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Administrative data

Description of key information

Vanadium dioxide is not acutely toxic via the oral, dermal, or inhalation route.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
1991-08-19 to 1991-09-30
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
adopted 24 February 1987
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Remarks:
The study states that the study was performed according to eg. "Good Laboratory Practice" Regulations of the EEC enacted in Germany in the "Chemikaliengesetz" dated March 14th, 1990, BGBL.I, pp. 521, 1990.
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
- Source: Lippische Versuchstierzucht HAGEMANN GmbH D-4923 Extertal 1
- Age at study initiation: approx. 40 - 60 days
- Weight at study initiation: 161 g - 200 g
- Fasting period before study: approx. 16 hours
- Housing: Animals were kept in groups of two or three in MAKROLON cages (type III). Granulated textured wood was used as bedding material (Granulat Typ A2, supplier: Messrs. BRANDENBURG, Inh. H.Brandenburg, D-2849 Goldenstedt).
- Diet: Standardized diet for rats 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
No further significant information on test animals was stated.
Route of administration:
oral: gavage
Vehicle:
other: hydroxypropyl-methylcellulose gel
Details on oral exposure:
VEHICLE
V2O3 technical grade pulverised was suspended in 0.8 % aqueous hydroxypropyl-methylcellulose gel (Methocel E 4 M).
Batch No.(Vehicle): MM 84097413
MAXIMUM DOSE VOLUME APPLIED: The volume of application was 50 ml/kg b.w. for all groups. (The dose interval factors were 1.21 and 1.47,)
No further significant information on details on oral exposure was stated.
Doses:
4640, 6810, 10000 and 14700 mg V2O3 technical grade pulverised/kg b.w.; 5620 mg/kg b.w. (only 5 females)
No. of animals per sex per dose:
5 males / 5 females
Control animals:
not specified
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 min, as well as 3 h, 6 h and 24 h 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. Observations on mortality were made at least once daily with appropriate actions taken to minimize 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.
- 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.
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: Attention was also paid to possible tremor, convulsions, salivation, diarrhoea, lethargy, sleep and coma. Changes in weight were calculated and recorded when survival exceeds one day.
No further significant information on details on study design was stated.
Statistics:
The LD50 was calculated by regression analysis.
Sex:
male
Dose descriptor:
LD50
Effect level:
8 713.1 mg/kg bw
Remarks on result:
other: Slope: 17.95; No estimation of the confidence limits possible, due to low number of animals employed and the steepness of the mortality curve.
Sex:
female
Dose descriptor:
LD50
Effect level:
5 639 mg/kg bw
Remarks on result:
other: Slope: 59.92; No estimation of the confidence limits possible, due to the low number of animals employed and the steepness of the mortality curve.
Mortality:
Lowest lethal dose: 5620 mg/kg b.w. p.o. for females and 6810 mg/kg b.w. p.o. for males. Animals died between 4 hours and 48 hours, where observed in abdominal position and comatose condition. Animals died between 4 hours and 48 hours.
Dose level and number of dead animals:
4640 mg/kg b.w. p.o.: 0/5 males; 0/5 females
5620 mg/kg b.w. p.o. (only females): 2/5 females
6810 mg/kg b.w. p.o.: 1/5 males; 5/5 females
10000 mg/kg b.w. p.o.: 1/5 males; 5/5 females
14700 mg/kg b.w. p.o.: 5/5 males; 5/5 females
Clinical signs:
Animals showed symptoms between 60 minutes and day 2.
5620 mg/kg b.w. p.o. (only females): slightly reduced motility (5/5 females), slight ataxia (5/5 females) and slight dysnoea (5/5 females)
6810 mg/kg b.w. p.o.: slightly reduced motility (5/5 males; 5/5 females), slight ataxia (5/5 males; 5/5 females), slight dyspnoea (5/5 males; 5/5 females)
10000 mg/kg b.w. p.o.: slightly to moderate reduced motility (5/5 males; 5/5 females), slight to moderate ataxia (5/5 males; 5/5 females), slight to moderate dyspnoea (5/5 males; 5/5 females)
14700 mg/kg b.w. p.o.: moderatly reduced motility (5/5 males; 5/5 females), moderate ataxia (5/5 males; 5/5 females), slight dyspnoea (5/5 males; 5/5 females), slightly reduced muscular tonus (5/5 males; 5/5 females)
Body weight:
There was no inhibition of body weight gain in males or females.
Gross pathology:
Autopsy of deceased animals:
6810 mg/kg b.w. p.o: stomach distended (1/1 male; 2/5 females); stomach and intestine distended (3/5 females)
10000 mg/kg b.w. p.o.: stomach and intestine distended ( 1/1 male, 4/5 females); liver pale (1/1 male; 1/5 females); intestinal wall reddened (1/5 females)
Autopsy of survivng animals: no pathological findings
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
According to the EEC-Commission directive of July 29th, 1983 on the approximation of the laws, regulations and administrative provisions relating to the classification, packaging and labelling of dangerous substances (83/467/EEC) and the results obtained under the present test conditions the test substance can be classified as relatively non-toxic (not classified) (LD50: > 2000 mg/kg b.w. p.o.) in the acute oral toxicity study in the rat.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw
Quality of whole database:
The GLP study is reliable with acceptabel restrictions.

