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Key value for chemical safety assessment

Additional information

Genetic toxicity

As no studies investigating the genetic toxicity 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 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 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).

Genetic toxicity in vitro

In vitro gene mutation study in bacteria

Since no studies investigating the investigating in vitro gene mutation in bacteria 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 sulphate (CAS 10043-01-3) and aluminium chloride, basic (CAS 1327-41-9) 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 10043-01-3 (aluminium sulfate)

An Ames test was performed according to OECD Guideline 471 and GLP with aluminium sulfate (CAS 10043-01-3) dissolved in water in Salmonella typhimurium strains TA 1535, TA 1537, TA 98 and TA 100 and in E. coli WP2uvr A (Verspeek-Rip, 2010). Test substance was tested in a preliminary test in strains TA100 and WP2uvrA at concentrations 3, 10, 33, 100, 333, 1000, 3330 and 5000 µg/plate with and without metabolic activation. Then the test item was tested in two independent experiments as well: 1) at concentrations 100, 333, 1000, 3330 and 5000 µg/plate in strains TA 1535, TA 1537 and TA 98 with and without metabolic activation and 2) at concentrations 33, 100, 333, 1000, 3330 and 5000 µg/plate in all strains with and without metabolic activation. Cytotoxic effects were observed in the absence of a metabolic activator at 3330 µg/plate and above (TA 1535 and TA 100), 1000 µg/plate (TA 1537 and TA 98) and in the presence of a metabolic activator at concentrations of 3330 µg/plate and above (TA 1535 and TA 1537), 50000 µg/plate (TA 98). No increase in the frequency of revertant colonies compared to concurrent negative controls were observed in all tested strains, neither in the presence nor in the absence of metabolic activation. Thus, aluminium sulphate did not induce gene mutations in all tested strains under the given test conditions.

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

An Ames test was performed according to OECD Guideline 471 and GLP with aluminium chloride, basic (1327-41-9) dissolved in water in Salmonella typhimurium strains TA 1535, TA 1537, TA 98 and TA 100 and in E. coli WP2uvr A (Verspeek-Rip, 2010). Test substance was tested in a preliminary test in strains TA100 and WP2uvrA at concentrations 3, 10, 33, 100, 333, 1000, 3330 and 5000 µg/plate with and without metabolic activation. Then the test item was tested in two independent experiments as well: 1) at concentrations 33, 100, 333, 1000, 3330 and 5000 µg/plate in strains TA 1535, TA 1537 and TA 98 with and without metabolic activation and 2) at concentrations 33, 100, 333, 1000, 3330 and 5000 µg/plate in all strains with and without metabolic activation. Cytotoxic effects were observed in the absence of a metabolic activator at 3330 µg/plate and above (TA 100), 1000 µg/plate and above (TA 1535, TA 1537 and TA 98) and in the presence of a metabolic activator at concentrations of 3330 µg/plate and above (TA 1535), 1000 µg/plate and above (TA 1537), and 5000 µg/plate (TA 98). No increase in the frequency of revertant colonies compared to concurrent negative controls were observed in all tested strains, neither in the presence nor in the absence of metabolic activation. Thus, aluminium chloride, basic did not induce gene mutations in all tested strains under the given test conditions.

In vitro cytogenicity in mammalian cells

Since no studies investigating the in vitro cytogenicity in mammalian cells of reaction mass of aluminium hydroxide and 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 sulphate (CAS 10043-01-3) and aluminium chloride, basic (CAS 1327-41-9) 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 10043-01-3 (aluminium sulfate)

An in vitro mammalian cell micronucleus test was performed with aluminium sulfate (CAS 10043-01-3) in human peripheral lymphocytes according to OECD Guideline 487 and GLP (Buskens, 2010). Duplicate cultures of human lymphocytes were evaluated for chromosome aberrations in the presence and absence of metabolic activation (rat liver S9-mix).

In the first experiment test substance concentrations of 100, 333 and 1000 µg/mL and 100, 300, and 700 µg/mL dissolved in medium were used without and with metabolic activation respectively. In the second experiment concentration of 100, 1000 and 1500 µg/mL in medium were used without S9. Mitomycin C, cyclophosphamide and colchicine were used as positive control substances. The test material demonstrated no sign cytotoxicity. All vehicle (solvent) controls presented mono-and bi-nucleated cells with micronuclei within the laboratory historical control data range. All the positive control materials induced statistically significant increases in the number of bi-nucleated cells with micronuclei indicating the adequate performance of the test and in the absence and presence of metabolic activation. The test material did not induce a statistically significant or biologically relevant increase in the number of mono- and bi-nucleated cells with micronuclei in the absence and presence of S9-mix, in either of the two independently repeated experiments. The test material was therefore considered to be non-clastogenic or aneugenic to human lymphocytes in vitro.

