Aluminium tribenzoate

Endpoint summary

Link to relevant study record(s)

Reference

Endpoint:

basic toxicokinetics, other

Remarks:

theoretical assessment

Type of information:

other: expert statement

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Theoretical assessment taking all currrently available relevant information into account, based on the REACH Guidance: Guidance on Information Requirements and Chemical Safety Assessment, Chapter R.7c Endpoint specific guidance. Since this is a theoretical assessment, the Klimisch value cannot be 1.

GLP compliance:

no

Type:

absorption

Results:

For risk assessment purposes 50% is used for oral and dermal absorption, for inhalation absorption 100% is used.

Conclusions:

A toxicokinetic assessment was performed based on the available data of aluminium tribenzoate. Based on the physical/chemical properties of the substance, absorption factors for this substance are derived to be 50% (oral), 100% (inhalation) and 50% (dermal) for risk assessment purposes. The bioaccumulation potential is expected to be low.

Description of key information

After exposure, a substance can enter the body via the gastrointestinal tract, the lungs and the skin. Since different parameters are relevant depending on the route of exposure, the three routes will be addressed individually.

After oral administration, in general, a compound needs to be dissolved before it can be taken up from the gastrointestinal tract. Aluminium tribenzoate is a white powder, which has a limited water solubility (42.7 mg/L at 20°C). In solution, the substance is expected to dissociate into its respective ions, aluminum and benzoate. No data are available on the dissociation constant(s) of aluminium tribenzoate, therefore it is unclear in which state (ionized or not ionized) the substance will be present under physiological circumstances in the stomach or intestinal tracts. The dissociation constant of benzoic acid is 4.19. This implies that at lower pH, e.g. in the stomach, benzoic acid is expected to be present in its ionic form. However, pH values vary along the gastro intestinal tract, so aluminium tribenzoate is expected to be present in both ionized and non-ionized form. Since it is generally considered that charged molecules do not readily diffuse across biological membranes, the state of the substance might hamper uptake at lower pH. However, it has been reported that after oral ingestion of benzoic acid and sodium benzoate, there is rapid absorption (of undissociated benzoic acid) from the gastrointestinal tract in experimental animals or humans2. In experimental animals, absorption of aluminium via the gastrointestinal tract is reported to be less than 1%, however this percentage is strongly influenced by solubility and pH. Organic complexing compounds, for example benzoate, are known to increase absorption. Overall it can be concluded that the substance will dissolve to some extent into the gastrointestinal fluids upon after oral exposure and uptake via passive diffusion (passage of small water-soluble molecules through aqueous pores or carriage across membranes with the bulk passage of water) is expected to take place to some extent. The moderate molecular weight (approx. 390) will not hamper this process. Aluminium tribenzoate has a moderate log P value (log Pow = -0.1 at 20°C), which will allow absorption by passive diffusion through lipid membranes.

Taking all information together it can be concluded that it is not clear in which form aluminium tribenzoate will be present at which stage of the gastro-intestinal tract. As this appears to be influenced by pH, it can be assumed that all forms (undissociated aluminium benzoate, Al3+ ions, with the benzoate present either as benzoate or benzoic acid) will be present at some stage. Its limited water solubility and charge (when present in ionized form) will limit passive absorption. Although its moderate log Pow and moderate molecular size favour oral uptake, this is not expected to exceed the hampering effects of charge and limited water solubility. Therefore, for risk assessment purposes oral absorption of aluminium benzoate is set at 50%. The oral toxicity data do not provide reason to deviate from the proposed oral absorption factor.

Once absorbed, distribution of the test substance throughout the body is likely to take place based on its water solubility and moderate molecular weight. Aluminium benzoate (or the dissociated benzoate) is metabolized in the liver and excreted mainly via urine, which will also be the route of excretion for the aluminium ion. Based on its moderate partition coefficient, it is not likely that it will significantly accumulate in adipose tissue. Therefore bioaccumulation is expected to be low.

Aluminium tribenzoate has a very low vapour pressure (< 2.1x10E-8 Pa at 25°C), which indicates that exposure to the substance is unlikely. However, since the particles are very small (MMAD is 2.725 µm, 90% of the material <5.077), particles may reach all regions of the respiratory tract. Once aluminium tribenzoate reaches these regions, it is likely to dissolve to some extent in the mucus lining the respiratory tract and to get absorbed. Although its ability to dissolve in water is limited, based on its limited molecular weight and moderate partition coefficient it can be expected to be absorbed. Based on the above data, for risk assessment purposes the inhalation absorption of aluminium tribenzoate is set at 100%.

The first layer of the skin, the stratum corneum, is a barrier for hydrophilic compounds. Based on its moderate log Pow (-0.1), crossing the first layer of the skin is expected to be hampered. Moreover, if aluminium tribenzoate dissociates into its respective ions, its ionic state can influence penetration as ions can bind to skin components which would further impede uptake. Furthermore, based on its limited water solubility (42.7 mg/L at 20°C) absorption through the skin is anticipated to be moderate. According to the guidance on dermal absorption, a default value of 100% skin absorption is generally used unless molecular mass is above 500 and log Pow is outside the range [-1, 4]. Since the substance has a molecular weight of approx. 390 and a log Pow just below 0, it does not meet either criteria. However, since uptake via the skin is expected to be hampered by its low water solubility, its moderate log Pow, its presence in ionic form and since oral and dermal uptake are considered to be similar, for risk assessment purposes the dermal absorption is set at 50%. The dermal toxicity data do not provide reason to deviate from the proposed dermal absorption factor.

Key value for chemical safety assessment

Bioaccumulation potential:

low bioaccumulation potential

Absorption rate - oral (%):

50

Absorption rate - dermal (%):

50

Absorption rate - inhalation (%):

100