Aluminium tributanolate

Endpoint summary

Description of key information

Upon contact with water or moisture (e.g. within mucous membranes) aluminium tributanolate hydrolyses immediately to butan-1ol and aluminium 3+ cations (as hydroxide and oxyhydroxide). Hence, the toxicokinetics are determined by the toxicokinetic behaviour of these two species

Inhalation studies with butan-1-ol in human volunteers and dogs show that a significant amount of butan-1-ol is absorbed through the lung (40% in humans and 55% in dogs, respectively). Although the data obtained from humans do not provide blood half-life values, the plasma levels of butan-1-ol were proportionally exposure-related, suggesting rapid elimination.

In vitro studies indicate that butan-1-ol can permeate human skin (epidermis and dermis). A skin absorption rate of 8.8 µg/cm²/min was determined in dogs.

The pattern of excretion and overall recovery observed in different experimental animals demonstrate complete absorption of butan-1-ol by the oral route.

Once absorbed, butan-1-ol is distributed throughout the organism, with highest concentrations found typically in the liver, kidneys and lungs. After oral administration to rats, a peak blood level was reached after 1 to 2 hours; butan-1-ol then disappeared rapidly from the blood with an estimated half-life of 1 hour.

Butan-1-ol is metabolised, primarily via alcohol and aldehyde dehydrogenases in the liver. This pathway involves oxidation to butyric acid and further degradation to shorter acids and ketones, ultimately to CO₂. A minor pathway involves conjugation, mainly as butan-1-ol-O-glucuronide or butan-1-ol-O-sulphate and excretion in urine. Some butan-1-ol may be excreted in urine or expired unchanged (ECETOC JACC 41 2003).

In a review by the US-EPA ( TOXICOLOGICAL REVIEW OF n-BUTANOL (CAS No. 71-36-3) In Support of Summary Information on the Integrated Risk Information System (IRIS) June 2011) it is concluded that butan-1-ol is readily absorbed following oral administration (80%; DiVincenzo and Hamilton, 1979a), moderately absorbed following an inhalation exposure (50%; DiVincenzo and Hamilton, 1979a; Astrand et al., 1976) and poorly absorbed following a dermal exposure (1%; Boman and Maibach, 2000). Once absorbed, butan-1-ol is rapidly distributed to many tissues including the liver, kidney, lung, brain and heart (Kaneko et al., 1994; DiVincenzo and Hamilton, 1979a).

 

No accumulation of aluminium in the brain or bones is seen in rats orally treated with Al(OH)3 for 9 weeks. No difference was observed between aged and young rats (Salina 1984). Similar results are reported by Zhou (2008), who found that oral administration of aluminium potassium sulfate ( 26-Al-labelled) was bioavailable to a very limited extend (0.29% for Al3+ and no difference between different tested ligands). In human volunteers about 0.01% of the dermally applied dose of aluminium chlorohydrate was absorbed (Fahrend 2001).

These data are indicative for a low absorption of aluminium via the oral and dermal route. Data in repeated dose studies with aluminium(III) species show in general no toxicity related to aluminium when applied via the oral route (the highest dose tested in these studies proves to be the NOAEL). For reproduction toxicity effects of aluminium intake on development and performance of cognitive tasks has been observed (NOAEL 8-10 mg/kg bw). These findings are indicative for some uptake of aluminium (III) species via the oral route.

 

Butan-1-ol: absorption dermal 10% (based on low molecular weight, logPow 0.88 and high water solubility and the data from review documents); absorption inhalation 50%; absorption oral 100% (default value)

Aluminium (hydroxide) as aluminium: absorption dermal 0.01 %; absorption inhalation 0%; absorption oral 10% (default value set as worst case)

A detailed toxicokinetic assessment can be found in section 13

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Absorption rate - oral (%):

100

Absorption rate - dermal (%):

10

Absorption rate - inhalation (%):

50

Additional information

The values are based on the absorption potential of butan-1-ol, as it is expected that aluminium (hydroxide) bioavailability via the inhalation and dermal route is very limited.