Ashes (residues), vanadium-contg.

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

September - October 2010

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP Guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2010

Report date:

2010

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Ashes (residues), vanadium-contg.

EC Number:

282-208-3

EC Name:

Ashes (residues), vanadium-contg.

Cas Number:

84144-87-6

Molecular formula:

Not available

Details on test material:

- Name of test material (as cited in study report): Vanadium concentrate
- Physical state: black powder
- Analytical purity: see IUCLID section 1.2
- Lot/batch No.: 14-45810
- Storage condition of test material: at room temperature, protected from light

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River, 97633 Sulzfeld, Germany
- Age at study initiation: 8-12 weeks
- Weight at study initiation:
- Fasting period before study: 16 to 19 hours
- Fasting period after study: 3 to 4 hours
- Housing: in groups in IVC cages, type III H, polysulphone cages on Altromin saw fibre bedding
- Diet: free access to Altromin 1324 maintenance diet for rats and mice
- Water: free access to tap water, sulphur acidified to a pH of approximately 2.8 (drinking water, municipal residue control, microbiological controls at regular intervals)
- Certificates of food, water and bedding are filed at BSL Bioservice
- Acclimation period: at least five days
- Other: female rats, non-pregnant, nulliparous

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3
- Humidity (%): 55 +/- 10
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12 /12

IN-LIFE DATES: From: To:

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 2 g/10 ml (2000 mg/kg bw); 0.3g / 10 ml (300 mg/kg bw)

MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg

Doses:

2000 and 300 mg/kg bw

No. of animals per sex per dose:

3 (2000 mg/kg) and 6 (300 mg/kg)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
* Clinical examination: careful examination several times on the day of dosing (at least once during the first 30 minutes and with special attention given during the first 4 hours post dose); thereafter, animals were observed for clinical signs once daily until the end of the observation period.
* Weighing: on day 1 (prior to administration) and on days 8 and 15
- Necropsy of survivors performed: yes/no
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other:

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

500 mg/kg bw

Mortality:

One animal of step 1 (treated with the test item at a dose of 2000 mg/kg) was found dead 3 days post-dose and two animals of step 1 were found dead 5 days post-dose. All animals of the second and third step (treated with the test item at a dose of 300 mg/kg) survived until the end of the study.

Clinical signs:

The most relevant clinical findings in the animals treated with the test item at a dose of 2000 mg/kg bw were piloerection, diarrhoea, wasp waist, nasal discharge and body weight loss.
All animals of the second and third step (treated with the test item at a dose of
300 mg/kg) survived until the end of the study.
The most relevant clinical findings in the animals treated with the test item at a dose of 300 mg/kg bw were piloerection and slightly reduced spontaneous activity. The clinical signs were observed only on the day of administration in these animals.

Body weight:

Throughout the 14-day observation period, the weight gain of the animals treated with the test item at a dose of 300 mg/kg bw, was within the normal range of variation for this strain.

Gross pathology:

Necropsy of the 2000 mg/kg group revealed bloody nose and mouth in two animals. And in one animal the stomach was filled with discoloured material (blue/black). The Jejunum, ileum with Peyers`s Patch, caecum, colon and rectum were very small and filled with liquid only.
At necropsy, no macroscopic findings were observed in any animal of the 300 mg/kg group.

Any other information on results incl. tables

Results per Step:

Step	Sex/No.	Dose (mg/kg)	Number of Animals	Number of Intercurrent Deaths
1	female/1-3	2000	3	3
2	female/4-6	300	3	0
3	female/7-9	300	3	0

Applicant's summary and conclusion

Interpretation of results:

Toxicity Category IV

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Based on an LD50 cut-off of 500 mg/kg bw the substance should be classified as harmful with the criteria given in Annex VI to Commission Directive 2001/59/EC as well as in Annex I of Regulation (EC) 1272/2008.

Executive summary:

In an acute oral toxicity study, groups (3or 6/sex) of female Wistar rats were given a single oral dose of Ashes (residues), vanadium-contg. in water at doses of 2000 or 300 mg/kg bw. Animals were then observed for 14 days.

Oral LD50 cut-off = 500 mg/kg bw. The test material is classified as harmful.

This acute oral study is classified as acceptable. It does satisfy the guideline requirement for an acute oral toxicity study OECD 423 in the rats.