Aluminium tributanolate

Endpoint summary

Description of key information

Upon contact with water or moisture (e.g. within mucous membranes) aluminium tributanolate hydrolyses immediately to butan-1ol and aluminium 3+ cations (as hydroxide and oxyhydroxide). Hence, toxicity is determined by the toxicity of these two species

A test following the protocol of OECD 429 was performed in mice treated with 5, 10 and 25% of butan-1-ol in distilled water during 3 consecutive days (Ryan 2000). On day 5 animals were treated with 3H-methylthymidine and the amount of 3H-TdR was measured in a cell suspension derived from the auricular lymphnodes (pooled/animal). The stimulation index was 1.6, 1.2 and 1.4 at 5, 10 and 25%. This is indicative for no sensitizing effects.

Basketter (1999) investigated the allergenic potential of a.o. aluminium chloride hexahydrate (5, 10 and 25% in petrolatum) in the Local Lymph Node Assay (LLNA). Groups of 4 CBA/Ca mice (7 to 12 weeks of age) were treated with 25 μL of substance or with an equal volume of the vehicle alone, on the dorsum of both ears. The mice were treated once daily for 3 days. Two days later, the mice were injected with 250 μL of phosphate buffered saline (PBS) with 20 μCi of tritiated thymidine (2 Ci mmol-l). The mice were killed 5 hours later and a single-cell suspension of lymph node cells was prepared by mechanical disaggregation. Aluminium chloride hexahydrate did not induce a lymph node proliferation response compared to concurrent vehicle-treated controls, and therefore the response was judged as negative. The results of this study add to the weight of evidence for a low sensitisation potential of aluminium 3+ cations.

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:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study without detailed documentation

Qualifier:

equivalent or similar to guideline

Guideline:

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

GLP compliance:

not specified

Type of study:

mouse local lymph node assay (LLNA)

Specific details on test material used for the study:

100%

Species:

mouse

Strain:

CBA:J

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Harlan Sprague Dawley Inc, Indianapolis IN, USA
- Age at study initiation: 6-12 weeks
- Weight at study initiation: no data


ENVIRONMENTAL CONDITIONS: no data

Animals were housed, fed and handled according to the USA Animal Welfare Act

Vehicle:

other: distilled water

Concentration:

0, 5, 10 and 20% v/v

No. of animals per dose:

5 females

Details on study design:

PRE-SCREEN TESTS: no data on pre-test and selection of the doses

MAIN STUDY:
Mice were treated for 3 consecutive days with 25 uL of the concentration at the dorsal site of the ears. After 5 days mice were injected with 3H-methylthymidine in PBS (20 uCi). Five hours thereafter mice were euthanised and draining auricular lymphnodes were removed (pooled per animal) and single cell suspensions were prepared by mechanical disaggregation through a nylon mesh (100 um pore size). Cell suspension were washed, precipitated with TCA and left overnight (at 4 degr C). After further preparation and suspension in scintillation cocktail the 3H-methylthymidine incorporation was measured by beta-scintillation counting (expressed as DPM/mouse)

Positive control substance(s):

other: the test contained several substances with positive results

Statistics:

NA

Parameter:

other: DPM

Value:

366

Variability:

± 44

Test group / Remarks:

control

Remarks on result:

other: SI =1

Parameter:

other: DPM

Value:

598

Variability:

± 157

Test group / Remarks:

5% group

Remarks on result:

other: SI = 1.6

Parameter:

other: DPM

Value:

451

Variability:

± 17

Test group / Remarks:

10% group

Remarks on result:

other: SI = 1.2

Parameter:

other: DPM

Value:

530

Variability:

± 91

Test group / Remarks:

25% group

Remarks on result:

other: SI = 1.4

Parameter:

SI

Value:

1

Test group / Remarks:

control

Parameter:

SI

Value:

1.6

Test group / Remarks:

5%

Parameter:

SI

Value:

1.2

Test group / Remarks:

10%

Parameter:

SI

Value:

1.4

Test group / Remarks:

20%

Cellular proliferation data / Observations:

No additional data available

Interpretation of results:

GHS criteria not met

Conclusions:

The substance is not sensitizing in the LLNA test

Executive summary:

A test following the protocol of OECD 429 was performed in mice treated with 5, 10 and 25% of the substance in distilled water during 3 consecutive days. On day 5 animals were treated with 3H-methylthymidine and the amount of 3H-TdR was measured in a cell suspension derived from the auricular lymphnodes (pooled/animal). The stimulation index was 1.6, 1.2 and 1.4 at 5, 10 and 25%. This is indicative for no sensitizing effects.

