Diantimony pentoxide

Endpoint summary

Additional information

Oral absorption:

It is well known that pentavalent antimonials have a low oral bioavailability, which is why the human pharmaceutical use of Sb(V) compounds up to this day needs to rely on other routes of administration, such as intravenous or even intramuscular.

For trivalent antimony compounds, a oral absorption factor of 1% has been recently agreed in the context of an EU RAR on diantimony trioxide, based on guideline-conform, GLP animal toxicokinetic data.

Studies of this reliability do not exist for pentavalent antimony, but the following weight of evidence approach can be taken, based on published data:

(i) Coughtrey et al. (1983) reiterate the ICRP evaluation of 1981 on gastrointestinal absorption: ICRP recommended for man that values of 10% for tartar emetic and 1% for all other compounds of antimony may be assumed.

(ii) ICRP (1996) retain their position of 1981, stating that they recommend 10% for tartar emetic and 1% for all other compounds of antimony.

(iii) Caughtrey et al. (1983) also calculated an oral absorption of 1% for Sb compounds, based on a comparison of daily dietary intake of Sb, and the total Sb body burdens of stable Sb isotopes. This has high relevance for humans, since it reflects absorption at normal dietary (low) intake levels, and especially since exposure via food and water may be assumed to be primarily to pentavalent antimony, since this is the most stable form under environmentally relevant conditions..

Overall, and by analogy to trivalent antimony, it is concluded that an oral absorption factor of 1% is similarly applicable to pentavalent antimony compounds.

Dermal absorption:

ATO transforms to soluble anionic Sb(III) species in water, and this dissolution is a prerequisite for any subsequent percutaneous transfer; percutaneous transfer of soluble Sb(III) species has been shown to be very low (i.e. 0.26% in in-vitro tests with human skin). Similarly, SHHA also transforms to anionic Sb(V) species upon dissolution in aquatic media. Given that Sb(V) species are an order of magnitude less toxic than Sb(III) species and considering the similar chemistry of dissolved Sb(III) generated from ATO, percutaneous transfer of pentavalent antimony species is not considered to represent a relevant route of entry into the body, so that the derivation of short- or long-term DNELs for systemic effects via the dermal route is not considered to be required.

In vitro bioaccessibility:

Sodium hexahydroxoantimonate (NaSb(OH)6) was exposed to five different synthetic body fluids for two different time periods, 2 and 24 hours. In parallel to the generation of bioaccessibility data, particle and surface characterisations were conducted.

- Particles of NaSb(OH)6 revealed a large number of smaller sized particles (about 1µm) and large size distributions (up to > 100µm).

- A pH and solution composition dependence was observed for the dissolution.

- Particles of NaSb(OH)6 dissolved better in acidic media: GST-pH 1.6:  94%, ALF-pH 4.5: 71%, ASW- pH 6.5: 61%, PBS-pH 7.4: 29 %, and GMb-pH 7.4: 32.5% after 24 hours of exposure.

Rates of antimony release from NaSb(OH)6 particles decreased with time in all media except in GMB. In GMB antimony release remained constant indicating that a protective surface layer against further dissolution may have been formed. The release rate differed in the media as follows: (release rates in mg /cm2/h corrected for measured surface area after 2 and 24 h): GST (0.176 to 0.052) > ALF (0.023 to 0.014) > ASW (0.017 to 0.01) > PBS (0.01 to 0.004) > GMB (0.003 to 0.004).