Ammonium trivanadium octaoxide

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2006-05-30 to 2006-06-28

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2006

Report date:

2006

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Version / remarks:

adopted 17 December 2001

Deviations:

yes

Remarks:

see below

Principles of method if other than guideline:

Minor deviations:
- According to the guideline, when during the first step of dosing 2-3 animals die, then the next lower dose should be tested. In this study a dose of 300 mg/kg b.w. killed all animals. However, a second group was tested at this dose level, because the time selected interval between first and second step was too short (delayed onset of death of animals from the 1st dosing). This is not relevant for the results.
- According to the guideline, microscopic examination of organs showing evidence of gross pathology in animals survivng 24 or more hours may also be considered because it may yield useful information. In this study evidence of gross pathology were found, but no microscopic examination was carried out ad-hoc.
- According to the guideline, the details of food and water quality must be included in the test report. The study report only stated for the food that it was analysed. No further information in regard to food and water quality was mentioned.
The study report stated that there were problems measuring the temperature and humidity data for the environmental conditions continuously, which was assumed to be of no relevance for the results of this study.

GLP compliance:

yes

Remarks:

The study report stated that this study meets the requirements of the OECD Principles of GLP, OECD Environment Health and Safety Publications, Series on Principles of Good Laboratory Practice and Compliance Monitoring No. 1, Paris 1998.

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Ammonium trivanadium octaoxide

EC Number:

235-384-0

EC Name:

Ammonium trivanadium octaoxide

Cas Number:

12207-63-5

Molecular formula:

NH4V3O8

IUPAC Name:

trivanadium(5+) ammonium octaoxidandiide

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

- Name of test material (as cited in study report): Ammoniumpolyvanadate ((NH4)2V6O16)
- Physical state: yellow powder
- Stability at conditions of storage: stable
- Stability in aqueous solutions: Stable
- Storage condition of test material: Room temperature

Test animals

Species:

rat

Strain:

Crj: CD(SD)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland GmbH, D-97633 Sulzfeld
- Age at study initiation: approx. 8 weeks at the time of the administration
- Weight at study initiation: 178 g - 200 g before administration
- Fasting period before study: Feed was withdrawn the evening before the administration of the test substance and was offered again about three h afterwards.
- Housing: Single caging in Makrolon cages type III (39 cm X 23 cm bottom area, 18 cm height). Wire mesh lids. Bedding material: Aspen wood chips, Fa ABEDD Dominik Mayr KEG, A-8580 Köflach, autoclaved.
- Diet (ad libitum): Altromin 1324 forte, gamma irradiated with 25 kGy60Co (Producer: Altromin GmbH, D-32791 Lage)
- Water (ad libitum): tap water from an automatic watering system
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: average of 22.5 °C
- Relative humidity: average of 66.2%
- Air exchanges: 12 per hour
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Details on oral exposure:

VEHICLE
A 0.1 % aqueous solution of Na-carboxymethylcellulose ("CMC" high viscosity, item No. C-5013, Lot. No. 98H0328 , Sigma) plus Tween 80 (Polyoxyethylensorbitanmonooleate, article No. 822187, Merck) was used as vehicle for the test substance.
- Justification for choice of vehicle: The test substance was not soluble in water. Aqueous CMC plus Tween 80 is a common vehicle for acute oral toxicity testing.

DOSE VOLUME APPLIED: 20 mL/kg b.w.. The individual dose volumes were calculated using the body weights determined on the day of the administration.

DOSAGE PREPARATION: The suspensions were prepared freshly before administration and were administered within 10 minutes after the preparation.

CLASS METHOD
- Rationale for the selection of the starting dose: As no prior information on the toxicity of the test substance was available, a starting dose of 300 mg of the test substance per kg body weight was chosen. The further proceeding was in accordance with the guidelin/directive. Due to the delayed onset of death in the animals of step 1 the test substance was also administered to another group with a dose of 300 mg/kg body weight (step 2).
No further significant information on details on oral exposure was stated.

Doses:

50 mg/kg b.w.
300 mg/kg b.w.

No. of animals per sex per dose:

Two groups of 3 females per dose level

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observations were performed within the periods 0 -0.5, 0.5 - 1, 1 -2, 2-4 and 4 - 6 hours after administration of the test substance and then at least once a day for a total of 2 weeks. Body weights were determined before administration, 7 days after administration and 14 days after administration. When early deaths occured the body weight was determined as soon as possible after finding.
- Necropsy of survivors performed: Yes, surviving animals were killed by inhalation of 80 % CO2 + 20 % air 14 days after administration and were also subjected to a necropsy including a gross pathological examination. Deceased animals were dissected and examined macroscopically in an attempt to identify the target organs.
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: Observations included but were not limited to changes in skin, fur, eyes, the occurence of secretions and excretions, autonomic activity, changes in gait, posture and the presence of convulsions. Body weight gain was calculated for each week of the study, i.e. between 0 and 7 days after administration, and between 7 days and 14 days after administration.
No further significant information on details on study design was stated.

Statistics:

not stated

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

200 mg/kg bw

Based on:

test mat.

Mortality:

300 mg/kg b.w., step 1: All animals died 3 d after administration
300 mg/kg b.w., step 2: All animals died between 2 and 6 d after administration
50 mg/kg b.w., step 3: All animals survived until the scheduled termination of the study
50 mg/kg b.w., step 4: All animals survived until the scheduled termination of the study.

Clinical signs:

other: Only animals at the high dose (300 mg/kg b.w.) were affected. No symptoms of reduced well-being were observed at the does of 50 mg/kg b.w. The observed findings at 300mg/kg b.w. with an onset 2 d after administration and lasting until death (i.e. to a max

Gross pathology:

Abnormal findings were present only in deceased animals (animals died spontaneously):
- glandular stomach, mucosa, ulcera (step 1: 3/3 females; step 2: 2/3 females)
- glandualr stomach, mucosa, erosion (step 2: 1/3 females)
- stomach, blood in the lumen (step 2: 1/3 females)
- small intestine, blood in the lumen (step 1: 1/3 females; step 2: 1/3 females)
- small intestine, ulcera (step 2: 1/3 females)
- anus, soiled with faeces (step 1: 3/3 females; step 2: 3/3 females)
- liver, large white foci (step 2: 2/3 females)
All other animals were normal at the necropsy 14 d after administration.

Applicant's summary and conclusion

Interpretation of results:

Category 3 based on GHS criteria

Conclusions:

The test substance caused gastrointestinal irritation and sings of discomfort at the dose of 300 mg/kg b.w. but no toxic effects at 50 mg/kg b.w. Shock from gastrointestinal lesions may have been the cause of death at the dose of 300 mg/kg bw.
The LD50 can be estimated at 200 mg/kg bw. according to annex 2 to OECD 423 (GHS: >50-300 mg/kg bw.; Category 3).
According to REGULATION (EC) No 1272/2008, a classification of "ammonium trivanadium octaoxide" is required (Acute toxicity Category 3; H301: Toxic if swallowed).