Registration Dossier

Diss Factsheets

Administrative data

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:
other: GLP-compliant guideline study, available as unpublished report, no restrictions, fully adequate for assessment.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1987
Report date:
1987

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

Test material

Constituent 1
Chemical structure
Reference substance name:
Zirconium di(acetate) oxide
EC Number:
225-924-3
EC Name:
Zirconium di(acetate) oxide
Cas Number:
5153-24-2
Molecular formula:
C4 H6 O5 Zr
IUPAC Name:
zirconium di(acetate) oxide
Details on test material:
- Name of test material (as cited in study report): zirconium-acetate
- Substance number: 86/194-1
- Physical state: colourless liquid
- Analytical purity: ca. 20% aqueous solution
- Lot/batch No.: 86/17818
- Storage condition of test material: room temperature

In vivo test system

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Lippische Versuchtierzucht, Hagemann GmbH & Co. KG, D-4923 Extertal 1, FRG
- Weight at study initiation: 260-298 g
- Housing: 5 per cage in Makrolon tpe IV cages
- Diet: Kliba 341.4 mm (Kaninchen-Meerschweinchen-Haltungsdiät), ad libitum
- Water: tap water, ca. 2 g of ascorbic acid per 10 L water was added to the drinking water twice a week; ad libitum
- Acclimation period: at least 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24
- Humidity (%): 30-70
- Photoperiod (hrs dark / hrs light): 12 / 12

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
other: water (intradermal induction)
Concentration / amount:
Test substance: about 20% aqueous zirconium acetate solution
- Intradermal induction: 25% of the test substance in aqua dest. resp. in Freund's adjuvant/aqua dest. (1:1)
- Epicutaneous induction: unchanged test substance
- First challenge (epicutaneous): unchanged test substance
- Second challenge (epicutaneous): unchanged test substance
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
other: water (intradermal induction)
Concentration / amount:
Test substance: about 20% aqueous zirconium acetate solution
- Intradermal induction: 25% of the test substance in aqua dest. resp. in Freund's adjuvant/aqua dest. (1:1)
- Epicutaneous induction: unchanged test substance
- First challenge (epicutaneous): unchanged test substance
- Second challenge (epicutaneous): unchanged test substance
No. of animals per dose:
20/dose in the test group; 10/dose in the control groups in the main study; 4/dose in the preliminary study
Details on study design:
RANGE FINDING TESTS: The test substance was applied 2 times for 24 hours within a period of 96 hours in order to detect non-specific phenomena that were not caused by a sensitisation reaction but could possibly be attributed to a shift in the irritation threshold. Readings were performed 24 and 48 hours after the beginning of application. The sites were scored according to Draize. 2 x 2 cm filter paper strips were applied to the skin of the flanks under an occlusive dressing. In the case of liquids the test filter paper strip was soaked in the test substance resp. test substance formulation; thus, the animals were exposed to about 0.15 g of the test substance resp. test substance formulation.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 6 intradermal injections (2 injections each of 0.1 ml Freund's adjuvant without the test substance emulsified with water in ratio 1:1; 2 injections each of 0.1 mL of the test substance formulation; 2 injections each of 0.1 mL Freund's adjuvant/water (1:1) with test substance). After one week percutaneous induction was carried out (single 48 hours appluication under occlusive conditions).
- Exposure period: 48 hours (percutaneous induction).
- Test groups: 20 animals
- Control group: two control groups (10/group) were given the same injections but without the test substance, only with the formulating agent. No percutaneous induction treatment was performed, since the test substance was applied unchanged and thus no solvent was used.
- Site: shoulder; the same region for both intradermal and percutaneous applications
- Frequency of applications: 6 simultaneous intradermal injections; one week later, single percutaneous administration
- Duration: one week before percutaneous challenge; 48 hours exposure; ca. 14 days later the first challenge.
- Concentrations: unchanged for percutaneous induction (as 20% aqueous solution); 25% of the test substance in water for intradermal induction

B. CHALLENGE EXPOSURE
- No. of exposures: 2
- Day(s) of challenge: the first one 14 days after intradermal induction; the second one week later
- Exposure period: 24 hours
- Test groups: 20 animals
- Control group: control group 1 (10 animals) was treated with the test substance during the 1st and 2nd challenge; control group 2 (10 animals) remained untreated in the 1st challenge and was treated in the 2nd challenge.
- Site: intact clipped flank
- Concentrations: unchanged (20% aqueous solution)
- Evaluation (hr after challenge): 24, 48 and 72 hours after beginning of application
Challenge controls:
In the first challenge, control group 1 (10 animals) was treated with the test substance; control group 2 (10 animals) remained untreated. In the second challenge, both control groups were treated with the test substance.
Positive control substance(s):
no

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
20% aqueous solution
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: 20% aqueous solution. No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
20% aqueous solution
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: 20% aqueous solution. No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
rechallenge
Hours after challenge:
24
Group:
test chemical
Dose level:
20% aqueous solution
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 24.0. Group: test group. Dose level: 20% aqueous solution. No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
rechallenge
Hours after challenge:
48
Group:
test chemical
Dose level:
20% aqueous solution
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 48.0. Group: test group. Dose level: 20% aqueous solution. No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
other: 1st reading / rechallenge
Hours after challenge:
24
Group:
other: 1st control group
Dose level:
20% aqueous solution
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: other: 1st reading / rechallenge. . Hours after challenge: 24.0. Group: other: 1st control group. Dose level: 20% aqueous solution. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
other: 2nd reading / rechallenge
Hours after challenge:
48
Group:
other: 1st control group
Dose level:
20% aqueous solution
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: other: 2nd reading / rechallenge. . Hours after challenge: 48.0. Group: other: 1st control group. Dose level: 20% aqueous solution. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
rechallenge
Hours after challenge:
24
Group:
other: 2nd control group (untreated in the 1st challenge)
Dose level:
20% aqueous solution
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 24.0. Group: other: 2nd control group (untreated in the 1st challenge). Dose level: 20% aqueous solution. No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
rechallenge
Hours after challenge:
48
Group:
other: 2nd control group (untreated in the 1st challenge)
Dose level:
20% aqueous solution
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 48.0. Group: other: 2nd control group (untreated in the 1st challenge). Dose level: 20% aqueous solution. No with. + reactions: 0.0. Total no. in groups: 20.0.

Any other information on results incl. tables

After intradermal induction distinct erythema and edema were observed at the injection sites of the control animals and the test animals which were applied with Freund's adjuvant/water (1:1). The test substance formulation in water or Freund's adjuvant/water (1:1) caused necrotic skin changes and distinct edema in the test animals. No skin changes were observed in the control animals which were applied with water.

After percutaneous induction, necrotic skin changes caused by the intradermal induction were observed in addition to distinct edema.

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information