Disodium wolframate

Endpoint summary

Description of key information

Sodium tungstate does not appear to be a skin sensitiser when tested on male albino Dunkin/Hartley guinea pigs (GLP and OECD Guideline 406 " Skin Sensitization").

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1998-03-24 to 1999-04-01

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

Study was performed according to OECD Guideline for Testing of Chemicals No. 406 "Skin Sensitization" and GLP.

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

GLP compliance:

yes

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

A 1999 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:

male

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: D. Hall, Newchurch, Staffs, UK.
- Age at study initiation: 4 to 7 weeks
- Weight at study initiation: 419 to 527 g
- Housing: Five suspended metal cages with wire mesh floors.
- Diet: Vitamin C enriched guinea-pig diet (Harlan Teklan 9600 FD2 SQC) - ad libitum. Hay was given thrice weekly.
- Water: ad libitum.
- Acclimation period: 12 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17.5 to 23.5
- Humidity (%): 40 to 59%
- Air changes (per hr): 15/hr
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 1998-03-24 To: 1998-04-24

Route:

intradermal

Vehicle:

other: Distilled water

Concentration / amount:

Induction intradermal injection: 5% w/v in sterile water for injection.
Induction topical application: 75% w/v in distilled water.
Topical challenge: 5 and 2.5% w/v in distilled water.

Route:

epicutaneous, occlusive

Vehicle:

other: Distilled water

Concentration / amount:

Induction intradermal injection: 5% w/v in sterile water for injection.
Induction topical application: 75% w/v in distilled water.
Topical challenge: 5 and 2.5% w/v in distilled water.

No. of animals per dose:

10 animals.

Details on study design:

RANGE FINDING TESTS: The intradermal and topical irritancy of a range of dilutions of the test substance was investigated to identify where possible (a) concentrations of the test substance that would produce irritation suitable for the induction phase of the main study and (b) a maximum non-irritant concentration by the topical route of administration for the challenge phase.
Animals for these investigations were pre-treated with an intradermal injection of Freund's complete adjuvant, 50:50 with water for irrigation (Ph. Eur.), approximately two weeks prior to the start of the preliminary investigations.


MAIN STUDY
A. INDUCTION INTRADERMAL EXPOSURE
- No. of exposures: Three pairs
- Test groups: 0.1 mL of FCA 50:50 with sterile water; 0.1 mL of test substance, 5% w/v in sterile water; 0.1 mL of test substance, 5% w/v in 50:50 mixture of FCA and sterile water for injection.
- Control groups: 0.1 mL of FCA 50:50 with sterile water, 0.1 mL of sterile water, and 0.1 mL of FCA 50:50 with sterile water.
- Site: Scapular area
- Concentrations: 5% w/v

MAIN STUDY
A. INDUCTION TOPICAL EXPOSURE
- No. of exposures: One
- Test groups: 0.4 mL of test substance, 75% w/v in distilled water
- Control group: Concurent no treatment.
- Site: Interscapular area
- Duration: 48 hours
- Concentrations: 75% w/v


B. CHALLENGE EXPOSURE
- No. of exposures: Single
- Test groups: 0.2 mL of test substance, 5% w/v in distilled water and 0.2 mL of test substance, 2.5% w/v in distilled water.
- Control group: Same as test group.
- Site: Anterior site on the flank and posterior site on the flank respectively.
- Concentrations: 5% w/v and 2.5% w/v respectively.
- Evaluation (hr. after challenge): two weeks

Challenge controls:

Control animals were not exposed within either induction period. Animals were exposed to the same concentrations of test substance as test animals.

Positive control substance(s):

yes

Remarks:

Hexyl cinnamic aldehyde (HCA), Benzocaine and 2-mercaptobenzothiazole (MBT)

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

0.1 mL of 2.5 and 5% w/v sodium tungstate in distilled water

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

no signs of ill health or toxicity were observed

Remarks on result:

other: see Remark

Remarks:

Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 0.1 mL of 2.5 and 5% w/v sodium tungstate in distilled water. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: no signs of ill health or toxicity were observed.

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

0.1 mL of 2.5 and 5% w/v in distilled water

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

no signs of ill health or toxicity were observed

Remarks on result:

other: see Remark

Remarks:

Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 0.1 mL of 2.5 and 5% w/v in distilled water. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: no signs of ill health or toxicity were observed.

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

positive control

Dose level:

10%

No. with + reactions:

10

Total no. in group:

10

Clinical observations:

Localised dermal reaction (restricted to a small area of the challenge site); dryness sloughing of the epidermis

Remarks on result:

positive indication of skin sensitisation

Remarks:

positive indication of skin sensitisation Reactions in anterior site, exposed to HCA (as supplied) and posterior site, exposed to HCA, 50% in Alembicol D

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

Distilled water - 0.1 ml

No. with + reactions:

0

Total no. in group:

2

Clinical observations:

Slight irritation

Remarks on result:

no indication of skin sensitisation

Remarks:

no indication of skin sensitisation

CLINICAL SIGNS:

No signs of ill health or toxicity were recorded.

INDUCTION:

-Intradermal injections: Necrosis was recorded at most sites receiving FCA in test and control animals. Slight to well-defined irritation was seen in test animals at sites receiving the test substance, 5% w/v in sterile water for injection. No irritation was observed in control animals receiving sterile water for injection.

-Topical application: Slight to well-defined erythema was observed in test animals following topical application with the test substance, 75% w/v in distilled water. Slight erythema was seen in most of the control guinea-pigs.

CHALLENGE:

There were no dermal reactions seen in any of the test or control animals. All ten test animals gave negative responses.

Interpretation of results:

GHS criteria not met

Conclusions:

The test substance did not produce evidence of skin sensitization (delayed contract hypersensitivity) in any of the ten test animals under the conditions of the assay.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

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 sodium tungstate is a respiratory sensitiser, as well as negative responses observed in both the skin sensitisation and skin irritation animal studies, sodium tungstate is not likely to be a respiratory sensitiser.

Justification for classification or non-classification

A skin sensitisation test of sufficient quality and tested in accordance with standard methodology was available for sodium tungstate. The results of this study showed that sodium tungstate did not cause skin sensitisation in guinea pigs. Therefore, no classification is warranted for the skin sensitisation endpoint. No respiratory sensitization study is available for sodium tungstate. Therefore, classification cannot be made due to lack of data. However, this endpoint is not required for REACH registration.