Registration Dossier

Administrative data

Description of key information

Acute oral toxicity: LD50 = 467 mg/kg bw (OECD 401; GLP; female rats)

Acute inhalation toxicity: LC50 > 4.3 mg/L air (analytical) (OECD 436; GLP)

Acute dermal toxicity: LD50 > 2500 mg/kg bw (OECD 402; GLP)

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:
1991-08-19 to 1991-09-30
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
Minor deviations: - According to the guideline, the relative humidity should be between 30 - 70 %. In this study the relative humidity was slightly higher (60 +/- 20 %). - According to the guideline, a stomach tube or a suitable intubation cannula should be used when the test substance is administered by gavage. The study report does not stated what was used in order to administered the test substance by gavage. -According to the guideline, after the substance has been administered, food may be withheld for a further 3 -4 hours. In the study report it was not stated if food was withheld after the administration of the test substance. - According to the guideline, the individual weights should be determined before the application of the test substance , which was done in this study. The individual weights were not provided in the report but only the average weight of the males and females per dose.
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
1987-02-24
Deviations:
yes
Remarks:
see rational for reliability
GLP compliance:
yes (incl. certificate)
Remarks:
signed 2009-11-12
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals 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: 150 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). 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
Route of administration:
oral: gavage
Vehicle:
other: hydroxypropyl-methylcellulose gel
Details on oral exposure:
VEHICLE
V2O5 analytical 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 20 ml/kg b.w. for all groups. (The dose interval factor was 1.47)
Doses:
215 mg/kg, 316 mg/kg, 464 mg/kg, 681 mg/kg and 1000 mg V2O5 analytical 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 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 experiment 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: 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.
Statistics:
The LD50 was calculated according to FINNEY (probit analysis).
Sex:
male
Dose descriptor:
LD50
Effect level:
474.2 mg/kg bw
95% CL:
> 379.01 - < 593.35
Remarks on result:
other: Slope: 7.82
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
466.93 mg/kg bw
Remarks on result:
other: Slope: 29.94; The LD50 was calculated by regressions analysis; no estimation of the confidence limits possible, due to the low number of animals employed and the steepness of the mortality curve.
Mortality:
Under the present test concitions first intolerance reactions (death) occured at 316 mg V2O5 analytical grade pulverised/kg b.w. p.o. The lowest lethal dose for males and females was 316 mg/kg b.w. p.o. Animals died between 48 hours and 7 days unobserved.
Dose level and number of dead animals:
316 mg/kg b.w. : 1/5 males; 1/5 females
464 mg/kg b.w. : 1/5 males; 2/5 females
681 mg/kg b.w.: 5/5 males; 5/5 females
1000 mg/kg b.w.: 5/5 males; 5/5 females
Clinical signs:
Reduced motility, ataxia and dyspnoea were observed from a dose-level of 464 mg/kg b.w. onwards. Animals showed symptoms between 24 h and days 2. The symptoms varied between slight and moderate.
Dose level:
464 mg/kg b.w. : reduced motility (4/5 males; 3/5 females); ataxia (5/5 males, 3/5 females); dyspnoea (5/5 males; 3/5 females)
681 mg/kg b.w.: reduced motility (5/5 males; 3/5 females); ataxia (4/5 males, 3/5 females); dyspnoea (4/5 males; 3/5 females)
1000 mg/kg b.w.: reduced motility (5/5 males; 5/5 females); ataxia (5/5 males, 5/5 females); dyspnoea (5/5 males; 5/5 females)
Body weight:
There was no inhibition of body weight gain seen in males or females.
Gross pathology:
Autopsy of deceased animals: There were no pathological findings in males or females.
Autopsy of surviving animals: There were no pathological findings in males or females.
Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
LD50 (female rats) = 466.93 mg/kg bw
According to the Regulation (EC) No 1272/2008 and subsequent adaptations, the substance is classifed as acutely toxic via the oral route (Category 4).
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
467 mg/kg bw
Quality of whole database:
GLP guideline studies with divanadium pentaoxide in three different grades (i.e. analytical-pulverized, technical-fused, technical-pulverised) exist.

