Methacrylic anhydride

Endpoint summary

Description of key information

LD50 rat, oral: 1550 mg/kg

LC50 rat, inhal.: 2.081 to 5 mg/l (aerosol).

No study was available for dermal exposure. For the metabolite donor substance MMA, a dermal study in rabbits is available with an LD50 of > 5000 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

Study period:

20.03.1984 - 10.04.1984

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

no

Specific details on test material used for the study:

- Name of test material (as cited in study report): Methacrylic anhydride (AMA 20)
- Analytical purity: not stated
- Impurities (identity and concentrations):
- Lot/batch No.: not stated

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source A. Truck & Sons Limited, Battlesbridge, Essex:
- Age at study initiation: 4-6 weeks
- Weight at study initiation: 108-135 g (males), 107-129 g (females)
- Fasting period before study: access for food only was prevented overnight prio to and approx. two hours after dosing
- Housing: animals were housed in groups of five in polypropylene cages with sawdust bedding
- Diet (e.g. ad libitum): standard laboratory rodent diet (rat and mouse expanded diet number 1 supplied by Special Diet Services Limited, Witham, Essex
- Water (e.g. ad libitum): mains tap water
- Acclimation period: in minimum five days prior to the start of the experiment

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 4 °C
- Humidity (%): 40-60%
- Air changes (per hr): 10 changes per hour
- Photoperiod (hrs dark / hrs light): 12 hour light/dark cycle

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Doses:

1000; 1710; 2924 and 5000 mg/kg

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: 0.5; 1; 2; 3; 4 and 5 hours follwing dosing and than at least once daily for 14 days
- Frequency of weighing: on day 0, 7 and 14
- The macroscpoic appearance of abnormal organs was recorded

Statistics:

Analysis of Data:
Using the mortality data obtained the acute oral median lethal dose (LD 50) and 95% confidence limits of the test material were calculated using the method oi' Litchfield, J.T. and Wilcoxon, F., (1949), J. Pharmac. Exp. Ther. 96,99.
Individual LD 50 values were calculated separately for males and females where possible.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

1 550 mg/kg bw

Based on:

test mat.

95% CL:

1 099 - 2 186

Sex:

male

Dose descriptor:

LD50

Effect level:

890 mg/kg bw

Based on:

test mat.

95% CL:

324 - 2 488

Sex:

female

Dose descriptor:

LD50

Effect level:

1 760 mg/kg bw

Based on:

test mat.

95% CL:

1 035 - 2 992

Mortality:

Using the mortality data the acute oral median lethal dose (LD 50) and 95% confidence limits of the test material were calculated by the prescribed statistical method to be:

Males and Females 1550 (1099-2186) mg/kg bw
Males Only 890 (324-2448) mg/kg bw
Females Only 1760 (1035-2992) mg/kg bw

Clinical signs:

other: Signs of reaction to treatment observed shortly after dosing in rats at all dose levels consisted of a hunched posture, lethargy, pilo-erection, a decreased respiratory rate, ptosis, pallor of the extremities and ataxia. Other effects observed in rats fro

Gross pathology:

Mortalities occurred in rats at all dose levels from within two hours to two days of dosing. Autopsy revealed pale or almost white areas on the liver and kidneys, especially where the organs lay adjacent to the stomach, haemorrhage of the stomach and intestines and sloughing of the non-glandular region of the stomach. Autopsy of the survivors killed on Day 14, revealed pallor of the liver and sloughing and hyperkeratinisation of the nonglandular region of the stomaeh. Adhesion of the liver to the
stornach was also seen in one male at 2924 mg/kg.

Summary of mortalities

Dose level mg/kg	Sex	Day         0		1	2	3	4	5	6	7	14	Total death at 14 days
1000	male female		2 5	1 5	1 5	1 5	1 5	1 5	1 5	1 5	1 5	4
1710	male female		4 5	3 2	3 2	3 2	3 2	3 2	3 2	3 2	3 2	5
2924	male female		4 5	1 2	1 1	1 1	1 1	1 1	1 1	1 1	1 1	8
5000	male female		0 4	0 2	0 0	0 0	0 0	0 0	0 0	0 0	0 0	10

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

Methacrylic anhydride is of moderate toxicity. Under EU and UN/OECD GHS the substance is Cat. 4 for acute oral toxicity. Oral LD50 males/females 1550 mg/kg

Executive summary:

In a valid OECD 401 study Methacrylic anhydride was tested in concentrations of 1000 -5000 mg/kg with male and female Sprague Dawley rats. The LD50 (male/female) was found to be 1550 mg/kg. Therefore Methacrylic anhydride is of moderate toxicity. Under EU and UN/OECD GHS the substance is Cat. 4 for acute oral toxicity.

