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Description of key information

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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable, well-documented publication which meets basic scientific principles.
Reason / purpose:
reference to same study
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
males only; body weight measurements and gross pathology not conducted
Principles of method if other than guideline:
Groups of 10 male Sprague-Dawley rats were given 296, 395, 500, 650, and 845 mg/kg of vanadyl sulfate pentahydrate (VOSO4 * 5H20) in 10 mM Tris-HCl-NaCl buffer (pH 7.4) by gavage. A control group receiving only the vehicle was also used during the study. The animals were observed for mortality and clinical signs during a 14 day observation period.
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Biocentre (Barcelona, Spain)
- Weight at study initiation: 200 - 250 g
- Diet (ad libitum): Panlab diet
- Water (ad libitum): water
Route of administration:
oral: gavage
Vehicle:
other: Tris-HCl-NaCl buffer
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED:
Solution concentrations were adjusted so that a 250 g rat received 1 mL.

DOSAGE PREPARATION:
The test material was dissolved in 10 mM Tris-HCl-NaCl buffer (pH 7.4)

To calculate the LD50 values, a preceding screening with small groups of two or three animals was carried out.

Doses:
296, 395, 500, 650, and 845 mg/kg
No. of animals per sex per dose:
10 males
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
Statistics:
The LD50 values were calculated according to the Litchfield and Wicoxon method.*

*Reference:
J.T. Kitchfield and F. Wilcoxon, A simplified method of evaluating dose-effect experiments. J. Pharmacol. Exp. Ther., 96 (1949) 99 - 113
Sex:
male
Dose descriptor:
LD50
Effect level:
448 mg/kg bw
Based on:
test mat.
95% CL:
>= 412.2 - <= 486.9
Remarks on result:
other: Dose level equivalent to 288.5 mg/kg bw of vanadium oxide sulfate (calculated from the data given in the publication); Dose level equivalent to 90.3 mg/kg bw vanadium (83.1 - 98.1; calculated)
Mortality:
The following relation between dosage and mortality in rats was seen (alive/tested):
296 mg/kg: 10/10
395 mg/kg: 6/10
500 mg/kg: 4/10
650 mg/kg: 3/10
845 mg/kg: 0/10
The majority of deaths were observed within the first 48 hours. Few deaths occurred between the second and the seventh days. No death occurred after 7 days.
Clinical signs:
The highest dosage of the vanadium compound caused intense diarrhoea, irregular respiration, increased cardiac rhythm and ataxia.
The most noticeable physical signs observed were: decreased locomotor activity, paralysis of the hind legs and decreased sensitivity to pain.
Most clinical and physical signs appeared within 24 hours, and most of them disappeared 48 hours after the administration of the vanadium compound.
Body weight:
no data
Gross pathology:
no data
Interpretation of results:
Toxicity Category IV
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
LD50 (male rats): 448 mg/kg bw (vanadium oxide sulfate pentahydrate)
According to the EC-Commission directive 67/548/EEC and its subsequent amendments, the test substance is classified as harmful if swallowed.
According to the EC-Regulation 1272/2008 and subsequent regulations, the test item is classified as Category 4.

LD50 (male rats) = 288.5 mg/kg (vanadium oxide sulfate)(calculate from data of the pentahydrate)
According to the EC-Commission directive 67/548/EEC and its subsequent amendments, the test substance is classified as harmful if swallowed.
According to the EC-Regulation 1272/2008 and subsequent regulations, the test item is classified as Category 3.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
288.5 mg/kg bw
Quality of whole database:
The study is reliable with acceptable restrictions. The study was conducted with vanadium oxide sulphate pentahydrate (least hydrated form commercially available). The LD50 value is conservatively calculated for vanadium oxide sulphate anhydrous.