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

 

An in vitro mammalian cell micronucleus test was performed with aluminium chloride, basic (CAS 1327-41-9) in human peripheral lymphocytes according to OECD Guideline 487 and GLP (Buskens, 2010). Duplicate cultures of human lymphocytes were evaluated for chromosome aberrations in the presence and absence of metabolic activation (rat liver S9-mix).

In the first experiment test substance concentrations of 100, 300 and 600 µg/mL and 300, 500 and 600 µg/mL dissolved in medium were used in a 3 h exposure and 27 h time fixation without and with metabolic activation respectively. In the second experiment concentration of 100, 300 and 600 µg/mL in medium were used in 24 h exposure and fixation without S9. Mitomycin C cyclophosphamide, and colchicine were used as positive control substances. The test material demonstrated no sign cytotoxicity. All vehicle (solvent) controls presented mono-and bi-nucleated cells with micronuclei within the laboratory historical control data range except in the presence of S9-mix. Although the number of bi-nucleated cells with micronuclei was above the historical control data range in the presence of S9-mix, the number of bi-nucleated cells with micronuclei was less than 10. All the positive control materials induced statistically significant increases in the number of bi-nucleated cells with micronuclei indicating the adequate performance of the test and in the absence and presence of metabolic activation. The test material did not induce a statistically significant or biologically relevant increase in the number of mono- and bi-nucleated cells with micronuclei in the absence and presence of S9-mix, in either of the two independently repeated experiments. The test material was therefore considered to be non-clastogenic or aneugenic to human lymphocytes in vitro.

 

The capability of aluminium sulphate for inducing micronuclei (MN) in human lymphocytes was studied after a 72-h exposure to 500, 1000, 2000, 4000 µM (corresponding to 1000, 2000, 4000, 8000 µM Al) (Migliore et al., 1999). Blood samples were obtained from two young, healthy donors. The cell cultures were exposed to the test solutions 24 h after PHA stimulation followed by a 48 h incubation period. The percentage of bi-nucleated cells was used as a parameter for proliferation. No obvious toxicity was observed. Aluminium sulphate induced significant increases of MN in bi-nucleated cells at most of the tested doses. Aluminium sulphate produced a significant 1.9- and 2.5-fold increase over controls at 1000 and 2000 µM (2000 and 4000 µM Al), respectively, in cells from donor A. In cells from donor B, a 2.3- to 3.5-fold increase over controls was induced, with the maximum induction observed at 1000 µM (2000 µM Al). The positive controls (Mytomicin C and griseofulvin) gave the expected results. The levels of MN in the negative controls were less than 1%. Production of both centromere negative and centromere positive MN was observed consistent with both clastogenic and aneuploidogenic potential, respectively.

In vitro gene mutation in mammalian cells

Since no studies investigating the in vitro gene mutation in mammalian cells 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 sulphate (CAS 10043-01-3) and aluminium chloride, basic (CAS 1327-41-9) 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 10043-01-3 (aluminium sulfate)

An in vitro mammalian cell gene mutation assay was performed with aluminium sulfate (CAS 10043-01-3) according to OECD guideline 476 and GLP in L5178Y mouse lymphoma cells (Verspeek-Rip, 2010). In the first experiment, aluminium sulfate was tested at concentrations of 0.1, 0.3, 1, 3, 10, 33, 100 and 333 µg/mL in the absence and presence of metabolic activation. The incubation time was 3 hours. In a second experiment the test substance was tested 1) at concentration of 1, 3, 10, 33, 333, 500, 600 and 666 µg/mL with incubation time of 24 h and without metabolic activation, and 2) at concentrations of 0.1, 0.3, 1, 3, 10, 33, 100 and 333 μg/mL with incubation time of 3 h and with metabolic activation. The spontaneous mutation frequencies in the solvent-treated control cultures were between the minimum and maximum value of the historical control data range and within the acceptability criteria of this assay. Positive control chemicals, methyl methane sulfonate and cyclophosphamide induced appropriate responses. In the absence of S9-mix, the test substance did not induce a significant increase in the mutation frequency in the first experiment. This result was confirmed in an independent repeat experiment with modifications in the duration of treatment time. In the presence of S9-mix, the test substance did not induce a significant increase in the mutation frequency in the first experiment. This result was confirmed in an independent repeat experiment with modifications in the concentration of the S9 for metabolic activation. It is concluded that aluminium sulfate is not mutagenic in the mouse lymphoma L5178Y test system under the experimental conditions described.