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:
2013-01-08 to 2013-03-04
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 436 (Acute Inhalation Toxicity: Acute Toxic Class Method)
Version / remarks:
adopted September 7, 2009
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: OECD Series on Testing and Assessment No. 125, Document No. ENV/JM/MONO (2010) 16, June 01, 2010
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Remarks:
signed 2009-11-12
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
other: Crl: CD(SD)
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories, Research Models and Services, Germany GmbH, Sandhofer Weg 7, 97633 Sulzfeld, Germany
- Age at study initiation: males: 8 weeks; females: 9 weeks
- Weight at study initiation: males: 235 - 247 g; females: 218 - 238 g
- Fasting period before study: feeding was discontinued approx. 16 hours before exposure; only tap water was then available ad libitum.
- Housing: granulated textured wood (Granulat A2, J. Brandenburg, 49424 Goldenstedt, Germany) was used as bedding material for the cages. During the 14-day observation period, the animals are kept by sex in groups of 3 animals in MAKROLON cages (type III plus).
- Diet (e.g. ad libitum): commercial diet, ssniff® R/M-H V1534 (ssniff Spezialdiäten GmbH, 59494 Soest, Germany)
- Water (ad libitum): drinking water
- Acclimation period: at least 5 adaptation days

The animals were randomised before use. They were acclimatised to the test apparatus for approx. 1 hour on 2 days prior to testing. The restraining tubes did not impose undue physical, thermal or immobilization stress on the animals.

ENVIRONMENTAL CONDITIONS
- Temperature: 22 °C ± 3 °C (maximum range)
- Relative humidity: 55 % ± 15 % (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: the study was carried out using a dynamic inhalation apparatus (RHEMA-LABORTECHNIK, 65719 Hofheim/Taunus, Germany) (air changes/h (≥ 12 times)) with a nose-only exposure of the animals according to KIMMERLE & TEPPER. The apparatus consists of a cylindrical exposure chamber (volume 40 L) which holds 10 animals in pyrex tubes at the edge of the chamber in a radial position.

- System of generating particulates/aerosols: the dust of the test material was generated with a rotating brush dust generator (RBG 1000, PALAS GmbH Partikel und Lasermesstechnik,76229 Karlsruhe, Germany).
The generator was fed with compressed air (5.0 bar) from a compressor (ALUP Kompressorenfabrik, 73257 Köngen, Germany) (air was taken from the surrounding atmosphere of the laboratory room and filtered using at in-line disposable gas-filter).
At the bottom of the exposure chamber, the air was sucked off at a lower flow rate than it was created by the dust generator in order to produce a homogenous distribution and a positive pressure in the exposure chamber (inflow 900 L/h, outflow 800 L/h).
A manometer and an air-flow meter (ROTA Yokogawa GmbH & Co. KG, 79664 Wehr/Baden, Germany) were used to control the constant supply of compressed air and the exhaust, respectively. Flow rates were checked hourly and the corrected if necessary.
The exhaust air was drawn through gas wash-bottles.