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:
2010-03-02 to 2011-06-01
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 436 (Acute Inhalation Toxicity: Acute Toxic Class Method)
Version / remarks:
2009-09-07
Deviations:
yes
Remarks:
Please refer to "Principles of method if other than guidelines" below.
Principles of method if other than guideline:
The limit test of this study (2 mg/L) was conducted in compliance with the requirements of the following test guidelines with the exception that body weights were not obtained 1 and 3 days after exposure: 1) US EPA Health Effects Testing Guideline, OPTTS 870.1300, entitled Acute Inhalation Toxicity, 1998 and 2) OECD test guideline 403 (1981). In order to reduce animal use and to provide an acute inhalation toxicity estimate and information for the Global Harmonized System (GHS) of classification and labelling for the test substance, all subsequent exposures were conducted in compliance with OECD test guideline 436 (2009) (with exception that body weights were not obtained 1 and 3 days after exposure). The initial subsequent exposures were determined by the study director in conjunction with the sponsor and any subsequent exposures were determined according to the scheme in Annex 3c of the OECD 436 test guideline.
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
no
Specific details on test material used for the study:
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: at room temperature in the original container
Species:
mouse
Strain:
B6C3F1
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories (Raleigh, NC)
- Age at receipt: 51 and 56 days
- Weight at receipt: 16 to 28 g
- Housing: animal were double-housed and then after randomization, single-housed, in stainless steel cages suspended over absorbent paper cage boards
- Diet (ad libitum, except during inhalation exposure): Certified Rodent Chow 5002 meal (PMI Nutrition International, Inc., Brentwood, MO)
- Water (ad libitum, except during inhalation exposure): City of Chicago water
- Quarantine period: approx. one week
During quarantine the mice were observed daily for signs of disease and general unthriftiness.
To condition the animals to placement and restraint in the nose-only holding tubes (CH Technologies, U.S.A., Westwood, NJ) and to reduce stress during the exposure phase, the animals were placed in the holding tubes over three days according to the following schedule: one hour on Day 1, two hours on Day 2 and three hours on Day 3 prior to their exposure.

ENVIRONMENTAL CONDITIONS
- Temperature: 18.0 to 22.0°C
- Relative humidity: 30 to 43%
- Air changes: minimum of 10 air changes per hour
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose only
Vehicle:
other: water
Mass median aerodynamic diameter (MMAD):
>= 1.68 - <= 1.93 µm
Geometric standard deviation (GSD):
>= 1.61 - <= 2.93
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus/Method of holding animals in test chamber: a 52-port, flow-past nose-only inhalation exposure chamber (Lab Products Inc., Seaford, DE) was used. The animals were restrained in nose-only exposure animal holding tubes (CH Technologies, U.S.A., Westwood, NJ). Each tube was placed in a pre-designated port of the inhalation exposure chamber.

- System of generating particulates/aerosols: the test atmosphere was created by generating an aerosol (with filtered air) of the test substance using a 6-Jet Collison Nebulizer (BGI Incorporated, Waltham, MA) positioned in the chamber. The test substance was weighed, dissolved in ASTM water, and poured into the Collison Nebulizer jar. The nebulizer used compressed air to aspirate the solution into a sonic velocity gas jet which impacted against a barrier (the inside of the jar) to remove the larger fraction of droplets. The resulting test atmosphere entered a mixing plenum where it may have been diluted with breathable quality compressed air in order to achieve the target concentration prior to introduction to the nose-only inhalation exposure chamber. The exhaust from the exposure chamber was moved through a high efficiency particulate air (HEPA) filter by a ring compressor and exhausted outside the building. Inlet and exhaust flows to and from the chamber were controlled and continuously monitored by rotometers.

T90 time was assessed to be approximately 30 seconds.

- Temperature, humidity, oxygen percentage in air chamber: oxygen percentage was measured once during the exposure with an Altair Oxygen Sensor and Detector (MSA Instrument Division, Pittsburgh, PA).
Inhalation exposure chamber temperature and relative humidity were monitored with a hand-held thermohygrometer (model # 8721, Control Company, Fisher Scientific, Friendswood, TX) and were recorded at approximately half-hour intervals during exposure.
Temperature (mean ± SD):
2.17 mg/L: 22.9°C ± 0.16
1.09 mg/L: 22.9°C ± 0.23
0.53 mg/L: 22.3°C ± 0.16
0.05 mg/L: 22.5°C ± 0.16
Relative humidity (mean ± SD):
2.17 mg/L: 99.9% ± 0.00%
1.09 mg/L: 99.9% ± 0.00%
0.53 mg/L: 99.9% ± 0.00%
0.05 mg/L: 58.8% ± 2.29
Oxygen (%):
2.17 mg/L: 20.8%
1.09 mg/L: 20.8%
0.53 mg/L: 20.8%
0.05 mg/L: 20.8%

- Method of particle size determination: aerosol particle size was monitored at least once per two hours during the exposure with a quartz crystal microbalance (QCM) Cascade Impactor (California Measurements Inc., Sierra Madre, CA). The mass median aerosol diameter (MMAD) and geometric standard deviation (GSD) were calculated from the mass accumulated on each stage of the QCM.

