Registration Dossier

Administrative data

Description of key information

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

As no studies investigating the skin sensitisation of reaction mass of aluminium hydroxide and aluminium nitrate and aluminium sulphate are available in accordance to Regulation (EC) No. 1907/2006 Annex XI, 1.5 a read-across from supporting substances (structural analogues) e.g. aluminium compounds was considered. Aluminium oxide, aluminium hydroxide and aluminium metal are insoluble in water under standard conditions. Based on these physico-chemical characteristics, it is likely that under physiological conditions, the absorption and associated bioavailability of aluminium hydroxide, aluminium oxide and aluminium metal will be low. Following oral absorption, aluminium is present in the body as the ionic species (Al3+), which is the determining factor the systemic effects of aluminium, including acute toxicity. Hence, it can be assumed that Al3+is the substance of biological interest and the toxicological effects can be attributed mainly to Al3+.

Following absorption of the substance used for read-across like aluminium salts (e.g., aluminium nitrate, aluminium chloride, aluminium sulphate, etc.) aluminium is present in the body as Al3+as well. Therefore, with appropriate consideration of bioavailability differences, it is reasonable to consider data obtained from aluminium salts, generally more soluble, in the hazard identification of the highly soluble reaction mass of aluminium hydroxide and aluminium nitrate and aluminium sulphate.

In conclusion, in terms of hazard assessment of toxic effects, available data for human health endpoints for various aluminium compounds can be read-across to reaction mass of aluminium hydroxide and aluminium nitrate and aluminium sulphate since the pathways leading to toxic outcomes are likely to be dominated by the chemistry and biochemistry of the aluminium ion (Al3+) (Krewski et al., 2007; ATSDR, 2008).

A detailed justification read-across is provided in the technical dossier (see IUCLID Section 13) as well as in the Chemical Safety Report (see Part B).

  

Skin sensitisation

Since no studies investigating the skin sensitisation potential of reaction mass of aluminium hydroxide and aluminium nitrate and aluminium sulphate are available in accordance to Regulation (EC) No. 1907/2006 Annex XI, 1.5 a read-across from supporting substances (structural analogues) aluminium chloride, basic (CAS 1327-41-9) and aluminium chloride (CAS 7446-70-0) was performed.

Read-across is justified based on the fact the pathways leading to toxic findings are likely to be dominated by the chemistry and biochemistry of the aluminium ion (Al3+) and consequently toxicological effects can be attributed mainly to Al3+.

 

CAS 1327-41-9 (aluminium chloride, basic)

A Guinea Pig Maximisation Test of Skin Sensitization was performed with the test substance according to OECD guideline 406 (Jones, 1986) and GLP. 20 female guinea pigs were treated with test substance and compared to 10 negative control animals. A 0.1% dilution of the test substance in water was used for intradermal induction symmetrically in two rows on each side of the spine and 50% used for epidermal induction on the shoulder region of test animals. All animals were challenged for 24 hours epicutaneously on the flank region with the 50% test. 24 and 48 hours after removal of the dressing, no positive skin were observed. Based on the study results no classification is required according to EU classification criteria for skin sensitisation.

 

CAS 7446-70-0 (aluminium chloride)

The test material was evaluated for its skin sensitisation potential in mouse in LLNA study equivalent to OECD Guideline 429 and not GLP compliant. Groups of four mice were treated with 25 µL of test material at concentrations of 5, 10 and 25%, or with an equal volume of the vehicle alone (petroulatum) on the dorsum of both ears, once daily for three consecutive days. Five days after the initiation of exposure, an injection of 250 µL phosphate buffered saline (PBS) containing 20 µCi ³H-thymidine (H³-TdR). Five hours later, the draining auricular lymph node cells were prepared from each mouse by mechanical disaggregation. A single cell suspension of lymph node cells was prepared from each mouse. Cells were prepared with 5% trichloroacetic acid at 4°C for 18 hours. ³H-thymidine incorporation determined by beta-scintillation counting. The stimulation index (SI) resulted to be 0.8, 0.8 and 0.7 at the concentration 5, 10 and 25% respectively. As the stimulation index was below 3, the test material was evaluated as non-sensitizing. Based on the study results no classification is required according to EU classification criteria for skin sensitisation.

 

 

References

 

ATSDR (Agency for Toxic Substances and Disease Registry) (2008).Toxicological Profile for Aluminum, Atlanta, Department of Health and Human Services, Public Health Service.

 

Krewski, et al. (2007).Human Health Risk Assessment for Aluminium, Aluminium Oxide, and Aluminium Hydroxide, A Report Submitted to the Environmental Protection Agency. J Toxicol Environ Health B Crit Rev. 10 Suppl 1:1-269.

 

 

Migrated from Short description of key information:

Based on read-across from supporting substances reaction mass of aluminium nitrate and aluminium sulphate has no skin sensitising potential.

Justification for selection of skin sensitisation endpoint:

Hazard assessment is conducted by means of read across from supporting substances (structural analogues) aluminium chloride, basic (CAS 1327-41-9) and aluminium chloride (CAS 7446-70-0). The available study is adequate and reliable based on the identified similarities in structure and intrinsic properties between source and target substances and overall quality assessment (refer to the endpoint discussion for further details)  

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

The available data on skin sensitisation of substances structurally related to reaction mass of aluminium hydroxide and aluminium nitrate and sulphate do not meet the criteria for classification according to Regulation (EC) 1272/2008 or Directive 67/548/EEC, and therefore conclusive but not sufficient for classification.