Ammonium wolframate

Endpoint summary

Description of key information

In an acute oral toxicity study conducted on rats and according to OECD 401, the LD50 was reported to be >2000 mg/kg. In an acute inhalation toxicity study conducted on rats, the 4hr-LC50 was reported to be >5.35 mg/L (5,350 mg/m3). In an acute dermal toxicity study conducted on rats and according to OECD 402, the LD50 was reported to be >2,000 mg/kg.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1998-02-24 to 1999-06-24

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

Well documented, scientifically sound study that was conducted in accordance to GLP and OECD guideline 401 with no deviation to the protocol.

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan UK Ltd, Bicester, Oxon, England
- Age at study initiation: 4 to 7 weeks
- Weight at study initiation: 80 to 108 g
- Fasting period before study: Access to food only was prevented overnight prior to and for approximately 4 hours after dosing.
- Housing: Housed in groups of 5 rats of the same sex in metal cages with wire mesh floors.
- Diet: Special Diet Services RM1(E) SQC expanded pellet- ad libitum
- Water: ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 to 22.5
- Humidity (%): 29 to 52%
- Air changes (per hr): 10 to 15
- Photoperiod (hrs dark / hrs light): 12/12 artificial light (0700 - 1900)

IN-LIFE DATES: From: 1998-02-24 To: 1998-03-10

Route of administration:

oral: gavage

Vehicle:

other: 1% w/v aqueous methylcellulose

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 20% w/v in 1% w/v aqueous methylcellulose

MAXIMUM DOSE VOLUME APPLIED :- 2000 mg/kg bodyweight

Doses:

2000 mg/kg bodyweight; administered at a dose volume of 10 mL/kg bodyweight.

No. of animals per sex per dose:

5 males and 5 females.

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: All surviving animals were killed on Day 15
- Mortality: Cages were checked at least twice daily for any mortalities.
- Clinical signs: Animals were observed soon after dosing and at frequent intervals for the remainder of Day 1. On subsequent days animals were observed once in the morning and again at the end of the experimental day (with exception of Day 15 - morning only). The nature and severity of the clinical signs and time were recorded at each observation.
- Bodyweight: Recorded on Days 1 (prior to dosing), 8 and 15. Individual weekly bodyweight changes and group mean bodyweights were calculated.
- Microscopic pathology: All animals were subjected to a macroscopic examination which consisted of opening the thoracic and abdominal cavities. The macroscopic appearance of all examined organs was recorded.

Statistics:

no data

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

There were no deaths in a group of ten rats (five males and five females ) following a single oral dose of Ammonium paratungstate at a dosage of 2000 mg/kg bodyweight.

Clinical signs:

other: Piloerection was observed in all rats within five minutes of dosing. This persisted and was accompanied on Day 1 only by hunched posture and abnormal faeces (characterised by soft to liquid and discoloured yellow/brown mucoid faeces), seen in all rats and

Gross pathology:

No macroscopic abnormalities were observed for animals killed at study termination on Day 15.

Interpretation of results:

GHS criteria not met

Conclusions:

The acute lethal oral dose to rats of ammonium wolframate was demonstrated to be greater than 2000 mg/kg bodyweight.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

Well documented, scientifically sound study that was conducted in accordance to GLP and OECD guideline 401 with no deviation to the protocol.

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1998-05-13 to 1999-05-28

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

Well documented, scientifically sound study that was conducted in accordance to GLP and generally accepted guidelines with no deviations to the protocol.

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River UK Ltd Manston Rd, Margate, Kent, England
- Age at study initiation: approximately 7 and 8 wks old
- Housing: Housed by sex in groups of 5 in holding cages (35 cm wide x 53 cm long x 25 cm high) made of stainless steel sheet and wire mesh and were suspended on a movable rack.
- Diet: SDS rat and mouse diet (RM1)- ad libitum
- Water: Tap water- ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 +/- 2
- Humidity (%): 55 +/- 10%
- Air changes (per hr): 12 to 15
- Photoperiod (hrs dark / hrs light): 12/12 (artificial light between 8 am and 8 pm daily)

IN-LIFE DATES: From: 1998-05-13 To: 1998-06-04

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Vehicle:

other: air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: The snout-only exposure chambers were of cylindrical form and made of aluminum alloy.

- Exposure chamber volume: 30 Litres

- Method of holding animals in test chamber: The rats were held for exposure in molded polycarbonate restraining tubes which were attached at evenly spaced ports in the cylindrical section of the chamber, and were designed to allow only the snout to project into the chamber. Each rat was restrained in a forward position by an adjustable foamed plastic stopper which also provided a seal for the tube.

- Source and rate of air: A supply of clean dried compressed air was connected to the WDF and the supply pressure was adjusted to give a flow rate of15 litres/minute measured at the generator outlet nozzle. The chamber exhaust was calibrated a the point of attachment to the chamber and adjusted to maintain the chamber at a slight negative pressure.

