Dihydrogen wolframate

Endpoint summary

Description of key information

No sensitisation data are available for tungstic acid; however, data are available for WO3, which were used for read-across. In a skin sensitisation study conducted on guinea pigs and according to OECD 406, WO3 was deemed to be not sensitizing.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

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

Adequacy of study:

key study

Study period:

2002-07-22 to 2002-11-14

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

Well documented, scientifically sound study that was conducted in accordance to GLP, OECD guideline 406 and Directive 96/54/EC, B.6, "Skin Sensitisation." 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 a K2.

Justification for type of information:

Tungstic acid (WO3•H2O) is the hydrated form of tungsten trioxide (WO3). Based on Annex V, hydrates and water free forms (anhydrous) of compounds can be regarded as the same substance for registration purposes. Therefore, tungstic acid will be considered equivalent to WO3. For more details on the rationale, refer to the attached description of the read-across approach (Annex 3).

Reason / purpose for cross-reference:

reference to other study

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Qualifier:

according to guideline

Guideline:

EU Method B.6 (Skin Sensitisation)

GLP compliance:

yes

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

A 2002 guinea pig sensitisation study was available of good quality. Therefore, there is no need to conduct a LLNA study as the guinea pig sensitisation study scientifically fulfills the endpoint. The OECD 406 method provides sensitisation information likely to arise from exposure to test substance via intradermical injection and/or epidermical application to guinea pigs. The guinea pig sensitisation test detects chemicals with moderate to strong sensitisation potential, as well as those with relatively weak sensitisation potential. In such methods activity is measured as a function of challenge-induced dermal hypersensitivity reactions elicited in test animals compared with controls. In addition, guinea pigs have been the animal of choice for predictive sensitisation tests for several decades (way before the LLNA became the test of choice).
The existing guinea pig data submitted here is of good quality as clear results are presented in this robust summary and test methodology followed OECD 406 guidelines, and conducted under GLP. This study it is considered acceptable according to page 266 in ECHA's Chapter r7a on Guidance on Information Requirements and Chemical Safety Assessment.

Species:

guinea pig

Strain:

Dunkin-Hartley

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Harlan Winkelmann, Gartenstrasse 27, D-33178 Borchen
- Age at study initiation: Approximately 5-7 weeks
- Weight at study initiation: 316-404 g
- Housing: Until day 0- housed singly in Makrolon cages type III; From day 0- group caging in plastic containers (6 control or 11 test substance animals per container)
- Diet (eg ad libitum): Altromin Maintenance Diet No. 3122- ad libitum
- Water (eg ad libitum): Tap water offered in Makrolon bottles with stainless steel canules- ad libitum
- Acclimation period: 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Average 22.0 ⁰C (step one), Average 21.9 ⁰C (step two)
- Humidity(%): Average 59.9% (step one), Average 56.4% (step two)
- Air changes (per hr): 12/hr
- Photoperiod (hrs dark / hrs light): 12 dark/12 light (6 am to 6 pm)

Route:

intradermal and epicutaneous

Vehicle:

petrolatum

Concentration / amount:

50% w/w

Route:

epicutaneous, occlusive

Vehicle:

petrolatum

Concentration / amount:

50% w/w

No. of animals per dose:

2 x 10 animals for the substance group
2 x 5 animals for the control group

Details on study design:

RANGE FINDING TESTS: Preliminary test with 2 female guinea pigs. FCA was administered intradermally and immediately after, the test substance was administered (50% in white petrolatum, w/w) epicutaneously to the sites of the intradermal injections to examine possible systemic effects. 7 days later 4 concentrations of the test substance were administered epicutaneously for 24 hours.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2
- Exposure period: 24 hours (exposure 1), 48 hours (exposure 2)
- Test groups: 2 groups both dosed at 50% w/w
- Control group: Dosed with white petrolatum only
- Site: Shaved, 2 cm x 4 cm filter papers with test substance applied and fixed with non-irritating tape (interscapular region)
- Frequency of applications: Day 0 and day 8
- Duration: 25 days
- Concentrations: 50% w/w or 0% w/w

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: day 22
- Exposure period: 24 hours
- Test groups: 2 groups both dosed at 50% w/w
- Control group: dosed with white petrolatum only
- Site: Shaved, 2 cm x 2 cm filter papers with test substance applied and fixed with non-irritating tape to the left flanks and vehicle to the right flanks.
- Concentrations: 50% w/w
- Evaluation (hr after challenge): 3 hours after end of challenge exposure

OTHER: Intradermal injections of FCA were administered directly before epicutaneous exposures. Also, before the second induction exposure, the animals were pretreated with n-dodecylsulfate, sodium salt (10% in white petrolatum, w/w).

Positive Control: Concentrations of HCA
10 females for the positive control substance group and 5 females for the negative control group.
70% in acetone (v/v) for the 1st epicutaneous induction
70% in acetone (v/v) for the 2nd epicutaneous induction
20% in acetone (v/v) for the challenge exposure

Challenge controls:

Blind reading of test and control animals. All animals administered 50% in white petrolatum, w/w epicutaneously.

