**3. Mechanism of binding of alginate and metals**

In the case of acute oral exposure to toxic metals, health damage can be reduced by immediate treatments such as induction of vomiting and/or the use of a laxative to promote excretion of the metal. However, in the case of chronic exposure, it is essential to use intrinsically safe absorption inhibitors and/or excretion accelerators that are suitable for long-term administration.

Although the effect of Alg on Sr or Cs absorption and excretion has already been reported, there is little information about its effect on other metals. Therefore, we investigated the relationship between the physical parameters of various metal ions, including toxic metal ions, and the binding affinity of these metal ions for Alg [11]. For this purpose, the binding constants (K, mM<sup>−</sup><sup>1</sup> ) and the binding amount with Alg were evaluated for Sr, Pb, Tb, Dy, Ca, Cd, Mg, Fe(II), Fe(III), Co, Al, Ni, Cs, Cu, Ag, Li, and K. Aqueous solutions of each metal salt and an equivalent amount of Na-Alg were mixed, and the amount of unbound metal remaining in the filtrate was determined using an atomic absorption photometer. The amount of bound metal was calculated from the amount of remaining unbound metal ion, and K values and the number of binding sites per 1 mg of Alg (n) were analyzed using double-reciprocal plots. The affinity of each metal ion for Alg was calculated by multiplying the n and *K* values. Moreover, the relationships between charge number and radius of these metals and their binding affinity were examined.

The order of K values was as follows: Sr2+ > Pb2+ > Tb3+ > Dy3+ > Ca2+ > Cd2+ > Mg2+ > Fe2+ > Fe3+ > Co2+ > Al3+ > Ni2+ > Cs+ > Cu2+ > Ag+ > Li+ >K+ . Moreover, metal ions with high K values tended to have ionic radii within the range of about 90–120 pm. On the other hand, the order of affinity for Alg was Pb2+ > Dy3+ > Tb3+ > Sr2+ > Ca2+ > Mg2+ > Cd2+ >Fe2+**,**Fe3+ >Cs+ >Al3+ >Co2+ >Ni2+ >Cu2+ >Ag+ >K+ >Li+ .

The *K* value and affinity for Alg both tended to be higher for divalent or trivalent metal ions than for monovalent ions. It is well established that Alg forms a cross-linked structure with divalent or trivalent metal ions, resulting in gel formation. These results might indicate that metal ions with an ionic radius of about 90–120 pm form more robust and water-insoluble gels (**Figure 2**) [11].

Overall, these results indicate that Alg would be effective as an excretion accelerator and/or absorption inhibitor for various toxic metal ions, especially divalent metals such as Pb and Cd.

**Figure 2.** *Relationships between K value, charge number and ionic radius of metal ions [11].*

It is noteworthy that the affinity between Alg and Cs is relatively small, even though we had previously shown that Ca-Alg is effective in promoting excretion and decreasing absorption of Cs in rats [9]. Therefore, not only the affinity between Alg and metals, but also other factors arising from the specific combination of Alg and metal ion, may influence excretion and/or absorption of individual metal ions in the presence of Alg.