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:

1 550 mg/kg bw

Quality of whole database:

Whole data base is consistent. For the hydrolysis product/primary metabolite methacrylaic acid In studies with diltuted test material, LD50 values above 2000 mg/kg were found. Based on the corrosive properties of methacrylic acid, the higher toxicity with the undiluted test material can be attributed to corrosivity rather than systemic toxicity.

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:

30.11.1999 - 09.10.2001

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.2 (Acute Toxicity (Inhalation))

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1300 (Acute inhalation toxicity)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

other: Acute inhalation toxicity, limit test

Limit test:

no

Species:

rat

Strain:

other: Hanlbm: WIST(SFP)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: RCC Ud, Biotechnology & Animal Breeding Division (RCC BAB) CH-4414 Füllinsdorf, Switzerland
- Age at study initiation: males: 9 weeks; females: 11 weeks
- Weight at study initiation: males: 242.4 - 250.2 g; females: 197.8-211.7g
- Fasting period before study:
- Housing: Animals were housed in groups of five per sex in Makrolon® type-IV cages with wire mesh tops and standard softwood bedding ("Lignocel", Schill AG, CH-4132 Muttenz, Switzerland).
- Diet: Animals had ad libitum access to pelleted standard Kliba 3433, rat maintenance diet, Batch No. 41/99 (Provimi Kliba AG, CH-4303 Kaiseraugst, Switzerland), except during the approximately 4-hour period, when they were restrained in exposure tubes. Results of the analyses for
contaminants and their limits of acceptability are included in Appendix E.
- Water: Animals had ad /ibitum access to community tap-water from Füllinsdorf, except during the approximately 4-hour period, when they were
restrained in exposure tubes.

- Acclimation period: From 01 to 05-DEC-2000 under laboratory conditions, after clinical health examination. Only animals without any visible sign
of iIIness were used for the study. A further clinical examination was performed on the day of exposure, prior to exposure start.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 - 23°C,
- Humidity (%): 25 and 42%
- Air changes (per hr): approximately 10-15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours artificial fluorescent light / 12-hours darkness

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Vehicle:

other: compressed filtered air (assumed to have approximately 3 % or less relative humidity)

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Method of Sachsse et al. (1973, 1976) The design of this chamber is based upon the fluid dynamic modelling of the test
atmosphere flow. It ensures a uniform test item distribution, provides a constant stream of "fresh" test item to each animal, and precludes
re-breathing the exhaled air

- Method of holding animals in test chamber: Animals were confined separately in restraint tubes which were positioned radially around the
flow-past, nose-only exposure chamber

- Method of conditioning air: The test atmosphere was generated in ambient conditions and diluted as necessary with compressed filtered air
(assumed to have approximately 3% or less relative humidity) to achieve the concentration required for this study.
- System of generating aerosols: The test atmosphere enters the INLET at the top under slight positive pressure and is distributed to
the entrance of each feed tube. It is then delivered through these tubes to the animal's nose . The inhalation exposure system is located inside a
ducted extraction cabinet.

EXPOSURE SYSTEM MONITORING
The concentration of the test item determined gravimetrically and by chemical analysis, the particle size distribution determined gravimetrically,
relative humidity, temperature and oxygen concentration were measured on test atmosphere samples collected directly from the feed tube in
the breathing zone of the animals, at an empty port of the exposure chamber delivering "fresh" test item to the animal's nose. This approach was
chosen in order to obtain representative samples of what was delivered to the animals. Airflow rates were determined for the recording of relative
humidity, temperature and oxygen concentration and during the collection of samples for the
determination of test item concentration using a dry-test meter and a pressure gauge (Schlumberger Industries SA, City of Geneva and Timeus & Co., Zürich, respectively), calibrated with a reference dry-test meter. Sampling airflow rates during the collection of impactor samples
were determined using a calibrated pressure gauge (Timeus & Co., Zürich).

-Nominal concentration: The nominal test atmosphere concentration was determined by weighing the syringe containing the test item and the
nebulizer before the beginning of pre-exposure aerosol generation and after the exposure to determine the quantity of test item used. Then the
weight used during the total of 4 hours and 30 minutes of aerosol generation (30 min pre-exposure aerosol generation plus 4 h
exposure) was divided by the total airflow volume to give the nominal test atmosphere concentration.

