Dodecaaluminium trimolybdenum dodecaoxide

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

23 Nov - 01 Dec 2011

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study. (The LLNA is not recommended for certain metals.)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2011

Report date:

2011

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)

Version / remarks:

(adopted July 2010)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.42 (Skin Sensitisation: Local Lymph Node Assay)

Version / remarks:

(EC Directive 2004/73/EC)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

GYEMSZI, National Institute for Quality- and Organizational Development in Healthcare and Medicines, National Institute of Pharmacy, Budapest, Hungary

Type of study:

mouse local lymph node assay (LLNA)

Test material

Test material information

Constituent 1

Reference substance name:

Dodecaaluminium trimolybdenum dodecaoxide

EC Number:

239-183-9

EC Name:

Dodecaaluminium trimolybdenum dodecaoxide

Cas Number:

15123-80-5

Molecular formula:

Al2Mo3O12

IUPAC Name:

dialuminium(3+) tris(dioxomolybdenumbis(olate))

Details on test material:

- Name of test material (as cited in study report): Aluminium molybdate
- Physical state/appearance: solid, white
- Analytical purity: > 99%
- Lot/batch No.: GRA 2011-10-13-01
- Storage: room temperature
- Expiry date: Nov 2018

In vivo test system

Test animals

Species:

mouse

Strain:

other: CBA/Ca

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: TOXI-COOP ZRT., H-1103, Budapest, Cserkesz u.90.
- Age at study initiation: 8 - 11 weeks
- Weight at study initiation: 17.9 - 22.5 g
- Housing: groups of 4, in type II polypropylene/polycarbonate cages
- Diet: Ssniff SM R/M-Z+H complete diet for rats and mice (Ssniff Spezialdiäten GmbH, D-59494 Soest, Germany); ad libitum
- Water: tap water; ad libitum
- Acclimation period: 7 and 14 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 30 - 70
- Photoperiod (hrs dark / hrs light): 12/12

Study design: in vivo (LLNA)

Vehicle:

dimethylformamide

Concentration:

10%, 25%, and 50%

No. of animals per dose:

4

Details on study design:

RANGE FINDING TESTS:
The preliminary irritation/toxicity screen was performed with 50% and 25% (w/v) as suspension in DMF.
No mortality, no obvious signs of systemic toxicty and no significant signs of irritation were observed. Thus, test item concentration of 50% was selected as the highest test concentration in the main test.

MAIN STUDY
ANIMAL ASSIGNMENT AND TREATMENT
- Name of test method: Local Lymph Node Assay
- Criteria used to consider a positive response: If the stimulation index (SI) value is increased at least 3-fold, the test substance is considered a skin sensitizer.

TREATMENT PREPARATION AND ADMINISTRATION:
Each mouse was topically treated with 25 µL of the appropriate formulations of the test item, the positive control substance and the vehicle using a pipette, on the dorsal surface of each ear. Each animal was dosed once a day on 3 consecutive days. There was no treatment on days 4, 5, and 6.
On day 6, the animals were intravenously injected via the tail vein with 250 µL of sterile PBS containing 20 µCi of ³H-methyl-thymmidine. Once injected, the mice were left for 5 hours (± 30 min).
Then, the mice were anaesthetized and sacrificed. The draining auricular lymph nodes were excised, removed and pooled per group.
A single cell suspension of lymph node cells was prepared.
For the measurement of incorporated radioactivity the vials were loaded into a beta-scintillation counter and ³HTdR incorporation was measured for up to 10 min per sample, expressed as the amount of radioactive disintegration per minute (DPM).
The stimulation index is calculated: SI = DPN treated/DPN neg. control (DPN = DPM divided by the number of pooled lymph nodes)
A stimulation index of >= 3 is an indication of a positive result.

VEHICLE
- Choice for vehicle: The following substances were tested as vehicle: Acetone: Olive oil 4:1 mixture (v/v) (AOO), N,N-Dimethylformamide (DMF), DMSO, and purified water. Based on the solubility, DMF was chosen as vehicle for the test substance and AOO as vehicle for positive control.

Positive control substance(s):

hexyl cinnamic aldehyde (CAS No 101-86-0)

Results and discussion

In vivo (LLNA)

Results

Results 1

Parameter:

SI

Remarks on result:

other: - negative control (DMF): 1.0 - 50%: 0.9 - 25%: 0.4 - 10%: 0.4 - positive control: 5.5 - negative control (AOO): 1.0

Results 2

Parameter:

other: disintegrations per minute (DPM)

Remarks on result:

other: - negative control (DMF): 7319 - 50%: 6377.5 - 25%: 3269.5 - 10%: 2948.5 - positive control: 40665.5 - negative control (AOO): 7390.5

Applicant's summary and conclusion

Interpretation of results:

not sensitising

Remarks:

Migrated information Criteria used for interpretation of results: EU