Registration Dossier

Toxicological information

Acute Toxicity: inhalation

Currently viewing:

Administrative data

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

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1993
Report Date:
1993

Materials and methods

Test guideline
Qualifier:
according to
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

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): n-Butyl Methacrylate
- Physical state: liquid
Two batches were used:
- Lot/batch No.: H19845
- Analytical purity: 99.56%
- Purity test date: no data
- Expiration date of the lot/batch: no data

- Lot/batch No.: H19924
- Analytical purity: 99.49%
- Purity test date: no data
- Expiration date of the lot/batch: no data

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals 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

Administration / exposure

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.

Results and discussion

Effect levels
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

Any other information on results incl. tables

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


Applicant's summary and conclusion

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.