Registration Dossier

Administrative data

Description of key information

Based on the read across from supporting substances (structural analogues), all the test available showed no irritating potential to human skin, while all available studies on the acute eye irritation potential showed severe eye damage.

Key value for chemical safety assessment

Skin irritation / corrosion

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

As no studies investigating the skin and eye irritation 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 aluminiumsulfatenitrate.

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 irritation

 

Since no studies investigating the skin irritation 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 sulphate (CAS 10043-01-3), aluminium chloride, basic (CAS 1327-41-9), aluminium chloride hydroxide sulphate (39290-78-3) and aluminium nitrate (CAS 13473-90-0) 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 10043-01-3 (aluminium sulphate)

Two animal studies investigating the skin irritation potential of aluminium sulphate (CAS 10043-01-3) are available. A primary dermal irritation study was conducted on three male rabbits using test substance aluminium sulphate as a solution, according to OECD Guideline 404 and GLP (Mercier, 1987)

Each animal received 0.5 mL test material. A single 4-hour, semi-occluded application of the test material to the intact skin produced immediately after patch removal very slight erythema at the test site of two animals. This effect disappeared after 24 hours after patch removal. Necrosis and ulceration were not reported.

 

In a second primary dermal irritation study was conducted on six albino rabbits using test substance aluminium sulphate, anhydrous according with the method is equivalent to OECD Guideline 404 with some deviations. The study was not designed and performed according to GLP (Bullock, 1973).

Each animal received test material on the abraded and intact skin. A single 4-hour, occluded application of the test material to the intact skin produced immediately after patch removal no skin irritation at the test site of the animals. At 24 and 48 h after initial application still no skin effects were seen. Necrosis and ulceration were not reported.

 

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

A primary dermal irritation test performed according to OECD Guideline 404 was performed on the treated skin of three rabbits (Hoffman, 1986). Each animal received 0.5 mL test material for 4 hours. At the end of the treatment no erythema and eschar formation nor oedema formation appeared on the treated skin of three animals.

CAS 39290-78-3 (aluminium chloride hydroxide sulphate)

A primary dermal irritation study was conducted on three male according to OECD Guideline 404 and GLP (Jouffrey, 1986).

Each animal received 0.5 mL test material. An initial test was performed in one animal with exposure periods of 3 minutes and 4 hours. As no cutaneous reactions were observed after an application of 3 minutes a confirmatory study was performed in two other animals. The single 4-hour, semi-occluded application of the test material to the intact skin of all three animals produced immediately after patch removal very slight erythema at the test site of one animal. This effect was gone at 24 hours after patch removal. Necrosis and ulceration were not reported.

Based on the results of the present study, it was concluded the test substance no skin irritating so the test material is classified as non-irritant to the skin.

 

In another primary dermal irritation study conducted on six albino rabbits with a method equivalent OECD Guideline 404 and not GLP, each animal received 0.5 mL test material on the abraded as well as on the intact skin (Coquet, 1978). A single 23-hour, occluded application of the test material to the intact skin produced 1 hour after patch removal no skin irritation at the test site of the animals. At 48 h after patch removal again no effects were seen.Necrosis and ulceration were not reported.

 

CAS 13473-90-0 (aluminium nitrate)

 

The primary cutaneous irritation of aluminium nitrate was tested in 3 to 6 male rabbit using OECD guideline 404, AFNOR and Cosmetic guidelines (Guillot, 1976). Each animal received 0.5 mL test material.

Authors state that the test substance was not irritating when tested according to the OECD protocol. A primary cutaneous irritation index of 0.35 was achieved. The maximum possible score was 8.0.

In addition the test substance was also tested according to a protocol for cosmetics which led to a primary cutaneous irritation index of 0.54 (slightly irritant) and according to the AFNOR protocol which led to a primary cutaneous irritation of 0.36 (not irritating).

It was not possible to evaluate the present study as reliable since individual erythema and edema score were not reported.

