Trialuminium bismuth hexaoxide

Endpoint summary

Description of key information

A mouse Local Lymph Node Assay (LLNA) is available for the substance the results of which provide an SI index less than 3. No study is available to assess respiratory sensitisation.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Reference 1

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

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

GLP compliance:

yes (incl. QA statement)

Type of study:

mouse local lymph node assay (LLNA)

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

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.

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.

Parameter:

SI

Value:

1.28

Test group / Remarks:

10 % (w/w)

Parameter:

SI

Value:

1.52

Test group / Remarks:

25 % (w/w)

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.

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

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.

Reference 2

Endpoint:

skin sensitisation: in vitro

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

an in vitro skin sensitisation study does not need to be conducted because adequate data from an in vivo skin sensitisation study are available

Justification for type of information:

In vivo LLNA required for other regulatory jurisdictions outside of REACH (e.g. requirements in China).

Reason / purpose for cross-reference:

data waiving: supporting information

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

As the SI index calculated at each dose is less than 3 the substance does not warrant classification for skin sensitisation in accordance with the CLP Regulation (EC No. 1272/2008, as amended).