Registration Dossier

Administrative data

Description of key information

Some treatment related effects, but toxicological significance not possible to determine.

Vanadium detected in kidneys with some accumulation; the highest concentrations were found in the highest test group.

This suggests some elimination, but potential for local (perhaps temporary?) accumulation.

The authors suggest that the top group showed adverse effect, with possible accumulation and changes in chemistry. However, in a one-generation reproduction study, ca 50 mg/kg/day was tolerated for up to 70 day exposure.

A NOAEL of 12 mg/kg/day is proposed based on this study and is used to estimate DNELs.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records
Reference
Endpoint:
sub-chronic toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
90 days
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Justification for type of information:
Sodium metavanadate was used for testing. This is accepted as a reliable source of water-soluble vanadium with dissociation under the acidic conditions of the stomach.
Vanadyl oxysulphate will also dissociate under acidic conditions and safety assessment base don exposure to soluble vandaium ions is considered acceptable for this assessment.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity in Rodents)
Principles of method if other than guideline:
Substance applied in drinking water
GLP compliance:
not specified
Limit test:
no
Specific details on test material used for the study:
Sodium vanadate was used for testing. This is accepted as a reliable source of water-soluble vanadium with dissociation under the acidic conditions of the stomach.
Vanadyl oxysulphate will also dissociate under acidic conditions and safety assessment base don exposure to soluble vandaium ions is considered acceptable for this assessment.
Species:
rat
Strain:
Sprague-Dawley
Sex:
male
Route of administration:
oral: drinking water
Vehicle:
water
Analytical verification of doses or concentrations:
not specified
Details on analytical verification of doses or concentrations:
Dose levels checked by monitoring water consumption and body weights.
Duration of treatment / exposure:
90 days
Frequency of treatment:
Continiuos in drinking water
Dose / conc.:
0 mg/L drinking water
Dose / conc.:
5 mg/L drinking water
Dose / conc.:
10 mg/L drinking water
Dose / conc.:
50 mg/L drinking water
No. of animals per sex per dose:
10 (males)
Control animals:
yes, concurrent vehicle
Observations and examinations performed and frequency:
Clinical observations including body weights.
Food consumption determined and mean daily diet consumption calculated
Body weight gain calculated
Blood chemistry checked

URINALYSIS: Yes
- Metabolism cages used for collection of urine: Yes
- Parameters checked: volume excreted
Sacrifice and pathology:
Gross necropsy and pathology conducted after termination.
Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
no effects observed
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
no effects observed
Ophthalmological findings:
not examined
Haematological findings:
no effects observed
Clinical biochemistry findings:
effects observed, treatment-related
Description (incidence and severity):
Changes in levels of total protein, with significant increase in top group along with increase in urea.
Not considered to be an adverse effect
Vanadium detected in kidneys with some accumulation; the highest concentrations were found in the highest test group.
This suggests some elimination, but potential for local (perhaps temporary?) accumulation.
Urinalysis findings:
no effects observed
Behaviour (functional findings):
not examined
Immunological findings:
not examined
Organ weight findings including organ / body weight ratios:
no effects observed
Gross pathological findings:
no effects observed
Neuropathological findings:
not examined
Histopathological findings: non-neoplastic:
effects observed, treatment-related
Description (incidence and severity):
Minor lesions on kidneys, lung and spleen in all groups, but more evident in highest treatment groups.
Histopathological findings: neoplastic:
no effects observed
Other effects:
no effects observed
Dose descriptor:
LOEL
Effect level:
ca. 50 mg/L drinking water
Based on:
test mat.
Remarks:
Sodium metavanadate
Sex:
male
Basis for effect level:
clinical biochemistry
Dose descriptor:
LOEL
Effect level:
ca. 8.21 mg/kg bw/day (nominal)
Based on:
test mat.
Remarks:
Sodium metavanadate
Sex:
male
Basis for effect level:
clinical biochemistry
Dose descriptor:
LOEL
Effect level:
ca. 3.45 mg/kg bw/day (nominal)
Based on:
element
Remarks:
Vanadium
Sex:
male
Basis for effect level:
clinical biochemistry
Key result
Dose descriptor:
LOEL
Effect level:
ca. 12 mg/kg bw/day (nominal)
Based on:
test mat.
Remarks:
Vanadyl oxysulphate
Sex:
male
Basis for effect level:
clinical biochemistry
Remarks on result:
other: Effect level estimated
Critical effects observed:
yes
Lowest effective dose / conc.:
12 mg/kg bw/day (nominal)
System:
other: Blood changes; cause not found
Organ:
blood
Treatment related:
yes
Dose response relationship:
yes
Relevant for humans:
not specified

Treatment levels based on drinking water concentration have been converted using reported consumption levels and body weights.

A molecular weight for sodium metavanadate of 122 has been used to convert to vanadium and then on to the registered substance, using a nominal molecular weight of 173 for vanadyl oxysulphate.

Conclusions:
Some treatment related effects, but toxicological significance not possible to determine.
Vanadium detected in kidneys with some accumulation; the highest concentrations were found in the highest test group.
This suggests some elimination, but potential for local (perhaps temporary?) accumulation.
The authors suggest that the top group showed adverse effect, with possible accumulation and changes in chemistry. However, in a one-generation reproduction study, ca 50 mg/kg/day was tolerated for up to 70 day exposure.
A NOAEL of 12 mg/kg/day is proposed based on this study and is used to estimate DNELs.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
NOAEL
12 mg/kg bw/day

Additional information

Justification for classification or non-classification