Eye irritation

 

Since no studies investigating the skin irritation 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 sulphate (CAS 10043-01-3), aluminium chloride, basic (CAS 1327-41-9) and aluminium nitrate (CAS 13473-90-0) 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 10043-01-3 (aluminium sulphate)

A study was conducted to assess the irritancy potential of a solution of aluminium sulfate to the eye of three rabbits. The study was performed according to OECD Guideline 405 and also according to GLP (Mercier, 1987)

A single application of 0.1 mL of the test material to the right eye of the rabbit produced redness of the conjunctivae. Furthermore, moderate chemosis and iridial congestion were observed amongst all three animals during the first 48 to 72 hours. Translucency of the cornea up to one-quarter was also apparent in one rabbit at the one hour examination.

Based on the results of the present study, it was concluded that the test compound, aluminium sulphate as a solution, induced a moderate eye irritation. It is not known whether reversibility of the eye effects would occur, as the observation period is only up to 3 days after application.

 

A second study (not GLP compliance) was conducted to assess the irritancy potential of aluminium sulphate hydrate to the eye of six rabbits with a method equivalent to OECD Guideline 405 (Jimenez, 1974).

A single application of 10 mg of the test material to one eye of the rabbit produced moderate to severe redness of the conjunctivae. Furthermore, moderate to severe chemosis and moderate to severe corneal opacity were observed amongst all animals during the first 72 hours. No iridial congestion was seen. Translucency of the cornea up to whole eye was also apparent in all rabbits up to 7 days.

Based on the results of the present study, it was concluded that the test compound, aluminum sulfate hydrate, induced a moderate to severe eye irritation. The effects observed in cornea and conjunctiva resulted to be not reversible within 7 days after application.

 

 

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

A study was conducted to assess the irritancy potential of test substance to the eye of rabbits de Jouffrey, 1996). The study was performed according to OECD Guideline 405 and GLP.

A single application of 0.1 mL of the test material to the left eye of the rabbit produced severe redness of the conjunctivae. Furthermore, marked chemosis and iridial congestion were observed amongst all three animals. Translucency of the cornea up to three-quarters was also apparent in two rabbits and in the remaining rabbit up to the whole area. The latter animal is killed on day 12 for ethical reasons. All three animals showed neovascularisation and one or two animals had also alopecia around the eye and white spots on the conjunctivae. Corneal lesions weren’t reversible after 21 days in 1 out of 2 animals.

Based on the results of the present study, it was concluded that the test compound, test substance, induced a severe eye irritation. The eye effects weren’t completely reversible within 21 days. Furthermore, one animal was killed due to severe eye effects.

 

CAS 13473-90-0 (aluminium nitrate)

 

0.1 g of the test substance was instilled in the lower conjunctival sac of the rabbit eye. Eyes were either not washed out or washed after 4 or 30 seconds. The test substance was judged as irritant if washed out after 4 seconds, as severely irritant if washed out after 30 seconds and as extremely irritant if not washed out. Due to the severity of the results, the test substance was judged to cause severe eye irritation.

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.

Justification for selection of skin irritation / corrosion endpoint:

Hazard assessment is conducted by means of read across from supporting substances (structural analogues) aluminium sulphate (CAS 10043-01-3), aluminium chloride, basic (CAS 1327-41-9), aluminium chloride hydroxide sulphate (39290-78-3) and aluminium nitrate (CAS 13473-90-0). 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)  

Justification for selection of eye irritation endpoint:

Hazard assessment is conducted by means of read across from supporting substances (structural analogues), aluminium sulphate (CAS 10043-01-3), aluminium chloride, basic (CAS 1327-41-9) and aluminium nitrate (CAS 13473-90-0). 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)  

Effects on eye irritation: corrosive

Justification for classification or non-classification

The available data on skin irritation of substances structurally related 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 67/48/EEC, and are therefore conclusive but not sufficient for classification.

The available data on eye irritation of substances structurally related to reaction mass of aluminium hydroxide and aluminium nitrate and aluminium sulphate meet the criteria for classification Eye Dam.1, H318 according to Regulation (EC) 1272/2008 and as classification Xi, R41 according to Directive 67/548/EEC. Solutions may be classified as Eye Irrit.2, H319 according to Regulation (EC) 1272/2008 and as classification Xi, R36 according to Directive 67/548/EEC when pH >2.