Hexaammonium wolframate

Endpoint summary

Description of key information

No skin or eye irritation data of sufficient quality are available for ammonium metatungstate (target substance); however, data are available for ammonium paratungstate, sodium metatungstate and sodium tungstate (source substances), which were used for read-across. In skin irritation studies conducted on rabbits according to OECD 404, ammonium paratungstate, sodium metatungstate and sodium tungstate

elicited no dermal irritation. In an eye irritation study conducted on rabbits according to OECD 405, instillation of ammonium paratungstate into the lower inverted lid of one rabbit elicited corneal opacification, iridial inflammation and considerable irritation. Reactions in the two remaining rabbits were confined to transient well-defined conjunctival irritation only. In an OECD 405 study with sodium tungstate, the mean corneal and iridial irritation scores were 0 at 24, 48 and 72 h. Therefore, based on available read-across eye irritation data, ammonium metatungstate is expected to be slightly irritating to the eye. Respiratory tract irritation data are not available, nor required under REACH.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

Endpoint:

skin irritation: in vivo

Type of information:

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

Adequacy of study:

key study

Study period:

1998-02-25 to 1998-02-28 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 OECD guideline 404 with no deviation to the protocol.

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 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan UK Ltd Bicester, Oxon, England
- Age at study initiation: 10 to 11 weeks
- Weight at study initiation: 2.2 to 2.6 kg
- Housing: Individually in metal cages with perforated floors
- Diet (e.g. ad libitum): STANRAB (P) SQC Rabbit Diet- ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: Acclimated, but period not stated.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 to 22.5
- Humidity (%): 39 to 56%
- Air changes (per hr): 19
- Photoperiod (hrs dark / hrs light): 12/12 artificial light (0700 - 1900)

IN-LIFE DATES: From: 1998-02-25 To: 1998-02-28

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

water

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g of the test substance was applied under a 25 mm x 25 mm gauze pad.

VEHICLE
- Amount(s) applied (volume or weight with unit): 0.5 mL distilled water

Duration of treatment / exposure:

4 hours

Observation period:

4 days

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: Approximately 24 hours prior to application of the test substance, hair was removed with electric clippers from the dorso-lumbar region of each rabbit exposing an area of skin approximately 100 mm x 100 mm.
- Type of wrap if used: Semi-occlusive dressing and gauze pad.
- Each treatment site was covered with "Elastoplast" elastic adhesive dressing for four hours. The animals were not restrained during the exposure period and were returned to their cages immediately after treatment. At the end of the exposure period, the semi-occlusive dressing and gauze pad were removed and the treatment site was washed.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Washed with warm water (35 degrees C) and area blotted dry with absorbent paper.
- Time after start of exposure: 4 hours

SCORING SYSTEM:
Local dermal irritation was scored according to Draize.

CLINICAL SIGNS:
All animals were observed daily for signs of ill health or toxicity.

DERMAL RESPONSES:
Examination of the treated skin was made on Day 1 (i.e. approximately 60 minutes after removal of the dressings) and on Days 2, 3, and 4 (equivalent to 24, 48 and 72 hours after exposure).

Irritation parameter:

erythema score

Basis:

mean

Remarks:

mean score for all 3 male rabbit

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Remarks:

No erythema

Irritation parameter:

edema score

Basis:

mean

Remarks:

mean score for all 3 male rabbits

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Remarks:

No edema

Irritant / corrosive response data:

No dermal response to treatment was observed in any animal throughout the study.

Other effects:

There were no signs of toxicity or ill health in any rabbit during the observation period.

Interpretation of results:

GHS criteria not met

Conclusions:

A single semi-occlusive application of Ammonium Paratungstate to intact rabbit skin for four hours elicited no dermal irritation.

Executive summary:

No skin irritation data of sufficient quality were available specifically on ammonium metatungstate (target substance). However, skin irritation 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:

skin irritation: in vivo

Type of information:

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

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

The study was conducted according to the OECD Guideline for Testing of Chemicals No. 404 "Acute Dermal Irritation/Corrosion".

