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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:
1993-12-20 to 1994-01-24
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
Minor deviation from the OECD 401 guideline occurred, but this had no impact on the results of the study: - information about individual body weights was not given.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1994
Report date:
1994

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 1991-07-25
Test type:
standard acute method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Sodium metavanadate
EC Number:
237-272-7
EC Name:
Sodium metavanadate
Cas Number:
13718-26-8
Molecular formula:
NaVO3
IUPAC Name:
sodium metavanadate
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
- Name of test material (as cited in study report): Sodium metavanadate
- Molecular formula: NaVO3
- Physical state: beige powder
- Storage condition of test material: at room temperature

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS - Sprague-Dawley/Crl:CD R BR
- Source: Charles River Deutschland GmbH, Niederlassung Sulzfeld, Sandhofer Weg 7, D-97633 Sulzfeld
- Age at start of adaptation: 25 - 30 days
- Weight at start of administration: 170 - 200 g
- Fasting period before study: feeding was discontinued approximately 16 hours before administration. Only tap water was offered ad libitum.
- Housing: granulated textured wood (Granulate type A2, supplier: BRANDENBURG, D-49424 Goldenstedt) was used as bedding material for the cages. The animals were kept in groups of 2 - 3 during housing in MAKROLON cages (type III).
- Diet: standardized diet Altromin 1324 (ALTROMIN GmbH, D-32791 Lage/Lippe)
- Water (ad libitum): tap water
- Acclimation 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: 0.8% aqueous hydroxypropyl-methylcellulose gel
Details on oral exposure:
VEHICLE
- Batch no.: MM90100512E

MAXIMUM DOSE VOLUME APPLIED: 20 mL/kg bw (dose interval factor: 2.15)

DOSAGE PREPARATION: The test substance was disollved or suspended in the vehicle.
Doses:
46.4, 100, 215 and 464 mg/kg bw
No. of animals per sex per dose:
5 males / 5 females
Control animals:
no
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 minutes, as well as 3, 6 and 24 hours after administration. During this follow-up period, the clinical signs 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 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. Changes in the weights were calculated and recorded as precisely as possible.
- 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 microscopic examination of all organs which show evident lesions is performed, if applicable. Autopsy and macroscopic inspection of the animals which died prematurely was carried out as soon as possible after exitus.
Statistics:
The LD50 was calculated according to FINNEY (Probit analysis).

Results and discussion

Effect levelsopen allclose all
Sex:
male
Dose descriptor:
LD50
Effect level:
212 mg/kg bw
Based on:
test mat.
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
169 mg/kg bw
Based on:
test mat.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
183 mg/kg bw
Based on:
test mat.
95% CL:
>= 140 - <= 238
Mortality:
46.4 mg/kg bw: no mortality
100 mg/kg bw: 1 female (day 3.5)
215 mg/kg bw: 3 males and 3 females (24 hours - 48 hours)
464 mg/kg bw: all males (24 hours - 48 hours) and all females (4 hours - 24 hours)
Clinical signs:
46.4 mg/kg bw: none

100 mg/kg bw: weak reduced motility (60 minutes - 24 hours; all males and females); weak ataxia (60 minutes - 24 hours; all males and females); weak dyspnoea (60 minutes - 24 hours; all males and females)

215 mg/kg bw: weak reduced motility (15 minutes - day 2; all males and females); weak/moderate ataxia (15 minutes - day 2; all males and females); weak ptosis (3 hours - 6 hours; all females); weak soft faeces (60 minutes - 6 hours; all males and females); weak dyspnoea (15 minutes - day 2; all males and females); weak pilo-erection (60 minutes - 24 hours all males and 30 minutes - 24 hours all females)

464 mg/kg bw: weak/moderate reduced motility (15 minutes - 24 hours all males and 15 minutes - 6 hours all females); weak/moderate ataxia (15 minutes - 24 hours all males and 15 minutes - 6 hours all females); weak ptosis (3 hours - 24 hours all males and 60 minutes - 6 hours all females); weak soft faeces (30 minutes - 24 hours all males and 30 minutes - 6 hours all females); weak/moderate dyspnoea (15 minutes - 24 hours all males and 15 minutes - 6 hours all females); weak pilo-erection (30 minutes - 24 hours all males and 30 minutes - 6 hours all females); abdominal position coma (prior to death) (4hours; 2 females)
Body weight:
No inhibition of body weight gain was observed.
Gross pathology:
46.4 and 100 mg/kg bw: no pathological findings
215 mg/kg bw: 3 males and 3 females had a slightly reddened gastro-intestinal wall
464 mg/kg bw: all males and all females had a slightly reddened gastro-intestinal wall

Applicant's summary and conclusion

Interpretation of results:
Toxicity Category III
Conclusions:
LD50 (male rats): 212 mg/kg bw
LD50 (female rats): 169 mg/kg bw
LD50 (male and female rats): 183 mg/kg bw (confidence limits: 140 - 238 mg/kg bw)
No-effect dose-level: 46.4 mg/kg bw
Lowest lethal dose-level: 215 mg/kg bw (males) and 100 mg/kg bw (females)
According to the EC-Regulation 1272/2008 and subsequent adaptations, the test item is classified as as acutely toxic via the oral route (Category 3).

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