Trialuminium bismuth hexaoxide

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2018

Report date:

2018

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of study:

mouse local lymph node assay (LLNA)

Test material

Test material information

Constituent 1

Reference substance name:

Trialuminium bismuth hexaoxide

EC Number:

235-552-3

EC Name:

Trialuminium bismuth hexaoxide

Cas Number:

12284-76-3

Molecular formula:

Al3BiO6

IUPAC Name:

bismuth;oxido(oxo)alumane

Test material form:

solid

In vivo test system

Test animals

Species:

mouse

Strain:

CBA/Ca

Remarks:

CBA/Ca (CBA/CaOlaHsd)

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Envigo RMS B.V., Inc., Horst, The Netherlands
- Females (if applicable) nulliparous and non-pregnant: yes
- Microbiological status of animals, when known: SPF
- Age at study initiation: 8 to 12 weeks old
- Weight at study initiation: 15 to 23 g
- Housing: Housed in suspended solid floor poylpropylene cages furnished with softwood wood flakes.
- Diet (e.g. ad libitum): Free access to rodent diet (Teklad Global Rodent diet).
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: At least 5 days
- Indication of any skin lesions: None noted

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25°C
- Humidity (%): 30 to 70%
- Air changes (per hr): At least 15 per hour
- Photoperiod (hrs dark / hrs light): 12 hours light/dark cycle

Study design: in vivo (LLNA)

Vehicle:

dimethyl sulphoxide

Concentration:

10, 25 and 50 (%w/w) in dimethyl sulfoxide

No. of animals per dose:

5 females per dose

Details on study design:

PRE-SCREEN TESTS:
- Compound solubility: Substance prepared as a suspension in DMSO.
- Irritation: No signs observed
- Systemic toxicity: No signs observed
- Ear thickness measurements: Not indicated (< 25% increase in ear thickness measurements)
- Erythema scores: No signs of local skin irritation noted.

MAIN STUDY

ANIMAL ASSIGNMENT AND TREATMENT
- Name of test method: Assigned at random to dose groups
- Criteria used to consider a positive response: The test item is regarded as a skin sensitiser if at least one concentration results in a threefold or greater increase in 3HTdR incorporation compared to control values. A test item producing a less than 3 fold increase will be classified as a non-skin sensitiser.

TREATMENT PREPARATION AND ADMINISTRATION: Test substance prepared as a suspension in DMSO. This vehicle produced the highest concentration that was suitable for dosing. The test item was formulated within 2 hours of being applied to the test system. It is assumed that the formulation was stable.

Positive control substance(s):

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

Statistics:

Data was processed to give group mean values for disintergrations per minute and standard deviations where appropriate. Individual and group mean disintergrations per minute values were assessed for dose response relationships. Data was first assessed for suitability by analysis of normality and homogeniety of variance. If the assumptions that the data are both normally distributed and has homogeniety of variances, then parametric one way analysis of variance (Anova) and Dunnett's multiple comparison procedure were used to determine statistical significance.

If the assumptions are not met, non-parametric Kruskal-Wallis Rank sum and Mann-Whitney U test procedures were used.

Results and discussion

Positive control results:

Positive control data from 24/02/2015 to 15/06/2017 was provided in various vehicles (including DMSO). All classifications of the positive control (i.e. positive response) were noted. The latest positive control study was conducted within 6 months of the currently reported study in the relevant vehicle.

In vivo (LLNA)

Results

Results 1

Parameter:

SI

Value:

1.28

Test group / Remarks:

10 % (w/w)

Results 2

Parameter:

SI

Value:

1.52

Test group / Remarks:

25 % (w/w)

Results 3

Parameter:

SI

Value:

2.1

Test group / Remarks:

50 % (w/w)

Cellular proliferation data / Observations:

DETAILS ON STIMULATION INDEX CALCULATION : The proliferation response of lymph node cells was expressed as the number of disintergrations per minute per animal and as the ratio of 3HTdR incorporation into lymph node cells of test nodes relative to that recorded for the control nodes (stimulation index).

EC3 CALCULATION: Not calculated as all SI values were less than 3.

CLINICAL OBSERVATIONS: No signs of systemic toxicity were noted in the test or control animals during the test. A greater than 25% increase in ear thickness were noted on Days 3 and 6 for the animals treated with the test subsance at concentrations of 25 and 50%. The Day 3 increase could be explained, in part, by the presence of residual test item on the ears post dose. The Day 6 result could be indicative of excessive irritation although this was not supported in the sighting test which showed the concentration to be suitable.

BODY WEIGHTS: Body weight change of the test animals between Days 1 and 6 were comparable to that observed in the corresponding control group animals over the same period.

Any other information on results incl. tables

Individual DPM per minute and SI.

Concentration (%w/w) in DMSO	Animal No.	dpm/animal	Mean dpm/animal (SD)	SI	Result
Vehicle	1-1	2092.49	2897.57 (±871.92)	Na	Na
	1-2	4204.67
	1-3	3096.01
	1-4	2994.35
	1-5	2100.34
10	2-1	3281.95	3700.47 (±595.64)	1.28	Negative
	2-2	3530.60
	2-3	4653.61
	2-4	3864.59
	2-5	3171.60
25	3-1	2768.79	4403.68 (±1138.93)	1.52	Negative
	3-2	5262.12
	3-3	5033.65
	3-4	5304.95
	3-5	3648.87
50	4-1	5276.66	6070.67*** (±1116.74)	2.10	Negative
	4-2	6070.55
	4-3	7223.04
	4-4	7109.31
	4-5	4673.80

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The test substance was considered not to be a skin sensitiser under the conditions of the test as the SI index values calculated were all less than 3.