Butyl methacrylate

Endpoint summary

Description of key information

n-butyl methacrylate is of low acute toxicity by oral (LD0/rat >2000 mg/kg) , dermal (LD0/rabbit >2000 mg/kg) and inhalation (4h-LC50/rat ca. 29 mg/l) routes.

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:

8/26/92 - 3/23/93

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:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Breeding Laboratories, Kingston, New York, USA
- Age at study initiation: approximately 7 veeks old
- Weight at study initiation:
- Fasting period before study: overnight prior to dosing, with food being returned to the animals approximately 4 hours after dosing
- Housing: singly in suspended, stainless steel, vire-mesh cages
- Diet (e.g. ad libitum): Purina Certified Rodent Chow #5002
- Water (e.g. ad libitum): tap water
- Acclimation period: 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23 ± 2
- Humidity (%): 50 ± 10
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 200 mg/ml
- Amount of vehicle (if gavage):  average dose volume was 2.2 ml for males and 1.7 ml for females
- Justification for choice of vehicle: solubility

MAXIMUM DOSE VOLUME APPLIED: no data

Doses:

2000 mg/kg

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

Observations for mortality were made daily throughout the study. Rats vere weighed and observed daily for clinical signs of toxicity (veekends excluded). All rats vere subjected to gross pathological examinations at the end of the 14-day observation period.

Statistics:

Not appropriate

Sex:

male/female

Dose descriptor:

LD0

Effect level:

>= 2 000 mg/kg bw

Mortality:

There were no deaths

Clinical signs:

other: There were no clinical signs of toxicity

Gross pathology:

There were no adverse findings at necropsy.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: other: REGULATIONS REGULATION (EC) No 1272/2008 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL of 16 December 2008

Conclusions:

In a valid guideline study, the acute oral (gavage) LD0 in  Crl:CD BR rats was >2000 mg/kg.

Executive summary:

In an OECD 401 and GLP study, a single dose of 2000 mg/kg n-butyl methacrylate were administered by intragastric intubation to fasted male and female rats. No deaths occurred and no clinical signs of toxicity were observed within 14 days after dosing. No compound-related gross abnormalities were detected at necropsy, and no target organ was identified. This substance is considered to have an LD0 > 2000 mg/kg,when administered as a single oral dose.

Endpoint conclusion

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

08-26-92 / 12-21-93

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Guideline study with acceptable restrictions

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

yes

Remarks:

No macroscopic examination was performed at sacrifice

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 Laboratories, Inc., Kingston, New York, USA
- Age at exposure initiation :eight to ten weeks
- Weight at study initiation: male rats weighed 214 to 355 grams and female rats weighed from 171 to 232 grams
- Housing: either singly or in pairs (sexes separate) in 8" x 14" x 8" suspended, stainless steel, wire-mesh cages
- Diet (e.g. ad libitum): Purina Certified Rodent Chow© #5002
- Water (ad libitum): tap water from the Wilmington Suburban Water Corporation
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23 ± 2
- Humidity (%): 50 ± 10
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

inhalation

Type of inhalation exposure:

nose/head only

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
During exposure, all rats were restrained in perforated, stainless steel or polycarbonate cylinders with conical nose pieces. The restrainers were inserted into the face plate of a 29-L cylindrical glass exposure chamber so that only the nose of each rat extended into the chamber.

Chamber airflow was set and recorded at the beginning of the four-hour exposure period. Chamber airflow ranged from 25 to 47 L/min, chamber temperature ranged from 21 to 25°C, chamber relative humidity ranged from 37 to 61%, and oxygen concentration was 21%..

Test atmospheres containing BMA aerosol were generated using a Spraying Systems or a Solo-Sphere Nebulizer. The test substance was either metered into the Spraying Systems nebulizer using a Harvard Apparatus Model 22 Infusion Pump or Fluid Metering Inc. Model RP G-150 Fluid Displacement Pump or placed in the reservoir of the Solo-Sphere Nebulizer. Filtered, high-pressure air introduced into the nebulizer swept the resulting atmosphere into the 29-L glass exposure chamber. The chamber concentration of BMA was controlled by varying the feed rate of test substance to the Spraying Systems nebulizer or varying the airflow to the Solo-Sphere nebulizer.