- Method of particle size determination: an analysis of the particle size distribution was carried out twice during 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 drawn through the cascade impactor for 5 minutes at a constant flow rate of 5 L/min. The slides were removed from the impactor and weighed on an analytical balance (SARTORIUS, type 1601 004, precision 0.1 mg). Deltas of slides’ weight were determined.
The mass median aerodynamic diameter (MMAD) was estimated by means of non-linear regression analysis. 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.
The Geometric Standard Deviation (GSD) of the MMAD was calculated from the quotient of the 84.1 % - and the 50 %- mass fractions, both obtained from the above mentioned non-linear regression analysis.
In addition, a sample of approx. 10 g test material was taken from the exposure chamber to determine the median physical particle size with a CILAS 715 by My-Tec, 91325 Adelsdorf, Germany. This determination was non-GLP.

- Temperature, humidity, pressure in air chamber, oxygen content and carbon dioxide concentration: the oxygen content in the inhalation chamber was 21%. It was determined at the beginning and at the end of the exposure with a DRÄGER Oxygen-analysis test set (DRÄGER Tube Oxygen 67 28 081). Carbon dioxide concentration did not exceed 1%.
Temperature (20.8 °C ± 0.1 °C (main study) or 20.9 °C ± 0.1 °C (satellite group)) and humidity (61.4 % ± 0.1 % (main study) or 55.0 % ± 0.1 % (satellite group)) were measured once every hour with a climate control monitor (testo 175-HZ data logger).

The whole exposure system was mounted in an inhalation facility to protect the laboratory staff from possible hazards.

Exposition started by locating the animals into the exposure chamber after equilibration of the chamber concentration for at least 15 minutes (t95 approximately 8 minutes).

Before initiating the study with the animals, a pre-test was carried out with the exposure system in order to verify that under the experimental settings chosen, the limit concentration of 5 mg/L air could be achieved by gravimetric analysis.

The tests with the main study animals and the recovery animals were conducted in the same inhalation chamber but on different days. Between the exposure times the chamber was cleaned carefully.

TEST ATMOSPHERE
- Brief description of analytical method used: the actual dust concentration in the inhalation chamber was measured gravimetrically with an air sample filter (Minisart SM 17598 0.45 μm) and pump (Vacuubrand, MZ 2C (Membrane Pump,Vacuubrand GmbH + Co. KG, 97877 Wertheim/Main, Germany)) controlled by a rotameter. Dust samples were taken once every hour during the exposure. For that purpose, a probe was placed close to the animals' noses and air was drawn through the air sample filter at a constant flow of air of 5 L/min for 1 minute. The filters were weighed before and after sampling (accuracy 0.1 mg).
Individual chamber concentration samples did not deviate from the mean chamber concentration by more than 1%.
- Samples taken from breathing zone: yes

TEST ATMOSPHERE
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.):
Main study: 2.340 µm (GSD: 3.19)
Satellite group: 2.464 µm (GSD: 3.12)
No smaller GSDs could be obtained with the test item supplied.
Analytical verification of test atmosphere concentrations:
yes
Remarks:
see above ("Details on inhalation exposure")
Duration of exposure:
4 h
Concentrations:
Main study (limit test):
- actual concentration: 5.05 ± 0.02 mg/L air
- nominal concentration: 7.78 mg/L air
Satellite group:
- actual concentration: 5.07 ± 0.03 mg/L air
- nominal concentration: 7.78 mg/L air
No. of animals per sex per dose:
Main study (limit test):
3 males / 3 females
Satellite group:
3 males / 3 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 24 hours (satellite group) and 14 days (main study)

- Frequency of observations and weighing: during the exposure period the animals were observed frequently. Following exposure, observations were made at least twice on the day of exposure and at least once each day and recorded systematically. A careful clinical examination was made at least once each day thereafter for a period of 14 days. Observations on mortality were made at least once daily (in the morning starting on test day 2) 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.
Cageside observations included, but were not limited to: changes in the skin and fur, eyes, mucous membranes, respiratory, circulatory, autonomic and central nervous system, as well as somatomotor activity and behaviour pattern.
Particular attention was directed to observation of tremor, convulsions, salivation, diarrhoea, lethargy, sleep and coma. The animals were also observed for possible indications of respiratory irritation such as dyspnoea, rhinitis etc.
Individual weights of animals were determined once during the acclimatisation period, before and after the exposure on test day 1, on test days 3, 8 and 15. Changes in weight were calculated and recorded when survival exceeded one day. At the end of the test, all animals were weighed and sacrificed.

