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Toxicological information

Acute Toxicity: oral

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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:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals 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 levelsopen allclose all
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:
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 from some dose levels only were gasping respiration and a comatose condition. In addition, a single female rat from the 2924 mg/kg dose level showed body tremors and at the 1710 mg/kg dose level one male rat showed a distended abdomen and facial oedema. Recovery of survivors,as judged by external appearance and behaviour, was apparently complete by Day 12, apart from a single male rat from the 1710 mg/kg dose level in which effects persisted up to and including Day 14.
Body weight:
Depressed bodyweight gains were recorded for male and female rats from the 1710 mg/kg and 2924 mg/kg dose levels during week one and week two. Bodyweight gains of rats dosed at 1000 mg/kg were within normal limits.
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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