Another factor to consider when studying the effects of chitosan is biodistribution so that the exact extent to which the medications encased by the chitosan will be distributed within the body can be determined. The oral dosage forms use chitosan as an excipient, although chitosan does not strictly fit the definition of excipient as it has many biological effects. It has been suggested that chitosan chelates fat and reduces cholesterol, but this and its mechanism are somewhat debatable. Apart from the impact that chitosan may have on bile salts and gastrointestinal milieu, the uptake of chitosan into the bloodstream is generally not investigated in oral administration studies. For the safety and toxicity of the chitosan nanoparticles, chitosan is widely regarded as being a non-toxic, biologically compatible polymer. It is approved for dietary applications in Japan, Italy and Finland, and it has been approved by the FDA for use in wound dressings. The modifications made to chitosan could make it more or less toxic, and any residual reactants should be carefully removed. However, the exact toxicity of chitosan was still examined as they are utilized in medical fields, which have the most intimate connection with humans. Chitosans (having different Mw and DD; <5 kDa, 65.4% DD; 5-10 kDa, 55.3% DD; and >10 kDa, 55.3% DD) were found to display little cytotoxicity against CCRF-CEM (human lymphoblastic leukemia) and L132 (human embryonic lung cells) (IC50> 1 mg/ml), from the research in 1999, conducted by Richardson et.al. In contrast to most reports, Carreño-Gomez et al. found chitosan (hydrochloride salt) to be relatively toxic (IC50 0.21± 0.04 mg/ml) against B16F10 (murine melanoma) cells. However, this study appears to have used solutions of the chitosan salts at the pH formed when dissolved for chitosan HCl in PBS (10 mg/ml) pH= 5.8. Nonetheless, despite this potential denial of harmlessness, the appreciation of the effect of the salt form of the polymer on its interaction with cells and macromolecules should be acknowledged.