- Necropsy of survivors performed: yes
Necropsy of all main study and satellite animals (3 + 3 males and 3 + 3 females) was carried out and all gross pathological changes were recorded:
- Satellite animals: necropsy at 24 hours after cessation of exposure, as this is likely to be the time at which any signs of respiratory irritation would have manifested;
- Main study animals: necropsy at the end of the 14-day observation period, also to assess whether any respiratory tract irritation persists or abates.

- Histopathology:
All main study and satellite animals were subjected to the same level of histopathological examination upon necropsy at the end of the respective observation period. During histopathology, attention was paid to alterations that might be indicative of respiratory irritation, such as hyperaemia, oedema, minimal inflammation, thickened mucous layer.
The following organs of all animals were fixed in 10 % (nose, i.e. head without brain, eyes and lower jaw) or 7 % (other organs) buffered formalin for histopathological examination:
- Nasal cavity, nasopharynx and paranasal sinus:
The tip and level 1 of the nose were taken from a cut just anterior to the incisor teeth. With tip removed, level 2 was taken approximately 2 mm posterior to free tip of the incisor teeth. Level 3 was cut through the incisive papilla. Level 4 was cut through the middle of the second palatal ridge, which is located just anterior to the molar teeth. Level 5 was cut through the middle of the molar teeth. All sections were embedded face down to yield a section from the anterior section, except the nose tip was embedded posterior surface down.
- Larynx
- Trachea
- Lungs (five levels)
Paraffin sections were prepared of all above mentioned organs and stained with haematoxylin-eosin.
Statistics:
Since no animal died prematurely, the calculation of an LC50 was not required.
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 5.05 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Mortality:
No animal died prematurely.
Clinical signs:
other: Under the present test conditions, a 4-hour inhalation exposure to Vanadium dioxide at a concentration of 5.05 mg/L air revealed slight ataxia on test day 1 immediately after the end of exposure until 30 minutes post exposure, slight dyspnoea (reduced fre
Body weight:
No influence on body weight gain was observed.
Gross pathology:
Macroscopic changes in the nasal cavity and lungs: marbled lungs were observed in all animals of the main study (14-day sacrifice) and in all satellite animals (24-hour sacrifice). Oedematous lungs were observed in 2 of 3 male or 3 of 3 female animals of the main study and 2 of 3 male or 3 of 3 female satellite animals, each. Lungs reduced in size were observed in all 6 animals of the main study.
Other findings:
- HISTOPATHOLOGY:

Microscopic changes in the nasal cavity and lungs

1. Test item-related histopathological changes:
The histomorphological examination of the trachea, larynx, lungs and the nose of male and female rats after inhalation of Vanadium dioxide did not reveal any morphological changes, considered to be related to the inhalation of the test item, in the main study animals (14-day sacrifice) and in the satellite animals (24-hour sacrifice).