TEST ATMOSPHERE
The atmospheric concentrations of the test chemicals were determined at approximately 30-minute intervals during the exposures by gravimetric analysis and gas chromatography.

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution:
One sample to determine particle size distribution (mass median aerodynamic diameter and percent particles less than 10 um diameter) was taken during each exposure with a Sierra® Series 210 cyclone preseparator/cascade impactor and a vacuum pump calibrated to a constant airflow.

About halfway through the 24 mg/1 experiment, it was noted that the aerosol distribution appeared to be non-uniform from the front to the back of the exposure chamber. The position of the chamber baffle was altered to attain a more homogeneous-appearing aerosol concentration. In addition, the rats were repositioned to compensate for the possible non-uniform chamber aerosol distribution.

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

13.8, 18.2, 23.9, 26.6, 28.6, 36.0 mg/L

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

Each group of rats was observed for mortality during the exposure and observed for mortality and clinical signs of toxicity immediately after being removed from the restrainers following exposure. During a 13- or 14-day post-exposure period, surviving rats were observed each day for mortality. Surviving rats were weighed and observed daily for clinical signs of toxicity. At the end of the recovery period, all surviving rats were sacrificed by carbon dioxide asphyxiation and discarded.

Statistics:

The LC50 was calculated using the method of Finney.

Key result

Sex:

male/female

Dose descriptor:

other: Approximate lethal concentration

Effect level:

29 mg/L air

Exp. duration:

4 h

Mortality:

Deaths occurred at BMA atmospheric concentrations of 29 mg/l or greater, see the table below.
In the 36 mg/l group, no rats died during exposure. Three female rats were found dead on test day 2.
In the 29 mg/l group, one male and one female rat died during exposure. Two male rats and two female rats were found dead on test day 2.
All rats in the 13.8, 18, 24, 27 mg/l survived the exposure and recovery period.

Clinical signs:

other: In the 36 mg/l group, following exposure, clinical observations included discharge, corneal opacity (one rat), gasping, irregular respiration, lethargy, lung noise, weakness, and wet fur. Diarrhea, hunched posture, and ruffled and stained fur developed du

Body weight:

In the 36 mg/1 group, rats showed sporadic slight body-weight losses throughout the recovery period.
In the 29 mg/1 group, rats showed severe body-weight losses on test day 2. All surviving male rats generally gained body-weight during the rest of the recovery period. All surviving female rats had sporadic body-weight gain with slight to moderate body weight losses during the recovery period.

Following exposure at 13.8, 18, 24, 27 mg/l, rats showed slight to severe body-weight losses on test day 2, and sporadic slight body-weight losses during the remainder of the recovery period.

Gross pathology:

No data

SUMMARY OF BMA CHAMBER CONCENTRATIONS AND ASSOCIATED RAT MORTALITY

TOTAL ATMOSPHERIC CONCENTRATION (mg/L)			N	AEROSOL/* VAPOR (%)	VAPOR CONCENTRATION		AEROSOL CONCENTRATION		MORTALITY
									(#DEATHS/#EXPOSED)
MEAN	ST.DEV.	RANGE			MEAN	ST.DEV.	MEAN	ST.DEV.	MALES	FEMALES
13.8	0.94	12-15	8	25 /75	10	0.68	3.5	0.36	0/5		0 /5
18	3.6	9.8-22	8	43 /57	10	0.36	7.9	3.3	0/5		0 /5
24	2.0	20-27	8	56 /44	10	0.42	13	2.3	0/5		0 /5
27	2.2	23-29	8	62 /38	10	2.1	17	2.5	0/5		0 /5
29	0.98	26-30	8	66 /34	9.8	0.29	19	0.75	3/5		3 /5
36	1.5	34-38	8	67 /33	12	0.66	24	1.2	0/5		3 /5

* Aerosol/vapor ratios were calculated using the mean aerosol and vapor concentrations for each exposure.

