Reaction mass of aluminium hydroxide and aluminium nitrate and aluminium sulphate

Endpoint summary

Description of key information

Based on the read across from supporting substances (structural analogues) approach, all available acute oral toxicity studies resulted in acute oral LD50 in rats greater than 2000 mg/kg bw.

The LC50 for was found to be > 5 mg/L air.

All the dermal toxicity studies available resulted in a LD50 > 2000 mg/kg bw.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

The available information comprises adequate, reliable (Klimisch score 2 due to read-across) studies from reference substances with similar structure and intrinsic properties. Read-across is justified based on the fact that following 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 (refer to endpoint discussion for further details).
Taken together, the information from these independent sources is consistent and provides sufficient weight of evidence for hazard assessment leading to an endpoint conclusion in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006.

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

The available information comprises adequate, reliable (Klimisch score 2 due to read-across) studies from reference substances with similar structure and intrinsic properties. Read-across is justified based on the fact that following 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 (refer to endpoint discussion for further details).
Taken together, the information from these independent sources is consistent and provides sufficient weight of evidence for hazard assessment leading to an endpoint conclusion in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006.

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

The available information comprises adequate, reliable (Klimisch score 2 due to read-across) studies from reference substances with similar structure and intrinsic properties. Read-across is justified based on the fact that following 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 common (refer to endpoint discussion for further details).
Taken together, the information from these independent sources is consistent and provides sufficient weight of evidence for hazard assessment leading to an endpoint conclusion in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006.

Additional information

As no studies investigating the acute toxicity 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) 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 if 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).

 

 

Acute oral toxicity

 

Since no studies investigating the acute oral 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) aluminium sulphate (CAS 10043-01-3) and aluminium nitrate nonahydrate (CAS 7784-27-2) was considered. Read-across is justified based on the fact that 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.

 

CAS 10043-01-3 (aluminium sulphate)

 

The test material was evaluated for its acute oral toxicity potential in rats when administered as oral doses at levels of 2000 mg/kg bw in Tween/water to females, 4640 mg/kg bw in Tween/water to males and 5000 mg/kg bw in water to males and females in a study according to OECD Guideline 401 and not GLP compliant (Bryant, 1976). No mortality occurred. No changes were observed at 2000 and 4640 mg/kg dose levels. At 5000 mg/kg clinical signs of toxicity included mild depression and ruffled fur. The toxicity symptoms disappeared normal after 1 (females) or 3 (males) days.

Thus, the LD50 of aluminium sulphate was found to be greater than 5000 mg/kg bw for males and females.

In a second study (OECD Guideline 401) not GLP compliant (Scholler, 1976) the test material was evaluated for its acute oral toxicity potential in rats when administered as oral doses at levels of 2000 mg/kg bw in water or in Tween/water to females and 5000 mg/kg bw in Tween/water to males and females. No mortality occurred in all ten females dosed at the 2000 mg/kg bw dose. No clinical changes were observed generally at this dose level. All ten animals at 5000 mg/kg bw died with deaths occurring on the first or second. Clinical signs of toxicity included depression and ruffled fur. Necropsy findings showed very red lung edges and/or swollen stomach.

The acute oral median lethal dose to rats of aluminium sulphate, hydrate was found to be greater than 2000 mg/kg bodyweight and less than 5000 mg/kg bw for females. For males the LD50is less than 5000 mg/kg

 

CAS 7784-27-2 (aluminium nitrate nonahydrate)

 

Aluminium nitrate was administered orally to rats and mice according to a study similar to OECD guideline 401 not GLP compliant. No mortality occurred during the study period. No clinical sings of toxicity were observed up to the end of the 14-day observation period. No effect on body weight was detected and finally no histopathological examination revealed any substance-related findings.

The LD50 resulted to be 3632 mg/kg bw in rats and 3980 mg/kg bw in mice.

 

Acute inhalation toxicity

 

Since no studies investigating the acute inhalation 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 substance (structural analogue) CAS 3290-78-3 (aluminium chloride hydroxide sulphate) was performed. Read-across is justified based on the fact that following 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.