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 404 (Acute Dermal Irritation / Corrosion)

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan UK Ltd, Bicester, Oxon, England.
- Age at study initiation: 10 to 12 weeks
- Weight at study initiation: 2.2 to 2.8 g
- Housing: Individually in stainless steel cages with perforated floors.
- Diet: Standard laboratory diet STANRAB (P) SQC Rabbit Diet was provided ad libitum.
- Water: Drinking water was provided ad libitum.
- Acclimation period: Yes


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 to 22.5
- Humidity (%): 36 to 58%
- Air changes (per hr): 19/hr
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

other: Distilled water

Controls:

not specified

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g

Duration of treatment / exposure:

~ 4 hours.

Observation period:

~60 minutes after removal of the dressing,
Days 24, 48, and 72 hours.

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: 100 mm x 100 mm
- Type of wrap if used: "Elastoplast" elastic adhesive dressing.


REMOVAL OF TEST SUBSTANCE
- Washing (if done): Washed with warm water.
- Time after start of exposure: Immediately after end of exposure period.


SCORING SYSTEM: Animals were scored based on the scoring system presented at each observation point.

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

No skin reactions were observed throughout the observation period.

Other effects:

No animals displayed any signs of ill health or toxicity throughout the observation period.

Interpretation of results:

GHS criteria not met

Conclusions:

There were no signs of toxicity or ill health in any rabbit during the observation period.
No dermal response to treatment was observed in any animal throughout the study.

Executive summary:

No skin irritation toxicity data of sufficient quality were available specifically on ammonium metatungstate (target substance). However, skin irritation 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.

Reference 3

Endpoint:

skin irritation: in vivo

Type of information:

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

Adequacy of study:

weight of evidence

Study period:

1990-11-27 to 1991-03-18

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

Well documented, scientifically sound study conducted in accordance to GLP and OECD 404. 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 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 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Broekman Institute, Someren, The Netherlands
- Age at study initiation: approx 15 weeks
- Weight at study initiation: 2751-2912 g
- Housing: Animals were housed individually in cages with perforated floors equipped with an automatic drinking system.
- Diet: Standard laboratory diet, (LKK-20, pellet diameter 4mm, Hope Farms, Woerden, The Netherlands) approximately 100 g per day.
- Water: Free access to tap water diluted with decalcified water.
- Acclimation period: at least 5 days before start of treatment

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Optimal temperature was 21 deg C. Fluctuations from this were noted, but were not considered to have affected study integrity.
- Humidity (%): Optimal relative humidity was 55%. Fluctuations from this were noted, but were not considered to have affected study integrity.
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

water

Remarks:

Distilled water was used only for the purpose to moisten the test substance to ensure contact with the skin.

Controls:

other: Contralateral flank of each treated animal was similarly prepared without test substance.

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied: 0.5 g of the test substance was moistened with distilled water and applied to the skin.

VEHICLE
- Amount(s) applied: No data was provided on the amount of distilled water used to moisten the test substance.

Duration of treatment / exposure:

4 hrs

Observation period:

72 hrs

Number of animals:

3 females

Details on study design:

TEST SITE
- Area of exposure: Approximately 24 hours before treatment, the dorsal fur was shaved with electric clippers, exposing an area of approximately 100 square centimeters (10cm x 10 cm). Prior to test substance administration, the animals were physically examined and the shaved area of skin was normal. On test day, the moistened test substance was applied to the intact skin of the shaved area of one flank, using a Metalline patch (2x3 cm) mounted to Micropore tape.
- % coverage: No data
- Type of wrap if used: The dressing described above was wrapped around the abdomen and secured with an elastic bandage.