- Gravimetric Determination of Aerosol Concentration: Samples from the test atmosphere were collected four times during exposure on Millipore®
durapore filters (Type HVLP, Polyvinylidenedilluoride membrane, pore size 0.45µm) loaded in a 47 mm in-line stainless steel filter sampling device
(Gelman Science Inc., Ann Arbor, Michigan, U.S.A.). Each filter was carefully weighed before and after sampling using a Mettler M3 analytical
balance (Mettler AG, CH-8604 Volketswil, Switzerland).
In pre-study technical trials (not performed according to GLP), comparison of the gravimetrically determined concentrations with those obtained by chemical analysis of aerosol samples trapped in acetone led to the conclusion that the gravimetrically determined aerosol concentrations are
underestimates of the true concentrations of the test atmosphere, as a result of evaporation.
Therefore, the main purpose of the gravimetrie determinations of aerosol concentration was to monitor roughly the aerosol concentration during
the exposure period, as the concentrations determined by chemical analysis were only available post exposure

- Particle Size Distribution and MMAD: The particle size distribution was determined twice during the exposure using a Mercer 7 stage
cascade impactor (Model 02-130, In Tox. Products Inc., Albuquerque, New Mexico, U.S.A.).
Representative samples of the test atmosphere were drawn through the impactor and the particles deposited according to their aerodynamic size onto stainless steel slips and the final filter stage, on each stage of the impactor. To obtain the mass deposited on each stage of the impactor, the steel
slips and the final filter stage were carefully weighed before and after sampling using a Mettler M3 analytical balance (Mettler AG, CH-8604 Volketswil, Switzerland).
The total mass (µg) deposited in the impactor was then calculated by adding together the mass deposited on each of the stainless steel slips and the
final filter stage. As the Effective Cut-off Diameters (ECD) represent the lower size limit of the particles collected on each stage, the
cumulative percent less than the indicated size was tabulated as a function of the ECD.
This data was used to calculate the mass median aerodynamic diameter (MMAD) and geometric standard deviation (GSD) using an Origin™ Technical Graphics and Data Analysis in Windows™ software program lrom MicroCal Software, Inc., Northampton, USA. The target range for the mass
median aerodynamic diameter was 1 to 4 µm.

- Oxygen Concentration: The oxygen concentration was continuously monitored and recorded during the exposure period using a calibrated
Oxopac RD device (Dräger AG, CH-8305 Dietlikon, Switzerland) connected to an analogue recorder. The results are reported at approximately
30 minute intervals from the start to the end of exposure.

- Relative Humidity / Temperature: The relative humidity and temperature were continuously monitored and recorded during the exposure period
using a calibrated Vaisala HMI 32 device from Kuenzli Elektronik, CH-8006 Zürich, Switzerland connected to an analogue recorder. The results are
reported at approximately 30 minute intervals from the start to the end of exposure.

Airflow Rate: The exposure airflow rate was adjusted before the start of pre-exposure aerosol generation and monitored indirectly through the test atmosphere generation and dilution systems. The airflow rates for aerosol generation and dilution were recorded nine times during the exposure
period, i.e. at approximately 30 minute intervals from the start to the end of the exposure, using a calibrated
pressure gauge and flow meter. The total airflow was maintained at 16.0 l/min, i.e. 6.0 I/min for aerosol generation in the nebulizer in addition to 10.0 I/min for dilution. The airflow rate per animal port was 1.0 I/min

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Remarks on duration:

single exposure

Concentrations:

Analytical Concentration
Sampling of test atmosphere for evaluation of concentrations by chemical analysis was performed 4 times during the inhalation exposure. The test
atmosphere was drawn through three wash bottles placed in series each containing 80 ml of acetone, cooled at approximately O°C (water ice).
The content of each wash bottle was transferred into 100 ml volumetric flasks, the wash bottles were rinsed with acetone, and the flasks made up to 100 ml with the rinsing. These solutions were forwarded at approximately 5°C to the Environmental Chemistry and Pharmanalytics Division of
RCC Ud, Zelgliweg 1, CH-4452 Itingen, Switzerland, attn. Dr. C. Knuppe, for chemical analysis.
The samples were analysed by gas chromatography with a flame ionisation detector (GC/FID).
The analytical method was based on that which was provided by the Sponsor

No. of animals per sex per dose:

One dose group:
Males: 1 - 5
Females: 6 - 10

Control animals:

no

Details on study design:

CLiNICAL OBSERVATIONS
The following observations and data were recorded:
Mortality:
Mortality was checked once daily during the acclimatisation phase, once before exposure on the day of exposure (test day 11), onee per hour during exposure, once after exposure on test day 1, and twice daily during the remainder of the observation period.
Clinical Signs:
Clinieal signs were reeorded once per hour during the 4-hour exposure period. In addition, clinical signs were recorded once after exposure on
test day 1, and once daily thereafter. Observations included, but were not limited to: changes in behaviour, somatomotor activity, body position,
respiratory and circulatory effects, autonomic effects such as salivation, central nervous system effects, e.g. tremors or convulsions, reactivity to
handling or sensory stimuli, altered strength, alteration of the skin, fur, nose, eyes and mucous membranes.
Body Weights
Body weights were recorded on test days 1 (before exposure), 4, 8 and 15 (day of necropsy) using a Mettler PM 4000 balance.

PATHOLOGY
Necropsy
Necropsies were performed by experienced prosectors under the management of a pathologist.
The animal which died spontaneously during the observation period was transferred to the pathology unit and necropsied as soon as it was found
dead. The animals surviving to the end of the observation period were transferred to the pathology unit and anaesthetised by an
intraperitoneal injection of NARCOREN (Rhone Merieux GmbH, D-88471 Laupheim, Germany) at a dose of at least 2.0 ml/kg body weight (equivalent to at least 320 mg sodium pentobarbitone/kg body weight) and sacrificed by exsanguination.
The animals were examined macroscopically and any abnormalities were recorded. The lungs, trachea, larynx and the head containing the
nasopharyngeal tissues were collected from all animals and fixed in neutral phosphate buffered 4 % formaldehyde solution. The lungs were instilled
with the fixative at a hydrostatic pressure of 30 cm H20. All collected organs/tissues are available for histopathological examinations, if requested by the Sponsor under separate contractual agreement.
The day of exposure was named test day 1 and counting was continued for the subsequent days of observation.
The first three recordings during exposure have revealed only grossly abnormal signs, as the animals were in restraint tubes, the fourth recording 'during exposure' was done outside the restraint tubes immediately after the end of exposure.


DATA COMPILATION
Body weights were recorded on-line into the Digital VAX computer system for compilation.
Mortality, clinical signs and macroscopical observations at necropsy were directly entered into the Digital VAX computer system during recording.
The exposure conditions and aerosol monitoring data (gravimetric concentrations and particle size) were recorded on data sheets, manually entered into Microsoft Excel97 tables and used for calculation of the mean and standard deviation values of the exposure, as appropriate.
The data for particle size distribution were manually entered into an Origin™ Technical Graphics and Data Analysis in Windows™ software program
for the calculation of the mass median aerodynamic diameter (MMAD) and geometrie standard deviation (GSD).
Individual values were rounded before printing as appropriate. All derived values, e.g. mean values
and standard deviations, represent the rounded results of calculations which used exact raw data values.

Statistics:

The LOGIT-Model was not used as only one group was exposed

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 2.081 - < 5 mg/L air (analytical)

Based on:

test mat.

Remarks:

measured concentration

Exp. duration:

4 h

Remarks on result:

other: 1/10 animals died after 4 hrs of exposure to 2.081 mg/L

Mortality:

Female no. 9 died on test day 3. All other animals were sacrificed as scheduled on test day 15.

Clinical signs:

other: The following clinical signs were recorded during and/or after the inhalation exposure. Markedly laboured respiration (5/5)1, marked breath sounds [rales] (5/5), moderate (males) / marked (females) red secretion from the nose (5/5), marked salivation (5/5

Body weight:

Marked body weight losses were seen in all surviving animals between test days 1 and 4 (mean body weight loss in the male animals -18.8%, mean body weight loss in the female survivors -19.6%). One male animal (no. 1) also showed a marked body weight loss (-9.1%) between test days 4 and 8. The other male animals showed a marginal to normal body weight gain between test days 4 and 8. Thereafter (test days 8 to 15), the body weight gain in the male animals was considered to be normal. From test day 4 until test day 15 three of the four female survivors gained body weight normally, whereas the other one (female no. 7) again lost body weight (-11.7%) between test days 8 and 15.

Gross pathology:

Macroscopical Findings
Dark red discoloration of the lungs was seen in female no. 9 which was found dead on test day 3. Examination of each other animaion the scheduled day of necropsy (test day 15) revealed several macroscopical findings in the lungs [incompletely collapsed (5/3)1, dark red discoloration (0/2) and darkred or reddish foci (5/1 )].