- Method of conditioning air: The test atmosphere was passed through an elutriation column to reduce, by sedimentation, the amount of non-respirable particulate in the test atmosphere.

- System of generating particulates/aerosols: The WDF was designed to produce and maintain atmospheres containing a particulate aerosol by suspending material scraped from the surface of a compressed powder in a stream of dry air. The concentration of the particulate aerosol in the air was determined by the rate at which the scraper blade is advanced into the compressed powder.

- Method of particle size determination: Two additional air samples were taken during the exposure, at a sampling rate of 2 Liters per minute, using a Marple cascade impactor. The samples were taken at 90 and 210 minutes of exposure. The volume of air sampled was measured using a wet-type gas meter. The amount of test material collected on the stages of the sampler was determined gravimetrically. The particle size distribution of the test atmosphere was assessed using linear regression analysis. The probit of the cumulative percentage of the total particles collected, smaller than the cut-point of each stage, was plotted against the logarithm of the cut-point of each stage.

- Temperature, humidity, pressure in air chamber: The air temperature in the exposure chamber was measured with a thermometer and the relative humidity was measured using a Vaisalla HM30 series hygrometer. The temperature and humidity were recorded at the start of exposure and then at 30-min intervals during the 4-hour exposure.

TEST ATMOSPHERE
- The test substance was processed using an ultracentrifugal mill in order to produce a powder suitable for generation of a test aerosol. The test substance was initially ground using a 1000 micron sieve. The milled test substance was then reprocessed twice using a 200 micron sieve and then once using an 80 micon sieve.
- Seven samples of air were removed from the test chamber during exposure in order to determine the concentration of the test aerosol. In the first instance, samples were obtained following equilibration and at approximately hourly intervals thereafter. Additional samples were obtained to monitor the chamber concentration following adjustments to the exposure system. A time weighted average was calculated from the individual data in order to prevent undue biasing of repeat samples in the overall mean. Each air sample was withdrawn, at a rate of 2 Liters per minute, through a pre-weighed glass fibre filter (Whatman GF/A) mounted in an open face filter holder. The filters were re-weighed following sampling for gravimetric analysis of the test aerosol. The volume of air sampled was measured using a wet-type gas meter.

- Samples taken from breathing zone: yes

TEST ATMOSPHERE (if not tabulated)
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): 5.1 um. Approximately 63% of the particles were less than 7 um in aerodynamics diameter and therefore of a respirable size.

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

Target concentration: 5 mg/L
Control animals were exposed to clean air only

No. of animals per sex per dose:

10 male and 10 females; allocated to 1 of 2 groups on arrival, each 5 males and 5 males.

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: Yes
- Other examinations performed: clinical signs, body weight, organ weights, histopathology

OBSERVATIONS:
The rats were observed intermittently for signs of reaction to the test substance during exposure and at least twice daily throughout the observation period.

CLINICAL SIGNS:
The clinical signs were recorded at the end of the chamber equilibration period, at 0.25, 0.5 and 1.0 hours and then at hourly intervals during the exposure. During the observation period a full clinical signs check was performed daily in the morning. The rats were checked for survival later in the day.

BODYWEIGHT:
All rats were weighed at least twice during the week prior to the exposure, immediately before exposure (Day 0) and weekly during the observation period.

FOOD CONSUMPTION:
The amounts of food consumed by each cage of rats was measured from weighday to weighday throughout the study. The daily mean intakes of food for each cage were calculated from the recorded data.

WATER CONSUMPTION:
A visual inspection of the water bottles was conducted daily.

MACROSCOPIC EXAMINATION:
All rats were subjected to a complete macroscopic examination. The lungs, liver and kidneys were removed and weighed.

Statistics:

no data

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 5.35 mg/L air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

other: The time weighted average (TWA) concentration of total particulate in the chamber air was in agreement with target.

Mortality:

There were no unscheduled deaths.

Clinical signs:

other: During Exposure: There were no treatment-related findings during exposure. - Soiling of the fur with excreta was seen in test and control rats from 1 hour of exposure. This finding was associated with the method of restraint. Observation Period: Irregul

Body weight:

The mean bodyweight gain (Day 0 to 7) of test rats was lower than that of the controls following exposure to ammonium paratungstate. Mean bodyweight gain of test rats in the second week of the observation period (Day 8 to 14) was higher than the controls such that Day 14 bodyweights of the male test rats were similar to control values.

Gross pathology:

Macroscopic pathology (Day 14): There were no treatment-related findings at necropsy. A dark focus was seen on the left lung of 1 male and 1 femaletest rat and 1 female control rat.

Other findings:

Food Consumption: A small reduction in the mean food consumption of test rats was apparent following exposure (Day 1 to 7). This is considered treatment-related.

Water consumption: A visual appraisal of the water bottles indicated that the amount of water consumed by the test rats was similar to that of the control rats.

Organ weights (Day 14): Mean organ weights of test rats were similar to control values.

