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Description of key information

LD50 oral, rat: 1320 mg/kg bw (undiluted)

LC50 inhal, rat: 7.1 mg/L (4 h, vapour/ aerosol mixture)

LD50 dermal, rabbit: 500 -1000 mg/kg bw

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
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
Specific details on test material used for the study:
Methacrylic acid (CAS: 79-41-4)
Purity: 99 % administered undiluted
Supplier: Merck
Species:
rat
Strain:
Wistar
Sex:
male
Details on test animals or test system and environmental conditions:
weight: 200 - 300 g
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.
Key result
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. Thetest was performed with five test concentrations of 0.9, 1.00, 1.25, 1.50, 1.75 g/kg bw and 8 to 10 animals per dose group.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
1 320 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:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Principles of method if other than guideline:
MAA aerosol/vapor (aerosol mass median diameter: 10, 6.5, 5.5, 7.2 um)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no
Specific details on test material used for the study:
2-propenoic acid, 2-methyl (methacrylic acid (MAA), Glacial Methacrylic acid
Lot 5-031342
Haskell No H-19762
purity: 98.5 %
clear liquid
Species:
rat
Strain:
other: Crl:CD BR
Sex:
male/female
Route of administration:
inhalation
Type of inhalation exposure:
nose only
Vehicle:
air
Details on inhalation exposure:
aerosol/vapor atmosphere
Analytical verification of test atmosphere concentrations:
yes
Remarks:
aerosol: gravimetric; vapor: gas chromatography
Duration of exposure:
4 h
Concentrations:
4.3, 5.9, 7.3, 8.2 mg/L
No. of animals per sex per dose:
5
Control animals:
yes
Details on study design:
Rats observed for 13-14 days and body weights collected.
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
7.1 mg/L air
Based on:
other: mixed exposure vapour/aerosol
Exp. duration:
4 h
Remarks on result:
other: saturated vapour approx 3.4-3.7 mg/L, aerosol 3,19 – 6.5 mg/l
Mortality:
Deaths occured at 5.9 mg/L or greater
Clinical signs:
other: In the 8.2 mg/l group all rats died during exposure. In the 7.3 mg/l group, two female rats died during exposure. One male rat was found dead on test day 2 and one male rat was found dead on test day 7. Following exposure, typical clinical observations we
Other findings:
Mortality is clearly associated with exposure to aerosol. Exposure to (saturated) vapour was +/- the same at all concentration levels (3.4-3.7 mg/L). Exposure to vapour alone was not associated with mortality, while exposure to aerosol increased (0.9-4.7 mg/L) in parallel to an increase in mortality.

SUMMARY OF MAA CHAMBER CONCENTRATIONS AND ASSOCIATED RAT MORTALITY

TOTAL ATMOSPHERIC

CONCENTRATION (mg/L)

 

AEROSOL/VAPOR

CONCENTRATION

RATIO *(%)

VAPOR

CONCENTRATION

AEROSOL

CONCENTRATION

MORTALITY

(# DEATHS/# EXPOSED)

MEAN

N

 

MEAN  ST.DEV.

MEAN  ST.DEV.

MALES

FEMALES

4.3

8

21 / 79

3.4 +/- 0.17

0.91 +/- 0.26

0 / 5

0 / 5

5.9

9

37 / 63

3.7 +/- 0.24

2.2 +/- 0.94

0 / 5

1 / 5

7.3

8

50 / 50

3.7 +/- 0.27

3.6 +/- 0.41

2 / 5

2 / 5

8.2

9

57 / 43

3.6 +/- 0.20

 4.7 +/- 1.8

5 / 5

5 / 5

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

Aerosol mass median diameters were 10, 6.5, 5.5, or 7.2 µm for concentrations of 4.3, 5.9, 7.3, 8.2 mg/L, respectively.

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
Using a valid experimental method, the 4 hour LC50 of MAA to male and female rats was 7.1 mg/L (1983 ppm; vapour/aerosol mix).
Mortality is clearly associated with exposure to aerosol. Exposure to (saturated) vapour was +/- the same at all concentration levels (3.4-3.7 mg/L). Exposure to vapour alone was not associated with mortality, while exposure to aerosol increased ( 0.9-4.7 mg/L) in parallel to an increase in mortality.
Executive summary:

Rats (5m/5f) were exposed to a vapour/aerosol mix at four doses between 4.3 and 8.2 mg/L (1201 - 2291 ppm) acc. OECD 403..

