Registration Dossier

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:
1989-03-16 to 1989-03-30
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1989
Report Date:
1989

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
adopted 1987-02-24
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: solution
Details on test material:
- Name of test material (as cited in study report): Vanadyloxalate solution in water
- Physical state: blue solution
- Storage condition of test material: room temperature
- Specific gravity: 1.1518 g/mL (determined by laboratory)

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS - SPF-quality, randomly bred
- Source: Charles River Wiga GmbH, Sulzfeld, FRG
- Age at study initiation: 7 weeks old at start of study
- Weight at study initiation: males: 234 - 286 g; females: 157 - 192 g
- Fasting period before study: animals were fasted overnight (prior to dosing) until approximately 4 hours after administration of the test substance
- Housing: At least five days prior to dosing (acclimatization period) the animals were housed five per sex to a cage, in polycarbonate cages containing purified sawdust (Woody Clean supplied by Broekman Institute, Someren, The Netherlands) as bedding material.
- Diet (ad libitum): a standard pelleted laboratory animal diet (RMH-B, pellet diameter 10 mm, Hope Farms, Woerden, The Netherlands)
- Water (ad libitum): tap-water
- Acclimation period: at least five days

ENVIRONMENTAL CONDITIONS
- Temperature: 18 - 20°C
- Relative humidity: 40 - 70%
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 0.43 mL/kg bw (dose level: 500 mg/kg bw), 0.87 mL/kg bw (dose level: 1000 mg/kg bw) and 1.74 mL/kg bw (dose level: 2000 mg/kg bw)
Doses:
500, 1000 and 2000 mg/kg bw corresponding to 0.43, 0.87 and 1.74 mL/kg calculated as follows: dose levels (g/kg) divided by specific gravity (1.1518 g/mL)
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: clinical observations were performed on the day of dosing (approximately 20 minutes, 2 and 3.45 hours after dosing) and once daily thereafter for 14 days.
Individual bodyweights were measured on day 1 (day of dosing), 9 (instead of day 8) and 15.
- Necropsy of survivors performed: yes, at the end of the study (day 15) all animals were anaesthetised by CO2/O2 inhalation, subsequently killed by CO2 and subjected to necropsy.
Statistics:
95% confidence interval calculated with U-distribution. Confidence validity check (i.e. if G < 1, 95% confidence interval valid according to Finney).

Results and discussion

Effect levelsopen allclose all
Sex:
male
Dose descriptor:
LD50
Effect level:
1 146 mg/kg bw
Based on:
test mat.
95% CL:
922 - 1 802
Sex:
female
Dose descriptor:
LD50
Effect level:
914 mg/kg bw
Based on:
test mat.
95% CL:
762 - 1 446
Sex:
male/female
Dose descriptor:
LD50
Effect level:
1 015 mg/kg bw
Based on:
test mat.
95% CL:
869 - 1 340
Mortality:
500 mg/kg bw: no mortality
1000 mg/kg bw: 4 animals
2000 mg/kg bw: 10 animals
These deaths all occurred within 8 days of dosing.
Clinical signs:
Lethargy and piloerection were noted among animals from the groups dosed at 2000 and 1000 mg/kg bw. A wet anal region/diarrhoea were seen among animals dosed at 2000 mg/kg bw and bloody nose encrustation and emaciation were noted for one animal dosed at 1000 mg/kg bw. None of the animals dosed at 500 mg/kg bw showed any clinical signs of toxicity.
Body weight:
All surviving animals showed bodyweight gain between days 1 and 15.
Gross pathology:
Macroscopic examination at necropsy, of animals dosed at 2000 or 1000 mg/kg bw that were found dead, revealed abnormalities which included haemorrhaging or red colouration of the glandular stomach or limiting ridge, enlargement of the stomach, diarrhoea/dirty anus, blood around the eye and/or nose and petechiae or haemorrhages in the thymus.
Macroscopic post mortem examination of surviving animals at termination did not reveal any treatment related abnormalities.

Applicant's summary and conclusion

Interpretation of results:
Toxicity Category IV
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
For the tested aqueous solution of 17% VO(C2O4), the following toxicity endpoints were derived:
LD50 (male rats): 1146 mg/kg bw (95% CL: 922 - 1802)
LD50 (female rats): 914 mg/kg bw (95% CL: 762 - 1446)
LD50 (male and female rats): 1015 mg/kg bw (95% CL: 869 - 1340)

The following toxicity endpoints can be estimated for an aqueous solution of 22.5% VO(C2O4):
LD50 (male rats): 866 mg/kg bw
LD50 (female rats): 691mg/kg bw
LD50 (male and female rats): 767 mg/kg bw

Thus, 17-22.5 % aqueous solutions of vanadium, oxalate complexes are classified harmful if swallowed (Directive 67/548/EEC) and meet according to EC-Regulation 1272/2008 and subsequent regulations criteria for Acute toxicity Category 4 (H302).

The following toxicity endpoints can be estimated for anhydrous VO(C2O4):
LD50 (male rats): 195 mg/kg bw
LD50 (female rats): 155 mg/kg bw
LD50 (male and female rats): 173 mg/kg bw

Vanadium, oxalate complexes (anhydrous) is classified toxic if swallowed (Directive 67/548/EEC) and meets according to EC-Regulation 1272/2008 and subsequent regulations criteria for Acute toxicity Category 3 (H301).