LC50 ESTIMATION AND CONCLUSIONS

The LC50 of Methacrylic Anhydride for acute 4-hour inhalation toxicity in male and female rats observed for a period of 15 days, was estimated to be higher than the achieved test concentration of 2.081 mg/I air (chemically determined mean test atmosphere concentration, approx. three quarters of which were aerosol and one quarter vapour). In addition, the LC50 is expected to be lower than 5 mg/lair due to the 10% mortality at 2.081 mg/I air in combination with severe clinical signs, initial body weight loss and macroscopical findings.

There was one premature death during the course of the study. All animals showed the following clinical signs with marked severity during and/or after the inhalation exposure: Laboured respiration, breath sounds [rales], salivation, a decrease in spontaneous activity and ruffled fur. In addition, the findings of moderate or marked red secretion from the nose and hunched posture

were seen in all animals and one male animal was seen slightly emaciated on four consecutive days, and one female animal was seen with a half closed eyelid on test day 1. After the exposure, in general the severity of the clinical signs noted diminished, and towards the end of the observation period all surviving animals were free from clinical signs. Marked body weight losses were seen in all animals from test day 1 to 4. Thereafter, the body weight gain returned to normal in most of the animals. At necropsy, eight of ten animals showed incompletely collapsed lungs. In six animals darkred or reddish foci were noted in the lungs and three females showed darkred discoloration of the lungs.

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

In concIusion, the LC50 of Methacrylic anhydride obtained in this study, was estimated to be greater than the aerosol concentration of 2.081 mg/I air (chemically determined mean test atmosphere concentration). In addition, the LC50 is expected to be lower than 5 mg/I air due to the 10% mortality at 2.081 mg/I air, severe clinical signs, initial body weight loss and macroscopical findings.

Executive summary:

Methacrylic anhydride was tested in an acute inhalation toxicity test acc. OECD 403. The purpose of this acute 4-hour inhalation toxicity study was to assess the acute inhalation toxicity of Methacrylic anhydride when administered to rats by nose-only, flow-past inhalation exposure for a single continuous 4-hour period, followed by an observation period of 14 days. The LC50 of Methacrylic anhydride obtained in this study, was estimated to be greater than the test concentration of 2.081 mg/I air (chemically determined mean test atmosphere concentration). In addition, the LC50 is expected to be lower than 5 mg/I air due to the 10% mortality at 2.081 mg/I air, severe clinical signs, initial body weight loss and macroscopical findings.

This study is classified as acceptable. This study satisfies the requirement for testing the acute inhalation toxicity.

 

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:

LC50

Value:

2 100 mg/m³ air

Quality of whole database:

The study with the highest quality was chosen. In addition there was only one information from a handbook available.

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Acute oral toxicity

Methacrylic anhydride had an LD50 of 1550 mg/kg in rats. This is consistent with undiluted methacrylic acid which had an LD50 of 1320 mg/kg (Elf Atochem, 1977). Based on the corrosive properties of methacrylic acid this effect can be attributed to corrosivity rather than systemic toxicity. In two other tests, where methacrylic acid as 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

Using a valid experimental method, the 4 hour LC50 of methacrylic anhydride to male and female rats was > 2.081 mg/l but is expected to be lower than 5 mg/l, because of 10 % mortality at that concentration in combination with servere body weight loss and organ effects in gross pathology. The analytical data indicate that at 2.081 mg/l about three quarters of the exposure concentration were present in the form of aerosol. Based on the vapour pressure of 0.9 hPa, the rest was considered to be vapour. This is consistent with an inhalation study with methacrylic acid, the hydrolysis product of MAAH under physiological conditions. There - in a similar dose range - mortailty after inhalation exposure was clearly associated with exposure to aerosol, but not to vapour - at comparable concentrations.

Acute dermal toxicity

No study available for MAAH.

For the metabolite donor substance MMA, a dermal study in rabbits is available with an LD50 of > 5000 mg/kg bw. As the QSAR prediction of Heylings (2012; see chapter "Toxicokinetics") indicates a lower potential of MAAH for dermal absorption than MMA, this study is appropriate to assume the absence of a systemic hazard after acute dermal exposure.

Justification for classification or non-classification

Acute oral toxicity

Methacrylic anhydride fulfils the criteria for acute toxicity category 4 (1272/2008/EC and UN GHS)

Acute inhalation toxicity

Exposure to methacryic anhydride fulfils the criteria for acute toxicity category 4, dust and mist (1272/2008/EC and UN GHS).

Acute dermal toxicity

The available information do not fulfil the criteria for classification under CLP (1272/2009/EC) or UN GHS.