Dipotassium tetraoxomolybdate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1990-07-05 to 1990-08-09

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1990

Report date:

1990

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

adopted 24 February 1987

Deviations:

no

GLP compliance:

yes

Remarks:

The study report states that the study was conducted in compliance with Good Laboratory Practice Standards, e.g. by the United Kingdom Compliance Programme, Department of Health & Social Security 1986 and subsequent revision, Department of Health, 1989.

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Diammonium dimolybdate

EC Number:

248-517-2

EC Name:

Diammonium dimolybdate

Cas Number:

27546-07-2

IUPAC Name:

Diammonium dimolybdate

Details on test material:

- Name of test material (as cited in study report): ammonium molybdate (There was a report amendment which stated that the ammonium molybdate tested in this study was in the form of ammonium dimolybdate).
- Physical state: white crystalline powder
- Analytical purity: > 99.9 %, calculated from reported Mo content (56.43%)
- Impurities (identity and concentrations): no relevant impurities > 1.0%
- Purity test date: 1990-06-06
- Storage condition of test material: at room temperature

No further significant information on test material was stated.

Test animals

Species:

rat

Strain:

other: CD

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: approximately four to six weeks of age in the main study
- Weight at study initiation: weight range of 110 to 135 g in the main study
- Fasting period before study: overnight prior to dosing
- Housing: housed in groups of up to five rats of the same sex in metal cages with wire mesh floors
- Diet (ad libitum): standard laboratory rodent diet (SDS LAD 1)
- Water (ad libitum): domestic quality potable water
- Acclimation period: eight days prior to the start of the main study


ENVIRONMENTAL CONDITIONS
- Temperature: mean daily minimum and maximum temperatures of the animal room were 24°C and 29°C respectively
- Humidity: mean daily relative humiditiy value was 67 % R.H.
- Air changes: approximately 15 air changes/hour
- Photoperiod (hrs dark / hrs light): 12 hour/12 hour

No further significant details on test animals were stated.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

Preliminary study:
A trial test was carried out to establish a dosing regimen for the main study.

Ammonium molybdate was prepared at various (w/v) concentrations in corn oil and administered at a volume of 10.0 ml/kg bodyweight. the test sunstance was prepared on the day of dosing.
Concentrations in vehicle: 32 % w/v, 40% w/v, 50% w/v (main study)

Main study:
The initial dose level was selected on the basis of the preliminary study. Further groups were dosed, after review of the results, to obtain a dose response curve and permit estimation of a median lethal dose.

Treatment procedure:
The appropriate dose volume of the test substance was administered to each rat using a syringe and plastic catheter (8 choke). The day of dosing wa designated Day 1.

No further significant details on oral exposure were stated.

Doses:

Preliminary study: 250 mg/kg bodyweight
Main study: 3200, 4000, 5000 mg/kg bodyweight

No. of animals per sex per dose:

Preliminary study: 2 males/2 females
Main study: 5 males/5 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: Preliminary study: 5 days; main study: 14 days; Test animals fasted approximately 4 hours after dosing.
- Frequency of observations and weighing: Preliminary study and main study: Animals were observed soon after dosing and at frequent intervals for the remainder of Day 1 (a minimum period of five hours). On subsequent days the animals surviving treatment were observed once in the morning and again at the end of the experimental day. Clinical signs were recorded at each observation. Main study: The individual bodyweights of rats were recorded on Days 1 (day of dosing), 8 and 15 or at death.
- Necropsy of survivors performed: yes
- Other examinations performed: Main study: The nature, severity, approximate time of onset and duration of each toxic sign were recorded. Also the approximate time of death of individidual rats was recorded.
All 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 cranial, abdominal anfd thoracic cavities. The macroscopic appearance of all examined tissues was recorded, and all livers and kidneys were preserved in buffered 10% formalin in order to satisfy any possible future requirement for further examination of these tissues.

No further information on study design were stated.

Statistics:

The data obtained from this study did not permit the fitting of a probit line using the standard method (Finney 1971, Probit Analysis, 3rd Edition, Cambridgeshire University Press). However, it was possible to fit a line if a fixed slope was assumed; a value of 8.333 (estimated from background data which consited of the average slope for all LD50 estimations carried out in the Department of Industrial Toxicology over a period of one year) was used. Confidence intervals using this approach should be interpreted as minimum intervals since uncertainty in estimating the slope is not allowed for.
A test for a difference between the sexes was carried out on the individual responses using a test for trend in contingency tables with dose as a stratifying factor (Mantel, N. (1963) J. Amer. Statist. Ass. 58: 690-700).

