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1.For future standard repeat-dose GLP animal studies a general limit of 20 mg/kg/day and a maximum concentration of 2%ofMeTHF or CPME would not be expected to contribute to any toxicity potentially exhibited by an active pharmaceutical ingredient containing these solvents. ÎÒµÄÒëÎÄÊÇ£º½«À´£¬±ê×¼µÄÖØ¸´¸øÒ©GLP¶¯ÎïÊÔÑ飬Ԥ²âƽ¾ù20 mg/kg/Ìì»òÕß×î¸ßŨ¶ÈΪ2%µÄMeTHF»ò CPME¾ù²»»áÒýÆðÈκÎDZÔڵ;ÐÔ¡£ ÎÒ·ÒëµÄ׼ȷ²»×¼È·ÄØ£¿ÓÐûÓиüºÃµÄÒë·¨£¿ 2.The exposures in the animal studies provide human PDE values of 6.2 and 7.4mg/day forMeTHF and CPME respectively based on a 60 kg individual and using extrapolation factors of 5 (rats to humans), 10 (individual variability), and 5 (animal exposure duration). ´Ë¾ä¼ÓÏ»®Ïß´¦ÈçºÎ·Òë¸üºÃÄØ£¿ |
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