Sodium metavanadate

Endpoint summary

Description of key information

Acute oral toxicity: LD50 = 169 mg/kg bw (OECD 401; GLP; female rats)

Acute inhalation toxicity: LC50 = 3.73 mg/ L air (OECD 403; GLP; female rats)

Acute dermal toxicity: LD50 > 2500 mg/kg bw (OECD 402; GLP; read-across from potassium vanadium trioxide)

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1993-12-20 to 1994-01-24

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

Minor deviation from the OECD 401 guideline occurred, but this had no impact on the results of the study: - information about individual body weights was not given.

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

1987-02-24

Deviations:

yes

Remarks:

see rational for reliability

GLP compliance:

yes (incl. QA statement)

Remarks:

signed 1991-07-25

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS - Sprague-Dawley/Crl:CD R BR
- Source: Charles River Deutschland GmbH, Niederlassung Sulzfeld, Sandhofer Weg 7, D-97633 Sulzfeld
- Age at start of adaptation: 25 - 30 days
- Weight at start of administration: 170 - 200 g
- Fasting period before study: feeding was discontinued approximately 16 hours before administration. Only tap water was offered ad libitum.
- Housing: granulated textured wood (Granulate type A2, supplier: BRANDENBURG, D-49424 Goldenstedt) was used as bedding material for the cages. The animals were kept in groups of 2 - 3 during housing in MAKROLON cages (type III).
- Diet: standardized diet Altromin 1324 (ALTROMIN GmbH, D-32791 Lage/Lippe)
- Water (ad libitum): tap water
- Acclimation 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

Route of administration:

oral: gavage

Vehicle:

other: 0.8% aqueous hydroxypropyl-methylcellulose gel

Details on oral exposure:

VEHICLE
- Batch no.: MM90100512E

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

DOSAGE PREPARATION: The test substance was disollved or suspended in the vehicle.

Doses:

46.4, 100, 215 and 464 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, 6 and 24 hours after administration. During this follow-up period, the clinical signs were observed at least once a day until all symptoms subsided, and thereafter each working day. 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 the weights were calculated and recorded as precisely as possible.
- 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 survive 24 hours or longer a microscopic examination of all organs which show evident lesions is performed, if applicable. Autopsy and macroscopic inspection of the animals which died prematurely was carried out as soon as possible after exitus.

Statistics:

The LD50 was calculated according to FINNEY (Probit analysis).

Sex:

male

Dose descriptor:

LD50

Effect level:

212 mg/kg bw

Based on:

test mat.

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

169 mg/kg bw

Based on:

test mat.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

183 mg/kg bw

Based on:

test mat.

95% CL:

>= 140 - <= 238

Mortality:

46.4 mg/kg bw: no mortality
100 mg/kg bw: 1 female (day 3.5)
215 mg/kg bw: 3 males and 3 females (24 hours - 48 hours)
464 mg/kg bw: all males (24 hours - 48 hours) and all females (4 hours - 24 hours)

Clinical signs:

other: 46.4 mg/kg bw: none 100 mg/kg bw: weak reduced motility (60 minutes - 24 hours; all males and females); weak ataxia (60 minutes - 24 hours; all males and females); weak dyspnoea (60 minutes - 24 hours; all males and females) 215 mg/kg bw: weak reduced m

Gross pathology:

46.4 and 100 mg/kg bw: no pathological findings
215 mg/kg bw: 3 males and 3 females had a slightly reddened gastro-intestinal wall
464 mg/kg bw: all males and all females had a slightly reddened gastro-intestinal wall

Interpretation of results:

Toxicity Category III

Conclusions:

LD50 (male rats): 212 mg/kg bw
LD50 (female rats): 169 mg/kg bw
LD50 (male and female rats): 183 mg/kg bw (confidence limits: 140 - 238 mg/kg bw)
No-effect dose-level: 46.4 mg/kg bw
Lowest lethal dose-level: 215 mg/kg bw (males) and 100 mg/kg bw (females)
According to the EC-Regulation 1272/2008 and subsequent adaptations, the test item is classified as as acutely toxic via the oral route (Category 3).