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:
1991-10-02 to 1991-11-13
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
Minor deviations: - According to the guideline, the weight variation in animals or between groups used in a test should not exceed +/- 20 % of the mean weight. The males of the group with the 2.42 mg/l air concentration were slightly outside this weight range. - According to the guideline, the relative humidity should be between 30 - 70 % in the animal room. In this study the relative humidity was slightly higher (60 +/- 20 %). -According to the guideline, animals should be tested with inhalation equipment designed to sustain a dynamic air flow of 12 to 15 air changes per hour. In this study in the high concentration group the air flow was 29.4 changes per hour. - According to the guideline, the duration of exposure should be at least 4 hours after equilibration of the chamber concentration. It was not stated if the 4 hours started after equilibration of the chamber concentration. - According to the guideline, weight changes should be calculated and recorded when survival exceeds one days. This is missing in this study. -The GSD for the MMAD is missing. - The 95 % confidence level for the females is missing.
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Version / remarks:
1981-05-12
Deviations:
yes
Remarks:
see "rational for reliability"
GLP compliance:
yes (incl. certificate)
Remarks:
The study report stated that the study was performed according to "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 and environmental conditions:
TEST ANIMALS
- Source: Lippische Versuchstierzucht HAGEMANN GmbH, D-4923 Extertal 1
- Age at study initiation: 52-69 days
- Weight at study initiation: 188 - 270 g (males; 164 - 206 g (females)
- Fasting period before study: approx. 16 hours
- Housing: Animales were kept in groups of two or three in Makrolon cages (type III). Granulated textured wood (type 2, supplied by Johannes Brandenburg, D-4937 Goldenstedt) was used as bedding material.
- Diet (ad libitum): 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
Route of administration:
inhalation: dust
Type of inhalation exposure:
nose only
Vehicle:
other: air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus & Exposure chamber volume: : The study was carried out using a dynamic inhalation apparatus with a nose only exposure of the animals according to KIMMERLE & TREPPER (Rhema-Labortechnik, D-6238 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.

- Source and rate of air: At the bottom of the exposure chamber the air was sucked off at the similar rate as created by the dust generator in order to produce a homogenous distribution in the exposure chamber. Air-flow meters (Rotameter, ROTA Apparate- und Maschinenbau, D-7867 Wehr 2/Baden) were used to control the constant supply of compressed air and vacuum. Flow rates were checked at least once/hour and corrected if necessary. Air flow was 480 l/h for the low and medium concentration, and 1175 l/h for the high concentration. The air change was 12.0 changes per hour for the low and medium concentration, and 29.4 changes per hour for the high concentration.

- System of generating particulates/aerosols: The dust was generated with a dust generator and dosing apparatus (BURGHART, D-2000 Wedel/Holstein). The generator was fed with compressed air from a compressor.

- 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 (1975).
The impactor is a device that classifies particles present in a sampleof air or gas into known size ranges. It does this by drawing the air sample through a cascade of progressively finer nozzles. The air jets from these impact on plane sampling surfaces (slides) covered with adhesive tape. Each stage represents an aerodynamic size range. The dust from the exposure chamber was sucked through the cascade impactor for 1.5 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 1601004, precision 10µg).
Respirable amount (particle size <= 4 µm)
Dose level 0.90 mg/l air:0.61 mg/l air
Dose level 2.42 mg/l air:2.01 mg/l air
Dose level 4.72 mg/l air: 3.52 mg/l air
The sample supplied had a particle size distribution of 55.9 % in the particle size range of 2.4 to 5.0 µm.

- Temperature, humidity: The temperature (GTH 1200 Digital Thermometer, Fa. Greisinger Electronic GmbH) and humidity (Sekunden-Hygrometer Typ 6100, Testoterm) was continuously monitored close to the nose of the animals in the inhalation chamber. The temperature was 19 °C - 21 °C and the relative humidity was 60 % - +/- 20 %.

TEST ATMOSPHERE (Test substance concentration)
- Brief description of analytical method used: The dust concentration in the inhalation chamber was measured with an air sample filter (Minisart SM 17598) and pump (water jet air pump controlled by a rotameter). Dust samples were taken during the first half and during the second half of the exposure. The Minisart SM 17598 filters were placed close to the animals' nose and sucked through with a constant flow of air of 300 l/h for 1 to 3 minutes. The filters were weighed before and after sampling (accuracy 0.01 mg).