SUMMARY OF BMA CHAMBER ENVIRONMENTAL CONDITIONS AND PARTICLE SIZE DISTRIBUTION

TOTAL CHAMBER CONCENTRATION (MG/L)	AIRFLOW (L/MIN)	N	TEMPERATURE RANGE(°C)	N	HUMIDITY RELATIVE RANGE	N	OXYGEN (%)	N	MASS MEDIAN AERODYNAMIC DIAMETER (µm)	GEOMETRIC STANDARD DEVIATION	PERCENT PARTICLES <10 pm
13.8	25	1	21- 24	4	41- 44	3	21	3	4.5	1.8	81
18	25	1	23- 25	4	41- 47	3	21	3	6.0	2.6	71
24	24	1	23- 24	4	60- 61	3	21	3	3.9	2.3	87
27	35	1	22- 23	4	45- 59	3	21	3	6.7	1.9	74
29	44	1	22- 23	4	37- 45	3	21	3	8.0	2.1	62
36	47	1	23- 25	4	40- 45	3	21	3	8.3	2.1	61

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: other: REGULATIONS REGULATION (EC) No 1272/2008 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL of 16 December 2008

Conclusions:

In a valid guideline study, groups of five rats exposed to atmospheres containing BMA aerosol and vapour in air for 4 hours. Exposure concentrations were 14, 18, 24, 27, 29 or 36 mg/l. Deaths occurred at 29 mg/l (4901 ppm) or greater BMA in air. The approximate lethal concentration was 29 mg/l.

Executive summary:

In an OECD 403 and GLP study with acceptable restriction (no macroscopic observation at sacrifice), six groups of five male and five female Sprague-Dawley rats each were exposedfor a single, four-hour period to atmospheres containing a mixture of n-BMA aerosol and vapor in air. Aerosol concentrations were determined by gravimetric analysis and vapor concentrations were determined by gas chromatography. During a 14-day recovery period, rats were weighed and observed for clinical signs of toxicity. Rats were exposed to 13.8, 18, 24, 27, 29, or 36 mg/l of BMA and the aerosol MMADs were 4.5, 6.0, 3.9, 6.7, 8.0 or 8.3 µm, respectively. Deaths occurred following exposure to n-BMA at concentrations of 29 mg/l or greater. Some important effects of exposure included slight to severe weight loss and signs of respiratory tract irritation. Surviving rats had an overall weight gain by the end of the recovery period.Under the conditions of this study, it was not possible to calculate the LC₅₀. The approximate lethal concentration for n-BMA was 29 mg/l.

Reference 2

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study well documented, meets generally accepted scientific principles, acceptable for assessment; although not performed under GLP itself, the study has been performed in an experienced GLP laboratory.

Principles of method if other than guideline:

The nasal toxicity of n-butyl methacrylate was investigated in the rat, by exposing groups of animals to 200 ppm (vapours)

GLP compliance:

no

Test type:

other: Investigation of the nasal toxicity in the rat

Limit test:

no

Species:

rat

Strain:

Fischer 344

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Olac, UK.
- Age at study initiation: no data
- Weight at study initiation: 225-250 g
- Housing: no data
- Diet (e.g. ad libitum): no data
- Water (e.g. ad libitum): no data
- Acclimation period: no data

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

Route of administration:

inhalation

Type of inhalation exposure:

whole body

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: no data
- Exposure chamber volume: no data
- Method of holding animals in test chamber: no data
- Source and rate of air: no data
- Method of conditioning air: no data
- System of generating vapours:
An atmosphere of test compound was generated by delivering a constant rate of chemical onto a distillation condenser, which was being heated to 60ºC by circulating water.
- Treatment of exhaust air: no data
- Temperature, humidity, pressure in air chamber: no data

TEST ATMOSPHERE
- Brief description of analytical method used:
Gas chromatography fitted with a dual packed column and a flame ionisation detector (FID) was used to quantify the concentration of the atmospheres within the exposure chambers, over the course of the exposure periods.
- Samples taken from breathing zone: no data

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: vapour

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

6 h

Concentrations:

Nominal: 200 ppm
Analytical: 195 +/- 25.1 ppm (chamber 1) and 193 +/- 28 ppm (chamber 2)

No. of animals per sex per dose:

5

Control animals:

yes

Details on study design:

After the exposure had been completed, the animals were immediately terminated (rising rate of CO2) and blood was taken and analysed for the
ester and MAA. Finally, the animals were processed for the examination of the nasal passages. The control group of animals were terminated by a rising concentration of CO2, and then processed for the examination of the nasal passages.

