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 48Â 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 |  |