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Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
08 Aug 2012 - 20 Aug 2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2012
Report date:
2012

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.42 (Skin Sensitisation: Local Lymph Node Assay)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.2600 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes
Type of study:
mouse local lymph node assay (LLNA)

Test material

Constituent 1
Chemical structure
Reference substance name:
Yttrium oxide (Y2O3), europium-doped
EC Number:
271-591-2
EC Name:
Yttrium oxide (Y2O3), europium-doped
Cas Number:
68585-82-0
Molecular formula:
Y2O3:Eu
IUPAC Name:
diyttrium(3+) europium trioxidandiide
Test material form:
solid: particulate/powder
Details on test material:
- Name of test material (as cited in study report): Yttrium Oxide, Europium-Doped
- Physical state: white powder

In vivo test system

Test animals

Species:
mouse
Strain:
other: CBA/J
Sex:
female
Details on test animals and environmental conditions:
- Source: Janvier, Le Genest-Saint-Isle, France.
- Age at study initiation: Young adult animals (approx. 9 weeks old)
- Weight at study initiation: Body weight variation was within +/- 20% of the sex mean (20-23g).
- Housing: Animals were group housed in labeld makrolon cages.
- Diet: Free access to pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany).
- Water: Free access to tap water.
- Acclimatisation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 -24
- Humidity (%): 40 - 70
- Air changes (per hr): approx 15
- Photoperiod (hrs dark / hrs light): 12/12

Temporary deviations from the maximum level of daily mean relative humidity occurred. The study integrity was not adversely affected by the deviations.

IN-LIFE DATES: From: 08Aug 2012 to 20Aug 2012

Study design: in vivo (LLNA)

Vehicle:
propylene glycol
Concentration:
0, 10, 25, 50%
No. of animals per dose:
5
Details on study design:
RANGE FINDING TESTS:
Two test substance concentrations were tested: 25% and 50% concentration, with two animals per concentration.

MAIN STUDY
ANIMAL ASSIGNMENT AND TREATMENT
- Name of test method: Local Lymph Node Assay
- Criteria used to consider a positive response: DPM values are presented for each animal and for each dose group. A Stimulation Index (SI) is
calculated for each group. The SI is the ratio of the DPM/group compared to DPM/vehicle control group. If the results indicate a SI ≥ 3, the test substance may be regarded as a skin sensitizer.

TREATMENT PREPARATION AND ADMINISTRATION:
Test substance preparation: The test substance formulations (w/w) were prepared within 4 hours prior to each treatment. Homogeneity was obtained to visually acceptable levels.
The vehicle was selected based on trial formulations performed at WIL Research and on test substance data supplied by the sponsor.

Induction - Days 1, 2 and 3; Excision of nodes - Day 6; Tissue processing for radioacitivity - Day 6; Radioactivity measurements - Day 7; Performed according to test guidelines.

Observations:
Mortality/Viability: Twice daily.
Body weights: On Day 1 (pre-dose) and Day 6 (prior to necropsy).
Clinical signs: Once daily on Days 1-6 (on Days 1-3 between 3 and 4 hours after dosing).
Irritation: Once daily on Days 1-6 (on Days 1 - 3 immediately after dosing) according to the numerical scoring system according to OECD. Furthermore, a description of all other (local) effects was recorded according to guidelines.

Necropsy: All animals surviving to the end of the study were sacrificed by intra-peritoneal injection with Euthasol® 20% (0.2 mL/animal).
Positive control substance(s):
hexyl cinnamic aldehyde (CAS No 101-86-0)
Statistics:
Not performed.

Results and discussion

Positive control results:
The six-month reliability check with Alpha-hexyl cinnamic aldehyde indicates that the Local Lymph Node Assay as performed at WIL Research is an appropriate model for testing for contact hypersensitivity (EC3 value is 16.5%).

In vivo (LLNA)

Resultsopen allclose all
Key result
Parameter:
SI
Value:
1.6
Test group / Remarks:
10%
Key result
Parameter:
SI
Value:
1.5
Test group / Remarks:
25%
Key result
Parameter:
SI
Value:
1.2
Test group / Remarks:
50%
Cellular proliferation data / Observations:
Mean DPM/animal values for the experimental groups treated with test substance concentrations 10, 25 and 50% were 610, 599 and 472 DPM respectively. The mean DPM/animal value for the vehicle control group was 393 DPM.

Any other information on results incl. tables

Results Pre-screen test:

At the 25% and 50% test substance concentration no signs of systemic toxicity were noted and very slight erythema was observed. Variations in ear thickness during the observation period were less than 25% from Day 1 pre-dose values. White test substance remnants were present on the dorsal surface of the ears of both animals at 25% and 50% respectively (Days 1-3), which did not hamper scoring of the skin reactions. Based on these results, the highest test substance concentration selected for the main study was a 50% concentration.

Other results - main study:

No mortality occurred and no clinical signs of systemic toxicity were observed in the animals of the main study. The body weight loss noted for some animals across the dose groups was considered not toxicologically significant since the changes were slight in nature and no concentration-related incidence was apparent. No irritation of the ears was observed in any of the animals examined. All auricular lymph nodes of the animals of the experimental and control groups were considered normal in size. No macroscopic abnormalities of the surrounding area were noted in any of the animals. White staining of test substance remnants on the dorsal surface of the ears was found in all animals treated with 25 or 50% of the test substance. This did not hamper scoring for erythema.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
In an LLNA skin sensitisation study, performed according to OECD/EC test guidelines, Yttrium Oxide, Europium-Doped is considered not to be a skin sensitiser, as the SI value appeared not to be ≥ 3 when tested up to 50%.
Executive summary:

An LLNA skin sensitisation study was performed according to OECD and EC test guidelines and GLP principles. The test substance (Yttrium Oxide, Europium-Doped) was applied at 10, 25 and 50% w/w. No mortality occurred and no clinical signs of systemic toxicity were observed in the animals of the main study. No toxicologically relevant weight changes were noted in any of the groups. All auricular lymph nodes of the animals of the experimental and control groups were considered normal in size. No macroscopic abnormalities of the surrounding area were noted in any of the animals.

The SI values calculated for the substance concentrations 10, 25 and 50% were 1.6, 1.5 and 1.2, respectively. Since there was no indication that the test substance elicited an SI ≥ 3 when tested up to 50%, Yttrium Oxide, Europium-Doped is not considered to be a skin sensitizer.