2. Non-test item-related histopathological changes:
Male and female animals of the main study (14-day sacrifice) and the satellite group (24-hour sacrifice):
- Observations made for the Nose (five levels):
The nasal cavity of level 1 to 5 revealed a normal squamous epithelium and a normal respiratory epithelium. The normal respiratory epithelium partially containing cilia consisted of three major cell types: the basal cells above the basement membrane, the ciliated epithelial and the secretory goblet cells.
Some rats showed minimal to mild subepithelial lympho-histiocytic infiltrations in the respiratory epithelium or lymphocytic follicular hyperplasia for nose levels 2 to 5.
A normal olfactory epithelium with 5 to 7 nuclear layers, normal basal cells, olfactory sensory cells and sustentacular cells was observed in all animals in level 2 to 5.
- Observations made for the lungs (five levels):
All 5 lung localizations revealed a normal lung structure with normal alveolar lumina and pneumocytes from type 1 and 2. A minimal to mild congestion and in two rats a pneumonic foci with neutrophilic granulocytes in the alveolar lumen are coincidental findings and thus not test item-related.
The trachea of some male and female animals revealed focal minimal to mild subepithelial lympho-histiocytic inflammatory reactions and some lymphocytic follicles with normal epithelial cells. The epithelium of the larynx was normal without inflammatory reactions.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
LC50 (rats, 4 hours) > 5.05 mg/L air (actual concentration)
Based on the results of the histopathological and macroscopic investigations, vanadium carbide does not require classification for respiratory irritation.
According to the EC-Commission directive 67/548/EC and its subsequent amendments, the test substance is not classified as acute toxic via the inhalation route or as respiratory irritant.
Also, according to the EC Regulation 1272/2008 and subsequent regulations, the test item is not classified as acute toxic via the inhalation route or as specific target organ toxicity - single exposure.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating conc.
Value:
5 050 mg/m³
Quality of whole database:
The GLP study is reliable without restrictions.

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
1991-08-21 to 1991-09-4
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
adopted 24 February 1987
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Remarks:
The study states that the study was performed according to eg. "Good Laboratory Practice" Regulations of the EEC enacted in Germany in the "Chemikaliengesetz" dated March 14th, 1990, BGBL.I, pp. 521, 1990.
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Lippische Versuchstierzucht HAGEMANN GmbH, D- 4923 Extertal 1
- Age at study initiation: approx. 40 - 60 days
- Weight at study initiation: 160 - 199 g
- Fasting period before study: approx. 16 hours
- Housing: Animals were kept in groups of two or three in MAKROLON cages (type III). Gradulated textured wood was used as bedding material (Granulat Typ A2, supplier: Messrs. BRANDENBURG, Inh. H.Brandenburg, D-2849 Goldenstedt)
- Diet: Standardized diet for rats 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
No further information was stated on test animals.
Type of coverage:
occlusive
Vehicle:
other: hydroxypropyl-methylcellulose gel
Details on dermal exposure:
TEST SITE
The test substance was applied on the shaved intact dorsal skin of rats (5 X 6 cm, 1/10 of body surface). The hair on the site of application was clipped with hair-clippers without causing injury approximately 24 hours before application. The site was situated on the animal's back between the fore and hind extremities and had an area of approx. 5 X 6 cm.
The test substance was applied to 8 layers of gauze and to the application site. The patch was covered with a plastic sheet and secured with adhesive plaster.

REMOVAL OF TEST SUBSTANCE
- Time after start of exposure: At the end of the exposure period, residual substance was removed with tepid tap water.

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): The volume of application was 20 ml/kg b.w.. The dose interval factor was 1.25.

VEHICLE
0.8 % aqueous hydroxypropyl-methylcellulose gel (Methocel E 4 M) served as vehicle for V2O3 technical grade pulverised.
Batch No.(Vehicle): MM 84097413
No further significant information on details on dermal exposure was stated.
Duration of exposure:
24 hours
Doses:
2000 mg and 2500 mg V2O3 technical grade pulverised/kg b.w.
No. of animals per sex per dose:
5 males / 5 females
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observations were performed immediatly, 5, 15, 30 and 60 min, as well as 3 h, 6 h and 24 h after administration. During the follow-up period changes in skin and fur, eyes and mucous membranes, and the respiratory, circulatory, autonomic and central nervous system and somatomotor activity and behaviour pattern were observed at least once a day until all symptoms have subsided, thereafter each working day. Attention was also paid to possible tremors, 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.
- 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 microscoic examination of all organs which show evident lesions was performed. Autopsy and macroscopic inspection of the animals which died prematurely were carried out as soon as possible after exitus.
- Other examinations performed: Changes in weight were calculated and recorded when survival exceeds one day. The skin was observed for the development of erythema and oedema and was rated as follows:
Erythema
0 = no erythema
1 = very slight erythema (barely perceptible)
2 = well-defined erythema
3 = moderate to severe erythema
4 = severe erythema (beet redness) to slight eschar formation (injuries in depth)
Oedema
0 = no oedema
1 = very slight oedema (barely perceptible)
2 = slight oedema (edges of area well defined by definite raising)
3 = moderate oedema (raised approx. 1 mm)
4 = severe oedema (raised more than 1 mm and extending beyond the area of exposure)
No further significant information on study design was stated.
Statistics:
The LD50 could not be calculated because none of the animals died prematurely.
Sex:
male
Dose descriptor:
LD50
Effect level:
> 2 500 mg/kg bw
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 500 mg/kg bw
Mortality:
None of the animals died prematurely.
Clinical signs:
Under the present test conditions no local or systemic intolerance reactions were observed up to the highest tested dose-level of 2500 mg V2O3 technical grade pulverised/kg b.w. by dermal administration to rats.
Body weight:
There was no inhibition of body weight gain in male or female rats.
Gross pathology:
There were no pathological findings in male or female rats.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the present test conditions dermal administration of up to 2500 mg V2O3 technical grade pulverised/kg b.w. did not cause any toxic effects in rats. According to directive 83/467/EEC, V2O3 technical grade pulverised can be classified as relatively non-toxic (not classified) in the acute dermal toxicity study in the rat.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw
Quality of whole database:
The GLP study is reliable with acceptabel restrictions.

