Molybdenum dioxide

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:

disodium molybdate

IUPAC Name:

disodium molybdate

Constituent 2

Reference substance name:

7631-95-0

Cas Number:

7631-95-0

IUPAC Name:

7631-95-0

Constituent 3

Reference substance name:

Disodium molybdate

EC Number:

231-551-7

EC Name:

Disodium molybdate

Cas Number:

7631-95-0

Molecular formula:

Na2MoO4

IUPAC Name:

231-551-7

Test material form:

solid: particulate/powder

Details on test material:

- Name of test material (as cited in study report): Sodium molybdate
- Physical state: white crystalline powder
- Analytical purity: 98.8 %, calculated based on Molybdenum content of 46.03%
- Impurities (identity and concentrations): no relevant impurities were stated (> 1.0 %).
- Purity test date: 1990-06-06
- Storage condition of test material: at room temperature

No further significant information was stated.

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: approximately 4 to 6 weeks
- Weight at study initiation (main study): weight range of 108 to 140 g
- Fasting period before study: Access to food only was prevented overnight prior to and approximately 4 hours after dosing.
- Housing: housed in groups of up to five rats of the same sex in metal cages with wire mesh floor.
- Diet (ad libitum): standard laboratory rodent diet (SDS LAD 1)
- Water (ad libitum): domestic quality potable water
- Acclimation period: 8 days prior to the start of the main study


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

No further significant information on test animals

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE & DOSAGE PREPARATION
Sodium molybdate was prepared at various (w/v) concentrations in corn oil and administered at a volume of 10 ml/kg bodyweight.
Concentration in vehicle: Dose 1: 32 % w/v; Dose 2: 50 % w/v; Dose 3: 64 % w/v.

MAXIMUM DOSE VOLUME APPLIED: 6400 mg/kg

Preliminary study:
A trial was carried out to establish a dosing regimen for the main study. Groups of two male and two female rats were dosed at 250 and 1000mg/kg bodyweight.

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).

No further significant details stated

Doses:

Preliminary study:
Dose 1: 250 mg/kg
Dose 2: 1000mg/kg
Main study:
Dose 1: 3200 mg/kg
Dose 2: 5000 mg/kg
Dose 3: 6400 mg/kg

No. of animals per sex per dose:

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

Control animals:

no

Details on study design:

- Duration of observation period following administration: Preliminary study 5 days and main study 14 days
- Frequency of observations and weighing: 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. Individual bodyweights of rats were recorded on Days 1 (day of dosing), 8 and 15 or at death.
Also, 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.
- Necropsy of survivors performed: yes. 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 and 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 significant details were stated.

Statistics:

The acute median lethal oral dose (LD50) to male and female rats was calculated using the method of Finney (1971, Probit Analysis, 3rd Edition, Cambridge University Press).
Separate LD50 values for males and females were estimated by undertaking probit analysis on the mortality data from the preliminary and main studies by fitting two parallel lines to 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-square test was carried out to check that the data did not contain any evidence of non-parallelism.
Where the slope was not significantly different from zero, approximate confidence limits were calculated by taking the LD 50 estimate given and multiplying and dividing twice by the standard error obtained after adjustment for heterogeneity. The standard errors presented for slopes do not take heterogeneity into account.

Results and discussion

Preliminary study:

The results of the preliminary study indicated that the acute median lethal oral dose to male and female rats of Sodium molybdate was greater than 1000 mg/kg bodyweight.

Effect levels

Effect levels 1

Sex:

male/female

Dose descriptor:

LD50

Effect level:

4 233 mg/kg bw

95% CL:

>= 2 733 - <= 6 556

Effect levels 2

Sex:

male

Dose descriptor:

LD50

Effect level:

4 040 mg/kg bw

95% CL:

>= 1 912 - <= 6 075

Effect levels 3

Sex:

female

Dose descriptor:

LD50

Effect level:

4 461 mg/kg bw

95% CL:

>= 2 396 - <= 7 350

Mortality:

There were deaths following a single oral dose of Sodium molybdate in 3/5 male and 1/5 female rats dosed at 3200 mg/kg bodyweight, in 1/5 male and 2/5 female rats dosed at 5000 mg/kg, and in 5/5 male and 5/5 female rats dosed at 6400 mg/kg. Deaths occurred from within one hour of dosing until Day 2.

Clinical signs:

other: 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) in 5/5 males and 5/5 females dosed at 3

Gross pathology:

Autopsy of rats that died during the study revealed no macroscopic abnormalities. Terminal autopsy revealed no macroscopic abnormailites.

Other findings:

Estimation of LD50 values
Combined sexes:
The slope of the probit line was 4.7 with a standard error of 1.9 using log. transformation of dose. The heterogeneity factor was significant (P<0.025). Consequently, approximate confidence limits were calculated by taking the LD50 estimate and multiplying and dividing twice by the standard error obtained. The confidence limits did not therefore take heterogeneity into account.

Separate sexes:
The slope of the parallel probit lines was 4.8 with a standard error of 2.0 using log. transformation of dose. The heterogeneity factor was not significant.

The difference between the lines for male and female rats was not statistically significant.

The chi-square test for parallelism gave no evidence of non-parallelism.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

(EU)