Hexaammonium wolframate

Endpoint summary

Description of key information

An acute oral toxicity of sufficient quality and conducted according to OECD 423 reported an LD50 of 1000<LD50<1373 mg/kg bw (ca. 746<LD50<1024 mg W/kg bw) for ammonium metatungstate. No acute dermal or inhalation toxicity data are available for ammonium metatungstate. However, acute dermal toxicity studies performed according to OECD 402 are available from limit studies with ammonium paratungstate, sodium metatungstate and sodium tungstate (source substances), which report dermal LD50 values >2000 mg/kg bw for all of the read-across substances. Acute inhalation toxicity studies performed according to OECD 403 are available for ammonium paratungstate and sodium tungstate, which report a 4-h LC50 >5.35 mg APT/L air (ca. 3.14 mg W/L air) for ammonium metatungstate and a 4-h LC50 >5.01 mg sodium tungstate/L air (ca. 2.94 mg W/L air) for sodium tungstate.

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:

2009-09-24 to 2010-12-20

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

GLP study conducted according to OECD Guideline 423: Acute Oral Toxicity-Acute Toxic Class Method, except that the second dose used after 2000 mg/kg was 1373 mg/kg instead of the recommended 300 mg/kg as the purpose of the study was not only to determine the acute oral toxicity of the test substance, but to aid in the classification according to the CLP regulations and to support a read-across strategy for tungsten substances.

Qualifier:

according to guideline

Guideline:

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

Deviations:

yes

Remarks:

The second dose used after 2000 mg/kg was 1373 mg/kg instead of 300 mg/kg.

GLP compliance:

yes

Remarks:

Statement, no certificate

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories (Portage, MI)
- Age at study initiation: 7-8 weeks at arrival
- Weight at study initiation: 170-198 g (bw of first shipment day after arrival), 186-201 g (bw of second shipment day after arrival)
- Fasting period before study: Yes, overnight
- Housing: Rats were individually housed in stainless steel wire cages suspendered over excrement pans. Absorbent pan liners were placed in the pan below the stainless steel mesh floor of each animal cage to absorb liquids.
- Diet (eg ad libitum): Certified Rodent Chow 5002 meal was provided ad libitum, except for an overnight fasting period immediately preceding test substance administration, and 3 to 4 hours after dosing.
- Water (eg ad libitum): Fresh city of Chicago water without additional treatment was available ad libitum.
- Acclimation period: ~1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17.4-23.6
- Humidity (%): 31-69
- Air changes (per hr): IITRI does not monitor animal room air changes daily; however, IITRI measures animal room air flow rates annually.
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

water

Remarks:

Milli-Q

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 100, 150 and 400 mg/ml

MAXIMUM DOSE VOLUME APPLIED: The maximum volume did not exceed 1 ml/100 g body weight.

DOSAGE PREPARATION: The test substance dosing formulations were prepared either one day prior to or on the day of dosing, by dissolving the bulk test substance in Milli-Q water and mixing until dissolved.

Doses:

2000, 1373, and 1000 mg/kg

No. of animals per sex per dose:

3 animals (2000 mg/kg), 6 animals (1373 mg/kg) and 6 animals (1000 mg/kg); See "any other information on materials and method" section.

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: All animals were observed at least once during the first 30 minutes after dosing, periodically during the first 24 hours (with special attention given during the first 4 hours) and at least once daily thereafter (for all surviving animals). Observations included any changes in skin and fur, eyes and mucous membranes, respiratory, circulatory and autonomic and central nervous systems, and somatomotor activity and behaviour pattern. Special attention was given to observations of tremors, convulsions, salivation, diarrhea, lethargy and coma. Body weights were determined one day after receipt and on the day of randomization to facilitate test subject selection. Body weights for study animals were measured on the day of treatment (prior to dosing), weekly thereafter (for all surviving animals), and at death.
- Necropsy of survivors performed: yes; A limited gross necropsy was performed on all animals which died during the study or were sacrificed at the end of the 14 day observation period. The necropsy on day 15 included examination of all body surfaces and orifices; and the external appearance of the brain, heart, lungs, spleen, liver, kidneys, gastrointestinal tract, urinary bladder and gonads. If external lesions were present, then the stomach and the rest of the gastrointestinal tract and the urinary bladder were opened and examined.

Statistics:

As a vehicle control group was not used, and the number of animals was not sufficient, statistical analyses on clinical observations, body weight and body weight gain were not conducted.

