Methacrylic acid

Endpoint summary

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).