Table 1.
Study design of four-week repeated intramuscular dose toxicity study in Sprague-Dawley rats and intradermal irritation study in New Zealand white rabbits.
Fig 1.
Body weight changes in a four-week repeated intramuscular dose toxicity study in Sprague-Dawley (SD) rats and an intradermal irritation study in New Zealand White (NZW) rabbits.
Body weight changes measured once a week in a) SD rats and b) NZW rabbits, for a total of five times during the study period. In SD rats, all substances were injected once every two weeks for four weeks (total three times; days 1, 15, 29) into one site of the gastrocnemius muscle of the right hindlimb. Neither male nor female rat groups showed significant differences in body weight on days 8, 15, 22, and 29 (Kruskal-Wallis test). In NZW rabbits, all substances were injected once into five sites of the back skin (total one time; day 1). There was no significant difference in body weight on days 8, 15, 22, and 29 in all groups (Kruskal-Wallis test).
Table 2.
Hematology, clinical biochemistry, and serum IgE and histamine levels in male Sprague-Dawley (SD) rats.
Table 3.
Hematology, clinical biochemistry, and serum IgE and histamine levels in female Sprague-Dawley (SD) rats.
Fig 2.
Histopathological section of the administration site in the four-week repeated intramuscular dose toxicity study in Sprague-Dawley (SD) rats.
Hematoxylin and eosin stained histopathological section (original magnification 100x) of the gastrocnemius muscle of the SD rats: a) Control group, male; b) Control group, female; c) Polysorbate 20–0.02 mg/kg, male; d) Polysorbate 20–0.02 mg/kg, female; e) Polysorbate 20–0.1 mg/kg, male; f) Polysorbate 20–0.1 mg/kg, female; g) Polysorbate 20–0.4 mg/kg, male; h) Polysorbate 20–0.4 mg/kg, female; i) Human serum albumin-0.06 mg/kg, male; j) Human serum albumin-0.06 mg/kg, female; k) Human serum albumin-0.12 mg/kg, male; l) Human serum albumin-0.12 mg/kg, female. Mild macrophage infiltration, neovascularization, inflammatory cells infiltration, and fat infiltration were observed with a similar degree and frequency in all administered groups. An arrow pointing up (↑) indicated macrophage infiltration and an arrow pointing down (↓) indicated neovascularization.
Fig 3.
Histopathological section of the administration site in the intradermal irritation study in New Zealand White (NZW) rabbits.
Hematoxylin and eosin stained histopathological section (original magnification 50x) of the dorsal back skin of the NZW rabbits: a) Control group; b) Polysorbate 20–0.02 mg/kg; c) Polysorbate 20–0.1 mg/kg; d) Polysorbate 20–0.4 mg/kg; e) Human serum albumin (HSA)-0.06 mg/kg; f) HSA-0.12 mg/kg, male. No histopathological findings were found at the site of administration in all administered groups.