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Description of key information

Short description of key information on bioaccumulation potential result: 
The toxicity of aluminium ammonium (bis)sulfate will mainly result from the aluminium ion, and differences in toxicity are likely due to variation in bioavailability due to differences in the form of the ingested compound and dietary constituents.
Regarding the powder granulometry of aluminium ammonium (bis)sulfate, the toxicity by inhalation is warranted due to the potential for the oral toxicity.
Short description of key information on absorption rate:
No absorption is expected to occur after dermal exposure to Aluminium ammonium (bis) sulfate.

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential

Additional information

Following ingestion, the aluminium ammonium (bis)sulfate is hydrolysed to ammonium sulphate and aluminium sulphate and then completely dissociated into the aluminium (Al3+), the ammonium (NH4+) and the sulfate (SO42-) ions in the acidic aqueous conditions of the gut such as in the stomach (pH≈2). Therefore, the hazard of this salt by oral route can be assessed by the effects of its dissociation products in a read-approach.

Only few data are available for ammonium and sulfate ions. However, the toxicity of aluminium ammonium (bis)sulfate will mainly result from the aluminium ion, and the differences in toxicity are likely due to variation in bioavailability due to differences in the form of the ingested compound and dietary constituents. In humans, most estimates of average gastrointestinal absorption of Aluminium under normal dietary conditions are in the range of 0.1 - 0.6 %, although some human studies indicate that absorption of the more bioavailable forms, particularly complexes of Aluminium with particular carboxylic acids, (e.g. Aluminium citrate), may be in the order of 0.5 - 5 %.

Once into the blood, Aluminium is believed to be present almost exclusively in the plasma where it is bound mainly to transferrin and to a lesser extent, also to albumin. From human dietary balance studies, it is clear that most of the ingested Aluminium is unabsorbed: Aluminium levels determined in feces ranged from 76 to 98 % of the oral dose. Following ingestion in humans, absorbed Aluminium from the blood is eliminated in the kidney and excreted in the urine

Regarding the granulometry of aluminium ammonium (bis)sulfate as a powder, the toxicity by inhalation is warranted due to the potential for the oral toxicity.

Regarding the aluminium ammonium (bis)sulfate physical state as water soluble inorganic powder, human exposure by dermal should be considered. However, neither systemic effect nor local effects are observed during the acute dermal testing, nor in skin and eye irritation studies. Moreover, no sensitisation potential of aluminium ammonium (bis)sulfate was observed in a relevant study. Therefore, local toxicity is not expected after aluminium ammonium (bis)sulfate exposure by dermal contact. Moreover, considering both the absence of systemic effects during the different testing by dermal route together with the physical state as a high molecular mass powder (906.6 g/mol), no absorption is expected to occur during dermal exposure to aluminium ammonium (bis)sulfate

 

Discussion on bioaccumulation potential result:

Oral exposure

Following ingestion, the aluminium ammonium (bis)sulfate is hydrolysed to ammonium sulphate and aluminium sulphate and then completely dissociated into the aluminium (Al3+), the ammonium (NH4+) and the sulfate (SO42-) ions in the acidic aqueous conditions of the gut such as in the stomach (pH≈2). Therefore, the hazard of this salt by oral route can be assessed by the effects of its dissociation products in a read-approach.

Only few data are available for ammonium and sulfate ions (presented below). However, the toxicity of aluminium ammonium (bis)sulfate will mainly result from the aluminium ion, and differences in toxicity are likely due to variation in bioavailability as it is explained below.

- At physiological pH in aqueous media, the ammonium ion is in equilibrium with un-ionized ammonia, according to the following equation:

NH4++ H2O → NH3+ H3O+

The ammonium ion serves a major role in the maintenance of the acid-base balance. In the normal pH range of blood, the NH4+/NH3 ratio is about 100 (WHO, 1986).

An ammonium ion via the equilibrium with ammonia is readily taken up into the body. Some evidence exists also for an active transport of the ammonium ion from the intestinal tract. It was shown that ammonia transport by the human colon still occurred when the luminal pH was reduced to 5, where non-ionized ammonia would be virtually absent (WHO, 1986). It is transported to the liver. Ammonium is metabolized to urea (WHO, 1986). Minor amounts of nitrogen are incorporated in the physiological N-pool (WHO, 1986).

- Absorption of sulfate depends on the amount ingested.No studies were located regarding distribution after exposure to Sulfate.Sulfate levels are regulated by the kidney through a reabsorption mechanism (OECD SIDS, 2004).No studies were located regarding the metabolism in humans and animals after exposure to Sulfate.

However, sulfate is a normal constituent of human blood and does not accumulate in tissues (OECD SIDS, 2004). 30 - 44 % of sulfate was excreted in the 24-h urine after oral administration of magnesium or sodium sulfate (5.4 g sulfate) in volunteers. At high sulfate doses that exceed intestinal absorption, sulfate is excreted in feces. Sulfate is usually eliminated by renal excretion. It has also an important role in the detoxification of various endogenous and exogenous compounds, as it may combine with these to form soluble sulfate esters that are excreted in the urine (OECD SIDS, 2004).