REMOVAL OF TEST SUBSTANCE
- Washing: The test substance was removed with a tissue moistened with tap water and then a dry tissue.
- Time after start of exposure: 4 hours

SCORING SYSTEM: Skin reactions were assessed at approximately 60 minutes, 24, 48 and 72 hours after the removal of the dressings and test substance. The following numerical scoring system was used to grade the skin lesions.
Erythema and Eschar Formation:
-No erythema-0
-Very slight erythema (barely perceptible)-1
-Well defined erythema-2
-Moderate to severe erythema-3
-Severe erythema (beet redness) to slight eschar formation (injuries in depth)-4
Oedema Formation:
-No oedema-0
-Very slight oedema (barely perceptible)-1
-Slight oedema (edges of area well defined by definite raising)-2
-Moderate oedema (raised approx. 1 mm)-3
-Severe oedema (raised more than 1 mm and extending beyond area of exposure)-4
The test results were evaluated according to the EEC general classification and labelling requirements for dangerous substances (Annex VI of the EEC Council Directive 67/548/EEC as amended by directive 83/467/EEC, September, 1983).
A primary irritation index was calculated by combining the average skin irritation scores for erythema and oedema after 24 and 72 hours. Using the following scoring system (Draize) for primary irritation index, the degree of irritation was obtained.
Primary Irritation Index:
-0: Non-irritating
-0.1-2.0: Mildly irritating
-2.1-5.0: Moderately irritating
-5.1-8.0: Severely irritating

Irritation parameter:

erythema score

Basis:

mean

Remarks:

of 3 animals

Time point:

other: 60 minutes

Score:

0.67

Max. score:

4

Reversibility:

fully reversible within: 24 hours

Remarks on result:

probability of weak irritation

Remarks:

1 animal showed no effects, 1 animal showed a response of "1", and the third animal had a response of "1" over 30% of the treated area.

Irritation parameter:

erythema score

Basis:

mean

Remarks:

of 3 animals

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: Not applicable

Remarks on result:

no indication of irritation

Remarks:

No erythema

Irritation parameter:

edema score

Basis:

mean

Remarks:

of 3 animals

Time point:

other: 2 hours

Score:

0

Max. score:

4

Reversibility:

other: Not applicable

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

mean

Remarks:

of 3 animals

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: Not applicable

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

2 animals initially showed very slight erythema that was reversed within 24 hours in both animals. No evidence of corrosion was observed in any animal.

Other effects:

There was no evidence of staining of the treated skin by the test substance. No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred.

The test substance resulted in a primary irritation index of 0 (non-irritating) when applied to the intact rabbit skin. According to the EEC criteria for classification and labelling requirements for dangerous substances (EEC Directive 83/467/EEC, Annex VI of the EEC Council Directive 67/548/EEC), the test substance is not labelled as a skin irritant.

Interpretation of results:

GHS criteria not met

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The test substance was evaluated for skin irritation potential in rabbits. The test substance resulted in a primary irritation index of 0 (non-irritating) when applied to the intact rabbit skin. According to the EEC criteria for classification and labelling requirements for dangerous substances (EEC Directive 83/467/EEC, Annex VI of the EEC Council Directive 67/548/EEC). The test substance need not be labelled as a skin irritant.

Executive summary:

No skin irritation data of sufficient quality were available specifically on ammonium metatungstate (target substance). However, skin irritation data is 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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Reference 1

Endpoint:

eye irritation: in vivo

Type of information:

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

Adequacy of study:

key study

Study period:

1998-03-16 to 1999-09-08

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

Study was conducted according to OECD Guideline for Testing of Chemicals No. 405: "Acute Eye Irritation/Corrosion". Statement of Compliance with Good Laboratory Practice Standards and Quality Assurance Statement included.

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 405 (Acute Eye Irritation / Corrosion)

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Harlan UK Ltd, Bicester, Oxon, England
- Age at study initiation: 11 to 13 weeks
- Weight at study initiation: 2.6 to 3.0 kg
- Housing: Individually in metal cages with perforated floors.
- Diet: Standard laboratory diet STANRAB (P) SQC Rabbit Diet was provided ad libitum.
- Water: Drinking water was provided ad libitum.
- Acclimation period: yes, no data


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18.5 to 20 C
- Humidity (%): 42 to 57%
- Air changes (per hr): 19/hr
- Photoperiod (hrs dark / hrs light): 12/12

Vehicle:

unchanged (no vehicle)

Controls:

other: contralateral eyes of each animal served as controls

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 100 mg

Duration of treatment / exposure:

Single instillation with no rinsing or removal.

Observation period (in vivo):

72 hours

Number of animals or in vitro replicates:

3

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no data

TOOL USED TO ASSESS SCORE: Observation of the eyes was aided by a hand held light.