TEST ATMOSPHERE
- Particle size distribution: The sample supplied had a particle size distribution of 55.9 % in the particle size range of 2.4 to 5.0 µm measured with a Malvern particle sizer.
Particle size (µm) and mean (concentration 0.90 mg/l air):
<0.5 µm: 1.33 %
0.5 µm: 12.80 %
1 µm: 22.25 %
2 µm: 52.36 %
4 µm: 68.25 %
8 µm: 75.84 %
16 µm: 90.17 %
>= 32 µm: 99.90 &
Particle size (µm) and mean (concentration 2.42 mg/l air):
<0.5 µm: 0.0 %
0.5 µm: 5.18 %
1 µm: 17.19 %
2 µm: 52.89 %
4 µm: 83.10 %
8 µm: 87.50 %
16 µm: 93.73 %
>= 32 µm: 100.01 %
Particle size (µm) and mean (concentration 4.72 mg/l air):
<0.5 µm: 1.87 %
0.5 µm: 8.85 %
1 µm: 31.02 %
2 µm: 69.52 %
4 µm: 74.59 %
8 µm: 78.18 %
16 µm: 91.77 %
>= 32 µm: 100.0 %
- MMAD:
Dose level 0.90 mg/l air: 2.44 µm
Dose level 2.42 mg/l air: 2.32 µm
Dose level 4.72 mg/l air: 2.01µm
Analytical verification of test atmosphere concentrations:
yes
Remarks:
see "details on inhalation exposure" above.
Duration of exposure:
4 h
Remarks on duration:
Exposition started by locating the rats into the exposure chamber.
Concentrations:
mean actual concentration 0.90 +/- 0.39 (nominal concentration: 1.9 mg/l air), 2.42 +/- 0.38 (nominal concentration: 7.4 mg/l air), 4.72 +/- 1.45 (nominal concentration: 8.6 mg/l air) mg V2O5 analytical grade pulverised/l air. 4.72 mg/l air was the highest concentration that could be generated in the inhalation chamber.
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: During and following espoxure, observations were made. 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. Individual body weights of the animals were determined 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. From animals which survived 24 hours or longer a microscopic examination of all organs which showed evident lesions was performed after preparation of paraffin sections and HE-staining..
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: Cageside observations included, but were not limited to, changes in the skin and fur, eyes, mucous membranes, respiratory, circulatory, autonomic and central nervous system, and somatomotor activity and behaviour pattern. Particluar attention was directed to observation of tremors, convulsions, salivation, diarrhoea. lethargy, sleep and coma.
Statistics:
The mass median aerodynamic diameter (MMAD) was estimated by means of nonlinear regression analysis (LICHFIELD & WILCOXON). The 32 mm particle size range was not included in the determination of the MMAD in order not to give undue weight to this value.
The LC50 (24 hours/14days) was calculated by regression analysis (if possible according to FINNEY).
Sex:
male
Dose descriptor:
LC50
Effect level:
11.09 mg/L air
95% CL:
> 0.68 - < 180.68
Exp. duration:
4 h
Remarks on result:
other: Slope: 1.783; LC50 was calcualted according to Finney (probit analysis)
Sex:
male
Dose descriptor:
LC0
Effect level:
2.42 mg/L air
Exp. duration:
4 h
Key result
Sex:
female
Dose descriptor:
LC50
Effect level:
4.29 mg/L air
Exp. duration:
4 h
Remarks on result:
other: Slope: 20.14; LC50 was calculated by regressiong analysis.
Sex:
female
Dose descriptor:
LC0
Effect level:
4.72 mg/L air
Exp. duration:
4 h
Mortality:
Death at 2.42 mg/l in males and 4.72 mg/l in females.
At the dose-level of 2.42 mg/l prematurely deceased animal (1/5 males) died 4 days after start of exposure.
At the dose level of 4.72 mg/l prematurely deceased animals (1/5 males; 4/5 females) died 2 days after start of exposure.
Clinical signs:
other: Dose level and toxic signs: 0.90 mg/l: no signs of systemic intolerance (males and females) 2.42 mg/l: Except for mortality no signs of systemic intolerance (males and females) 4.72 mg/l: except for mortalitiy no signs of systemic intolerance (males and
Body weight:
There was no inhibition of body weight gain in males or females.
Gross pathology:
Autopsy of deceased animals:
lungs haemorrhagic: 4.72 mg/l (1/1 males; 3/4 females). All further deceased animals showed no pathological findings.
Autopsy of surviving animals:
lungs haemorrhagic: 2.42 mg/l air (2/4 males; 1/5 females)
Lungs haemorrhagic and light dark coloured: 4.72 mg/l air (1/4 males)
All further scarificed animals showed no pathological findings.
The histopathological changes found in the lungs were:
2.42 mg/l air: vascular congestion (2/2 males); oedema (1/2 males) and (inital) haemorrhagic bronchopneumonia (2/2 males)
4.72 mg/l air: vascular congestion (2/2 males; 3/3 females); oedema (1/2 males; 2/3 females) and (inital) haemorrhagic bronchopneumonia (2/2 males; 3/3 females)
These changes can be regarded as unspecific effects which can normally occur after the administration of a dust.
Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
LC50 (female rats) = 4.29 mg/L air
According to the Regulation (EC) No 1272/2008 and subsequent adaptations, the substance is classifed as acutely toxic via the inhalation route (Category 4).
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LC50
Value:
4.3 mg/m³
Quality of whole database:
GLP guideline studies with divanadium pentaoxide in three different grades (i.e. analytical-pulverized, technical-fused, technical-pulverised) exist.

