Vanadyl pyrophosphate

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1990

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP compliant study conducted in accordance with internationally recognised test methods

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1990

Report date:

1990

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Vanadyl pyrophosphate

EC Number:

406-260-5

EC Name:

Vanadyl pyrophosphate

Cas Number:

58834-75-6

Molecular formula:

V2P2O9

IUPAC Name:

divanadium(4+) (phosphonatooxy)phosphonate dioxidandiide

Details on test material:

- Name of test material (as cited in study report): BTN/A
- Chemical name: Vanadyl pyrophosphate
- Chemical formula: (VO)2P207
- Relative molar mass: 307.8
- Physical state Fine, dark-brown powder
- Lot/batch No.:0003
- Purity: Vanadium - 30.1%, phosphorous 21.0% by weight
- Storage condition of test material: Cool, dry, well ventilated room

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

Animals
Young adult rats of the CD strain (remote Sprague-Dawley origin), supplied by Charles River (U.K.) Limited, Margate, Kent, England, were six to eight weeks old on arrival. The animals had been bredunder barriered conditions and travelled from the supplier to the animal-holding room in sealed boxes with filter protected air-vents. The albino rat was selected for this study as it has been widely accepted as the standard laboratory species for use in acute toxicity tests. The strain has been used for toxicological purposes since its establishment under S.P.F. conditions in 1955. The animals were housed in stainless steel grid cages measuring 54 x 33 x 20 cm, (Steven Clarke Fabrications Ltd., Alva, Clackmannanshire, Scotland)The grid floors ensured rapidremoval of waste material to undertrays which were cleaned as necessary. Five animals of the same sex were housed in each cage, unless reduced by mortality. The cages were suspended in mobile stainless steel racks.

Husbandry
The animals were held in a limited-access rodent facility. All rooms were kept at slight positive pressure relative to the outside and each had its own filtered air supply giving approximately 15 complete air changes per hour without re-circulation. Target values for temperature and relative humidity were 21°C (range 18°-25°C) and 55% R.H. (range 40%-70% R.H.), respectively. The achieved values were monitored daily. Electric time-switches regulated a lighting cycle of 12 hours of artificial light per day. An emergency generator was available to maintain the electricity supply in the event of a powerfailure. All personnel entering the building changed into clean protective clothing and wore a gown, gloves, plastic over-shoes and face mask
to service animal-holding areas. A commercially-available complete pelleted rodent diet (Laboratory Animal Diet No. 1, from Biosure, Manea, Cambridgeshire, England) was fed without restriction. The manufacturer supplied analytical data with each batch of diet which included concentrations of nutritional components, aflatoxins and selected heavy metals, pesticides and micro-organisms. The diet contained no added antibiotic or other chemotherapeutic or prophylactic treatment. Animals had free access to tap water supplied in a single bottle per cage and re-filled as required. The water was supplied by the East Anglian Water Company to meet the World Health Organisation International Standard. Regular reports from the local Water Authority recorded the known chemical and bacteriological quality of the water. There was no information indicating that normal levels of common contaminants, or any specific contaminants, would influence the outcome of the study.
Pre-exposure period
Clean cages were prepared the day before delivery of the animals. On arrival, each animal was inspected before being accepted. All animals were weighed on arrival and the range·of bodyweight was recorded. Five rats of the same sex were non-selectively allocated to each cage. Tail tattoos identifying each individual within the cage were made within one day of delivery. The sex of each animal was checked at the same time. An acclimatisation period of at least six days was allowed before administration of the test material. A daily check on the general condition of the ·animals was made during this time and the record was consulted before each cage of animals was accepted for use in the study. On the day before dosing, each cage was labelled with details of the schedule number, unique cage reference number, treatment regime, animal identification numbers, sex of occupants, Project Licence number and responsible licensee. The dorsum between the limb-girdles was clipped free of hair as close to the skin as possible using Oster small animal clippers. The exposed application site of each rat was examined before the animal was allocated to study. Bodyweight was recorded on the day prior to dosing and was in the range 250 - 260 g for males and 186 - 219 g for females. Theanimals were seven to nine weeks old at this time.

Preparation of test material
Fresh aliquots of the test material were dispensed on the morning of administration and any surplus remaining after dosing was
destroyed on the same day. The dosage was calculated and expressed gravimetrically in terms of the material as received.
TEST ANIMALS
- Source: Charles River (UK) Ltd, Margate, Kent, ENgland
- Age at study initiation: 7 - 9 weeks
- Weight at study initiation: Males: 250 - 260g; females: 186 - 219 g
- Fasting period before study: n/a
- Housing: 5 animals of same sex / cage; in stainless steel cages with grid floor
- Diet (e.g. ad libitum): Pelleted rodent diet, Biosure, Cambridge, England, ad libitum
- Water (e.g. ad libitum): Municipal tap water, ad libitum
- Acclimation period: at least 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 - 25 deg C
- Humidity (%): 40 - 70%
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12 hours light / 12 hours dark

IN-LIFE DATES: From: 1990-03-09 To: 1990-03-23

Administration / exposure

Type of coverage:

occlusive

Vehicle:

maize oil

Details on dermal exposure:

The dose was determined for each animal according to its bodyweight on the morning of dosing. The test material was placed on a gauze patch and moistened by application of 0.2 ml distilled water immediately before dosing. This was intended to ensure good contact between the test material and the skin surface and to simulate the maximum adverse conditions of the product in use. The gauze patch was placed on the closely-clipped dorsum and was occluded with aluminium foil. The foil was kept in place and protected by a bandage of waterproof plaster (IISl ee k", Smith and Nephew Limited) wrapped twice around the trunk of the body with sufficient tension to ensure the dose remained securely in place. On completion of dosing, the animals were accommodated individually in Type RB3 cages measuring 45 x l8 x 20 cm (North Kent Plastics Limited, Dartford, Kent, England). The dressings were removed 24 hours after administration. The dermal site was gently wiped with wet disposable towels to remove residual test material. The animals were then returned to their original cages.

Duration of exposure:

24 hours

Doses:

2000 mg/kg.body weight

No. of animals per sex per dose:

1 group of 5 males and 5 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical signs: 5 times on day of dosing and twice daily thereafter. Bodyweights: Weekly (Days 1, 8 and 15)
- Necropsy of survivors performed: Yes

Statistics:

Not applicable

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

There was no mortality:.
Male: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0
Female: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0

Clinical signs:

other: There was no systemic sign of reaction to treatment. The only local sign of reaction to treatment at the dermal application site was black discolouration of teh treated skin in all animals on Day 2. The change was considered to be a staining effect of the

Gross pathology:

Necropsy, on Day 15, revealed no significant macroscopic lesion.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of this study, the acute percutaneous median lethal dosage (LD50) of the test material was greater than 2000 mg/kg.

Executive summary:

Acute dermal toxicity has been investigated using OECD/EU test methods. The median lethal dose (LD50) of the substance following administration of a single dermal dose to the rat for a 24 hour period is > 2000 mg/kg body weight