TEST ATMOSPHERE
- Brief description of analytical method used: the concentration of the test substance in the test atmosphere was monitored gravimetrically by filter-collected samples. One sample was taken from the breathing zone of the animals every hour of exposure. The gravimetric sampling train consisted of a pre-weighed filter in a series with a dry-gas meter connected to a constant flow vacuum pump. The dry-gas meter measured the corresponding volume of chamber air sampled and the weight to volume ratio was determined to obtain the aerosol mass concentration. All filter-collected samples were weighed, and all filters were analysed chemically by ICP-MS for determination of vanadium content and to calculate the test atmosphere concentration.
Aerosol concentration was monitored with a real-time aerosol sensor (model #pDR-1000AN, MIE, Inc. Bedford, MA). The sensors were employed as a real-time indicator of short term changes in aerosol concentration.
- Samples taken from breathing zone: yes

TEST ATMOSPHERE
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.):
2.17 mg/L: 1.93 µm (GSD: 1.61 to 1.88)
1.09 mg/L: 1.81 µm (GSD: 2.39 to 2.44)
0.53 mg/L: 1.84 µm (GSD: 1.73 to 1.92)
0.05 mg/L: 1.68 µm (GSD: 2.75 to 2.93)

A group of five male and five female mice was exposed to an aerosol of vanadyl sulfate in a nose-only inhalation exposure chamber for 4 hours at a concentration of 2.0 mg/L. Due to the mortality observed at the 2.0 mg/L exposure concentration an additional group of three male and three female mice was exposed to an aerosol of vanadyl sulfate in a nose-only inhalation exposure chamber for 4 hours at a concentration of 1.0 mg/L. Due to the mortality observed at the 1.0 mg/L exposure concentration an additional group of three male and three female mice was exposed to an aerosol of vanadyl sulfate in a nose-only inhalation exposure chamber for 4 hours at a concentration of 0.5 mg/L. Due to mortality observed at the 0.5 mg/L exposure concentration a fourth group of three male and three female mice was exposed to an aerosol of vanadyl sulfate in a nose-only inhalation exposure chamber for 4 hours at a concentration of 0.05 mg/L. Surviving animals were observed for a 14-day post-exposure period.
Analytical verification of test atmosphere concentrations:
yes
Remarks:
Please refer to the field "Details on inhalation exposure" above.
Duration of exposure:
4 h
Concentrations:
actual concnetrations: 0.05, 0.53, 1.09, and 2.17 mg/L
target concentrations: 0.05, 0.5, 1.0 and 2.0 mg/L
No. of animals per sex per dose:
2.17 mg/L: 5 males / 5 females
1.09 mg/L: 3 males / 3 females
0.53 mg/L: 3 males / 3 females
0.05 mg/L: 3 males / 3 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: animals were observed for signs of toxicity during the exposure, immediately after the exposure and at least once daily during the 14-day post-exposure observation period. Body weights were determined one day after animal receipt, prior to randomization, on Day 1 prior to exposure, and one week after exposure. All surviving animals were weighed on the day of their scheduled necropsy, prior to euthanasia. Body weights of animals found dead were also collected prior to necropsy. Body weight changes were calculated for mice surviving more than 24 hours.

