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Toxicological information

Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Meets generally accepted scientific standards, well documented and acceptable for assessment.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1990
Report date:
1991

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:
An OECD Testing guideline 406, GLP-conformant study is available and sufficient for classification. Conduct of an additional LLNA is not considered necessary.

Test material

Constituent 1
Chemical structure
Reference substance name:
Divanadyl pyrophosphate
EC Number:
407-130-0
EC Name:
Divanadyl pyrophosphate
Cas Number:
65232-89-5
Molecular formula:
(VO)2P2O7
IUPAC Name:
Divanadyl pyrophosphate
Details on test material:
- Name of test material (as cited in study report): E-326 Catalyst
- Physical state: grey/green powder
- Analytical purity: 96%
- Lot/batch No.: 326-104
- Storage condition of test material: room temperature

In vivo test system

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Olac Limited, Bicester, Oxfordshire, UK.
- Age at study initiation: seven to eight weeks.
- Weight at study initiation: 339 - 469 g.
- Housing: 5 animals per cage.
- Diet: Guinea pig F.D.1 (Special Diet Services, Essex, UK), ad libitum and regular supplement of autoclaved hay.
- Water: tap water ad libitum.
- Acclimation period: 13 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 15 - 23 °C.
- Humidity (%): 40 - 70 %.
- Air changes (per hr): 15.
- Photoperiod (hrs dark / hrs light): 12 h / 12 h.

:

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
water
Concentration / amount:
First induction: 0,5 % in distilled water; 0,5 % in FCA;
Second induction: 30 % in distilled water;
Challenge: 30 % in distilled water; 5 % in distilled water;
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
First induction: 0,5 % in distilled water; 0,5 % in FCA;
Second induction: 30 % in distilled water;
Challenge: 30 % in distilled water; 5 % in distilled water;
No. of animals per dose:
20
Details on study design:
RANGE FINDING TESTS:
A. INDUCTION EXPOSURE
intradermal induction
- Details of exposures: single exposure comprising 6 intradermal injections per animal
- No. of animals: 4
- Site: the skin overlying the scapulae
- Concentrations: 30%, 10%, 5%, 3%, 1% and 0.5% w/v E-326 catalyst in distilled water or in FCA
- Evaluation: 24, 48 and 168 hours after injection

percutaneous induction
- Details of exposures: single intradermal injection of 0.1 ml FCA seven days before occlusive topical application of the test substance to 4 test sites per animal
- Exposure period of topical application: 48 h
- No. of animals: 2
- Site: Flanks
- Concentrations: 0.4 ml of 50%, 30%, 10% and 5% E-326 catalyst in distilled water
- Evaluation: 24 h and 48 h after removal of the dressing

B. CHALLENGE EXPOSURE
- Details of exposures: Single intradermal injection of 0.1 ml FCA twenty-five days before occlusive topical application of the test substance to 4 test sites per animal
- Exposure period: 24 h
- No. of animals: 3
- Site: flanks
- Concentrations: 0.03 ml of 30%, 10%, 5% and 3% w/v E-326 catalyst in distilled water
- Evaluation (hr after challenge): 24 h and 48 h after removal of the dressing

The concentrations chosen for use in induction and challenge were to be well-tolerated locally and systemically. They were selected on the following
criteria: intradermal injections were not to cause necrosis or ulceration of the skin, topical induction was to cause, at most, a weak or moderate inflammatory response and the concentration used at challenge was to be at the highest sub-irritant level.

MAIN STUDY
A. INDUCTION EXPOSURE
intradermal induction
- Details of exposures: single exposure comprising 6 intradermal injections per animal
- No. of animals: 20 per group
- Site: back, in parallel to the spinal cord
- Concentrations: FCA 0.5% w/v; E-326 catalyst in distilled water; 0.5% w/v E-326 catalyst in FCA (in the control groups, the test substance was replaced by distilled water)
- Evaluation: 24, 48 and 144 hours after injection

percutaneous induction
- Details of exposures: 7 days after intradermal induction, occlusive dressing
- Exposure period of topical application: 48 h
- No. of animals: 20 per group
- Concentrations: 0.6 ml 30% w/v E-326 catalyst in distilled water (in the control groups, the test substance was replaced by distilled water)
- Evaluation: 24 h and 48 h after removal of the dressing

B. CHALLENGE EXPOSURE
- Details of exposures: 14 days after intradermal induction; occlusive dressing to three sites per animal
- Exposure period: 24 h
- No. of animals: 20 per group
- Site: flanks
- Concentrations: 0.03 ml 5% w/v E-326 catalyst in distilled water; 0.03 ml 30% w/v E-326 catalyst in distilled water; distilled water
- Evaluation (hr after challenge): 24 h and 48 h after removal of the dressing
Positive control substance(s):
not specified

Results and discussion

Positive control results:
no data

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
30 %
No. with + reactions:
10
Total no. in group:
20
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 30 %. No with. + reactions: 10.0. Total no. in groups: 20.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
30 %
No. with + reactions:
5
Total no. in group:
20
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 30 %. No with. + reactions: 5.0. Total no. in groups: 20.0.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
30 %
No. with + reactions:
2
Total no. in group:
20
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 30 %. No with. + reactions: 2.0. Total no. in groups: 20.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
30 %
No. with + reactions:
1
Total no. in group:
20
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 30 %. No with. + reactions: 1.0. Total no. in groups: 20.0.
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
5 %
No. with + reactions:
3
Total no. in group:
20
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 5 %. No with. + reactions: 3.0. Total no. in groups: 20.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
5 %
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 5 %. No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
5 %
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 5 %. No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
5 %
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 5 %. No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
0 %
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 0 % . No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
0 %
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 0 % . No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0 %
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 0 % . No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0 %
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 0 %. No with. + reactions: 0.0. Total no. in groups: 20.0.

Applicant's summary and conclusion

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