Reference 2

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

1999

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study without detailed documentation

Qualifier:

equivalent or similar to guideline

Guideline:

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

Deviations:

yes

Remarks:

:

GLP compliance:

no

Type of study:

mouse local lymph node assay (LLNA)

Species:

mouse

Strain:

CBA

Sex:

not specified

Details on test animals and environmental conditions:

Species and strain: mouse, 4 CBA/Ca
Source: Harlan Olac, Bicester, UK.
Justification of species and strain: Mouse is the preferred animal for this test (OECD TG#429)
Sex: not stated
Body weight range at the beginning of the study: not stated
Age at testing: 7 to 12 weeks
No further details mentioned

Vehicle:

other: petrolatum

Concentration:

5.0%, 10.0%, and 25.0%

No. of animals per dose:

4

Details on study design:

Two days after the last exposure, the mice were injected with 250 µL of phosphate buffered saline (PBS) containing 20 µCi of tritiated thymidine (from Amersham International, Amersham, UK). Five hours later, the mice were killed, draining lymph nodes excised and a single-cell suspension of the pooled lymph node samples was prepared.

The lymph node cell suspension was washed in excess PBS, precipitated with 5% trichloroacetic acid (TCA) at 4 ºC for 18 hours. After resuspension in TCA, β-scintillation counting was used to measure tritium incorporation.

The method used to kill the animals was not reported.

Observations:
Proliferation of cells in the lymph nodes.

- A positive result was defined as a threefold or greater proliferation than in the concurrent vehicle treated controls.

Positive control substance(s):

other: positive results were seen for metal salts of gold, beryllium, cobalt, mercury, platinum and tin that were tested in parallel

Statistics:

NA

Positive control results:

positive responses were noted

Key result

Parameter:

SI

Value:

>= 0.7 - <= 0.8

Test group / Remarks:

5% 0.8; 10% 0.8; 25% 0.7

Parameter:

EC3

Remarks on result:

not determinable

Remarks:

all values SI values < 3

Parameter:

SI

Value:

0.8

Test group / Remarks:

5%

Parameter:

SI

Value:

0.8

Test group / Remarks:

10%

Parameter:

SI

Value:

0.7

Test group / Remarks:

25

The results for aluminium chloride hexahydrate were negative. There was no information on the irritancy of the tested concentration from a pre-test

Interpretation of results:

GHS criteria not met

Conclusions:

Aluminium chloride hexahydrate did not show sensitizing potential under the conditions used in this assay.

Executive summary:

Basketter et al. (1999) investigated the allergenic potential of 13 metal salts including aluminium chloride hexahydrate (99% purity) in the Local Lymph Node Assay (LLNA). Groups of 4 CBA/Ca mice (7 to 12 weeks of age) were treated with 25 μL of substance or with an equal volume of the vehicle alone, on the dorsum of both ears. The mice were treated once daily for 3 days. Two days later, the mice were injected with 250 μL of phosphate buffered saline (PBS) with 20 μCi of tritiated thymidine (2 Ci mmol^-l). The mice were killed 5 hours later and a single-cell suspension of lymph node cells was prepared by mechanical disaggregation. A substance was considered a skin sensitizer the proliferation in the lymph nodes of treated mice was 3-fold or greater than that in the concurrent vehicle-treated controls. Aluminium chloride hexahydrate administered in petrolatum (vehicle) at test concentrations of 5.0%, 10.0% and 25.0% did not induce a lymph node proliferation response compared to concurrent vehicle-treated controls, and therefore the response was judged as negative. The results of this study add to the weight of evidence for a low sensitisation potential of aluminium 3+ cations.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

None of the hydrolysis products is expected to cause sensitization of the skin.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Based on the outcome of the studies with both hydrolysis products of aluminium tributanolate, the substance has not to be classified for sensitizing properties according to Regulation EC 1272/2008.