Sex:

female

Dose descriptor:

LD50

Effect level:

> 1 000 - < 1 373 mg/kg bw

Remarks on result:

other: Estimated

Mortality:

The three animals from Group 1, which were dosed at 2000 mg/kg, all died; the six animals in groups 2 and 3, which were dosed at 1373 mg/kg, all died; no animal deaths occurred in groups 4 and 5, which were dosed at 1000 mg/kg.

Clinical signs:

other: Clinical observations observed during the post dosing periods included: Group 1 (2000 mg/kg): discolored inguinal fur, discolored urine, rough coat, and redness around nose fur. Groups 2 and 3 (1373 mg/kg): rough coat, salivation, emaciation, diarrhea,

Gross pathology:

Gross necropsy observations seen in animals that died included dark red small intestine, dark red fluid in the stomach, red foci on the stomach, dilated urinary bladder, enlarged cervical lymph node, enlarged and red mesenteric, mandibular and bronchial lymph nodes, pale liver and kidney, and clear fluid in the pleural cavity. The six animals in the 1000 mg/kg group had no gross observations at necropsy.

The dose formulations prepared at 150 mg/ml were within 10% of the target concentration. The dose formulation prepared at 400 mg/ml was found to be 118 % of its target value. Chemical analysis was not performed on the 1000 mg/kg (100 mg/ml) formulation as the standard practice at IITRI is to verify at least two formulations: The results of the formulations analysis (the 400 mg/ml formulation was 18% higher than the target and the 150 mg/ml formulation was 10% higher than the target) would indicate that the 100 mg/ml formulation was prepared within the target range.

Interpretation of results:

GHS criteria not met

Conclusions:

The estimated oral LD50 of treated female Sprague Dawley rats was >1000-<1373 mg/kg.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

1 000 mg/kg bw

Quality of whole database:

GLP study conducted according to OECD Guideline 423

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: inhalation

Type of information:

read-across based on grouping of substances (category approach)

Adequacy of study:

supporting study

Study period:

1998-05-13 to 1999-05-28

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

Well documented, scientifically sound study that was conducted in accordance to GLP and generally accepted guidelines with no deviations to the protocol. The reliability of this study for this substance tested is a K1, but in application of read-across to a different substance, ECHA's guidance specifies that the score can be a maximum of a K2.

Justification for type of information:

1. HYPOTHESIS FOR THE CATEGORY APPROACH: The hypothesis is that properties are likely to be similar or follow a similar pattern because of the presence of a common metal ion, in this case tungstate.
2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES):
Source: Ammonium paratungstate
Target: Ammonium metatungstate
3. CATEGORY APPROACH JUSTIFICATION: See Annex 3 in CSR
4. DATA MATRIX: See Annex 3 in CSR

Reason / purpose for cross-reference:

read-across: supporting information

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 Wright Dust Feed Mechanism (WDF) and the supply pressure was adjusted to give a flow rate of 15 litres/minute measured at the generator outlet nozzle. The chamber exhaust was calibrated at 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 was 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)

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 body weight 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 ( °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 paratungstate is therefore in excess of 5.35 mg/L of air.

Executive summary:

No acute inhalation toxicity data of sufficient quality were available specifically on ammonium metatungstate (target substance). However, acute inhalation toxicity data are available on ammonium paratungstate (source substance), which are used for read-across. Due to similar water solubility for the target substance compared to the source substance, the resulting read-across from the source substance to the target substance is appropriate to estimate of potential toxicity for this endpoint. For more details, refer to the read-across category approach description in the Category section of this IUCLID submission or Annex 3 of the CSR.

Reference 2

Endpoint:

acute toxicity: inhalation

Type of information:

read-across based on grouping of substances (category approach)

Adequacy of study:

key study

Study period:

1998-5-12 to 1999-05-28

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

Conducted similar or equivalant to OECD 403 and per GLP guidelines. The reliability of this study for this substance tested is a K1, but in application of read-across to a different substance, ECHA's guidance specifies that the score can be a maximum of a K2.

Justification for type of information:

1. HYPOTHESIS FOR THE CATEGORY APPROACH: The hypothesis is that properties are likely to be similar or follow a similar pattern because of the presence of a common metal ion, in this case tungstate.
2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES):
Source: Sodium Tungstate
Target: Ammonium metatungstate
3. CATEGORY APPROACH JUSTIFICATION: See Annex 3 in CSR
4. DATA MATRIX: See Annex 3 in CSR

Reason / purpose for cross-reference:

read-across: supporting information

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

yes

Remarks:

however, the deviations from the protocol did not affect the objectives and integrity of the study.