 

 

CAS 3290-78-3 (aluminium chloride hydroxide)

 

The assessment of acute inhalation toxicity of aluminium chloride hydroxide sulphate in the rat was carried out according to OECD Guidelines 403, EU Method B.2 (Acute Toxicity (Inhalation)); EPA OPPTS 870.1200, and JMAFF, 12 Nousan, Notification No 8147, November 2000, including the most recent partial revisions (Huygevorrt, 201 ).

The test substance was administered as an aerosol by inhalation for 4 hours to one group of five male and five female rats.

The mean actual dry test substance concentration was 1.6 ± 0.5 mg/L, corresponding to 6.1 ± 1.8 mg/L of the neat test substance (correction factor 3.7 for the evaporable water content). The mean nominal concentration was 9.4 mg/L resulting in a generation efficiency (ratio of mean actual concentration and nominal concentration of neat test substance) of 65%. 

No mortality occurred. Clinical signs observed among most animals after exposure included lethargy, hunched posture and/or piloerection on days 1 and/or 2 after exposure. No clinical signs were observed during exposure

The body weight gain shown by the animals over the study period was considered to be normal. No abnormalities were found at macroscopic post mortem examination of the animals. Thus, the acute inhalation LC50 is > than 5 mg/L.

 

 

Acute dermal toxicity (aluminium chloride hydroxide)

 

Since no studies investigating the acute oral 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) aluminium sulphate (CAS 10043-01-3) and aluminum chloride hydroxide sulphate (CAS 3290-78-3) was considered. Read-across is justified based on the fact that following 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.

 

 

CAS 10043-01-3 (aluminium sulfate, hydrate)

 

Aluminium sulfate, hydrate was evaluated for its acute dermal toxicity potential in a limit test carried out with a method equivalent to the OECD Guideline 402 (Acute Dermal Toxicity) with deviations (Scholler, 1976) and not GLP compliant.

For 24 hours 5000 mg/kg bw test substance was applied to the skin of two male and female rabbits. This application produced some skin irritation such as erythema and haemorrhaging after treatment. No mortality occurred. All rabbits exhibited normal appearance and behaviour on day 2. The gross necropsy showed no significant gross changes, with the exception of 1 male animal which had pale lungs.

The acute Dermal LD₅₀of aluminium sulfate, hydrate applied to the skin for 24 hours, is greater than 5000 mg/kg bw.

 

 

CAS 39290-78-3 (aluminium chloride hydroxide)

 

The acute dermal toxicity potential of aluminium chloride hydroxide was investigated in a limit test study conducted with according to OECD Guideline 402 (Acute Dermal Toxicity), EU Method B.3 (Acute Toxicity (Dermal)), EPA OPPTS 870.1200 (Acute Dermal Toxicity) , and JMAFF Guidelines (2000), including the most recent revisions and GLP compliant (Stitziger, 2010).

2000 mg/kg bw were occlusively applied on the skin of 5 rats for 24 h. This application produced chromodacryorrhoea (snout) in 2/5 females and piloerection in 1/5 male on day 1. No mortality was observed during the study period. Body weights gains of all dose groups were within the normal ranges in males and females during the whole study period. Thus, the LD50 was found to be > as 2000 mg/kg bw.

 

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 acute toxicity – oral endpoint

Hazard assessment is conducted by means of read across from supporting substances (structural analogues) aluminium sulphate (CAS 10043-01-3) and aluminium nitrate nonahydrate (CAS 7784-27-2). All available studies are 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 acute toxicity – inhalation endpoint

Hazard assessment is conducted by means of read across from supporting substances (structural analogues) aluminium chloride hydroxide sulfate (CAS 3290-78-3). 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 acute toxicity – dermal endpoint

Hazard assessment is conducted by means of read across from supporting substances (structural analogues) aluminium sulfate (CAS 10043-01-3) and aluminium chloride hydroxide sulphate (CAS 3290-78-3). 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 classification or non-classification

The available data on acute toxicity of substances related to the 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 conclusive but not sufficient for classification.