Aluminium triethanolate

Endpoint summary

Description of key information

A robust OECD 429 (LLNA) study is available assessing the skin sensitising potential of the substance.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

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

GLP compliance:

yes (incl. QA statement)

Type of study:

mouse local lymph node assay (LLNA)

Species:

mouse

Strain:

CBA/Ca

Remarks:

CBA/CaCrl

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Charles River (UK) Ltd.
- Females (if applicable) nulliparous and non-pregnant: yes
- Microbiological status of animals, when known: SPF
- Age at study initiation: Approximately 8 to 10 weeks old
- Weight at study initiation: 17 to 24g
- Housing: The animals were housed in cages that conformed to the ‘Code of Practice for the Housing and Care of Animals Bred, Supplied or Used for Scientific Purposes’ (Home Office, London, 2014). The animals were housed in groups of up to five during acclimatisation. From the day prior to dosing (Day-1), the preliminary test animal was individually housed. Main study animals were housed in pairs.
- Diet (e.g. ad libitum): 5LF2 EU Rodent Diet 14%, was freely available to the animals at all times.
- Water (e.g. ad libitum): Mains water was provided, ad libitum, via cage-mounted water bottles.
- Acclimation period: 8 to 15 days
- Indication of any skin lesions: None

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25°C
- Humidity (%): 38 to 70%
- Air changes (per hr): At least 15
- Photoperiod (hrs dark / hrs light): 12 hours light/dark cycle

Vehicle:

propylene glycol

Concentration:

5, 10 and 25 % w/v (as well as control and positive control)

No. of animals per dose:

4 females

Details on study design:

PRE-SCREEN TESTS:
- Compound solubility: The vehicle for the test article was propylene glycol. The vehicle was chosen because it was the vehicle listed in the protocol that produced an overtly stable solution, emulsion or dispersion at the highest attainable concentration.
- In the absence of toxicological information regarding irritation and/or systemic toxicity, a preliminary screening test was conducted with one animal. The mouse was treated by daily application of 25 µL of the test article at the maximum suitable concentration (25% w/v in propylene glycol) to the dorsal surface of each ear for three consecutive days (Days 1, 2 and 3). The mouse was observed daily for any signs of toxicity or irritation at the application site. The body weight was recorded on Day-1 and prior to termination on Day 6. Both ears were observed for erythema and scored.

MAIN STUDY

ANIMAL ASSIGNMENT AND TREATMENT
- Name of test method: LLNA - pooled method
- Criteria used to consider a positive response: The test result is not valid for those groups producing an SI value of 3.0 or more when the sites of application have shown excessive irritation and for those groups that have shown indications of systemic toxicosis. The test article is regarded as a sensitiser when the maximum value of the SI is 3.0 or above. The test article is classified as a non-sensitiser when the maximum value of the SI is less than 3.0. (This result is unchanged by observations of irritation at sites of application of the test formulation).

TREATMENT PREPARATION AND ADMINISTRATION: Each mouse was manually restrained with both auditory pinnae left free. The outer aspect of both pinnae of each mouse was treated by direct application of the appropriate test or control formulation (0.025 mL/pinna) dispensed from an automatic micro pipette. The five groups of four female mice were subjected to application of the vehicle control, positive control or one of the test formulations to the outer aspect of the auditory pinnae, once daily on Days 1, 2 and 3. On Day 6 the mice were placed in a thermacage in order to dilate the peripheral blood vasculature and thus facilitate intravenous dosing. Each mouse was transferred to a cylindrical restrainer. A plastic syringe and fine gauge hypodermic needle were used to administer 0.25 mL phosphate buffered saline incorporating 20 µCi of 3HTdR into a tail vein of each mouse by slow bolus injection. After this treatment, the mice were returned to their cages. Approximately five hours after intravenous injection of the 3HTdR, all mice were killed by exanguination under a deep plane of inhalation anesthesia. Killing was organised to minimise the interval between death and the recovery of the auricular lymph nodes to no more than fifteen minutes.

Positive control substance(s):

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

Statistics:

No applicable for pooled method

Positive control results:

Positive control group provided a group DPM of 426 (SI index 5.84) indicating validity of the test.

Parameter:

SI

Value:

1.03

Variability:

NA - pooled method

Test group / Remarks:

5 % w/v

Parameter:

SI

Value:

1.49

Variability:

NA - pooled method

Test group / Remarks:

10 % w/v

Parameter:

SI

Value:

1.58

Variability:

NA - pooled method

Test group / Remarks:

25 % w/v

Parameter:

SI

Value:

5.84

Variability:

NA - pooled method

Test group / Remarks:

Postive control

Cellular proliferation data / Observations:

DETAILS ON STIMULATION INDEX CALCULATION : The scintillation counter provided data including the DPM value (disintegrations per minute during a ten minute period). The DPM value for each test group was divided by the DPM for the control group to provide the Stimulation Index (SI) value for each test group.

EC3 CALCULATION - Not applicable as SI less than 3 at all exposures.

CLINICAL OBSERVATIONS: There were no clinical signs indicative of a systemic effect of treatment among mice treated with the vehicle or with 5, 10 or 25% w/v formulations of the test article. The vehicle and test formulation application sites remained free of irritation.


BODY WEIGHTS: There was no indication of a treatment related effect on body weight.

Group DPMs and Stimulation Index (SI):

Concentration	Group number	Group DPM	Stimulation Index (SI)
Vehicle	1	73	NA
5 (w/v)	2	75	1.03
10 (w/v)	3	109	1.49
25 (w/v)	4	115	1.58
Positive control	5	426	5.84

Interpretation of results:

GHS criteria not met

Conclusions:

The Local Lymph Node Assay demonstrated that the substance does not have the potential to cause skin sensitisation under the conditions of the test.

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

The substance was not deemed to be a skin sensitiser under the conditions of the available LLNA (OECD 429) study.