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

169 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1994-01-10 to 1994-02-15

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

Minor deviations from the OECD 403 guideline occurred, but they had no impact on the results of the study: - the humidity was <17 % for optimal dust distribution (recommended 30-70%) - the air change rate was slightly greater than 15/h. - no 95th percentile was calculated.

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Version / remarks:

1981-05-12

Deviations:

yes

Remarks:

see rational for reliability

GLP compliance:

yes (incl. QA statement)

Remarks:

signed 1991-07-25

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS - Sprague-Dawley/Crl:CD R BR
- Source: Charles River Wiga GmbH, Niederlassung Sulzfeld, Sandhofer Weg 7, D-97633 Sulzfeld
- Age at start of adaptation: 35 - 50 days
- Weight at study initiation (immediately before exposure): males. 173 - 199 g; females: 173 - 192 g
- Fasting period before study: food was discontinued approximately 16 hours before exposition.
- Housing: granulated textured wood (type 2, supplied by: Johannes Brandenburg, D-49424 Goldenstedt-Arkeburg) was used as bedding material. During the 14- day observation period the animals were kept in group-caged by sex in groups of two or three in MAKROLON cages (type III).
- Diet (ad libitum): standardized diet for rats ALTROMIN 1324 (ALTROMIN GmbH, D-32791 Lage/Lippe)
- Water (ad libitum): tap water
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 22°C ± 3°C (maximum range)
- Relative humidity: 50% ± 20% (maximum range)
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

inhalation: dust

Type of inhalation exposure:

nose only

Vehicle:

clean air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus/Exposure chamber volume/Method of holding animals in test chamber: the study was carried out using a dynamic inhalation apparatus (air changes/h. ≥ 12 x) with a nose only exposure of the animals according to KIMMERLE & TEPPER (RHEMA-LABORTECHNIK, D-65719 Hofheim/Taunus).
The apparatus consists of a cylindrical exposure chamber (volume 40 L) which holds a maximum of 20 animals in pyrex tubes at the edge of the chamber in a radial position.

- System of generating particulates/aerosols: the dust was generated with a rotating brush dust generator (RBG 1000, PALAS GmbH Partikel und Lasermesstechnik, D-76131 Karlsruhe. The generator was fed with compressed air from a compressor (air was taken from the surrounding atmosphere of the laboratory room and filtered using an in-line disposable gas-filter). At the bottom of the exposure chamber the air was sucked off at a lower rate than it was created by the dust generator in order to produce a homogenous distribution and a positive pressure in the exposure chamber.
Different concentrations were established by means of a combination of different settings of the dosing apparatus and different values of air flow.

- Method of particle size determination: an analysis of the particle size distribution was carried out during the first and during the second half of the exposure period using a cascade impactor according to MAY (MAY, K.R. 'Aerosol impaction jets', J. Aerosol Sci. 6, 403 (1975), RESEARCH ENGINEERS Ltd., London N1 5RD, UK).
The dust from the exposure chamber was sucked through the cascade impactor for 2 to 5 minutes at a constant flow rate of 5 L/min. The slides were removed from the impactor and were weighed on an analytical balance (SARTORIUS, type 1601 004, precision 10 µg).
The mass median aerodynamic diameter (MMAD) was estimated by means of nonlinear regression analysis (LITCHFIELD & WILCOXON). The 32 µm particle size range and the filter (particle size range < 0.5 µm) were not included in the determination of the MMAD in order not to give undue weight to these values.

- Treatment of exhaust air: the exhaust air was sucked through 3 gas wash-bottles filled with tap water. The outlet of the inhalation apparatus was in a DIN certified fume cupboard.

