Ammonium trioxovanadate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1991-12-11 to 1992-01-27

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1992

Report date:

1992

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

signed 1991-07-25

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Ammonium trioxovanadate

EC Number:

232-261-3

EC Name:

Ammonium trioxovanadate

Cas Number:

7803-55-6

Molecular formula:

H4N.O3V

IUPAC Name:

ammonium trioxovanadate

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

- Name of test material (as cited in study report): Ammonium metavanadate
- Physical state: light-beige, solid, amorphous powder
- Storage condition of test material: at room temperature

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS - Sprague-Dawley, Tif:RAI f (SPF)
- Source: Lippische Versuchstierzucht, HAGEMANN GmbH, D-4923 Extertal 1
- Age at study initiation: approximately. 40 - 60 days
- Weight at study initiation: 159 - 199 g
- Fasting period before study: feeding was discontinued approximately 16 hours before administration. Only tap water was offered ad libitum.
- Housing: granulated textured wood was used as bedding material for the cages (Granulat Typ A2, supplier: Messrs. BRANDENBURG, Inh. H. Brandenburg, D-2849 Goldenstedt). During the observation period, surviving animals were kept in groups of 2 - 3 animals in MAKROLON cages (type III).
- Diet: standardized diet for rats and mice ALTROMIN 1324 (supplied by: ALTROMIN GmbH, D-4937 Lage/Lippe)
- Water (ad libitum): tap water
- Quarantine period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 22°C ± 3°C (maximum range)
- Relative humidity: 60% ± 20% (maximum range)
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: 0.8% aqueous hydroxypropyl-methylcellulose gel

Details on oral exposure:

VEHICLE
- Batch no.: MM 84097413B

MAXIMUM DOSE VOLUME APPLIED: 20 mL/kg bw (dose interval factor: 2.15)

DOSAGE PREPARATION: Ammonium metavanadate was suspended in 0.8% aqueous hydroxypropyl-methylcellulose gel.

Doses:

male and female rats: 100, 215, and 464 mg/kg bw
female rats only: 46.4 mg/kg bw

No. of animals per sex per dose:

5 males / 5 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observations were performed immediately, 5, 15, 30 and 60 minutes, as well as 3 hours, 6 hours and 24 hours after administration. During the follow-up period, changes of skin and fur, eyes and mucous membranes, respiratory and circulatory, autonomic and central nervous system and somatomotor activity as well as behaviour pattern were observed at least once a day until all symptoms subsided, and thereafter each working day. Attention was also paid to possible tremor, convulsions, salivation, diarrhoea, lethargy, sleep and coma. Observations on mortality were made at least once daily with appropriate actions taken to minimise loss of animals during the study. Individual body weights were recorded before administration of the substance, thereafter in weekly intervals up to the end of the study, and at death. Changes in weight were calculated and recorded when survival exceeds one day.
- Necropsy of survivors performed: yes; at the end of the experiments all surviving animals were sacrificed dissected and inspected macroscopically. All gross pathological changes were recorded. from animals which survived 24 hours or longer a microscopic examination of all organs which show evident lesions is performed. Autopsy and macroscopic inspection of rats which died prematurely were carried out as soon as possible after exitus.

Statistics:

The LD50 was calculated by regression analysis and probit analysis (FINNEY). The mortality rates at 24 hours ad at 14 days were used.

Results and discussion

Effect levels

Effect levels 1

Sex:

male

Dose descriptor:

LD50

Effect level:

218.1 mg/kg bw

Based on:

test mat.

Remarks on result:

other: LD50 after 14 days; Slope: 14.98

Effect levels 2

Sex:

female

Dose descriptor:

LD50

Effect level:

141.4 mg/kg bw

Based on:

test mat.

Remarks on result:

other: LD50 after 14 days; Slope: 9.32

Effect levels 3

Sex:

male/female

Dose descriptor:

LD50

Effect level:

169.33 mg/kg bw

Based on:

test mat.

95% CL:

126.86 - 226.03

Remarks on result:

other: LD50 after 14 days; Slope: 4.52

Effect levels 4

Sex:

male

Dose descriptor:

LD50

Effect level:

371.1 mg/kg bw

Based on:

test mat.

Remarks on result:

other: LD50 after 24 hours; Slope: 7.86

Effect levels 5

Sex:

female

Dose descriptor:

LD50

Effect level:

212.48 mg/kg bw

Based on:

test mat.

Remarks on result:

other: LD50 after 24 hours: Slope: 14.98

Effect levels 6

Sex:

male/female

Dose descriptor:

LD50

Effect level:

275.87 mg/kg bw

Based on:

test mat.

95% CL:

203.71 - 373.57

Remarks on result:

other: LD50 after 24 hours; Slope: 4.36

Mortality:

46.4 mg/kg bw: none
100 mg/kg bw: 2 females (day 3)
215 mg/kg bw: 2 males (24 hours - day 4)/ 4 females (24 hours - day 3)
464 mg/kg bw: 5 males (4 hours - day 4) / 5 females (70 minutes - 24 hours)

Clinical signs:

other: Male rats: 46.4 mg/kg bw: none 100 mg/kg bw: none 215 mg/kg bw: slight/moderate reduced motility (3 hours - day 2; 5 males); slight/moderate ataxia (3 hours - day 2; 5 males); slight/moderate dyspnoea (3 hours - day 2; 5 males); moderate muscular hypotoni

Gross pathology:

Animals that died prematurely:
215 mg/kg bw: 1/2 males and 3/4 females had reddened intestinal mucosa
464 mg/kg bw: 4/5 males had (severely) dark liver and reddened intestinal mucosa; 5/5 females had severely dark liver and (severely) reddened intestinal mucosa
All further deceased animals showed no pathological findings.
Surviving animals (sacrificed) (male and female):
no pathological findings

Applicant's summary and conclusion

Interpretation of results:

Toxicity Category III

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

LD50 (male rats) = 218.07 mg/kg bw
LD50 (female rats) = 141.43 mg/kg bw
LD50 (male and female rats) = 169.33 mg/kg bw (CL: 126.86 - 226.03 mg/kg bw)
The lowest lethal dose was 215 mg/kg bw (males) and 100 mg/kg bw (females), the no-effect level was 100 mg/kg bw (males) and 46.4 mg/kg bw (females).
According to the EC-Commission directive 67/548/EEC and its subsequent amendments, the test substance is classified as toxic if swallowed.
According to the EC-Regulation 1272/2008 and subsequent regulations, the test item is classified as Category 3.