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. 2014 Jul 11;13:70. doi: 10.1186/1475-2891-13-70

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