 

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

An in vitro mammalian cell gene mutation assay was performed with aluminium chloride, basic (CAS 1327-41-9) according to OECD guideline 476 and GLP in L5178Y mouse lymphoma cells (Verspeek-Rip, 2010). In the first experiment, aluminium chloride, basic was tested at concentrations of 0.1, 0.3, 1, 3, 10, 33, 100 and 333 µg/mL in the absence and presence of metabolic activation. The incubation time was 3 hours. In a second experiment the test substance was tested 1) at concentration of 1, 3, 10, 33, 100, 250, 333 and 500 µg/mL with incubation time of 24 h and without metabolic activation, and 2) at concentrations of 0.1, 0.3, 1, 3, 10, 33, 100 and 333 μg/mL with incubation time of 3 h and with metabolic activation. The spontaneous mutation frequencies in the solvent-treated control cultures were between the minimum and maximum value of the historical control data range and within the acceptability criteria of this assay. Positive control chemicals, methyl methane sulfonate and cyclophosphamide induced appropriate responses. In the absence of S9-mix, the test substance did not induce a significant increase in the mutation frequency in the first experiment. This result was confirmed in an independent repeat experiment with modifications in the duration of treatment time. In the presence of S9-mix, the test substance did not induce a significant increase in the mutation frequency in the first experiment. This result was confirmed in an independent repeat experiment with modifications in the concentration of the S9 for metabolic activation. It is concluded that aluminium chloride, basic is not mutagenic in the mouse lymphoma L5178Y test system under the experimental conditions described.

Genetic toxicity in vivo

Since no studies investigating the genetic toxicity in vivo 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 hydroxide (CAS 21645-51-2) and aluminium sulphate octadecahydrate (CAS 7784-31-8) 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+.

 

Chromosome aberration

CAS 1344-24-1 (aluminium oxide)

In a following OECD guideline 474, suspensions of aluminium oxide were administered to female Wistar rats (5 animals per group) by oral gavage (Balasubramanyam et al., 2009a). Concentrations of 500, 1000 and 2000 mg aluminium oxide/kg bw in 1% Tween 80/doubly-distilled water were used. These concentrations correspond to 265, 529 and 1058 mg Al/kg bw. Three types of aluminium oxide particles were examined: bulk material (50 to 200 µm in diameter), 30 and 40 nm aluminium oxide particles, respectively. A negative control group was treated with the vehicle only. A positive control group received a single intraperitoneal dose of 40 mg/kg bw of cyclophosphamide.

A dose-response relationship was evident for the number of MN-PCEs for both groups treated with nanomaterials (30 and 40 nm aluminium oxide particles). No statistically significant effect was evident for the larger particles, aluminium oxide bulk material.

 

CAS 7784-31-8 (aluminium sulphate octadecahydrate)

An earlier study used high dose levels of aluminium sulphate (250 and 500 mg/kg bw (20 and 40 mg Al/kg bw)) as a known inducer of micronucleated polychromatic peripheral erythrocyte (mnPCE) formation (Roy et al., 1992) in murine bone marrow cells. A significant increase in mnPCEs was induced 24 hrs after a second aluminium intraperitoneal dose of 500mg/kg bw in Swiss albino mice. No changes were seen at the 250 mg/kg bw dose level.

A single-dose experiment in male Swiss albino mice was conducted to determine the effect of priming with ascorbic acid and a fruit extract on clastogenic effects due to exposure to lead and aluminium (Dhir et al., 1990). Groups of mice (6 per dose) were administered aluminium sulphate by intraperitoneal injection at 250, 500 and 1000 mg/kg bw (corresponding to 0, 20.2, 40.5, 81.0 mg Al/kg bw). The non-primed exposed groups from this study are potentially informative for the current hazard identification. Chromosome aberrations (CAs) were assessed 24 hours after the administration of the test compound. Chromosome and chromatid breaks were counted as single breaks and rearrangements as two breaks. Gaps were not included. 50 metaphase plates were scanned per animal. The mitotic index (MI) was determined as the number of metaphases in 1000 cells per animal. Both positive and negative controls were employed. A dose-dependent increase in chromosome breaks per bone marrow cell was reported. The number of CA per cell was 0.02 ± 0.01 in the negative control (mean ± SEM), 0.10 ± 0.01 in the 250 mg/kg dose group, 0.14 ± 0.02 in the 500 mg/kg dose group and 0.18 ± 0.01 in the 1000 mg/kg dose group. A significant decrease in mean mitotic index relative to the negative saline control was observed at 500mg/kg and 1000 mg/kg. In the 250 mg/kg dose group, the MI was 96% of the level in the negative saline control. In the 500 mg/kg group the MI was 80% of the negative control and in the 1000 mg/kg group it was 43%. Given the concurrent reduction in mitotic index, the increase in CA could be an indirect result of cytotoxicity.

