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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:
1991-12-18 to 1992-01-27
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1992
Report date:
1992

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
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:
Potassium vanadium trioxide
EC Number:
237-388-8
EC Name:
Potassium vanadium trioxide
Cas Number:
13769-43-2
Molecular formula:
KVO3
IUPAC Name:
potassium metavanadate
Test material form:
solid: particulate/powder
Details on test material:
- Name of test material (as cited in study report): Potassium metavanadate
- Physical state: light-grey, solid amorphous fine 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, Tif:RAI f (SPF)
- Source: Lippische Versuchstierzucht, HAGEMANN GmbH, D-4923 Extertal 1
- Age at study initiation: approximately. 40 - 60 days
- Weight at study initiation: 160 - 199 g
- Fasting period before study: feeding was discontinued approximately 16 hours before administration. Only tap water was offered ad libitum.
- Housing: granulated textured wood was used as bedding material for the cages (Granulat Typ A2, supplier: Messrs. BRANDENBURG, Inh. H. Brandenburg, D-2849 Goldenstedt). During the observation period, surviving animals were kept in groups of 2 - 3 animals in MAKROLON cages (type III).
- Diet: standardized diet for rats and mice 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: 0.8% aqueous hydroxypropyl-methylcellulose gel
Details on oral exposure:
VEHICLE
- Batch no.: MM 84097413B

MAXIMUM DOSE VOLUME APPLIED: 20 mL/kg bw (dose interval factors: 2.15 and 1.47)

DOSAGE PREPARATION: Potassium metavanadate was suspended in 0.8% aqueous hydroxypropyl-methylcellulose gel.

Doses:
100, 215, 316 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 hours, 6 hours and 24 hours 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. Attention was also paid to possible tremor, 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. Changes in weight were calculated and recorded when survival exceeds one day.
- 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.
Statistics:
The LD50 was calculated according to FINNEY (Probit analysis) or by regression analysis. The mortality rates at 24 hours and at 14 days were used.

Results and discussion

Effect levelsopen allclose all
Sex:
male
Dose descriptor:
LD50
Effect level:
317.94 mg/kg bw
Based on:
test mat.
Remarks on result:
other: LD50 after 14 days; Slope: 29.88
Sex:
female
Dose descriptor:
LD50
Effect level:
313.84 mg/kg bw
Based on:
test mat.
Remarks on result:
other: LD50 after 14 days; Slope: 29.88
Sex:
male/female
Dose descriptor:
LD50
Effect level:
322.79 mg/kg bw
Based on:
test mat.
Remarks on result:
other: LD50 after 14 days; Slope: 29.88
Sex:
male
Dose descriptor:
LD50
Effect level:
423.45 mg/kg bw
Based on:
test mat.
95% CL:
322.57 - 555.89
Remarks on result:
other: LD50 after 24 hours; Slope: 7.67
Sex:
female
Dose descriptor:
LD50
Effect level:
383.05 mg/kg bw
Based on:
test mat.
Remarks on result:
other: LD50 after 24 hours; Slope: ~ 59.8
Sex:
male/female
Dose descriptor:
LD50
Effect level:
398.55 mg/kg bw
Based on:
test mat.
95% CL:
352.62 - 450.47
Remarks on result:
other: LD50 after 24 hours; Slope: 12.78
Mortality:
100 mg/kg bw: none
215 mg/kg bw: none
316 mg/kg bw: 2 males (24 hours - day 4) / 3 females (52 hours - day 4)
464 mg/kg bw: 5 males (120 minutes - day 4) / 5 females (100 minutes - 24 hours)
Clinical signs:
Male rats:
100 mg/kg bw: none
215 mg/kg bw: slight reduced motility (3 hours - 6 hours; 5 males); slight ataxia (3 hours - 6 hours; 5 males); slight dyspnoea (3 hours - 6 hours; 5 males); slight muscular hypotonia (6 hours; 5 males)
316 mg/kg bw: slight/moderate reduced motility (30 minutes - day 2; 5 males); slight/moderate ataxia (30 minutes - day 2; 5 males); slight/moderate dyspnoea (30 minutes - day 2; 5 males); moderate muscular hypotonia (6 hours - 24 hours; 5 males)
464 mg/kg bw: slight to severe reduced motility (15 minutes - day 2; 5 males); moderate/severe ataxia (15 minutes - day 2; 5 males); slight/moderate dyspnoea (15 minutes - day 2; 5 males); slight/moderate muscular hypotonia (15 minutes - day 2; 5 males)

Female rats:
100 mg/kg bw: none
215 mg/kg bw: slight reduced motility (3 hours - 6 hours; 5 females); slight ataxia (3 hours - 6 hours; 5 females); slight dyspnoea (3 hours - 6 hours; 5 females); slight muscular hypotonia (6 hours; 5 females)
316 mg/kg bw: slight/moderate reduced motility (30 minutes - day 2; 5 females); slight/moderate ataxia (30 minutes - day 2; 5 females); slight/moderate dyspnoea (30 minutes - day 2; 5 females); moderate muscular hypotonia (6 hours - 24 hours; 5 females)
464 mg/kg bw: slight to severe reduced motility (15 minutes - 6 hours; 5 females); moderate/severe ataxia (15 minutes - 6 hours; 5 females); moderate dyspnoea (15 minutes - 6 hours; 5 females); moderate muscular hypotonia (15 minutes - 6 hours; 5 females)
Body weight:
Moderate inhibition of body weight gain of male rats was observed at the 316 mg/kg bw dose level.
Gross pathology:
Animals that died prematurely:
316 mg/kg bw: 1/2 males had reddened intestinal mucosa
464 mg/kg bw: 4/5 males had a dark liver and reddened intestinal mucosa; 2/5 females had a severely dark liver and reddened intestinal mucosa; 2/5 females had a severely dark liver and severely reddened intestinal mucosa; 175 females had reddened intestinal mucosa
All further deceased animals showed no pathological findings.
Surviving animals (sacrificed) (male and female):
No pathological findings

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
Based on a GLP-compliant guideline study according to OECD 401 and the derived LD50 values for male and female rats of 317.94 mg/kg bw and 313.84 mg/kg bw, respectively, the LD50 (male and female rats) of 322.79 mg/kg bw was determined. The lowest lethal dose was 316 mg/kg bw whereas the no-effect-level was 100 mg/kg bw.

According to the EC-Regulation 1272/2008 and its subsequent adaptations, potassium metavanadate meets classification criteria for acute toxicity (oral) Category 4.

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