Results and discussion

Effect levels

Effect levels 1

Sex:

male/female

Dose descriptor:

LD50

Effect level:

3 883 mg/kg bw

95% CL:

>= 3 371 - <= 4 468

Effect levels 2

Sex:

male

Dose descriptor:

LD50

Effect level:

3 884 mg/kg bw

95% CL:

>= 3 178 - <= 4 735

Effect levels 3

Sex:

female

Dose descriptor:

LD50

Effect level:

3 883 mg/kg bw

95% CL:

>= 3 178 - <= 4 735

Mortality:

There were deaths following a single oral dose of Ammonium molybdate among male and female rats dosed at 4000 mg/kg bodyweight (females: 3/5;males: 3/5) and 5000 mg/kg bodyweight (females: 5/5; males: 5/5). Deaths occured from within one hour of dosing to within 5 hours of dosing.

Clinical signs:

Pilo-erection was observed in all rats within five minutes of dosing and throughout the remainder of Day 1. This sign was accompanied on Day 1 and/or at later intervals by:
-abnormal body carriage (hunched posture) and abnormal gait (waddling) in 5/5 males and 5/5 femlaes dosed at 3200 and 4000 mg/kg, and in 3/5 male rats treated at 5000 mg/kg;
- lethargy in 5/5 males and 5/5 female rats dosed at 3200 mg/kg, in 3/5 males and 2/5 females dosed at 4000 mg/kg, and in 3/5 males and 3/5 females dosed at 5000 mg/kg
- decreased respiratory rate in 5/5 males and 5/5 females dosed at 3200 mg/kg, in 3/5 males and 2/5 females dosed at 4000 mg/kg and 3/5 males, and 3/5 females dosed at 5000 mg/kg
- pallor of the extremities in 5/5 males and 5/5 females dosed at 3200 mg/kg and 4000 mg/kg, and in 3/5 males and 3/5 females dosed at 5000 mg/kg
- ptosis in 3/5 males and 2/5 females dosed at 4000 mg/kg, and in 3/5 males and 3/5 females dosed at 5000 mg/kg
- diarrhoea in 5/5 males and 4/5 females dosed at 4000 mg/kg, and in 3/5 males and 3/5 females dosed at 5000 mg/kg
- ataxia in 1/5 males and 3/5 females dosed at 5000 mg/kg

Recovery of surviving rats, as judged by external appearance and behaviour, was complete by Day 3 (4000 mg/kg) or Day 5 (3200 mg/kg).

Body weight:

Bodyweight losses or no change in bodyweight were recorded for all decedents.
Slightly low bodyweight gains were recorded for 5/5 surviving males at 3200 and 4000 mg/kg, and 1/5 female rat dosed at 4000 mg/kg on Day 8, and for 3/5 females treated at 3200 mg/kg on day 15. These rats achieved anticipated bodyweight gains on Days 15 and 8 respectively; all other rats achieved anticipated bodyweight gains throughout the study.

Gross pathology:

Autopsy of rats that died during the study revealed thickening of the glandular region of the stomach in all rats dosed at 5000 mg/kg as the only macroscopic abnormality.
Terminal autopsy revealed no macroscopic abnormalities.

Any other information on results incl. tables

Preliminary study:

The results of the preliminary study indicated that the acute median lethal oral dose to male and female rats of Ammonium molybdate was greater than 250 mg/kg bodyweight. As a result of the limited toxicity seen at this dosage (pilo-erection was recorded for all rats on Day 1 only), an initial treatment level of 5000 mg/kg bodyweight was decided upon for the main study.

Estimation of LD50 values:

Combined sexes:

When a fixed slope of 8.333 was assumed the acute median lethal oral dose of Ammonium molybdate and its 95% confidence limits were estimated to be 3883 (3371 to 4468) mg/kg bodyweight.

Separate sexes:

When a fixed slope of 8.333 was assumed to the values were:

males: 3884 (3178 to 4735) mg/kg bodyweight

females: 3883 (3178 to 4735) mg/kg bodyweight

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU