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Toxicological information

Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Study period:
2005-10-24 to 2005-12-27
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
The solubility of aluminium lanthanum trioxide (AlLaO3) is low since dissolution of AlLaO3 in water resulted in La concentrations < 0.01 mg/L and Al concentrations < 0.03 mg/L after 34 days. The dissolution of AlLaO3 in water results in Al (3+) (=Al(H2O)6 (3+)) ions and La (3+) ions. Thus, the toxicological moieties of concern are aluminium and lanthanum ions. Thus, in the assessment of toxicity, data available for different aluminium and lanthanum substances are read-across since aluminium and lanthanum ions determine the toxicological potential of aluminium lanthanum trioxide, i.e. are the common toxicological moieties of concern. The effects of the substance aluminium lanthanum trioxide with regard to skin sensitisation are predicted to be equal to the effects of Al (3+) ions and La (3+) ions.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2005
Report date:
2005

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
EU Method B.6 (Skin Sensitisation)
Version / remarks:
1996
Deviations:
no
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
1992
Deviations:
no
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
A reliable guinea pig maximisation study has been performed, which would not justify conducting an additional LLNA due to animal welfare.

Test material

Constituent 1
Chemical structure
Reference substance name:
Lanthanum oxide
EC Number:
215-200-5
EC Name:
Lanthanum oxide
Cas Number:
1312-81-8
Molecular formula:
La2O3
IUPAC Name:
Lanthanum oxide
Details on test material:
not specified
Specific details on test material used for the study:
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
Storage condition of test material : at room temperature (20 ± 5 °C), light protected

In vivo test system

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS:
- Source: Charles River Deutschland GmbH
- Age at study initiation: 5 - 6 weeks
- Weight at study initiation: 336 - 392 g
- Housing: individually in Makrolon type-4 cages with standard softwood bedding
- Diet: pelleted standard Provimi Kliba 3418, ad libitum
- Water: community tap water from Füllinsdorf, ad libitum
- Acclimation period: 13 days

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 3 °C
- Humidity: 30 - 70 %
- Air changes: 10 - 15 per hr
- Photoperiod: 12 hrs dark / 12 hrs light

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal
Vehicle:
other: PEG 300
Concentration / amount:
15 % or 25 % (w/w) of the test item
Day(s)/duration:
Day 1
Route:
epicutaneous, occlusive
Vehicle:
other: PEG 300
Concentration / amount:
50 % (w/w) of the test item
Day(s)/duration:
day 8 (duration: 48 hours)
Adequacy of induction:
other: pretreated with 10 % SDS
Challenge
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
other: PEG 300
Concentration / amount:
50 % (w/w) of the test item
Day(s)/duration:
day 22 (duration: 24 hours)
No. of animals per dose:
15 (main study: 5 in control group, 10 in test group), 3 (pretest)

Details on study design:
* RANGE FINDING TEST:
>>> INTRADERMAL INJECTIONS:
One guinea pig was intradermally injected into the clipped flank at concentrations of B = 25 % and C = 15 % (w/w) of the test item in PEG 300. Due to the high viscosity of the application dilution and the obstacle caused by the tissues, it was not technically possible to inject the liquid dilution at concentration of A = 50 % (w/w) into the intra-cellular space.
Dermal reactions were assessed approximately 24 hours later.
Based on the results, the test item concentration of 25 % was selected for intradermal induction in the main study. However, due to the high viscosity of the test item preparation, the two first animals of the test group could not be applied successfully (only partial application) intracutaneously with the test item concentration of 25 % (w/w) in PEG 300. Therefore, the next lower concentration of 15 % (w/w) tested in the pretest was selected.

>>> EPIDERMAL APPLICATION:
4 patches of filter paper were saturated with the test item at D = 50 % (technically the highest possible concentration to be applied sufficiently), E = 25 %, F = 15 % and G = 10 % (w/w) in PEG 300 and applied to the clipped and shaved flanks of 2 guinea pigs. The patches were covered by a strip of aluminum foil and firmly secured by elastic plaster wrapped around the trunk and covered with impervious adhesive tape.
21 hours after removal of the dressing the application site was depilated in order to visualize any resulting erythema.
3 hours later (48 hours from the epidermal application) the skin reaction was observed and recorded. After this observation a second observation (approximately 72 hours from the epidermal application) was made and once again recorded.
Based on the results obtained the concentration selected for induction and challenge in the main study was 50 % (w/w).


* MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2
- Type of epicutaneous induction: occlusive
- SLS application: yes (0.5 mL at 10% w/w)
- Exposure period: on D1 (intradermal) and D8 (epidermal, 48-hr exposure)
- Test groups:
>>> Intradermal induction:
1) 1:1 (v/v) mixture of Freund's Complete Adjuvant and physiological saline
2) The test item at 25 % or 15 % (w/w) in PEG 300
3) The test item at 25 % or 15 % (w/w) in a 1:1 (v/v) mixture of Freund's Complete Adjuvant and physiological saline
>>> Epidermal application: test item at 50 % (w/w) in PEG 300
- Control group:
>>> Intradermal induction:
1) 1:1 (v/v) mixture of Freund's Complete Adjuvant and physiological saline
2) PEG 300
3) 1:1 (w/w) mixture of PEG 300 in a 1:1 (v/v) mixture of Freund's Complete Adjuvant and physiological saline
>>> Epidermal application: PEG 300 only
- Site: dorsal skin of the scapular region
- Frequency of applications: not applicable
- Duration: 8 days (duration of the induction phase)
- Concentrations: 15 or 25 % w/w by intradermal injection, 50 % by epidermal application

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day of challenge: day 22
- Exposure period: 24 hours
- Test groups: test item in the vehicle only (+ vehicle only in the other flank)
- Control group: test item in the vehicle only (+ vehicle only in the other flank)
- Site: left (test item) and right (vehicle) flanks
- Concentrations: 50% (w/w)
- Evaluation: 48 hr after the beginning of the challenge

- Statistics: descriptive statistics were calculated for body weights. No inferential statistics were used.
Challenge controls:
Please refer to the field "Details on study design" above.
Positive control substance(s):
yes
Remarks:
hexyl cinnamic aldehyde (CAS No 101-86-0) (regularly control)

Results and discussion

Positive control results:
hexyl cinnamic aldehyde was tested in the same conditions as described above. Based on the findings, hexyl cinnamic aldehyde at 1% in PEG 300 was considered as a skin sensitizer.
The positive control was not included in the study, but put in an other report , as regularly control.

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
50 % of the test item
No. with + reactions:
0
Total no. in group:
5
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
50%
No. with + reactions:
0
Total no. in group:
10
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
1% of the postive control
No. with + reactions:
4
Total no. in group:
10
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
50% of the test item
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
In the control group, no skin reactions were observed in the animals when treated with either PEG 300 only or when treated with the test item at 50 % (w/w) in PEG 300.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
50% of the test item
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
No mortality, no sign of systemic toxicity and no effect on body weight were observed during the study. In the test group, no skin reactions were observed in the animals when treated with either PEG 300 or the test item at 50 % (w/w) in PEG 300.
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
1% of the positive control
No. with + reactions:
1
Total no. in group:
10

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The substance is not a skin sensitiser.
According to Regulation (EC) No 1272/2008 and subsequent adaptations, the substance does not require classification as skin sensitiser.
Executive summary:

The sensitisation potential of Lanthane oxide was evaluated on Dunkin-Hartley guinea pigs according to the maximisation method of Magnusson and Kligman, described in EU method B.6, and in compliance with Good Laboratory Practice.

Ten test and five control guinea pigs were included in this study. Induction was carried out as the following:

- on day one, animals were injected by the intracutaneous route with Lanthane oxide (15 and 25% % w/w in PEG 300) +/- Freund Complete Adjuvant (treated group) or with PEG 300 +/- Freund Complete Adjuvant (control group) or with Freund Complete Adjuvant alone (both groups);

- on day 7, the same region received a topical application of sodium lauryl sulfate (10 % w/w in paraffinum perliquidum) in order to induce local irritation;

- on day 8, a 48-hour topical occlusive application was performed with Lanthane oxide at 50 % w/w in PEG 300 (test animals) or the vehicle (controls).

- on day 22, the control and test animals were challenged by a cutaneous application of the test substance at 50 % w/w in PEG 300 to the left flank. The right flank served as control and received the vehicle only. The test substance and the vehicle were maintained under an occlusive dressing for 24 hours.

Skin reactions (erythema and oedema) were evaluated approximately 24 and 48 hours after removal of the dressing.

No clinical signs and no deaths related to treatment were noted during the study.

After the challenge application, at the 24-hour and 48-hour readings, no cutaneous reactions were noted.

In this study, Lanthane oxide is not a dermal sensitizer.