title: In vitro and in vivo safety evaluation of low molecular weight chitosans prepared by hydrolyzing crab shell chitosans with bamboo shoots chitosanase.
abstract: Our previous study demonstrated that the oral administration of low molecular weight chitosans (LMWC), prepared by hydrolyzing crab shell chitosans with bamboo shoots chitosanase in an appropriate dose, reduced aristolochic acid-induced renal lesions in mice. The objectives of this study were to evaluate the safety of LMWC using genetic and animal toxicity assays. Two assays for genotoxicity were performed: the chromosomal aberration of Chinese hamster ovary cells (CHO-K1 cells) (in vitro) and micronucleus assays in mice (in vivo). Acute oral toxicity and 28-day repeated feeding toxicity tests were performed via the oral gavage method in Sprague-Dawley (SD) rats. LMWC did not induce an increase in micronucleus ratios in vivo, and the chromosome aberration assay indicated that the LMWC was safe in terms of clastogenicity in doses up to 5.0 mg/ml. No acute lethal effect at a maximum tested dose of 5.0 g LMWC/kg body weight (bw) was observed in rats. The results of the 28-day study revealed no adverse effects on the body weight, feed consumption, hematology, blood biochemical parameters, organ weights or pathology. The no observed adverse effect level (NOAEL) of LMWC in rats was 1.0 g/kg bw for the subacute toxicity study.
authors.affiliation: Department of Food and Nutrition, Providence University, Taichung, Taiwan, Republic of China.
authors.forename: Ya-Min
authors.initials: YM
authors.lastname: Chang
authors.affiliation: Department of Medical Laboratory Science and Biotechnology, Central Taiwan University of Sciences and Technology Taichung, Taiwan, Republic of China.
authors.forename: Yu-Jing
authors.initials: YJ
authors.lastname: Lee
authors.affiliation: Graduate Institute of Veterinary Pathology, National Chung Hsing University, Taichung, Taiwan, Republic of China.
authors.forename: Junn-Wang
authors.initials: JW
authors.lastname: Liao
authors.affiliation: Department of Food and Nutrition, Providence University, Taichung, Taiwan, Republic of China.
authors.forename: Jyun-Kai
authors.initials: JK
authors.lastname: Jhan
authors.affiliation: Department of Food and Nutrition, Providence University, Taichung, Taiwan, Republic of China. Electronic address: ctchang@pu.edu.tw.
authors.forename: Chen-Tien
authors.initials: CT
authors.lastname: Chang
authors.affiliation: Department of Food and Nutrition, Providence University, Taichung, Taiwan, Republic of China. Electronic address: ycchun@pu.edu.tw.
authors.forename: Yun-Chin
authors.initials: YC
authors.lastname: Chung
mesh_terms: D000818:Animals; D031723:Bambusa / Q000201:enzymology*; D048271:Chitosan / Q000494:pharmacology*; D003445:Crustacea; D006026:Glycoside Hydrolases / Q000378:metabolism*; D006868:Hydrolysis; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008970:Molecular Weight; D018520:Plant Shoots / Q000201:enzymology*
chemical_list: D048271:Chitosan; D006026:Glycoside Hydrolases; C019868:chitosanase
keywords: Acute toxicity; Chromosome aberration; Low molecular weight chitosans; Mouse erythrocyte micronucleus; Subacute toxicity