- Temperature, humidity, air flow and oxygen content: a manometer and an air-flow (Rotameter, ROTA Apparate- und Maschinenbau, D-79664 Wehr/Baden) were used to control the constant supply of compressed air and the exhaust, respectively. Flow rates were checked once per hour and corrected if necessary. Air changes per hour were 23 - 47.5.
The oxygen content in the inhalation chamber was 19%. The oxygen content was determined at the beginning and at the end of the exposure with a DRÄGER Oxygenanalysis test set (DRÄGER Tube Oxygen 67 28 081).
The exposure system was installed in a facility with a room temperature of 22°C ± 2°C and a relative humidity of 50% ± 20%.
Temperature (GTH 1200 Digital Thermometer, GREISINGER ELECTRONIC GmbH, D-93128 Regenstauf) and humidity (Sekunden-Hygrometer Typ 6100, TESTOTERM) within the inhalation chamber were measured and recorded once per hour (Temperature: 18.9°C - 21.9°C; humidity: 10.4% - 16.6%). Humidity within the inhalation chamber had to be kept at this low value in order to ensure an adequate particle size distribution.

Exposition started by locating the rats into the exposure chamber after equilibration of the chamber concentration for at least 15 minutes.

TEST ATMOSPHERE
- Brief description of analytical method used: the dust concentration in the inhalation chamber was measured with an air sample filter (SARTORIUS filter; Minisart SM 17598; 0.45 µm) and pump (Vacuubrand GmbH + Co., Otto-Schott-Straße 25, D-97877 Wertheim/Main). Dust samples were taken at least one every hour.
By means of a piece of silicon tubing, the filter was connected to an air flow meter (Rotameter, ROTA Apparate- und Maschinenbau, D-79664 Wehr/Baden) attached to the pump. The filters were weighed before and after sampling (accuracy: 10 µg)
- Samples taken from breathing zone: yes

TEST ATMOSPHERE
- MMAD (Mass median aerodynamic diameter):
0.48 mg/L air: 5.10 µm
2.58 mg/L air: 6.57 µm
4.13 mg/L air: 7.11 µm
- Respirable amount (particle size ≤4 µm):
0.48 mg/L air: 0.24 mg/L air
2.58 mg/L air: 0.62 mg/L air
4.13 mg/L air: 0.97 mg/L air

Analytical verification of test atmosphere concentrations:

yes

Remarks:

refer to "Details on inhalation exposure" above

Duration of exposure:

4 h

Concentrations:

Nominal concentrations:
2.11, 13.53 and 26.52 mg/L air
Actual concentrations:
0.48 ± 0.04, 2.58 ± 0.22 and 4.13 ±0.13 mg/L air
4.13 mg/L air was the highest amount of the test substance that could be generated in the inhalation chamber.

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: during and following exposure, observations were made and recorded systematically; individual records were maintained for each animal. A careful clinical examination was made at least once each day until all symptoms subsided, thereafter each working day.
Observations on mortality were made at least once daily with appropriate actions taken to minimize loss of animals to the study, e.g. necropsy or refrigeration of those animals found dead and isolation or sacrifice of weak or moribund animals.
Individual body weights of the animals were determined immediately before the exposure, after 1 week and at study termination.
- Necropsy of survivors performed: yes; necropsy of all animals was carried out and all gross pathological changes were recorded. Histopathology was not carried out as no relevant lesions were observed macroscopically.

Statistics:

The LC50 was calculated by means of regression analysis.

Sex:

male

Dose descriptor:

LC50

Effect level:

4.93 mg/L air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

other: Slope: 11.0

Key result

Sex:

female

Dose descriptor:

LC50

Effect level:

3.73 mg/L air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

other: Slope: 19.2

Sex:

male/female

Dose descriptor:

LC50

Effect level:

4.13 mg/L air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

other: Slope: 15.1

Sex:

male

Dose descriptor:

LC0

Effect level:

4.13 mg/L air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Sex:

female

Dose descriptor:

LC0

Effect level:

4.13 mg/L air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Mortality:

All deaths after end of exposure
0.48 and 2.58 mg/L air: no mortality
4.13 mg/Lair: 1 male (48 hours) and 4 females (0 - day 5)

Clinical signs:

other: All symptoms after end of exposure. 0.48 mg/L air: none 2.58 mg/L air: weak lacrimation (0 minutes; 1 male); weak salivation (0 minutes; 4 males and 4 females); nose and/or snout reddened (0 minutes; 4 males and 4 females); weak apathy (15 - 60 minutes;

Body weight:

No inhibition of body weight gain was observed.