- Animal studies showed that Aluminium absorptionviathe gastrointestinal tract is usually less than 1%. The main factors influencing absorption are solubility, pH and chemical species (ATSDR, 2008; PHG, 2001; WHO, 1997; JECFA, 2001, 1989).

Human studies indicate that only a small percentage of Aluminium that is normally ingested in the diet and drinking water is absorbed. Most estimates of average gastrointestinal absorption of Aluminium under normal dietary conditions are in the range of 0.1 - 0.6 %, although some human studies indicate that absorption of the more bioavailable forms, particularly complexes of Aluminium with particular carboxylic acids, (e.g.Aluminium citrate), may be on the order of 0.5 - 5 % (ATSDR, 2008; PHG, 2001).

Bioavailability of Aluminium varies mainly due to differences in the form of the ingested compound and dietary constituents (i.e.the kinds and amounts of ligands in the stomach with which absorbable Aluminium species can be formed). Although the range of fractional absorption is low compared to many other chemicals; Aluminium uptake can significantly increase following oral exposure depending on conditions, including long-term ingestion, the presence of certain dietary components such as citrate, and when large quantities are ingested (e.g.during use of antacids) (ATSDR, 2008; PHG, 2001).

Once into the blood, Aluminium is believed to be present almost exclusively in the plasma where it is bound mainly to transferrin and to a lesser extent, also to albumin. It was observed that 89% of the Aluminium in serum is bound to citrate and transferrin which may play a significant role in the distribution of Aluminium (ATSDR, 2008; PHG, 2001; WHO, 1997). Normal levels of Aluminium in serum are approximately 1–3 μg/L (ATSDR, 2008).

There are limited data on distribution of Aluminium in humans but the distribution of Aluminium in animals after oral exposure has been evaluated in a number of studies (ATSDR, 2008). These studies are particularly informative because they demonstrate that, although bioavailability of Aluminium is low, Aluminium tissue concentrations can increase substantially following oral exposure, and provide information on distribution of Aluminium in various tissues. Animal evidence suggests that Aluminium accumulates in the brain (grey matter) where it is preferentially distributed to the hippocampus. In addition to the distribution of Aluminium to the brain, bone, muscle and kidneys of orally exposed animals, there is limited animal evidence indicating that Aluminium has the potential to cross the placenta and accumulate in the foetus and to be distributed to some extent to the milk of lactating mothers (ATSDR, 2008; PHG, 2001).

From human dietary balance studies, it is clear that most of the ingested Aluminium is unabsorbed: Aluminium levels determined in feces ranged from 76 to 98 % of the oral dose (ATSDR, 2008; PHG, 2001). Following ingestion in humans, absorbed Aluminium from the blood is eliminated in the kidney and excreted in the urine (ATSDR, 2008; PHG, 2001; WHO, 1997).

Excretion data collected in animal studies are consistent with the results from human studies where the difference in the excretion rates most likely reflects differences in gastrointestinal absorption.

There is insufficient information to comment on biliary excretion of Aluminium in humans (WHO, 1997).

 

Inhalation exposure

Regarding the aluminium ammonium (bis) sulfate physical state as an inhalable fraction containing powder, human exposure by inhalation should be considered even if the vapour pressure is low.

The granulometry of aluminium ammonium (bis)sulfate showed no detectable particles in the alveolar fraction (< 10 µm) and less than 10% of total particles in the inhalable fraction (< 100 µm). These particles are expected to be exhaled, some are trapped in the nasopharyngeal and upper respiratory areas and deposited in the gastrointestinal tract by mucosal movement and mucocilliary action. Consequently, the toxicity by inhalation is warranted due to the potential for the oral toxicity.

References:

- OECD SIDS Initial Assessment Profile (2004) Ammonium sulfate; CAS N°: 7783 -20 -2. UNEP publication.

- Agency for Toxic Subctances and Disease Registry / ATSDR (2008) Toxicological profile for Aluminium, U. S. Department of Health and Human services,Public Health Service, September 2008, 357 p.

- World Health Organisation / WHO (1997), Environmental Health Criteria n°194 - Aluminium. International Programme on Chemical Safety.

- Public Health Goal / PHG (2001) Aluminium in Drinking Water, April 2001, 74 p.

- Joint FAO/WHO Expert Commitee on Food Additives / JECFA (2001) JECFA / IPCS, INCHEM. Aluminium, 1 p.

- JECFA (1989) JECFA / IPCS, INCHEM. Aluminium, 28 p.

Discussion on absorption rate:

Regarding the Aluminium ammonium (bis) sulfate physical state as water soluble inorganic powder, human exposure by dermal should be considered.

However, neither systemic effect nor local effects are observed during the acute dermal testing, nor in skin and eye irritation studies. Moreover, no sensitisation potential of aluminium ammonium (bis)sulfate was observed in a relevant study. Therefore, local toxicity is not expected after Aluminium ammonium (bis)sulfate exposure by dermal contact. Moreover, considering both the absence of systemic effects during the different testing by dermal route together with the physical state as a high molecular mass powder, no absorption is expected to occur after dermal exposure to Aluminium ammonium (bis) sulfate