 

In a methodological weak study oral administration of aluminium sulfate at doses 0, 212, 265, 353, 530, 1060, 2120 mg/kg bw) day corresponding to 0, 17, 22, 28, 43, 85, 172 mg Al/kg bw/day to laboratory bred Rattus norvegicus was performed to observe the effects of different concentration of aluminium following gavage on bone marrow chromosomes (Roy et al., 1991). Following treatment with aluminium sulphate the mitotic index decreased in direct proportion to the dose used. The decrease was highly pronounced with the two higher doses (1060 and 2120 mg). Statistical analysis following the trend test showed a highly significant negative value which indicated a dose dependent inhibition of dividing cell frequency. However, no relationship could be deduced between inhibition and the duration of exposure.

The frequency of abnormal cells increased in direct proportion to both dose and duration of exposure to aluminium sulphate. During all three sampling times the trend test p value was found to be highly significant. A duration dependent effect was not found with the lower (212 mg) dose. Most aberrations were chromatid breaks. Translocations were recorded in higher doses.

 

Comet assay

In the Balasubramanyam et al. (2009b) study described above, the percentage of tail DNA (% Tail DNA) migration in rat peripheral blood cells was assessed using the alkaline comet assay. Genotoxic effects were evaluated in groups of 5 female Wistar rats 4, 24, 48 and 72 h after single doses of 500, 1000 and 2000 mg/kg bw of nanosized aluminium oxide (30 and 40 nm, respectively) and aluminium oxide bulk material (50-200 µm). The corresponding aluminium doses were 264.6, 529.2 and 1058.4 mg Al/kg bw. The % Tail DNA was estimated from 150 cells per rat. Both aluminium oxide nanoparticles showed statistically significant dose related increases in % Tail DNA at the two higher concentrations. The results showed the highest levels of damage 24 hours after dosing, with a subsequent decrease at 48 and 72 hours suggesting either cell death or DNA repair. Aluminium oxide bulk material did not induce statistically significant changes over control values.

 

Conclusion

The available information does not provide indications for a mutagenic potential of aluminium compounds in bacteria (Krewski et al, 2007,Verspeek-Rip, 2010). No or not significant mutations were found at the thymidine kinase (tk) locus of mouse lymphoma L5187Y cells treated with aluminium sulfate and aluminium chloride, basic at any of the doses tested (Verspeek-Rip, 2010). In vitro studies with human blood lymphocytes showed that aluminium sulfate and aluminium chloride, basic are considered to be non-clastogenic or aneugenic to human lymphocytes in vitro.

 

A methodologically weaker in vitro study with human blood lymphocytes showed positive responses to aluminium sulphate for micronuclei formation (Migliore et al., 1999).

The most relevant and methodologically strongest in vivo studies are those conducted by Balasubramnyam et al. (2009).

In the studies by Balasubramanyam et al. (2009), the genotoxic effects of aluminium oxide particles were investigated in vivo. Single doses of aluminium oxide particulate suspensions were administered to rats by oral gavage. The study results were positive for the nano-sized materials with evidence of a dose-response relationship, while the genotoxicity levels for aluminium oxide bulk material (50 to 200 μm diameter particles) were not statistically significantly different from those for the control. The relevance of the results with nanomaterials for hazard assessment is unclear as the observed effects may have been related to the presence of nanoparticles as foreign bodies in the cells rather than to the chemical properties of the test material itself. Low toxicity, poorly soluble substances, such as aluminium oxide, have produced inflammatory effects in vitro, when present as nanoparticles. The proposed mechanism of action is the production of reactive oxygen species (ROS) (Donaldson and Stone, 2003; Nel et al., 2006; Oberdörster et al., 2005, 2007; Duffin et al., 2007; Dey et al., 2008). Current scientific knowledge does not allow differentiation of genotoxic effects due to the physical (nanoparticle) nature from genotoxic effects due to the chemical characteristics of the test substance (Landsiedel et al., 2009; Singh et al., 2009; Gonzalez et al., 2008). However, in the current scientific debate regarding the genotoxic effects of nanoparticles of many different substances, the possibility that nanoparticles stimulate an inflammatory response leading to oxidative stress in the cells and consequently to DNA damage is the most accepted hypothesis. Balasubramanyam et al. (2009) reported tissue aluminium oxide levels elevated in a dose-response manner for the groups treated with nano-sized materials, consistent with transfer of the nano-sized particles across the gastrointestinal mucosa (Florence, 1997; Hagens et al., 2007). A particle size dependence of gastrointestinal absorption was apparent. Aluminium oxide levels in the tissues of animals dosed with the larger 50 to 200 μm diameter particles were not elevated to a statistically significant level, consistent with the notion of a low bioavailability of aluminium compounds (see Toxicokinetics).