Gross pathology:

0.48 and 2.58 mg/L air: no pathological findings
4.13 mg/L air: nose with haemorrhagic incrustation and small intestines distended were observed at 4.13 mg/L air in 1 deceased female, lungs with dark-red foci and a dark red liver were observed in another deceased female. These changes can be regarded as unspecific effects which usually occur after the inhalation exposure to a dust.

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

LC50 (male rats): 4.93 mg/L air (analytical)
LC50 (female rats): 3.73 mg/L air (analytical)
LC50 (male and female rats): 4.13 mg/L air (analytical)
According to the EC-Regulation 1272/2008 and subsequent adaptations, the test item is classified acutely toxic via the inhalation route (Category 4).

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LC50

Value:

3 730 mg/m³ air

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Data waiving:

other justification

Justification for data waiving:

other:

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 500 mg/kg bw

Additional information

Read across-acute dermal toxicity performed with KVO3:

KVO₃and NaVO₃are vanadates with similar solubility potential, i.e. 124 g/L at pH 9 and 215 g/L at pH 8.8, respectively, and similar V content, i.e. 36.9% and 41.8%, respectively. Potassium and sodium are (i) ubiquitous in the environment (air, soil and water), (ii) key nutrients and intrinsically present in the human body due to a natural background in all dietary sources, and (iii) normal constituents of all body fluids and main blood minerals, and maintain electrolyte or acid-base (pH) balance as well as a proper fluid. Potassium and sodium belong to the ten most common elements in the human body, by mass ca. 0.4% and 0.2%, respectively, and functions in the body cover cellular transport, water regulation, blood pressure control, nerve conduction, muscular contraction as well as enzymatic reactions and other metabolic activities. In consequence, because of the intrinsic nature of sodium and potassium as endogenous physiological compounds and because of similar solubility characteristics of KVO₃and NaVO₃, read-across of dermal toxicity data from KVO₃to NaVO₃is justified.

Acute oral toxicity

Sodium metavanadate is toxic if swallowed as the LD50 (rats, females) as determined in the reliable GLP-study (Leuschner, 1994) is 169 mg/kg bw.

Acute inhalation toxicity

Sodium metavanadate is harmful if inhaled as the LC50 (rats, females) is 3.73 mg/L air (analytical).

Acute dermal toxicity

Acute toxicity testing via the dermal route is not considered to be scientifically justified. Following the HERAG guidance for metals and metal salts (see section 7.1.2 of the technical dossier, dermal absorption), a dermal absorption rate in the range of maximally 0.1-1.0 % can be anticipated. Dermal absorption in this order of magnitude is not considered to be “significant”. Furthermore, results of a dermal toxicity study of the structural analogue KVO3 also indicate a lack of toxicity via the dermal route.

Justification for classification or non-classification

Sodium metavanadate requires classification as toxic if swallowed (Category 3) and harmful if inhaled (Category 4) according to Regulation (EC) 1272/2008. Classification of sodium metavanadate for acute toxicity via the dermal route is not required according to Regulation (EC) 1272/2008.

Specific target organ toxicant (STOT) – single exposure: oral and inhalation

The classification criteria according to regulation (EC) 1272/2008 as specific target organ toxicant (STOT) – single exposure, oral and inhalation are not met since no reversible or irreversible adverse health effects (local or/and systemic) were observed below lethal levels in addition to this effects which were responsible for the death of the animals. Hence, no classification required.

Specific target organ toxicant (STOT) - single exposure: dermal

The classification criteria according to Regulation (EC) 1272/2008 as specific target organ toxicant (STOT) – single exposure dermal are not met since any adverse health effects, including reversible and irreversible, were not observed immediately or delayed after exposure.