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

ca. 0.67

Max. score:

3

Reversibility:

fully reversible within: 72 hours

Remarks on result:

probability of weak irritation

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

ca. 0.33

Max. score:

3

Reversibility:

fully reversible within: 72 hours

Remarks on result:

probability of weak irritation

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

ca. 0.67

Max. score:

3

Reversibility:

fully reversible within: 72 hours

Remarks on result:

probability of weak irritation

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

ca. 0.67

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Remarks on result:

probability of weak irritation

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

ca. 0.33

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Remarks on result:

probability of weak irritation

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

ca. 0.33

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Remarks on result:

probability of weak irritation

Irritant / corrosive response data:

No corneal damage of iridial inflammation was observed.
A diffuse crimson coloration of the conjuctivae with partial eversion of the eyelids was seen in one animal. Transient hyperaemia of blood vessels with slight swelling was observed in the remaining two animals. These reactions had resolved by either two or three days after instillation.

Other effects:

There were no signs of toxicity or ill health in any rabbit during the observation period.

Interpretation of results:

GHS criteria not met

Conclusions:

Instillation of the test substance into the rabbit eye elicited transient, very slight to well-defined conjunctival irritation.

Executive summary:

No eye irritation toxicity data of sufficient quality were available specifically on ammonium metatungstate (target substance). However, eye irritation 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.

Reference 2

Endpoint:

eye irritation: in vivo

Type of information:

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

Adequacy of study:

key study

Study period:

1998-03-02 to 1998-03-23

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 405 with no deviation to the protocol.

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 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Harlan UK Ltd, Bicester, Oxon, England
- Age at study initiation: 10 to 16 weeks
- Weight at study initiation: 2.3 to 3.6 kg
- Housing: Individually in metal cages with perforated floors.
- Diet (e.g. ad libitum): STANRAB (P) SQC Rabbit Diet ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: Acclimated, but period not stated.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 to 22.5
- Humidity (%): 38 to 65%
- Air changes (per hr): 19
- Photoperiod (hrs dark / hrs light): 12/12 artificial light (0700 - 1900 hours)

IN-LIFE DATES: From: 1998-03-02 To: 1998-03-23

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 100 mg
- In compliance with the study guideline, the weight of the test substance, which when gently compacted occupied a volume of 0.1 mL, was measured: 219, 205, 218 mg (Weight of 0.1 mL test material (mg)).

Duration of treatment / exposure:

Single instillation

Observation period (in vivo):

21 days

Number of animals or in vitro replicates:

3

Details on study design:

- The eyes of each animal were examined prior to instillation of the test substance to ensure that there was no pre-existing corneal damage, iridial or conjunctival inflammation.
- One animal was treated in advance of the others, to ensure that if a severe response was produced, no further animals would be exposed.
- In compliance with the study guideline, the weight of the test substance, which when gently compacted occupied a volume of 0.1 mL, was measured.
- A volume of 0.1 mL of test substance exceeded 100 mg, therefore in accordance with the protocol 100 mg was placed into the lower inverted lid of one eye of each animal.
- The eyelid was then gently held together for one second before releasing. The contralateral eye remained untreated.

OBSERVATIONS:
- Clinical Signs: All animals were observed daily for signs of ill health or toxicity.
- Ocular Responses: Examination of the eyes was made after 1 hour and 1, 2 and 3 days after instillation (approximately 24, 48 and 72 hours). Additional observations were made 4 days after instillation in two animals and 5 through 21 days after instillation in one animal.
SCORING SYSTEM: Ocular irritation was assessed using the prescribed numerical system with respect to the Cornea, Iris, Conjuctivae and Chemosis.