GLP compliance:

yes (incl. QA statement)

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: 7 to 8 wks
- Housing: By sex in groups of 5 in metal cages and wire mesh.
- Diet: SDS rat and mouse diet (RM1) ad libitum
- Water: tap water ad libitum
- Acclimation period: 6 days


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


IN-LIFE DATES: From: May 6, 1998 To: May 26, 1998

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 used for the exposures were of cylindrical form and made of aluminium alloy. The chambers have an enclosed volume of 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 generator and the supply presure was adjusted to give a flow rate of 15 litres/min. measured at the generator outlet nozzle. The chamber exhaust airflow was calibrated at the point of attachment to the chamber and adjusted to maintain the chamber at a slightly 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 Wright Dust Feed mechanism (WDF), the Fast WDF was used for generation of test atmosphere. The generator was designed to produce and maintain atmospheres containing dust by suspending material scraped from the surface of a compressed powder in a stream of dry air. The concentration of dust in the air is determined by the rate at which the scraper blade is advanced into the compressed powder.

- Method of particle size determination: The Mass median aerodynamic diameter (MMAD) of the airborne dust was 5.1 um. Approximately 65% of the particles were less than 7 um in aerodynamic diameter and of a respirable size.

- 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 Casella Type T6900 relative humidity meter. The temperature and relative humidity were recorded at the start of exposure and then at 30-min. intervals during the 4-hr exposure.


TEST ATMOSPHERE
- Brief description of analytical method used: The nominal concentration of the test substance was calculated from the total amount of sodium tungstate dihydrate dispersed by the generator and the total volume of air flowing through the exposure system during the period of generation.

- Samples taken from breathing zone: yes, in the fist instance, samples were obtained following equilibration and at approximately hourly intervals after. An addtional sample was obtained to monitor the chamber concentration following adjustment to the exposure system. Each air sample was withdrawn, at a rate of 2 litres per minute, through a pre-weighed glass fibre filter (Whatman GF/A) mounted in an open face filter holder. The filters were weighed again following sampling for gravimetric analysis of the test aerosol. The volume of air sampled was measured using a wet-type gas meter.


TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: Two additional air samples were taken during the exposure, at a sampling rate of 2 litres per min., using a Marple cascade impactor. The samples were taken at 98 and 225 min. 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.

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

Time weighted average: 5.01 mg/L Gravimetric concentration

No. of animals per sex per dose:

10 males and 10 females divided into 2 groups (5 males and 5 females).

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Rats were observed intermittently for signs of reaction to the test substance during exposure and at least twice daily through the observation period.
- Necropsy of survivors performed: yes, At the end of the 14-day observation period, the rats were killed by intraperitoneal injection.
- 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. Clinical signs were recorded immediately post exposure and than at 1 hour and 2 hours post exposure.
-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 bottle was conducted each day.
-Macroscopic examination: All rats were subjected to a complete macroscopic examination. The lungs, liver and kidneys were removed, and weighed.

Statistics:

no data

Preliminary study:

The conditions used during Preliminary Generation Trials were selected for exposure of rats in order to generate an anticipated chamber concentration close to target (5 mg/L). Re-milling of the test substance and modification of generation conditions did not significantly reduce the particle size of the dust aerosol.

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 5.01 mg/L air

Exp. duration:

4 h

Mortality:

There were no unscheduled deaths during the study.
The LC50 (4-hour) for sodium tungstate dihydrate was determined to be in excess of 5.01 mg/L.

Clinical signs:

other: DURING EXPOSURE Wet fur on the head and around the mouth was observed in all test rats from 1 hour of exposure. Soiling of fur with excreta was noted in both control and test rats and was associated with the method of restraint used during exposure. OBSE

Body weight:

The mean bodyweight gain of male test rats was lower than that of the controls following exposure to sodium tungstate dihydrate. The mean bodyweight gain of female test rats was similar to control values.

Gross pathology:

There was slight congestion of the lungs of 2 male and 2 female test rats. Moderate congestion of the liver was also noted in 2 male test rats.
Dark foci were seen on the lungs of 2 male test rats; this finding is not uncommon in untreated rats.

