Registration Dossier

Administrative data

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information
Aluminium nitride dissolves into aluminium and ammonia/ammonium ion. The Al compound is considered the relevant moiety for risk assessment. The genotoxic potential of aluminium is assessed by a weight of evidence approach regarding several in vitro and in vivo studies with various highly soluble aluminium compounds. In summary these studies are considered negative with respect to genotoxicity, therefore aluminium nitride is considered to be not genotoxic.
Link to relevant study records
in vitro gene mutation study in mammalian cells
Type of genotoxicity: gene mutation
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
weight of evidence
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Similar to OECD guideline 476. Aluminium chloride used as read across partner.
equivalent or similar to
OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)
GLP compliance:
not specified
Type of assay:
mammalian cell gene mutation assay
Target gene:
Thymidine kinase (TK)
Species / strain / cell type:
mouse lymphoma L5178Y cells
Metabolic activation:
Test concentrations with justification for top dose:
570, 580, 590, 600, 625 µg/mL
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: water
Untreated negative controls:
Negative solvent / vehicle controls:
True negative controls:
Positive controls:
Positive control substance:
620 µg/mL
Details on test system and experimental conditions:

- Exposure duration: 4 h
- Expression time (cells in growth medium): 2 days
- Selection time (if incubation with a selection agent): 12 days

SELECTION AGENT (mutation assays): trifluorothymidine (TFT)

- Method: percent total survival
Evaluation criteria:
A test agent will be considered positive if a dose-realated response is obtained in which two or more concentrations elicit a greater than 2-fold increase in mutation frequency over the solvent control with a minimum of 10% survival.
Species / strain:
mouse lymphoma L5178Y cells
Metabolic activation:
Cytotoxicity / choice of top concentrations:
Vehicle controls validity:
Untreated negative controls validity:
not examined
Positive controls validity:
Additional information on results:
- Effects of pH: after adding the chemical to the medium, a dramatic change in pH occured over the 4h expression period

Remarks on result:
other: all strains/cell types tested
Migrated from field 'Test system'.

Table1: Mutagenic response after treatment with AlCl3

Chemical Dose [µg/mL] Percent total survival Mutation frequency Increase over solvent (-fold)
Solvent 0 100 2.5 -
EMS 620 31 85.0 34.0
AlCl3 625 63 5.6 2.2
  600 38 5.0 2.0
590 42 4.9 2.0
580 88 4.3 1.7
570 69 5.0 2.0
Interpretation of results (migrated information):
negative without metabolic activation

The test substance AlCl3 did not induce gene mutation in the TK locus in L5178Y mouse lymphoma cells under the tested experimental conditions.
Executive summary:
In a mammalian cell gene mutation assay conducted similar to OECD guideline 476, L5178Y mouse lymphoma cells cultured in vitro were exposed to AlCl3, solved in water, at concentrations of 570, 580, 590, 600, and 625 µg/mL in the absence of mammalian metabolic activation. The induced mutation frequencies without metabolic activation were not increased by more than 2 fold in comparison to the untreated control, except the 625 µg/mL dose group dose with a 2.2 fold increase. The results of the mutant frequencies did not fulfill the criteria for a positive study result outcome. The positive control did induce the appropriate response.

In summary, the test item AlCl3 did not induce gene mutation in L51178Y mouse lymphoma cells.

This study is classified as acceptable and satisfies the requirement for test guideline OECD 476 for in vitro mutagenicity (mammalian forward gene mutation) data.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Additional information

Additional information from genetic toxicity in vitro:

No substance specific genotoxicity studies are available for aluminium nitride (target substance). The genotoxic potential of aluminium nitride is assessed by its dissolution products aluminium and ammonium ions. Ammonium is an endogenous compound, formed at concentrations of 79 mmol/kg bw/day. Therefore, the nitride component of aluminium nitride is considered to be of minor impact and negligible for the assessment of the genotoxicity. The genotoxic potential of aluminium nitride is thus based on the aluminium component and assessed by read across with aluminium salts, mainly aluminium chloride and aluminium sulfate. Due to a lower water solubility of aluminium nitride compared to the source substances the resulting bioavailability (toxicity potential) would also be expected to be lower. Therefore, the read-across to the source substances aluminium chloride and aluminium sulfate is adequately protective. Details on the read-across rational are provided in section 13.

Aluminium chloride was tested negative in the Bacillus subtilis Rec mutagenicity screening assay. This assay is detecting DNA damage, which is subjected to cellular recombination repair (Kada et al., 1980). Caicedo et al., 2007 reported, that aluminium chloride was tested negative in an in vitro Comet assay. Oberly et al., 1982 reported negative results in a L5178Y mouse lymphoma mutagenicity assay (OECD 476) using aluminium chloride. Two in vitro studies (Banasik et al., 2005 (in vitro MNT), Lima et al., 2007 (in vitro CA)) found genotoxic effects of aluminium chloride only concomitant to severe cytotoxicity. The positive effect is not considered relevant due to the increased cytotoxicity, disqualifying a distinction of genotoxic from cell toxic events.

In a mammalian cell micronucleus test conducted similar to OECD guideline 487, human lymphocytes were exposed in vitro to aluminium sulfate at concentrations of 0, 500, 1000, 2000 and 4000 µM without metabolic activation for 48 hours. The results revealed a slight increase in micronucleus frequency. As in both blood donor experiments no dose-relationship was observed (the micronucleus frequency of the highest dose tested in donor 1 was even below the negative control values). Overall, the results are considered ambiguous due to the before mentioned reasons.

Supporting data was received by the review article by Krewski et al., 2007. In a weight of evidence evaluation of the data presented by Krewski, it can be stated, that aluminium compounds are not genotoxic in the absence of cytotoxicity.

As above explained, the nitride component of aluminium nitride is considered to be of minor impact and negligible for the assessment of the genotoxicity of aluminium nitride. Nevertheless, one study by Shimizu et al., 2005 is available, in which ammonia was tested negative in a reverse gene mutation assay in bacteria (OECD 471).

In summary of the available data from various read-across partners with higher solubility compared to AlN, no genotoxic effects at non-cytotoxic concentrations were observed. Therefore, it can be concluded that aluminium nitride can be considered as not genotoxic.

Justification for selection of genetic toxicity endpoint
One of several reliable studies used in a weight of evidence approach.

Justification for classification or non-classification

Based on data from soluble aluminium compounds, aluminium nitride is considered negative regarding mutagenicity.