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Toxicological information

Acute Toxicity: oral

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Administrative data

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.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1991
Report date:
1991

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
1987-02-24
Deviations:
yes
Remarks:
see rational for reliability
GLP compliance:
yes (incl. QA statement)
Remarks:
signed 2009-11-12
Test type:
standard acute method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Divanadium pentaoxide
EC Number:
215-239-8
EC Name:
Divanadium pentaoxide
Cas Number:
1314-62-1
Molecular formula:
V2O5
IUPAC Name:
divanadium pentaoxide
Test material form:
solid: particulate/powder
Details on test material:
- Name of test material (as cited in study report): Divanadium pentaoxide analytical grade pulverised (V2O5)
- Physical state: beige, solid (powder)
- Stability under test conditions: Stable during the course of the study
- Storage condition of test material: Dry, in closed container at room temperature
- Median particle size: 3.0 - 3.9 µm

Test animals

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: 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

Administration / exposure

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).

Results and discussion

Effect levelsopen allclose all
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.

Applicant's summary and conclusion

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).

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