Following the termination of the animals, the heads were removed, the brain excised and the nasal cavity perfused with 10% formol saline through the nasopharynx. The head was then immersed in formol saline followed by decalcification in 20% formic acid. Following decalcification, the head was processed for six sections of the nasal passages
and routinely stained with haematoxylin and eosin prior to histopathological
examination. The six sections of the nasal passages were chosen to represent a broad
cross-section of the rat URT.

Statistics:

Not appropriate

Sex:

male

Dose descriptor:

other: NOAEC nasal irritation

Effect level:

>= 200 ppm

Exp. duration:

6 h

Mortality:

No mortality during exposure

Clinical signs:

other: Animals behaved normally throughout the exposure period.

Body weight:

No data

Gross pathology:

no data

Other findings:

All six levels of the nasal passages of rats exposed to nBMA were normal in appearance.

Conclusions:

Exposure of male Fisher 344 for 6 hours to 200 ppm n-BMA did not induce histological changes in the nasal passages.

Executive summary:

In an inhalation study, in F344 rats, using specialist histopathology techniques to study the nasal tissues, n-butyl methacrylate did not produce lesions in the olfactory region of the nasal cavity following exposure at 200 ppm for 6 hrs.

Endpoint conclusion

Dose descriptor:

LC50

Value:

29 000 mg/m³ air

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:

other: see 'Remark'

Remarks:

DATA QUALITY: Study was conducted in accordance with a recognized scientific procedure for determining the acute dermal toxicity of a test substance, following GLP regulations. The study meets national and international scientific standards and provides sufficient information to support the conclusions regarding the acute dermal toxicityof n-Butyl Methacrylate.

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Hare Marland, Hewitt, NJ, USA
- Age at study initiation: young adult
- Weight at study initiation: 2550 +/- 103 g for males and 2536 +/- 59 g for females
- Housing: singly in stainless steel , wire-mesh cages
- Diet (e.g. ad libitum): Purina certified high fiber rabbit chow #5325
- Water (e.g. ad libitum): tap water
- Acclimation period: 2 weeks

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 2
- Humidity (%): 50 +/- 10
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: 190 cm²
- % coverage: 10
- Type of wrap if used: oclusive

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes, with soap and water
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg
- Constant volume or concentration used: no

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:

The day before dosing each rabbit's hair  was shaved between the scapular and lumbar region of the back. Animals  were fitted with a plastic Elizabethan collar toprevent ingestion. The  test material was then spread evenly over a gauze pad (about 190 sq. cm or  10% of the bodysurface area) and then this was applied to the exposed  skin site and held in contact by impervious bandages for 24 hours. After 24  hours the bandages were removed and the skin sites washed with soap and  water. Dermal effects were scoredaccording to Draize. Animals were  observed for mortality,body weight change (days 1, 7 adnd 14) and general  behavior throughout the study. All animals were subjected to a  gross necropsy after a 14 day observation period.

Statistics:

Not applicable

Sex:

male/female

Dose descriptor:

LD0

Effect level:

>= 2 000 mg/kg bw

Mortality:

There were no deaths. 

Clinical signs:

other: Slight to moderate erythema but no edema was observed in all animals 1 day after application of the test substance. Red spots vere observed in the treated skin of 1 animal. By day 4 after application, no or moderate to severe erythema but no edema vas obs

Gross pathology:

Treatment-related discoloration vas noted in the treated area of 4 male and 2 female rabbits at necropsy. Other gross observations vere believed to be spontaneous and/or incidental lesions. No target organ vas identified.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: other: REGULATION (EC) No 1272/2008 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL of 16 December 2008

Conclusions:

In a valid guideline study the acute dermal LD0 in rabbits was >2000 mg/kg bw.

