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A recent evaluation of HSP and PFP aqueous extracts in rats found no observed adverse effect levels (NOAELs) of 7.5 g/kg and 15 g/kg, respectively, for single-dose administration and 15 g/kg for 14-day repeated dosing, with no lethality observed at any tested dose ( In a zebrafish model, decoctions prepared from Fuzi produced in five different regions of China were compared, and significant regional differences were observed pertaining to acute toxicity, with LC 50 values ranging from 4.223 mg/mL for Jiangyou-Fuzi (highest toxicity) to 29.62 mg/mL for Ludian-Fuzi (lowest toxicity), which may be related to differences in the DDA content among these geo-authentic and non-geo-authentic materials ( Taken together, these data indicate that acute toxicity of Fuzi is driven primarily by DDAs, is greatly reduced by hydrolysis to MDAs through adequate decoction or processing, and can be significantly influenced by both the pathological state of the recipient and the geographical origin of the raw material
