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Toxicological information

Acute Toxicity: dermal

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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
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: 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 402 (Acute Dermal 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:
yes

Test material

Constituent 1
Reference substance name:
divanadium trioxide
IUPAC Name:
divanadium trioxide
Constituent 2
Reference substance name:
Divanadium trioxide
EC Number:
215-230-9
EC Name:
Divanadium trioxide
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 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 levelsopen allclose all
Sex:
male
Dose descriptor:
LD50
Effect level:
> 2 500 mg/kg bw
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 500 mg/kg bw
Mortality:
None of the animals died prematurely.
Clinical signs:
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.
Body weight:
There was no inhibition of body weight gain in male or female 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.

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