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1991-08-20 to 1991-09-17
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
Minor deviations: - According to the guideline, a limit test of at least 2000 mg/kg bw can be carried out. In this study one additional concentration above the limit dose was also tested. - According to the guideline, the individual weights should be determined before the application of the test substance , which was done in this study. The individual weights were not provided in the report but only the average weight of the males and females per dose. - The guideline suggested that the rats should be in the weight range of 200 to 300 g at the beginning of the study but in this study the rats were in the weight range of 166 -181 g. - According to the guideline, the rats should be housed indivdually. In this study they were housed in groups of two or three rats. - According to the guideline the relative humidity should be between 30 - 70 %. In this study the relative humidity was slightly higher (60 +/- 20 %). - According to the guideline, the test substance should be applied to the skin. In this study the test substance was applied first to the patch and the patch was placed onto the skin.
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
1987-02-24
Deviations:
yes
Remarks:
see rational for reliability
GLP compliance:
yes (incl. certificate)
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 14 th, 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 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: 166 - 181 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
Type of coverage:
occlusive
Vehicle:
other: hydroxypropyl-methylcellulose
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 extremeties 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 V2O5 analytical grade pulverised.
Batch No.(Vehicle): MM 84097413
Duration of exposure:
24 hours
Doses:
2000, 2500 mg V2O5 analytical 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 erythemy (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)
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 testd dose-level of 2500 mg V2O5 analytical grade pulverised /kg b.w. by dermal administration to rats.
Body weight:
There was no inhibition of body weight gain seen in male or female rats dosed at 2000 or 2500 mg/kg b.w.
Gross pathology:
No pathological findings
Interpretation of results:
GHS criteria not met
Conclusions:
LD50 (rats) > 2500 mg/kg bw
According to the EC-Regulation 1272/2008 and subsequent regulations, the test item is not classified as acute toxic via the dermal route.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 500 mg/kg bw
Quality of whole database:
GLP guideline studies with divanadium pentaoxide in three different grades (i.e. analytical-pulverized, technical-fused, technical-pulverised) exist.

Additional information

Acute toxicity, oral

Divanadium pentaoxide in three different grades (i.e. analytical-pulverized, technical-fused, technical- pulverised) is harmful if swallowed (LD50≥ 221 < 2000 mg/kg b. w. p. o.) based on results of acute oral toxicity studies in the rat.

Acute toxicity, inhalative

Divanadium pentaoxide in three different grades (i.e. analytical-pulverized, technical-fused, technical- pulverised) is harmful if inhaled (LC50(4h) ≥ 2.21 < 5 mg/L) based on results of acute inhalation toxicity studies in the rat.

Acute toxicity, dermal

No acute toxicity was observed in rats after dermal administration of up to 2500 mg V2O5/kg b.w. in three different grades (i.e. analytical-pulverised, technical-fused, technical-pulverised).

The following information of V2O5 powder (analytical grade) is taken into account for the hazard / risk assessment:

Acute toxicity - oral: (LD50: 467 mg/kg b.w. p.o.)

Acute toxicity - inhalation: harmful (LD50: 4.3 mg/L)

Acute toxicity - dermal: non-toxic (LD50: > 2500mg/kg b.w. p.o.)

Justification for classification or non-classification

Oral toxicity
According to EC Regulation 1272-2008, divanadium pentaoxide need to be classified for acute oral toxicity study as follows:

analytical grade - pulverised:       Category 4 (LD50≥ 467mg/kg b.w. p.o.), H302: Harmful if swallowed

technical grade - fused:              Category 4 (LD50≥ 658mg/kg b.w. p.o.), H302: Harmful if swallowed

technical grade - pulverized:       Category 3 (LD50≥221 mg/kg b.w. p.o.), H301: Toxic if swallowed

Inhalation toxicity

According to EC Regulation 1272/2008, divanadium pentaoxide in three different grades (i.e. analytical-pulverized) need to be classified as Category 4, H 332: Harmful if inhaled.

Acute toxicity, dermal

No acute toxicity was observed after dermal administration of up to 2500 mg V2O5 /kg b.w. in rats in three different grades (i.e. analytical-pulverised). According to EC Regulation 1272 /2008, V2O5 can be classified as relatively non-toxic based on results in acute dermal toxicity studies in the rat.

Respiratory irritation:

Based on human data, exposure to divanadium pentaoxide may result in respiratory irritation (see Section 7.3). Thus, criteria for classification in STOT-SE Category 3 - respiratory tract irritation are met. According to the EC Regulation 1272/2008, divanadium pentaxoide is classified STOT SE Category 3: H335: May cause respiratory irritation.