Erbium tetraoxide vanadium

Endpoint summary

Description of key information

No acute toxicity studies with erbium tetraoxide vanadium are available, thus the acute toxicity will be addressed with existing data on the dissociation products. Erbium tetraoxide vanadium is not acutely toxic via the oral route.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Reference 1

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:

2011-01-31 to 2011-03-03

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

adopted 2001-12-17

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

signed 2011-01-21

Test type:

acute toxic class method

Limit test:

no

Species:

rat

Strain:

Crj: CD(SD)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River (UK) Ltd
- Age at study initiation: approximately eight to twelve weeks of age prior to dosing (Day 1)
- Weight at study initiation: 205 - 235 g (Day 1)
- Fasting period before study: overnight prior to and approximately four hours after dosing
- Housing: they were housed in groups of three rats of the same sex, in solid bottomed polycarbonate cages with a stainless steel mesh lid. Each cage contained a quantity of autoclaved wood flake bedding.
- Diet (ad libitum, for exception please refer to "Fasting period before study" above): standard rodent diet (Rat and Mouse No. 1 Maintenance Diet); This diet contained no added antibiotic or other chemotherapeutic or prophylactic agent.
- Water (ad libitum): potable water
- Acclimation period: at least 5 days before treatment

During the acclimatisation period, each cage of animals was provided with a soft white untreated chew block and a plastic shelter for environmental enrichment. The wood blocks were removed from the cage of animals for the same period as the food on the day prior to dosing.

ENVIRONMENTAL CONDITIONS
- Temperature: 19 to 23°C
- Relative humidity: 40 to 70%
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

DOSAGE PREPARATION: the test substance was formulated at a concentration of 30 and 200 mg/mL in the vehicle and
administered at a volume of 10 mL/kg bodyweight. The test substance formulations were prepared on the day of dosing.
Formulations were mixed using a vortex mixer just before the dosing procedure.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: as no previous toxicological information was available the initial dose level was 300 mg/kg.

Doses:

300 and 2000 mg/kg

No. of animals per sex per dose:

6 female animals

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: cages of rats were checked at least twice daily for any mortalities. Animals were observed for clinical signs soon after dosing and at frequent intervals for the remainder of Day 1. On subsequent days, animals were observed once in the morning and again at the end of the experimental day (with the exception of Day 15 - morning only). The nature and severity, where appropriate, of the clinical signs and the time were recorded at each observation. The body weight of each rat was recorded on Days 1 (prior to dosing), 8 and 15. Individual weekly bodyweight changes and group mean bodyweights were calculated.
- Necropsy of survivors performed: yes
All animals were humanely killed on Day 15 by carbon dioxide asphyxiation.
All animals were subject to a macroscopic examination which consisted of opening the cranial, thoracic and abdominal cavities. The macroscopic appearance of all examined organs was recorded.

Statistics:

not applicable

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: LD50 cut off value: 5000 mg/kg bw

Mortality:

There were no deaths during the study.

Clinical signs:

other: There were no clinical signs of reaction to treatment throughout the study.

Gross pathology:

No abnormalities were noted in any animal at the macroscopic examination at study termination on Day 15.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

LD50 (female rats) > 2000 mg/kg bw (LD50 cut off value: 5000 mg/kg bw)
According to the EC-Commission directive 67/548/EEC and its subsequent amendments, vanadium carbide nitrate is not classified as acute toxic via the oral route.
According to the EC-Regulation 1272/2008 and subsequent regulations, vanadium carbide nitrate is not classified as acute toxic via the oral route.

Reference 2

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:

2010-08-05 to 2010-08-31

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study reliable without restrictions

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

, adopted 2001-12-17

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:

Crj: CD(SD)

Sex:

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: Approx. 8 weeks
- Weight at study initiation: 163 - 191 g
- Fasting period before study: Feeding was discontinued approx. 16 hours before administration.
- 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 were kept in groups of 3 animals in MAKROLON cages (type III plus).
- Diet: 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

ENVIRONMENTAL CONDITIONS
- Temperature: 22°C ± 3°C (maximum range)
- Relative humidity: 55% ± 15% (maximum range)
- Photoperiod (hrs dark / hrs light): 12/12
No further information on the test animals was stated.

