Registration Dossier

Toxicological information

Skin sensitisation

Currently viewing:

Administrative data

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.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1999
Report date:
1999

Materials and methods

Test guideline
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.

Test material

Constituent 1
Chemical structure
Reference substance name:
Disodium wolframate
EC Number:
236-743-4
EC Name:
Disodium wolframate
Cas Number:
13472-45-2
Molecular formula:
Na2WO4
IUPAC Name:
disodium dioxotungstenbis(olate)
Details on test material:
- Name of test material (as cited in study report): Sodium Tungstate Dihydrate
- Substance type: Active
- Physical state: White Powder
- Analytical purity: 99.9%
- Storage condition of test material: Room Temperature

In vivo test system

Test animals

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

Study design: in vivo (non-LLNA)

Inductionopen allclose all
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.
Challengeopen allclose all
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)

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
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

Any other information on results incl. tables

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.

Applicant's summary and conclusion

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.