Dimethyl 2,2'-azobis(2-methylpropionate)

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

17.10.1985 - 31.10.1985

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1986

Report date:

1986

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

unknown

Molecular formula:

unknown

IUPAC Name:

unknown

Test material form:

liquid

Specific details on test material used for the study:

received 12 September 1985

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

Equal numbers of male and female CD rats of the Sprague-Dawley derived strain were obtained from Charles River U.K. Limited, Margate, Kent, England. They were in a weight range of 110 to 150 g prior to dosing (Day 1) in the main study and approximately four to six weeks of age. All the rats were acclimated to the experimental environment for a minimum period of 7 days prior to the start of the main study.
The rats were randomly allocated to cages within the treatment groups. They were housed in groups by sex in metal cages with wire mesh floors. A standard laboratory rodent diet (Labsure LAD 1) and water were provided ad libitum. The batch of diet used for the study was analysed for certain chemical and microbiological contaminants. Access to food only was prevented overnight prior to and approximately 4 hours after dosing.
Results of routine chemical examination of water at source (Grafham Final Water) as conducted quarterly by the Anglian Water Authority, are made available to Huntingdon Research Centre.
The mean daily minimum and maximum temperatures of the animal room were 21 °C and 22 °C respectively and the mean daily relative humidity value was 55%. The rate of air exchange was maintained at approximately 15 air changes/hour. Lighting was controlled by means of a time switch to 12 hours artificial light in each 24 hour period.
Each animal was identified by cage number and ear punching.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

Decomposition Product of V-601 (colourless liquid) was administered as supplied by the Sponsor at a volume not exceeding 3.8 ml/kg.
The stability and absorption of the test substance were not determined.
The appropriate dose volume of the test substance was administered to each rat using a syringe and plastic catheter.

Doses:

1000, 1600, 2500 and 4000 mg/kg bodyweight

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

Observations:
Animals were observed soon after dosing; then at frequent intervals for the remainder of Day 1. On subsequent days the animals were observed at least twice per day. Clinical signs were recorded at each observation.
The animals on the preliminary and main studies were observed for 5 and 14 days respectively, after dosing.
The following were recorded on the main study:
Approximate time of death of individual rats.
The nature, severity, approximate time of onset and duration of each toxic sign.
Individual bodyweights of rats on Days 1 (day of dosing), 8 and 15 and at death.

Post mortem examination:
Surviving animals on the main study were killed on Day 15 by carbon dioxide asphyxiation. All animals that died during the study and those killed on Day 15 were subjected to a macroscopic post mortem examination which consisted of opening the abdominal, thoracic and cranial cavities. The macroscopic appearance of abnormal organs when present was recorded.

Statistics:

The acute median lethal oral dose (LD50) to male and female was calculated using the method of:
Finney (1971) Probit Analysis (3rd Edition) Cambridge University Press.
Seperate LD50 values for males and females were estimated by undertaking probit analysis on the mortality data by fitting two parallel lines on the data (males only and females only) using the technique described by Finney (1978, Statistical Method in Biological Assay, 3rd Edition, Charles Griffin, London). A chi-squared test was carried out to check that the data did not contain any evidence for non-parallelism.

Results and discussion

Preliminary study:

The results of the preliminary study indicated that the acute median lethal oral dose of Decomposition Product of V-601 was between 1000 and 2500 mg/kg bodyweight.

Effect levels

Effect levels 1

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

2 369 mg/kg bw

Based on:

test mat.

95% CL:

>= 1 941 - <= 2 986

Effect levels 2

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

2 567 mg/kg bw

Based on:

test mat.

95% CL:

>= 1 948 - <= 3 574

Effect levels 3

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

2 181 mg/kg bw

Based on:

test mat.

95% CL:

>= 1 627 - <= 2 960

Mortality:

Mortalities occured amongst rats dosed at 1600 mg/kg and above within 22 and 47 hours of dosing.

Clinical signs:

other: Signs of reaction to treatment observed shortly after dosing in all rats were pilo-erection, abnormal body carriage (hunched posture), abnormal gait (waddling), lethargy, decreased respiratory rate, pallor of the extremities and increased salivatio. These

Gross pathology:

Autopsy revealed slight pallor of the liver and kidneys among animals that died.
Terminal autopsy findings were normal.

Applicant's summary and conclusion

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

The acute median lethal oral doses (LD50) and their 95% confidence limits to rats of V-601 Decomposition Product were estimated to be:
Males and females combined: 2369 (1941 to 2986) mg/kg bodyweight
Males only: 2567 (1948 to 3574) mg/kg bodyweight
Females only: 2181 (1627 to 2960) mg/kg bodyweight

Executive summary:

The acute median lethal oral dose of Decomposition Product V-601 and its 95% confidence limits were estimated to be:

Males and females combined: 2369 (1941 to 2986) mg/kg bodyweight

The slope of the probit line was 6.9 with a standard error of 1.9 using log transformation of dose. The heterogeneity factor was not significant.

When probit analysis was carried out by fitting the parallel lines the values were:

Males only: 2567 (1948 to 3574) mg/kg bodyweight

Females only: 2181 (1627 to 2960) mg/kg bodyweight

The slope of the probit line was 7.1 with a standard error of 1.9 using log transformation of dose. The heterogeniety factor was not significant.