Route of administration:

oral: gavage

Vehicle:

other: hydroxypropylmethylcellulose

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: The administration volume was 10 mL/kg b.w.

DOSAGE PREPARATION: Vanadium (metal powder) was suspended to the appropriate concentration in 0.8% aqueous hydroxypropylmethylcellulose (Methocel; batch no. 09 D14-N28, Fagron GmbH & Co., 22885 Barsbüttel, Germany).
No further information on the oral exposure was stated.

Doses:

2000 mg/kg b.w.

No. of animals per sex per dose:

1 dose level group of 6 female animals

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observations were performed before and immediately, 5, 15, 30 and 60 min, as well as 3, 6 and 24 hours after administration.
During the follow-up period of two weeks, changes of skin and fur, eyes and mucous membranes, respiratory and the 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, 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 to minimize loss of animals during the study. Individual body weights were recorded before administration of the test item and thereafter in weekly intervals up to the end of the study.
- Necropsy of survivors performed: Yes
All animals were sacrificed, dissected and inspected macroscopically. All gross pathological changes were recorded.
- Other examinations performed: Changes in weight were calculated and recorded.
No further information on the test material was stated.

Statistics:

Not applicable

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred.

Clinical signs:

other: A single oral administration of 2000 mg vanadium (metal powder)/kg b.w. to female rats did not reveal any signs of toxicity. No clinical signs were observed.

Gross pathology:

No pathological changes were observed at necropsy.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

LD50 (rats, females) >2000 mg/kg b.w.
According to the EC-Commission Directive 67/548/EEC and its subsequent amendments on the approximation of the laws, regulations and administrative provision relating to the classification, packaging and labelling of dangerous substances and the results obtained under the present test conditions vanadium (metal powder) is non-toxic if swallowed, hence, no labelling is required.
Also, according to the EC Regulation 1272/2008 and subsequent regulations, the test material is not classified for acute oral toxicity.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Quality of whole database:

Two GLP-studies are reliable without restrictions, studies were conducted with vanadium carbide nitride and vanadium metal; read across is performed.

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

In order to evaluate toxicological properties of the substance erbium tetraoxide vanadium, information on the assessment entities erbium ions (i.e. erbium oxide) and vanadium ions were considered. For a documentation and justification of that approach, please refer to the separate document attached to section 13, namely Read Across Assessment Report for erbium tetraoxide vanadium.

The toxicity ofErbium tetraoxide vanadiummay reasonably be considered to be determined by the bioavailability of the assessment entity"vanadium ions" since there are not any indications that the assessment entity “erbium ions” (i.e. erbium oxide) would be classified as hazardous for human health under Regulation (EC) No 1272/2008.As a first surrogate for bioavailability, the solubility of a test substance may be used. Erbium tetraoxide vanadium (0.017 mg V/L & Er < LOD after 51 days; 20°C), vanadium carbide nitride (0.01 mg/L; 20°C/pH 6.8) and vanadium metal (0.15 mg/L; 20°C/pH 5.8) are substances that are also poorly / sparingly soluble in water.Read-across from vanadium compounds with similar or lower water solubility, i.e. vanadium carbide nitride and vanadium metal, is considered acceptable because kinetic data indicate a similar solubility potential.Vanadium carbide nitride and vanadium metal powder are non-toxic if swallowed since respective LD50 values (rats, females) are above 2000 mg/kg bw. By read-across based on a lower solubility potential, erbium tetraoxide vanadium is considered to be also non-toxic. The classification criteria according to Regulation (EC) 1272/2008 as specific target organ toxicant (STOT) – single exposure, oral are not met since adverse health effects, including reversible and irreversible, were not observed immediately or delayed after exposure.

Thus, the available information indicates that erbium tetraoxide vanadium is not acutely toxic or harmful via the oral route. Therefore, classification of erbium tetraoxide vanadium for acute toxicity via the oral route is not required according to Regulation (EC) 1272/2008.