Divanadium trioxide

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1991-08-21 to 1991-09-4

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Guideline study without restrictions 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. - 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 160 -199 g. - According to the guideline, the rats should be housed individually. 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. - 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 402 (Acute Dermal Toxicity)

Version / remarks:

adopted 24 February 1987

Deviations:

yes

Remarks:

see rational for reliability

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:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Divanadium trioxide

EC Number:

215-230-9

EC Name:

Divanadium trioxide

Cas Number:

1314-34-7

Molecular formula:

O3V2

IUPAC Name:

Divanadium trioxide

Test material form:

other: solid

Details on test material:

- Name of test material (as cited in study report): Divanadium trioxide technical grade pulverised (V2O3)
- Physical state: dark gray, solid
- Stability under test conditions: Stable during the course of the study
- Storage condition of test material: Dry, in closed container at room temperature
- Other: Median particle size range 34 -55 µm
No further significant 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: 160 - 199 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
No further information was stated on test animals.

Administration / exposure

Type of coverage:

occlusive

Vehicle:

other: hydroxypropyl-methylcellulose gel

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 extremities 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 V2O3 technical grade pulverised.
Batch No.(Vehicle): MM 84097413
No further significant information on details on dermal exposure was stated.

Duration of exposure:

24 hours

Doses:

2000 mg and 2500 mg V2O3 technical 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 erythema (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)
No further significant information on study design was stated.

Statistics:

The LD50 could not be calculated because none of the animals died prematurely.

Results and discussion

Effect levels

Effect levels 1

Sex:

male

Dose descriptor:

LD50

Effect level:

> 2 500 mg/kg bw

Effect levels 2

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 500 mg/kg bw

Mortality:

None of the animals died prematurely.

Clinical signs:

other: Under the present test conditions no local or systemic intolerance reactions were observed up to the highest tested dose-level of 2500 mg V2O3 technical grade pulverised/kg b.w. by dermal administration to rats.

Gross pathology:

There were no pathological findings in male or female rats.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the present test conditions dermal administration of up to 2500 mg V2O3 technical grade pulverised/kg b.w. did not cause any toxic effects in rats. According to directive 83/467/EEC, V2O3 technical grade pulverised can be classified as relatively non-toxic (not classified) in the acute dermal toxicity study in the rat.