Table 2

Safety tests of hyaluronan
Test procedure Substance Origin Molecular weight Subject Result Reference
Daily oral administration test for 8 weeks HA Chicken comb 9 × 105 Human No abnormalities in hematology due to 240 mg/kg body weight/day for 12 weeks Sato, T. et al. (2009) [63]
Daily oral administration test for 1 year HA Chicken comb 9 × 105 Human No abnormalities on clinical observations due to oral administration of 200 mg/kg body weight/day for 1 year Tashiro, T. et al. (2012) [7]
Single-dose toxicity test Sodium hyaluronate Chicken comb Not shown Mouse LD50 (mg/kg body weight) > 2400 Nagano, K. et al. (1984) [55]
LD50 (mg/kg body weight) > 1200 Nagano, K. et al. (1984) [56]
Sodium hyaluronate Chicken comb Not shown Rat LD50 (mg/kg body weight) > 800 Nagano, K. et al. (1984) [55]
LD50 (mg/kg body weight) > 1200 Nagano, K. et al. (1984) [56]
Microbial fermentation 16.8 × 105 LD50 (mg/kg body weight) > 200 Morita, H. et al. (1991) [57]
Sodium hyaluronate Chicken comb Not shown Rabbit LD50 (mg/kg body weight) > 1000 Nagano, K. et al. (1984) [55]
LD50 (mg/kg body weight) > 900 Nagano, K. et al. (1984) [56]
Repeated-dose toxicity test HA Microbial fermentation 3 × 105 rat No abnormalities on clinical observations due to administration in doses equivalent to 0, 34, 235, 3536 mg/kg body weight/day. Oe, M. et al. (2011) [58]
Sodium hyaluronate Chicken comb Not shown NOAEL 48 mg/kg body weight, or more Ishihara, M. et al. (1996) [59]
Antigenicity test Sodium hyaluronate Microbial fermentation 18.8 × 105 Bacteria (Ames test) No mutagenicities to S. typhimurium (TA1535, TA1537, TA98, or TA100) or E.coli (WP 2 urA) Sugiyama, C. et al. (1991) [60]
Not shown 21.2 × 105 No mutagenicities to S. typhimurium (TA98, TA100, TA1535, or TA1537) or E.coli (2 urA) Onishi, M. et al. (1992) [61]
Chicken comb 20.0–21.2 × 105 Mouse, rat, rabbit No antigenicity on PCA reaction in mice or guinea pigs Takemoto, M. et al. (1992) [62]
No antigenicity on active systemic anaphylactic reaction in guinea pigs

Kawada et al.

Kawada et al. Nutrition Journal 2014 13:70   doi:10.1186/1475-2891-13-70

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