- Necropsy of survivors performed: yes
All exposed animals, including those found dead, were subjected to necropsy. At the end of the observation period, all surviving animals were euthanized and subjected to a necropsy. The necropsy included examination of all body surfaces and openings, and examining the external appearance of the brain, heart, liver, kidneys, lungs (especially any changes in the immediately associated and exposed respiratory tract), gastrointestinal tract, spleen, gonads and the urinary bladder. The gastrointestinal tract and the urinary bladder were opened and examined if lesions were present. Respiratory tracts were saved and fixed, abnormal tissue were also retained for possible pathologic evaluation, when considered needed. All decedents were also subject to the necropsy procedures described above.
Statistics:
The LC50 value was estimated based on the mortality results according to the shceme in Annex 3c of the OECD 436 test guideline (adopted September 2009).
Preliminary study:
not applicable
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
0.125 other: mg/L (actual conc.)
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
other: LC50 cut off value according to the scheme in Annex 3c of the OECD 436 (2009)
Mortality:
- 2.17 mg/L: all mice, with the exception of one female, died within five days of being exposed to the test substance (four males on the day of exposure [Day 1], one male and one female on Day 2, one female on Day 3, and two females on Day 5).
- 1.09 mg/L: all six mice died within three days of being exposed to the test substance (two males and two females on the day of exposure [Day 1], and one male and one female on Day 3).
- 0.53 mg/L: all six mice died within three days of being exposed to the test substance (two males on the day of exposure [Day 1], one male on Day 2 and three females on Day 3).
- 0.05 mg/L: no animals died after exposure to the test substance
Clinical signs:
other: Wet inguinal fur was seen following exposures on Day 1 for those animals that survived past Day 1. Skin/fur discolouration (blue) was observed in one or two animals on Day 1 following exposure to 1.0 and 0.5 mg/L of the test substance. Other clinical sign
Body weight:
All surviving mice gained weight during the study.
Gross pathology:
- 2.17 mg/L: discoloured lungs (pale pink to dark red, some mottled and some with foci) were observed in all animals, with the exception of one male and one female that had no gross lesions.
- 1.09 mg/L: discoloured lungs (pale pink to dark red, one mottled and one with a red focus) were observed in all animals, with exception of one male that had no gross lesions.
- 0.53 mg/L: mottled and/or discoloured lungs (pale pink to dark red) were observed in all animals, with the exception of one female that had no gross lesions.
- 0.05 mg/L: no gross lesions were observed at necropsy in any animal.
Interpretation of results:
Category 2 based on GHS criteria
Conclusions:
LC50 (4 hours, male and female mice) = 0.125 mg/L (cut off value)
According to the Regulation (EC) No 1272/2008 and subsequent adaptations, the substance is acutely toxic via the inhalation route (Category 2; H330).
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LC50
Value:
125 mg/m³
Quality of whole database:
Acute, nose-only inhalation testing was performed in mice and rats of both sexes in GLP-compliant studies. VOSO4 was administered as an aerosol in water. Thus,results are not directly relevant for aerosolized particles. A monomodal particle-size distribution with an MMAD that is beyond the common inhalability of rats is displayed by vanadium oxide sulphate pentahydrate and indicates a low inhalative potential. Vanadium oxide sulphate is manufatured and marked in solution only and as such needs to be classified and labelled accordingly.

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:
LD50
Value:
4 450 mg/kg bw
Quality of whole database:
A study performed by Kinkead & Wolfe (1980) indicated that vanadium oxide sulphate is not acute toxic via the dermal route (LD50 4450 mg/kg bw.). The study was rated with RL3 since vanadium oxide sulphate was not moistened before application to skin. Hence, the result should only be used for orientating purposes. Skin contact in production and/or use cannot be ruled out. 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”.

Additional information

Justification for classification or non-classification

The available information indicates that vanadium oxide sulphate (anhydrous) is acutely toxic via the oral route (LD50 < 300 mg/kg bw.). Therefore, classification of vanadium oxide sulphate for acute toxicity is required according to Directive 67/548/EEC and Regulation (EC) 1272/2008.

Vanadium oxide sulphate (anhydrous) should be classified as "Acute Tox. 3 and labelled with H301: Toxic if swallowed; in accordance with Regulation (EC) 1272/2008.

Acute, nose-only inhalation testing was performed in mice and rats of both sexes in GLP-compliant studies and VOSO4 was administered as an aerosol in water. Thus, results are not directly relevant for aerosolized particles. A monomodal particle-size distribution with an MMAD that is beyond the common inhalability of rats is displayed by vanadium oxide sulphate pentahydrate and indicates a low inhalative potential. Vanadium oxide sulphate is manufatured and marked in solution only and as such needs to be classified and labelled accordingly.

Specific target organ toxicant (STOT) – single exposure

The classification criteria according to Regulation (EC) 1272/2008 as specific target organ toxicant (STOT) – single exposure, oral, inhalation, or dermal are not met since adverse health effects, including reversible and irreversible, were not observed immediately or delayed after exposure except the effects that lead to animal death at concentrations relevant for C&L as acute toxic via oral route.