Executive summary:

In an OECD 402 and GLP study, a single dose of n-butyl methacrylate was applied to the shaved, intact skin of 5 male and 5 femaleNew Zealand White rabbits at a dosage of 2000 mg/kg of body weight. The application site was occluded for 24 hours. The rabbits were observed for 14 days following application.

No rabbits died within 14 days after dosing. No to severe erythema and no to severe edema were observed in the treated rabbits during the study. Superficial necrosis was observed in 1 rabbit on day 4 after application of the test substance and in most other rabbits by day 12 after application. Two rabbits also exhibited necrosis during the study. No target organ was identified at necropsy.

Under the conditions of this test, the acute dermal LD0 for n-butyl methacrylate was greater than 2000 mg/kg of body weight.

Endpoint conclusion

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Additional information

Oral route

In an OECD 401 study, a single dose of 2000 mg/kg n-butyl methacrylate were administered by intragastric intubation to fasted male and female rats (Sarver, 1993). No deaths occurred and no clinical signs of toxicity were observed within 14 days after dosing. No compound-related gross abnormalities were detected at necropsy, and no target organ was identified. This substance is considered to have an LD0 >= 2000 mg/kg,when administered as a single oral dose.

Inhalation route

In an OECD 403 and GLP study with acceptable restriction (no macroscopic observation at sacrifice), six groups of five male and five female Sprague-Dawley rats each were exposed for a single, four-hour period to atmospheres containing a mixture of nBMA aerosol and vapor in air (Kelly, 1993). Aerosol concentrations were determined by gravimetric analysis and vapor concentrations were determined by gas chromatography. During a 14-day recovery period, rats were weighed and observed for clinical signs of toxicity.Rats were exposed to 14, 18, 24, 27, 29, or 36 mg/l of nBMA and the aerosol MMADs were 4.5, 6.0, 3.9, 6.7, 8.0 or 8.3 µm, respectively. Deaths occurred following exposure to nBMA at concentrations of 29 mg/l or greater. Some important effects of exposure included slight to severe weight loss and signs of respiratory tract irritation. Surviving rats had an overall weight gain by the end of the recovery period.Under the conditions of this study, it was not possible to calculate the LC₅₀. The approximate lethal concentration for nBMA was 29 mg/l.

In an inhalation study (Jones, 2002) in F344 rats, using specialist histopathology techniques to study the nasal tissues, n-butyl methacrylate did not produce lesions in the olfactory region of the nasal cavity, the target for methacrylate esters, following exposure at 200 ppm for 6 hrs.

The available data indicate that all members of the category including nBMA are of low acute inhalation toxicity. The vapour pressure of the esters drops markedly across the category such that already in the case of the butyl esters the observed toxicity is above the saturated vapour pressure as indicated by the fact that the studies were performed with mixtures of vapour and mist.

Dermal route

In an OECD 402 and GLP study, a single dose of n-butyl methacrylate was applied to the shaved, intact skin of 5 male and 5 female New Zealand White rabbits at a dosage of 2000 mg/kg of body weight (Sarver, 1993). The application site was occluded for 24 hours. The rabbits were observed for 14 days following application. No rabbits died within 14 days after dosing. No to severe erythema and no to severe edema were observed in the treated rabbits during the study. Superficial necrosis was observed in 1 rabbit on day 4 after application of the test substance and in most other rabbits by day 12 after application. Two rabbits also exhibited necrosis during the study. No target organ was identified at necropsy. Under the conditions of this test, the acute dermal LD0 for n-butyl methacrylate was >= 2000 mg/kg of body weight. In conclusion, the available data for nBMA indicate that the ester is of low acute dermal toxicity.

Justification for classification or non-classification

According to the available data and CLP as well as US-GHS(2009) criteria, no classification is warranted for acute toxicity.