Other findings:

- Organ weights: Mean organ weights for test rats were similar to control values.
-Food consumption: There was no treatment-related effect.
-Water consumption: A visual appraisal of the water bottles indicated that the amount consumed by the test rats was similar to that of the control rats.

Interpretation of results:

GHS criteria not met

Conclusions:

The rat inhalation LC50 was determined to be in excess of 5.01 mg/L.

Executive summary:

No acute inhalation toxicity data of sufficient quality were available specifically on ammonium metatungstate (target substance). However, acute inhalation toxicity data are available on sodium tungstate (source substance), which are used for read-across. Due to similar water solubility and toxicity for the target substance compared to the source substance, the resulting read-across from the source substance to the target substance is appropriate for this endpoint. In addition, read-across is appropriate because the classification and labelling is similar for the source substance and target substance, the PBT/vPvB profile is the same, and the dose descriptors are, or are expected to be, conservative for the target substance. For more details, refer to the read-across category approach description in the Category section of this IUCLID submission or Annex 3 of the CSR.

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 generally accepted guidelines with no deviations to the protocol. The reliability of this study for this substance tested is a K1, but in application of read-across to a different substance, ECHA's guidance specifies that the score can be a maximum of a K2.

Acute toxicity: via dermal route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: dermal

Type of information:

read-across based on grouping of substances (category approach)

Adequacy of study:

supporting study

Study period:

1998-02-24 to 1999-06-24

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

Well documented, scientifically sound study that was conducted in accordance to GLP and OECD guideline 402 with no deviation to the protocol. The reliability of this study for this substance tested is a K1, but in application of read-across to a different substance, ECHA's guidance specifies that the score can be a maximum of a K2.

Justification for type of information:

1. HYPOTHESIS FOR THE CATEGORY APPROACH: The hypothesis is that properties are likely to be similar or follow a similar pattern because of the presence of a common metal ion, in this case tungstate.
2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES):
Source: Ammonium paratungstate
Target: Ammonium metatungstate
3. CATEGORY APPROACH JUSTIFICATION: See Annex 3 in CSR
4. DATA MATRIX: See Annex 3 in CSR

Reason / purpose for cross-reference:

read-across: supporting information

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 (e.g. ad libitum): Special Diet ServicesRM1(E) SQC expanded pellet- ad libitum
- Water (e.g. 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 degrees 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.

Executive summary:

No acute dermal toxicity data of sufficient quality were available specifically on ammonium metatungstate (target substance). However, acute dermal toxicity data are available on ammonium paratungstate (source substance), which are used for read-across. Due to similar water solubility for the target substance compared to the source substance, the resulting read-across from the source substance to the target substance is appropriate to estimate of potential toxicity for this endpoint. For more details, refer to the read-across category approach description in the Category section of this IUCLID submission or Annex 3 of the CSR.

Reference 2

Endpoint:

acute toxicity: dermal

Type of information:

read-across based on grouping of substances (category approach)

Adequacy of study:

supporting study

Study period:

1990-09-26 to 1991-01-14

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

Well documented, scientifically sound study conducted according to OECD Guideline 402 and GLP. The reliability of this study for the substance tested is a K1, but in application of read-across to a different substance ECHA’s guidance specifies that the score can be a maximum of K2.

Justification for type of information:

1. HYPOTHESIS FOR THE CATEGORY APPROACH: The hypothesis is that properties are likely to be similar or follow a similar pattern because of the presence of a common metal ion, in this case tungstate.
2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES):
Source: Sodium Metatungstate
Target: Ammonium metatungstate
3. CATEGORY APPROACH JUSTIFICATION: See Annex 3 in CSR
4. DATA MATRIX: See Annex 3 in CSR

Reason / purpose for cross-reference:

read-across: supporting information

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

Version adopted February 24, 1987.

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: BRL Ltd, Basel, Switzerland
- Age at study initiation: Approximately 9 weeks
- Weight at study initiation: Males (243 - 260 g); Females (176 - 195 g)
- Fasting period before study: None
- Housing: 5 per sex per cage, polycarbonate cages with purified sawdust bedding (Woody SPF, Broekman Inst., Someren, The Netherlands)
- Diet: Kliba 343 pellets from Klingentalmuhle AG, Kaiseraugst, Switzerland, ad libitum.
- Water: tap water ad libitum
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 deg C
- Humidity (%): 55%
- Air changes (per hr): 15 per hour
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: September 26, 1990 To: October 10, 1990