Additional information

Speciation:

Upon dissolution, vanadium substances transform inartificial body fluids, including PBS, sweat, gastric juice and lung fluid, predominantly to the pentavalent form,except in artificial lysosomal fluid; here, even pentavalent forms are converted almost completely to tetravalent species already after a short period of time (for more information on in vitro bioaccessibility testing, please refer IUCLID section 7). Thus, it can be assumed that vanadium speciation in body fluids is controlled by the conditions of the respective medium but not by the vanadium source.

Read across concept:

The toxicity of vanadium dioxide may reasonably be considered to be determined bythe bioavailability ofvanadium. As a first surrogate for bioavailability, the water solubility of a test substance may be used. Vanadium dioxide and vanadium trioxide are moderately soluble in water (0.471 g/L at 20°C/pH 4.2; 0.35 g/L at 20°C/pH 3, respectively)whereas divanadium pentaoxide is soluble at 0.92g/L at 20°C/pH 2.7.

 

In sum, read-across from vanadium compounds with similar water solubility is considered acceptable because toxicokinetic data for all substances indicates a similar bioavailability.

Acute oral toxicity (read across from divanadium trioxide)

Vanadium dioxide is non-toxic if swallowed as the LD50 (rats, females) > 2000 mg/kg bw.

Acute inhalation toxicity

Vanadium dioxide is non-toxic if inhaled as the LC50 (rats, females) > 5000 mg/m3.

Acute dermal toxicity (read across from divanadium trioxide)

Vanadium dioxide is non-acutely toxic via dermal route as the LD50 (rats, females) > 2500 mg/kg bw.


Justification for selection of acute toxicity – oral endpoint
No study performed with vanadium dioxide available. However, read across to a reliable GLP study performed with divanadium trioxide is fully justified.

Justification for selection of acute toxicity – inhalation endpoint
There is only one reliable study available.

Justification for selection of acute toxicity – dermal endpoint
A study performed with vanadium dioxide is not available. However, read-across to a reliable GLP-conform study of divanadium trioxide is fully justified. Nevertheless, recalculation of the LD50 of divanadium trioxide to vanadium dioxide would result in a LD50 < 2000 mg/kg bw. In addition, a study of divanadium pentaoxide, a vanadium oxide with a higher vanadium content, is included to support the discriminating dose of vanadium dioxide for acute dermal toxicity of 2000 mg/kg bw. The recalculation of the LD50 of divanadium pentaoxide to vanadium dioxide results in a LD50 > 2000 mg/kg bw. Thus, a potential for acute toxicity via the dermal route can be excluded for vanadium dioxide.

Justification for classification or non-classification

The available information indicates that vanadium dioxide is not acutely toxic or harmful. Therefore, classification of vanadium dioxide for acute toxicity is not required according to Directive67/548/EEC and Regulation (EC) 1272/2008.

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 any adverse health effects, including reversible and irreversible, were not observed immediately or delayed after exposure.

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