Methacrylic anhydride

Acute Toxicity: oral

Administrative data

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

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1984

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Methacrylic anhydride

EC Number:

212-084-8

EC Name:

Methacrylic anhydride

Cas Number:

760-93-0

Molecular formula:

C8H10O3

IUPAC Name:

2-methylprop-2-enoyl 2-methylprop-2-enoate

Test material form:

liquid

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

Test animals

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

Administration / exposure

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.

Results and discussion

Effect levels

Effect levels 1

Sex:

male/female

Dose descriptor:

LD50

Effect level:

1 550 mg/kg bw

Based on:

test mat.

95% CL:

1 099 - 2 186

Effect levels 2

Sex:

male

Dose descriptor:

LD50

Effect level:

890 mg/kg bw

Based on:

test mat.

95% CL:

324 - 2 488

Effect levels 3

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.

Any other information on results incl. tables

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

Applicant's summary and conclusion

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.

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