Mortality is clearly associated with exposure to aerosol. Exposure to (saturated) vapour was +/- the same at all concentration levels (3.4-3.7 mg/L). Exposure to vapour alone was not associated with mortality, while exposure to aerosol increased ( 0.9-4.7 mg/L) in parallel to an increase in mortality (measured aerosol concentration: 3.6 +/- 0.41 mg/l to 4.7 +/- 1.8 mg/l).

The 4 hour LC50 of MAA to male and female rats was 7.1 mg/L air (vapour/aerosol mix).

Classification is based on mortality to aersol : LC50 (inhal.) 3,19 – 6.5 mg/l

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LC50
Value:
7 100 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:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Remarks:
Screening test; 2 animals per dose group, summarized description of the method used and the results.
Qualifier:
according to guideline
Guideline:
other: dermal toxicity screening
Principles of method if other than guideline:
Screen for dermal toxicity/absorption, 2 animals per group
GLP compliance:
no
Limit test:
no
Specific details on test material used for the study:
Purity not specified, typically >= 98 %
Species:
rabbit
Strain:
not specified
Sex:
not specified
Type of coverage:
not specified
Vehicle:
water
Details on dermal exposure:
Substance prepared 50% in water
Doses:
0.5, 1.0 and 2.0 g/kg.
No. of animals per sex per dose:
2/group
Sex:
not specified
Dose descriptor:
LD50
Effect level:
>= 500 - <= 1 000 mg/kg bw
Mortality:
Dose (mg/kg)    mortality
500              0/2
1000             2/2
2000             2/2
Clinical signs:
other: At 500 mg/kg (50 % solution in water)  there was slight weight loss and the skin was severely burned. At 1000 mg/kg the animals died overnight.
Other findings:
Toxicity due to dermal corrosion.
Interpretation of results:
Category 3 based on GHS criteria
Conclusions:
In a valid screening study, the acute dermal LD50 in rabbits of MAA was 500-1000 mg/kg bw.
Executive summary:

In a valid screening study, the acute dermal LD50 in rabbits of MAA was 500-1000 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
500 mg/kg bw

Additional information

Acute oral toxicity


Undiluted methacrylic acid had an LD50 of 1320 mg/kg (Elf Atochem, 1977). Based on the corrosive properties of the substance this effect can be attributed to corrosivity rather than systemic toxicity. In two other tests, where the test material had been administered as a 25 % dilution in water (Dow, 1957) or a 10 % dilution in corn oil (Eastman, 1979), the LD50 was above 2000 mg/kg in both cases.


 


Acute inhalation toxicity


Rats (5m/5f) were exposed to a vapour/aerosol mix at four doses between 4.3 and 8.2 mg/L (1201 - 2291 ppm) acc. OECD 403.


Mortality is clearly associated with exposure to aerosol. Exposure to (saturated) vapour was +/- the same at all concentration levels (3.4-3.7 mg/L). Exposure to vapour alone was not associated with mortality, while exposure to aerosol increased (0.9-4.7 mg/L) in parallel to an increase in mortality (measured aerosol concentration: 3.6 +/- 0.41 mg/l to 4.7 +/- 1.8 mg/l).


The 4 hour LC50 of MAA to male and female rats was 7.1 mg/L air (vapour/aerosol mix).


Classification is based on mortality to aerosol : LC50 (inhal.) 3,19 – 6.5 mg/l


 


Acute dermal toxicity


In a valid screening study, the acute dermal LD50 in rabbits of MAA was 500-1000 mg/kg bw.

Justification for classification or non-classification

Acute oral toxicity


MAA fulfils the criteria for acute toxicity category 4 (1272/2008/EC and UN GHS); systemic toxicity is however considered as secondary to its corrosive properties.


 


Acute inhalation toxicity


Exposure to MAA vapour alone is not lethal (no classification). Exposure to MAA aerosols fulfils the criteria for acute toxicity category 4 (1272/2008/EC and UN GHS).


 


Acute dermal toxicity


The dermal toxicity (LD50 500 -1000 mg/kg) is in the range for category 3 (1272/2008/EC and UN GHS).

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