight gain for females occurred during the first week following exposure in all groups exposed to allyl methacrylate; weight gain was similar to control in the second week following exposure. Neurobehavioral evaluations immediately following the 4-hour exposures showed decreased motor activity and effects that included flattened posture, drooping eyelids, ataxia or tip-toe gait, decreased or no locomotor activity, stupor, no response to external stimulation, abnormal air righting reflex and decreased grip strength. At necropsy, discoloration of tissues (e.g. liver, thymus, lungs and stomach) was observed in some animals found dead. However, most of the animals found dead or sacrificed were without findings. Therefore, the relationship of the findings to toxicity of allyl methacrylate was uncertain. The 1- and 4-hour LC50 values were 1545 and 310 ppm (7.97 and 1.56 mg/L), respectively (Mitsubishi Rayon America, 1997; cited in OECD SIDS, 2009). It should be noted that the original study report is currently unavailable and this summary is based solely on the OECD dossier (reliability uncertain).

Dermal:

Penetration of rabbit skin was estimated by a technique closely skin to the one-day cuff method of Draize, using groups of four male albino New Zealand rabbits (Smyth, 1969). The fur was removed from the entire trunk by clipping, and the dose was retained beneath an impervious plastic film. The animals were immobilized during the 24-hour contact period, after which the film was removed, the rabbits were caged for the subsequent 14-day observation period and the LD50 was 467 mg/kg bw. Also this study was performed before GLP and OECD guidelines were established and therefore only basic data were available.

Justification for classification or non-classification

Based on the particular LD50 and LC50 values allyl methacrylate has to be classified according to EU (DSD; Directive 67/548/EEC) and GHS criteria (CLP; Regulation (EC) No 1272/2008):

Acute oral: Acute toxic cat. 4 (H302: Harmful if swallowed.)

Acute inhalative: Acute toxic cat. 2 (H330: Fatal if inhaled.)

Acute dermal: Acute toxic cat. 3 (H311: Toxic in contact with skin.)