Biomedical Engineering Reference
In-Depth Information
6.3
Biocomapatibility and Toxicology of Chitin
and Chitosan
h e low toxicity proi le of chitosan compared with other natural polysac-
charides is another of its many attractive features. Chitin is a normal con-
stituent of sea food and mushrooms, both of which are considered to be
non-toxic and safe for human consumption, except for a very small per-
centage of the population that is allergic to seafood products, due to the
presence of proteinaceous impurities [27]. High quality chitin and chito-
san, at er complete removal of toxic and contaminating bioburden as pro-
teins, heavy metals and pyrogens, are biocompatible and safe for use. US
FDA has proclaimed chitosan to be Generally Recognised As Safe (GRAS),
a designation used to indicate that a chemical or substance added to foods
and beverages is considered safe.
h e safety in terms of inertness and low or no toxicity has been dem-
onstrated by
in vivo
toxicity studies. Its oral LD
50
(median lethal dose) in
mice was found to be in excess of 16 g/kg/day, which is higher than that of
sucrose [28]. In the acute toxicity test, the LD
50
was reported as over 15 g/
kg orally in rats, over 10 g/kg subcutaneously in mice, 5.2 g/kg intraperito-
neally in mice and 3.0 g/kg in rats [29].
An extensive toxicological study with PROTASAN
TM
UP (chitosan glu-
tamate, ultrapure DDA 83 %) (Pronova Biomedical, Oslo, Norway)
where
administration was done by oral and parenteral routes for assays of hyper-
sensitisation, mutagenicity and cytotoxicity, showed its essentially non-
toxic nature in rats (see Table 6.1) [30].
Intravenous injections of chitosan oligomers (DP 2-8) in rabbits at low
dose (4.5 mg/kg) or higher dose (7.1-8.6 mg/kg/day) did not cause any
noticeable physiological symptoms, except increased hexosamine value
and lysozyme activity in blood, returning to normal on cessation of treat-
ment [31] At relatively high doses, deleterious ef ects were found in dogs
Table 6.1
Toxicology of chitosan glutamate (protasan
tm
up) in rats [30].
Application
No toxic ef ect seen at
Application for
Oral
Up to 600 mg/kg /day
13 weeks
Intravenous
Up to 25 mg/kg
Once
Intraperitoneal
Bolus injection, up to 500 mg/kg
7 days
Nasal mucosa
Up to 3 mg per rat per day
7 days