Positive control substance(s):

yes

Remarks:

hexyl cinnamic aldehyde (HCA)

Positive control results:

7/10 animals (70%) represented also the net rate of animals sensitised by HCA.

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

50% w/w

No. with + reactions:

0

Total no. in group:

20

Clinical observations:

No positive skin reaction in any animal at any reading time

Remarks on result:

no indication of skin sensitisation

Remarks:

Reading: 1st reading. Hours after challenge: 24. Group: test group. Dose level: 50 % w/w. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: No positive skin reaction in any animal at any reading time .

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

50% w/w

No. with + reactions:

0

Total no. in group:

20

Clinical observations:

No positive skin reaction in any animal at any reading time

Remarks on result:

no indication of skin sensitisation

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

Vehicle

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

No positive skin reaction in any animal at any reading time

Remarks on result:

no indication of skin sensitisation

Remarks:

Hours after challenge: 24 Group: negative control. Dose level: 0 % w/w. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: No positive skin reaction in any animal at any reading time.

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

Vehicle

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

No positive skin reaction in any animal at any reading time

Remarks on result:

no indication of skin sensitisation

Remarks:

Hours after challenge: 48 Group: negative control. Dose level: 0 % w/w. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: No positive skin reaction in any animal at any reading time.

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

positive control

Dose level:

70% in actone

No. with + reactions:

7

Total no. in group:

10

Clinical observations:

Very slight to severe erythema and/or oedema in 7/10 animals 24 and/or 48 hours after challenge exposure

Remarks on result:

positive indication of skin sensitisation

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

positive control

Dose level:

70% HCA for induction and 20% HCA for challenge

No. with + reactions:

7

Total no. in group:

10

Clinical observations:

Very slight to severe erythema and/or oedema in 7/10 animals 24 and/or 48 hours after challenge exposure

Remarks on result:

positive indication of skin sensitisation

Mortality

All animals survived till the end of the study.

Body weight

- Step 1: There were no significant differences in the mean body weights between the animals of the test substance group and those of the control group on Days 0 and 25.

- Step 2: There were no significant differences in the mean body weights between the test substance group and the control group on Day 0. On Day 25 the mean body weight of the test substance group animals was slightly, but statistically, higher than that of the control animals. This was of no biological significance and was regarded as a random event.

General observations

Immediately after the beginning of all epicutaneous exposures (inductions, challenge) the motor activities of all animals were increased. This is due to the dressings which restrict the freedom of movement. Soon afterwards the behaviour was regular again. Except of the observations described above no abnormal behaviour or clinical signs were detected during the experiment in the animals.

Skin reactions after the intradermal FCA administration

Cranial and caudal injection sites: Local irritations were observed in all animals beginning on the day after the injections. The irritations started with local erythema, which became more severe and led to ulcerations. Lesions did not heal until the end of the study. These local alterations are known effects of Freund's adjuvant.

Skin reactions after the first and the second induction exposure

All animals of both groups had severe erythema and oedema in the interscapula region which were attributed to the effects of the adjuvant.

Interpretation of results:

GHS criteria not met

Conclusions:

None of the animals in the test substance group were regarded as sensitised.

Executive summary:

No skin sensitisation data are available for tungstic acid (target substance). However, skin sensitisation data are available for tungsten trioxide (source substance), which were used for read-across. Tungstic acid (WO3•H2O) is the hydrated form of tungsten trioxide (WO3). Based on Annex V, hydrates and water free forms (anhydrous) of compounds can be regarded as the same substance for registration purposes. Therefore, tungstic acid is considered equivalent to WO3. For more details on the rationale, refer to the attached description of the read-across approach.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

No skin sensitisation data are available for tungstic acid (target substance). However, acute skin sensitisation data are available for WO3 (source substance), which were used for read-across. Tungstic acid (WO3•H2O) is the hydrated form of tungsten trioxide (WO3). Based on Annex V, hydrates and water free forms (anhydrous) of compounds can be regarded as the same substance for registration purposes. Therefore, tungstic acid will be considered equivalent to WO3. For more details on the rationale of the read-across approach, refer to the read-across category approach document (Annex 3).

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information:

Although no study data specifically evaluating the potential respiratory sensitisation effects are available, based on the lack of human case reports indicating that tungstic acid is a respiratory sensitiser, as well as negative responses observed in both the skin sensitisation and skin irritation animal studies on WO3, tungstic acid is not likely to be a respiratory sensitiser.

Justification for classification or non-classification

No skin sensitisation data are available for tungstic acid. WO3 did not cause skin sensitisation in the Guinea Pig in a skin sensitisation study, which was used for read-across. Therefore, no classification is required for the skin sensitisation endpoint based on the available data. No respiratory sensitisation studies are available for tungstic acid. Therefore, classification cannot be made due to lack of data. However, this endpoint is not required for REACH registration.