Safety assessment of non-animal chondroitin sulfate sodium: Subchronic study in rats, genotoxicity tests and human bioavailability.
Chondroitin sulfate, an amino sugar polymer made of glucuronic acid and N-acetyl-galactosamine, is used in dietary supplements to promote joint health. Commonly used chondroitin sulfate is of animal origin and can pose potential safety problems including bovine spongiform encephalopathy (BSE). The objective of the present study was to investigate potential adverse effects, if any, of microbial derived chondroitin sulfate sodium (CSS) in subchronic toxicity, genotoxicity and bioavailability studies. In the toxicity study, Sprague Dawley rats (10/sex/group) were gavaged with CSS at dose levels of 0, 250, 500 and 1000 mg/kg body weight (bw)/day for 90-days. No mortality or significant changes in clinical signs, body weights, body weight gain or feed consumption were noted. Similarly, no toxicologically relevant treatment-related changes in hematological, clinical chemistry, urinalysis and organ weights were noted. Macroscopic and microscopic examinations did not reveal treatment-related abnormalities. In vitro mutagenic and clastogenic potentials as evaluated by Ames assay, chromosomal aberration test and micronucleus assay did not reveal genotoxicity of CSS. In pharmacokinetic study in human, CSS showed higher absorption as compared to chondroitin sulfate of animal origin. The results of subchronic toxicity study supports the no-observed-adverse-effect level (NOAEL) for CSS as 1000 mg/kg bw/day, the highest dose tested.
Gnosis S.p.A., Via Lavoratori Autobianchi, 1, 20832 Desio, MB, Italy.
Niccolò
N
Miraglia
Gnosis S.p.A., Via Lavoratori Autobianchi, 1, 20832 Desio, MB, Italy.
Davide
D
Bianchi
Gnosis S.p.A., Via Lavoratori Autobianchi, 1, 20832 Desio, MB, Italy.
Antonella
A
Trentin
Department of Life Sciences, University of Modena and Reggio Emilia, Via Campi 213/D, Modena, MO, Italy.
Nicola
N
Volpi
Soni and Associates Inc., 973 37th Place, Vero Beach, FL 32960, USA. Electronic address: msoni@soniassociates.net.
Madhu G
MG
Soni
D000818:Animals; D001682:Biological Availability; D002417:Cattle; D002809:Chondroitin Sulfates / Q000494:pharmacology*; D002869:Chromosome Aberrations / Q000139:chemically induced*; D004249:DNA Damage / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D015162:Micronucleus Tests; D009152:Mutagenicity Tests / Q000379:methods*; D019055:No-Observed-Adverse-Effect Level; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012449:Safety; D059550:Toxicity Tests, Subchronic / Q000379:methods*
D002809:Chondroitin Sulfates
Bioavailability; Chondroitin sulfate sodium; Dietary supplement; Safety; Toxicity