Registration Dossier

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:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
study was already available before registration
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
Vehicle:
water
Concentration / amount:
0.2 mL FCA
0.2 mL of 0.5% TS in destilled water
0.2 mL of 0.5% TS in FCA
Day(s)/duration:
day 1
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
0.6 mL of 30% TS in distilled water
Day(s)/duration:
application on day 8, occlusive dressing for 48 hours
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
0.03 mL of 30% TS in distilled water and 0.03 mL of 5% TS in distilled water
Day(s)/duration:
application on day 22, occlusive dressing for 24 hours
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
20
Positive control substance(s):
no
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
destilled water (0%TS)
No. with + reactions:
0
Total no. in group:
20
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
destilled water (0% TS)
No. with + reactions:
0
Total no. in group:
20
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
destilled water (0% TS)
No. with + reactions:
0
Total no. in group:
20
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
destilled water (0% TS)
No. with + reactions:
0
Total no. in group:
20
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
30% TS in water
No. with + reactions:
2
Total no. in group:
20
Remarks on result:
other: slight erythema
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
30% TS in water
No. with + reactions:
1
Total no. in group:
20
Remarks on result:
other: eschar formation
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
30% TS in water
No. with + reactions:
10
Total no. in group:
20
Remarks on result:
other: 4 animals with slight erythema, 1 with moderate erythema and 5 with eschar formation
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
30% TS in water
No. with + reactions:
5
Total no. in group:
20
Remarks on result:
other: 1 animal with slight erythema and 4 animals with eschar formation
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
5% TS in water
No. with + reactions:
0
Total no. in group:
20
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
5% TS in water
No. with + reactions:
0
Total no. in group:
20
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
5% TS in water
No. with + reactions:
3
Total no. in group:
20
Remarks on result:
other: 2 animals with slight erythema and 1 animal with eschar formation
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
5% TS in water
No. with + reactions:
0
Total no. in group:
20

Signs of irritation during induction: Intradermal administration in the range 5 % to 30 % w/v in distilled water caused moderate erythema and black and/or green discolouration 24 and 48 hours after administration.

Evidence of sensitisation of each challenge concentration: A significant dermal response (slight erythema or a more marked reaction) was apparent in 12 test and three control animals challenged with 30 % test substance in distilled water and in three test and no control animals challenged with the 5 % formulation. No dermal response was observed in any test or control animals following challenge with distilled water alone.

The incidence of significant responses in the test animals was markedly greater than in the controls and was in excess of the EC limit value (30 %) for classifying the test material as a dermal sensitiser. It is therefore, concluded that, under the conditions of this study, repeated administration caused delayed contact hypersensitivity in the guinea-pig.

Interpretation of results:
sensitising
Remarks:
Migrated information
Conclusions:
Classification: May cause sensitization by skin contact
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

Based on the available data andaccording to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008 Divanadyl pyrophosphate (CAS 65232-89-5) has to classified as Skin Sens 1B (H317).