Type of coverage:

occlusive

Vehicle:

water

Remarks:

purified by reverse osmosis

Details on dermal exposure:

TEST SITE
- Area of exposure: 5 x 5 cm (25 sq. cm) for males, 3.5 x 5 cm (18 sq. cm) for females; clipped area on the back of the animal.
- Type of wrap if used: gauze patch, aluminum foil and flexible bandage

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Residue removed with a tissue moistened with tap water.
- Time after start of exposure: 24 hr

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw
- Constant volume or concentration used: yes
- For solids, paste formed: yes

VEHICLE
- Amount(s) applied (volume or weight with unit): equal w/w of water added when preparing dose.
- Concentration (if solution): N/A
- Lot/batch no. (if required):N/A
- Purity: puried by reverse osmosis

Duration of exposure:

24 hr

Doses:

2000 mg/kg body weight (single limit dose)

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

- Frequency of observations and weighing:
-- Mortality/Viability: At periodic intervals on the day of dosing (day 1) and twice daily thereafter for 14 days.
-- Body weights: Day 1 (pre-administration), 8 and 15
-- Symptoms: At periodic intervals on the day of dosing (day 1) and once daily thereafter for 14 days.

- Necropsy of survivors performed: yes

- Other examinations performed: All signs of reaction to treatment were recorded with particular attention paid to changes in the skin (treated skin), fur, eyes and mucous membranes, as well as to behaviour pattern, tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma. Macroscopic findings were recorded at necropsy.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No deaths occurred during the study.

Clinical signs:

other: Bloody eye encrustation was noted in 1 male on day 1 and 1 female on day 2. Treated skin revealed erythema, sore spot and scabs. With the exception of one female with scabs, all skin abnormalities had disappeared by the end of the observation period.

Gross pathology:

Macroscopic post-mortem examination did not reveal any abnormalities.

Other findings:

No data.

Interpretation of results:

GHS criteria not met

Conclusions:

The dermal LD50 value of the test substance in rats of either sex was found to be > 2000 mg/kg bw.

Executive summary:

No acute dermal toxicity data of sufficient quality were available specifically on ammonium metatungstate (target substance). However, acute dermal toxicity data are available on sodium metatungstate (source substance), which are used for read-across. Due to similar water solubility for the target substance compared to the source substance, the resulting read-across from the source substance to the target substance is appropriate to estimate of potential toxicity for this endpoint. For more details, refer to the read-across category approach description in the Category section of this IUCLID submission or Annex 3 of the CSR.

Reference 3

Endpoint:

acute toxicity: dermal

Type of information:

read-across based on grouping of substances (category approach)

Adequacy of study:

key study

Study period:

1998-03-09 to 1999-06-24

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

Study was performed per OECD guideline 402 and per GLP. The reliability of this study for this substance tested is a K1, but in application of read-across to a different substance, ECHA's guidance specifies that the score can be a maximum of a K2.

Justification for type of information:

1. HYPOTHESIS FOR THE CATEGORY APPROACH: The hypothesis is that properties are likely to be similar or follow a similar pattern because of the presence of a common metal ion, in this case tungstate.
2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES):
Source: Sodium Tungstate
Target: Ammonium metatungstate
3. CATEGORY APPROACH JUSTIFICATION: See Annex 3 in CSR
4. DATA MATRIX: See Annex 3 in CSR

Reason / purpose for cross-reference:

read-across: supporting information

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

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 wks
- Weight at study initiation: 235 to 300 g
- Housing: Individually in metal cages with wire mesh floors.
- Diet: ad libitum - Special Diet Services RM1(E) SQC expanded pellet.
- Water: ad libitum
- Acclimation period: 18 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 22.5 C
- Humidity (%): 29 to 50%
- Air changes (per hr): 10 to 15
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: March 9, 1998 To: March 23, 1998

Type of coverage:

occlusive

Vehicle:

water

Details on dermal exposure:

TEST SITE
- Area of exposure: dorso-lumbar region
- % coverage: 10%
- Type of wrap if used: Porous gauze with a non-irritating dressing covered by a waterproof dressing encircled firmly around the trunk of the animal.


REMOVAL OF TEST SUBSTANCE
- Washing: with warm water and blotted dry with absorbent paper.
- Time after start of exposure:24 hrs


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bodyweight
- Constant volume or concentration used: yes
-Test material was applied by spreading it evenly over the prepared skin.