Chamber concentration of ammonium paratungstate:

The time weighted average (TWA) concentration of total particulate in the chamber air was 5.35 mg/L and was in agreement with target.

MMAD

The MMAD was higher than the ideal range (1 um to 4 um) at 5.1 um, for an acute inhalation study and was attributable to the nature of the sample of test substance supplied.

Chamber air temperature and relative humidity:

Temperature (degrees C)

Control- Mean 20.7 +/- 0.36

2 (Test)- Mean 20.7 +/- 0.50

Relative Humidity

Control- Mean 20 +/- 2.1

2 (Test)- Mean 39 +/- 2.7

There were no extremes of chamber air temperatures or humidity considered likely to have influenced the results of the study.

Interpretation of results:

GHS criteria not met

Conclusions:

There were no deaths following a four-hour exposure of rats to a particulate aerosol generated from ammonium paratungstate at a concentration of 5.35 mg/L. The LC50 (4-hour) for ammonium wolframate is therefore in excess of 5.35 mg/L of air.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

5 350 mg/m³ air

Quality of whole database:

Well documented, scientifically sound study that was conducted in accordance to GLP and OECD guideline 403 with no deviation to the protocol.

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1998-02-24 to 1999-06-24

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

Well documented, scientifically sound study that was conducted in accordance to GLP and OECD guideline 402 with no deviation to the protocol.

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan UK Ltd, Bicester, Oxon, England
- Age at study initiation: 8 to 11 weeks
- Weight at study initiation: 214 to 245 g
- Housing: Individually in metal cages with wire mesh floors.
- Diet (eg ad libitum): Special Diet ServicesRM1(E) SQC expanded pellet- ad libitum
- Water (eg ad libitum): ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 to 22.5
- Humidity (%): 29 to 52%
- Air changes (per hr): 10 to 15
- Photoperiod (hrs dark / hrs light): 12/12 artificial light (0700 - 1900)

IN-LIFE DATES: From: February 24, 1998 To:March 10, 1998

Type of coverage:

occlusive

Vehicle:

other: 1% w/v aqueous methylcellulose

Details on dermal exposure:

TEST SITE
- Area of exposure: Dorso-lumbar region
- % coverage: 10 %
- Type of wrap if used: The treatment area (approximately 50 mm x 50 mm) was covered with porous gauze with a waterproof dressing encircled firmly around the trunk of the animal.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Washed with warm water (30 to 40 °C)
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bodyweight; maximum practical concentration of 200% w/v in 1% aqueous methylcellulose and administered at a dose volume of 1 mL/kg bodyweight.
- Constant volume or concentration used: Yes

VEHICLE
- Concentration (if solution): 1 % w/v aqueous methylcellulose

Duration of exposure:

24 hours

Doses:

Single dose of 2000 mg/kg bodyweight

No. of animals per sex per dose:

5 males and 5 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: Yes, all animals were killed on Day 15
- Mortality: Cages of rats were checked at least twice daily for any mortalities.
- Clinical signs: Animals were observed soon after dosing and at frequent intervals for the remainder of Day 1. On subsequent days animals were observed once in the morning and again at the end of the experimental day (with the exception of Day 15 -morning only). The nature of the clinical signs and time were recorded at each observation.
- Dermal responses: Local dermal irritation at the treatment site was assessed daily using the numerical scoring system presented below.
- Bodyweight: The bodyweight of each rat was recorded on Days 1 (prior to dosing), 8 and 15. Individual weekly bodyweight changes and group mean bodyweights were calculated.
- Macroscopic pathology: All animals were subjected to a macroscopic examination which consisted of opening the abdominal and thoracic cavities. The macroscopic appearance of all tissues was recorded and macroscopic abnormalities were preserved.

Statistics:

no data

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

There were no deaths.
The acute lethal dose to rats of Ammonium paratungstate was demonstrated to be greater than 2000 mg/kg bodyweight.

Clinical signs:

other: There was no evidence of a systemic response in any animal throughout the study period.

Gross pathology:

No macroscopic abnormalities were observed for animals killed at study termination on Day 15.

Other findings:

No dermal irritation was seen in any animal during the study.

Interpretation of results:

GHS criteria not met

Conclusions:

The acute lethal dermal dose to rats of ammonium paratungstate was demonstrated to be greater than 2000 mg/kg bodyweight.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

Well documented, scientifically sound study that was conducted in accordance to GLP and OECD guideline 402 with no deviation to the protocol.

Justification for classification or non-classification

Acute toxicity studies of sufficient quality and tested in accordance with standard methodology showed that the acute oral LD50 was >2000 mg/kg in rats, the acute dermal LD50 was >2000 mg/kg, and the acute inhalation LC50 was >5.35 mg/L/4h for ammonium paratungstate. The oral LD50 cutoff value for classification is 2000 mg/kg, the dermal LD50 cutoff value for classification is 2000 mg/kg, and the inhalation LC50 cutoff value for classification is 5.0 mg/L/4 hr for dusts and mists. Therefore, no classification is required for ammoium paratungstate.