The positive results observed in studies of aluminium sulphate reported by Dhir et al. (1990) and Roy et al. (1992) occurred with non-physiologically-relevant intraperitoneal administration of the test substances and were methodologically weaker. Thus, on a weight of evidence approach, aluminium compounds in non-nanoparticle size ranges do not induce genotoxic effects in somatic cells in vivo when administered by a physiologically relevant route.

Taken together, the weight of evidence does not support a systemic mutagenic hazard for soluble and insoluble aluminium compounds. Therefore, independently of possible unspecific pH effects, there are no indications for a genotoxic potential of reaction mass of aluminium nitrate and aluminium sulphate specifically related to its chemical identity.

 

References

 

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

 

Dey S, Bakthavatchalu V,et al.(2008). Interactions between SIRT1 and AP-1 reveal a mechanistic insight into the growth promoting properties of alumina (Al2O3) nanoparticles in mouse skin epithelial cells. Carcinogenesis 29(10): 1920-1929.

 

Donaldson K, Stone V (2003), Current hypotheses on the mechanisms of toxicity of ultrafine particles, Ann.Ist.Super.Sanita 39: 405-410

 

Duffin R, Tran L, Brown D et al. (2007). Proinflammogenic effects of low-toxicity and metal nanoparticles In Vivo and In Vitro: Highlighting the role of particle surface area and surface reactivity. Inhalation Toxicology 19: 849-856.

 

Florence AT. (1997). The oral absorption of micro- and nanoparticulates: Neither exceptional or unusual. Pharmaceut Res 14(3): 259-266.

 

Gonzalez L, Lison D, Kirsch-Volders M. (2008).Genotoxicity of engineered nanomaterials: A critical review. Nanotoxicology 2(4): 252-273.

 

Hagens WI, Oomen AG, de Jong WH et al. (2007). What do we (need to) know about the kinetic properties of nanoparticles in the body? Reg Toxicol Pharmacol 49: 217 229.

 

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.

 

Landsiedel R, Kapp MD, Schulz M, et al.(2009). Genotoxicity investigations on nanomaterials: Methods, preparation and characterization of test material, potential artifacts and limitations - Many questions, some answers. Mutat Res 681: 241-258.

 

Nel A, Xia T, Madler L, Li N (2006). Toxic potential of materials at the nanolevel, Science 311: 622-627

 

Oberdorster G, Oberdorster E, Oberdorster J (2005).Nanotoxicology: An emerging discipline evolving from studies of ultrafine particles, Environmental Health Perspectives 113: 823-839

Oberdorster G, Stone V, Donaldson K (2007).Toxicology of nanoparticles: A historical perspective, Nanotoxicology 1: 2-25

 

Singh N, Manshian B, Jenkins GJS et al. (2009). Nanogenotoxicology: The DNA damaging potential of engineered nanomaterials. Biomaterials 3891-3914.

 

 

 

 

 

Justification for selection of genetic toxicity endpoint

Hazard assessment is conducted by means of read across from supporting substances (structural analogues) aluminium sulfate (CAS 10043-01-3), aluminium chloride, basic (CAS 1327-41-9) and aluminium oxide (CAS 134424-1), and aluminium sulphate octadecahydrate (CAS 7784-31-8). 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).

Short description of key information:

Based on read-across from aluminium compounds within a weight of evidence approach:

In vitro:

Negative results in bacterial systems (Ames tests with Salmonella typhimurium and E.coli strains)

Negative results in mammalian cell gene mutation assays (mouse lymphoma L5178Y cells - tk forward mutation assay)

Negative results in vitro cytogenicity in mammalian cells (in vitro micronucleus test)

In vivo:

Negative results in mammalian erythrocite micronucleus tests

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

The available data on genetic toxicity of structurally related substances to reaction mass of aluminium hydroxide and aluminium nitrate and aluminium sulphate

do not meet the criteria for classification according to Regulation (EC) 1272/2008 or Directive 67/548/EEC, and therefore are conclusive but not sufficient for classification.