TOOL USED TO ASSESS SCORE: Handheld light

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

2

Reversibility:

fully reversible within: 21 days

Remarks on result:

probability of weak irritation

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

no indication of irritation

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 21 days

Remarks on result:

probability of weak irritation

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Remarks:

density

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2.3

Max. score:

4

Reversibility:

fully reversible within: 21 days

Remarks on result:

probability of weak irritation

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2.6

Max. score:

3

Reversibility:

fully reversible within: 21 days

Remarks on result:

probability of weak irritation

Remarks:

redness

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 21 days

Remarks on result:

probability of weak irritation

Remarks:

redness

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.6

Max. score:

3

Reversibility:

fully reversible within: 21 days

Remarks on result:

probability of weak irritation

Remarks:

redness

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2.6

Max. score:

4

Reversibility:

fully reversible within: 21 days

Remarks on result:

probability of mild irritation

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

Corneal opacification (Grade 2) and iridial inflammation (Grade 1) was observed in one animal. Vascularization of the cornea was observed 14 days after instillation. A beefy red colouration of the conjuctivae, swelling with eyelids about half closed and a white discharge was also noted in this animal. Ocular reactions gradually ameliorated and the eye was normal 21 days after instillation.

Responses in the remaining two animals were transient in nature and confined to a diffuse crimson colouration to the conjuctivae, with above normal swelling of the eyelids in one of the rabbits. These reactions had resolved by either three or four days after instillation.

Other effects:

Clinical signs: There were no signs of toxicity or ill health in any rabbit during the observation period.

Interpretation of results:

GHS criteria not met

Conclusions:

Instillation of Ammonium Paratungstate into the rabbit eye elicited corneal opacification, iridial inflammation and considerable conjunctival irritation in one animal. Reactions in the two remaining rabbits were confined to transient well-defined conjunctival irritation only.

Executive summary:

No eye irritation sufficient quality were available specifically on ammonium metatungstate (target substance). However, eye irritation 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.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

No skin irritation/corrosion data are available for ammonium metatungstate (target substance). However, data are available for ammonium paratungstate, sodium metatungstate and sodium tungstate (source substances), which were used in the weight-of-evidence for read-across approach. 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

No skin or eye irritation data are available for ammonium metatungstate (taregt substance). However, skin irritation data are available on ammonium paratungstate and sodium metatungstate (source substances).

In skin irritation studies performed according to OECD 404 with ammonium paratungstate, sodium metatungstate and sodium tungstate, all rabbits received a score of 0 for both erythema and oedema over the course of 24, 48 and 72 h. Therefore, based on WoE from the available data of the read-across substances, ammonium metatungstate does not warrant classification for skin irritation.

It is necessary, however, to note that in addition to WO₄^2- ions, ammonium cations (NH4⁺) will also be present when ammonium metatungstate dissociates upon contact with the sweat or the aqueous ocular membrane. Ammonia itself is classified as a Category 1B skin irritant according to CLP. Ammonia is not classified for eye irritation according to either of these classification schemes. Ammonium paratungstate (APT) and ammonium metatungstate (AMT) have similar water solubilities, but APT would be expected to release more ammonium ions (10 moles of NH4⁺ for APT compared to 6 moles for AMT) upon contact with sweat on the surface of the skin. Therefore, any concerns regarding the potential toxicity of the ammonium ion released from AMT when in contact with sweat are sufficiently addressed from read-across to skin irritation data on APT. Therefore, based on the WoE from the available data for tungsten substances with and without ammonia (ie ammonium paratungstate, sodium metatungstate and sodium tungstate), ammonium metatungstate does not warrant classification for skin irritation.

In an eye irritation study performed on three animals according to OECD 405 with ammonium paratungstate, one animal received a mean score of 2.6 for conjunctiva redness, while the 2 other animals received a score of 1 and 0.6. The minimum eye score that would dictate a Category 2 classification for eye irritation under CLP for conjunctival redness is ≥ 2 in 2/3 animals. One animal out of the three received scores greater than or equal to the cut-off value for CLP classification for cornea opacity, iritis and conjunctiva oedema (chemosis), but the remaining two animals received a score of 0. In another study performed according to OECD 405 with sodium tungstate, no signs of corneal or iridial irritation were observed at 24, 48 and 72 h. Therefore, based on Weight of Evidence from the available data of the read-across substance, ammonium metatungstate does not warrant classification for eye irritation.

Respiratory tract irritation data are not available, therefore, classification cannot be made due to lack of data. In addition, this endpoint is not required under REACH.