Duration of exposure:

24 hrs

Doses:

2000 mg/kg bodyweight, single dose.
Maximum practical concentration of 250% w/v in distilled water and administered at a dose volume of 0.8 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
- Frequency of observations and weighing: Animals were observed at lest twice daily for mortalities through 14 days.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, histopathology
-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 and severity of the clinical signs and time were recorded at each observation.
-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.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

There were no deaths and no evidence of a systemic response in any animal throughout the study.

Clinical signs:

other: Slight erythema only was observed in three rats following removal of the dressings on Day 2 which was still evident in two animals on Day 3 before resolving in all instances by Day 4. No dermal irritation was seen in the remaining seven animals.

Gross pathology:

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

Interpretation of results:

GHS criteria not met

Conclusions:

There were no deaths and no evidence of a systemic response in any animal throughout the study following a single dermal application of the test substance to rats at a dose level of 2000 mg/kg-bw. The acute lethal dose was determined to be greater than 2000 mg/kg bw.

Executive summary:

No acute dermal toxicity data of sufficient quality were available specifically on ammonium metatungstate (target substance). However, acute dermal toxicity data are available on sodium tungstate (source substance), which are used for read-across. Due to similar water solubility and toxicity for the target substance compared to the source substance, the resulting read-across from the source substance to the target substance is appropriate for this endpoint. In addition, read-across is appropriate because the classification and labelling is similar for the source substance and target substance, the PBT/vPvB profile is the same, and the dose descriptors are, or are expected to be, conservative for the target substance. For more details, refer to the read-across category approach description in the Category section of this IUCLID submission or Annex 3 of the CSR.

Endpoint conclusion

Endpoint conclusion:

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. The reliability of this study for this substance tested is a K1, but in application of read-across to a different substance, ECHA's guidance specifies that the score can be a maximum of a K2.

Additional information

An acute oral toxicity study for ammonium metatungstate (target substance) of sufficient quality and tested in accordance with standard methodology is available. However, no acute toxicity data of ammonium metatungstate are available for the inhalation or dermal routes of exposure. Acute inhalation and dermal toxicity data of sufficient quality are available for ammonium paratungstate, sodium metatungstate and sodium tungstate (source substances), which were used in the weight-of-evidence for read-across approach.

 

Due to similar water solubility and toxicity for the target substance compared to the source substances, the resulting read-across from the source substances to the target substance is appropriate as an reasonable estimate of potential toxicity for this endpoint. In addition, read-across is appropriate because the classification and labeling is similar for the source substances and target substance, the PBT/vPvB profile is the same, and the dose descriptors are, or are expected to be, similar. For more details, refer to the read-across category approach description in the Category section of this IUCLID submission or Annex 3 of the CSR.

Justification for classification or non-classification

An acute oral toxicity study on ammonium metatungstate (AMT) of sufficient quality and tested in accordance with standard methodology reported a 1000<LD50<1373 mg AMT/kg bw (ca. 746<LD50<1025 mg W/kg bw). For substances with an acute oral LD50 between 300 and 2000 mg/kg, a classification of category 4 is warranted under the Classification, Labelling, and Packaging Regulation (CLP). Therefore, based on the available data, ammonium metatungstate is classified as a category 4 acute oral toxicant. No acute inhalation or dermal toxicity data are available on ammonium metatungstate; however, data are available for read-across substances ammonium paratungstate, sodium metatungstate and sodium tungstate. Three acute dermal studies (limit tests) of sufficient quality and tested in accordance with standard methodology reported LD50s of >2000 mg/kg bw for APT (ca. >1409 mg W/kg bw), sodium metatungstate (ca. >1478 mg W/kg bw) and sodium tungstate (ca. >1251 mg W/kg bw). The CLP classification limit value for a category 4 is 2000 mg/kg bw; therefore, based on the weight of evidence (WoE) of the available LD50 values from the source substances, ammonium metatungstate is not classified as an acute dermal toxicant. An acute inhalation study of sufficient quality and tested in accordance with standard methodology reported a 4-h LC50 value of >5.35 mg APT/L and a 4-h LC0 of >5.01 mg sodium tungstate/L air (ca. 2.94 mg W/L air). The CLP classification limit value for a category 4 dust or mist is 5 mg/L; therefore, based on the WoE of the available LC50 values for ammonium paratungstate and the LC0 of >2.94 mg W/L for sodium tungstate, ammonium metatungstate is not classified as an acute inhalation toxicant.