Molybdic acid

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 1990-08-15

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

guideline study - no microscopic examination were carry out even macroscopic abnormailties were found in animals. It was not clear if the abnormalities were found in animals surviving 24 or more hours in which case microscopic examination should have been carried out.

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:

yes

Remarks:

No microscopic examination were carry out even macroscopic abnormailties were found in animals. It was not clear if the abnormalities were found in animals surviving 24 or more hours in which case microscopic examination should have been carried out.

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:

Molybdenum trioxide

EC Number:

215-204-7

EC Name:

Molybdenum trioxide

Cas Number:

1313-27-5

Molecular formula:

MoO3

IUPAC Name:

molybdenum trioxide

Details on test material:

- Name of test material (as cited in study report): Pure molybdic oxide
- Physical state: light grey powder
- Analytical purity: > 99.9 %, calcualted from reported Mo content (66.63%)
- 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 details on test material were 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 131 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: minimum period of seven days prior to the start of the main study


ENVIRONMENTAL CONDITIONS
- Temperature (°C): mean daily minimum and maximum temperatures of the animal room were 22°C and 26°C respectively
- Humidity (%): mean daily relative humiditiy value was 59 % R.H.
- Air changes (per hr): 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 was carried out to establish a dosing regimen for the main study.
Pure molybdic oxide was prepared at various (w/v) concentrations in corn oil and administered at a volume of 10.0 ml/kg bodyweight. The test substance was prepared on the day of dosing.
Concentrations in vehicle: 20% w/v, 25 %w/v, 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 was designated Day 1.

No further significant details on oral exposure were stated.

Doses:

Preliminary study: 126, 500 and 2500 mg/kg mg/kg bodyweight
Main study: 2000, 2500, 3200, 4000 and 5000 mg/kg bodyweight

No. of animals per sex per dose:

Preliminary study:2 males / 2 females
Main study: 5 males / 5 males (Exceptions: 2500 mg/kg bodyweigth only 5 males tested; 4000 mg/kg bodyweight only 5 females tested)

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 period of six 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 approximately time of death of individaul 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 acute median lethal oral dose (LD50) to male and female rats was calculated using the method fo Finney (1971, Probit Analysis, §rd Edition, Cambridge University Press).
Separate LD50 values for males and females were estimated by undertaking probit analysis on the mortality data from the main study 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.

Results and discussion

Effect levels

Effect levels 1

Sex:

male

Dose descriptor:

LD50

Effect level:

2 689 mg/kg bw

95% CL:

>= 2 334 - <= 3 141

Effect levels 2

Sex:

female

Dose descriptor:

LD50

Effect level:

3 830 mg/kg bw

95% CL:

>= 3 271 - <= 4 319

Mortality:

Deaths were seen in 1/5 male rats dosed at 2500 mg/kg bodyweight, in 5/5 males dosed at 3200 mg/kg, in 5/5 females dosed at 4000 mg/kg, and in 5/5 males and 4/5 females dosed at 5000 mg/kg. A majority of deaths occured from within 5 hours of dosing until Day 3. One female rat dosed at 4000 mg/kg was sacrificed in extremis on Day 4.

Clinical signs:

other: other: other: Pilo-erection was observed in all rats within five minutes of dosing and thoughout the remainder of Day 1. This sign was accompanied on Day 1 and/or at later intervals by: - Abnormal body carriage (hunched posture), abnormal gait (waddling)

Gross pathology:

Autopsy of rats that died during the study revealed dark kidneys in two males treated at 5000 mg/kg, and pale areas on the liver (in close proximity of the stomach) in one female rat dosed at 5000 mg/kg as the only macroscopic abnormalities.
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 rats of Pure molybdic oxide was greater than 2500 mg/kg bodyweight.

Estimation of LD50 values

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

Males 2689 (2334 to 3141) mg/kg bodyweight

Females: 3830 (3271 to 4319) mg/kg bodyweight

The slope of the parallel probit lines was 17.1 with a standard error of 4.8 using log. transformation of dose. The heterogeneity factor was not significant.

The mortality response curves: The difference between the lines for male and female rats was statistically significant (P< 0.005). Hence, there is a difference in the susceptibility of each sex to the test compound. A combined LD50 value was not therefore given since, as this is the mean value of the male and female LD50 estimations, 50% mortality would be expected, but would not actually occur, at this dose level.

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

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU