Registration Dossier

Diss Factsheets

Administrative data

Description of key information

GPMT: negative

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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Meets generally accepted scientific standards, well documented and acceptable for assessment.
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.
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.

:
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;
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
Positive control results:
no data
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.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (sensitising)
Additional information:

The potential of E-326 catalyst (Divanadyl pyrophosphate, CAS 65232-89-5) to cause delayed contact hypersensitivity in guinea-pigs was assessed by the Magnusson-Kligman Maximisation Test according to OECD 406. The closely-clipped dorsa of ten male and ten female Dunkin-Hartley guinea-pigs were subject to intradermal injections of Freunds Complete Adjuvant, 0.5% w/v E-326 catalyst in distilled water and 0.5% w/v E-326 catalyst in the adjuvant on Day 1. Seven days later the same area of skin was treated by topical application of 30% w/v E-326 catalyst in distilled water and the test site was covered by an occlusive dressing for 48 hours. The same induction procedures were carried out on a contemporaneous control group, except that the test material was replaced by vehicle in all doses. On Day 22, all animals were challenged by occluded application of distilled water to the left flank and, 30% and 50% w/v E-326 catalyst in distilled water to two sites on the right flank. The occlusive dressings were removed on the following day and the condition of the test sites was assessed approximately 24 and 48 hours later. Challenge application of 30% w/v E-326 catalyst in distilled water caused a significant response (slight erythema or a more marked reaction) in twelve test and three control animals. Challenge application of 5% w/v E-326 catalyst in distilled water caused a significant response in three test and no control animals. Challenge application of distilled water alone caused no dermal reaction.

It was concluded that, under the conditions of this study, repeated administration of E-326 catalyst caused delayed contact hypersensitivity in guinea-pigs.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Currently there is no substance specific data on Vanadate(1-), oxo[phosphato(3-)-κO]-, hydrogen, hydrate (2:2:1) for skin sensitization available. However data from the source compound Divanadyl pyrophosphate (CAS 65232 -89-5) can be taken into account for hazard assessment.

Based on the available data and according to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008 Vanadate(1-), oxo[phosphato(3-)-κO]-, hydrogen, hydrate (2:2:1) has to be classified as Skin Sens 1B (H317).