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Administrative data

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

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:
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

Test material

Constituent 1
Reference substance name:
divanadium trioxide
IUPAC Name:
divanadium trioxide
Constituent 2
Chemical structure
Reference substance name:
Divanadium trioxide
EC Number:
215-230-9
EC Name:
Divanadium trioxide
Cas Number:
1314-34-7
Molecular formula:
O3V2
IUPAC Name:
215-230-9
Constituent 3
Reference substance name:
1314-34-7
Cas Number:
1314-34-7
IUPAC Name:
1314-34-7
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
- Name of test material (as cited in study report): Divanadium trioxide technical grade pulverised (V2O3)
- Physical state: dark-grey, solid
- Stability under test conditions: Stable during the course of the study
- Storage condition of test material: Dry, in closed containers at room temperature
- Other: Median particle size range 34 - 55 µm
No further signficant information on test material was stated.

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: 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.

Administration / exposure

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.

Results and discussion

Effect levelsopen allclose all
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:
other: 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/
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

Applicant's summary and conclusion

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.

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