{"id":80467,"date":"2019-02-21T00:00:50","date_gmt":"2019-02-26T08:03:18","guid":{"rendered":"http:\/\/www.05921.net\/index.php\/80467\/"},"modified":"2019-02-26T16:03:24","modified_gmt":"2019-02-26T08:03:24","slug":"a4190bb172","status":"publish","type":"post","link":"https:\/\/www.05921.net\/index.php\/80467\/","title":{"rendered":"\u300aICH Q3C\uff08R7\uff09\u6742\u8d28\uff1a\u6b8b\u7559\u6eb6\u5242\u7684\u6307\u5bfc\u539f\u5219\u300b\u4e2d\u6587\u5f81\u6c42\u610f\u89c1\u7a3f"},"content":{"rendered":"
\n

\u7eed20190120\u63a8\u9001\uff1a<\/span><\/p>\n

\u7b2c\u4e8c\u90e8\u5206\uff1a<\/span><\/strong><\/p>\n

\u6742\u8d28\uff1a\u6b8b\u7559\u6eb6\u5242\uff08\u4fee\u8ba2\uff09<\/span><\/strong><\/p>\n

\u56db\u6c22\u544b\u5583\u7684 PDE<\/span><\/strong><\/p>\n

ICH \u534f\u8c03\u4e09\u65b9\u6307\u5bfc\u539f\u5219<\/span><\/strong><\/p>\n

\u5728 2002 \u5e74 9 \u6708 12 \u65e5\u7684 ICH \u6307\u5bfc\u59d4\u5458\u4f1a\u4f1a\u8bae\u4e0a\u8fdb\u5165 ICH \u8fdb\u7a0b\u7b2c\u56db\u9636\u6bb5\uff0c\u5e76\u5728 2005 \u5e74<\/span><\/p>\n

11 \u6708\u7eb3\u5165\u6838\u5fc3\u6307\u5bfc\u539f\u5219\uff0c\u5efa\u8bae ICH \u7684\u4e09\u65b9\u76d1\u7ba1\u673a\u6784\u91c7\u7eb3\u8be5\u6307\u5bfc\u539f\u5219<\/span><\/p>\n


<\/span><\/p>\n

      ICH Q3C \u6307\u5bfc\u539f\u5219\u5728 1997 \u5e74 12 \u6708\u8fdb\u5165\u7b2c 5 \u9636\u6bb5\u3002\u4e13\u5bb6\u5de5\u4f5c\u7ec4\uff08EWG\uff09\u7684\u6210\u5458\u8fbe<\/span>\u6210\u4e00\u81f4\u610f\u89c1\uff1a\u5982\u679c\u6709\u53ef\u9760\u7684\u548c\u66f4\u76f8\u5173\u7684\u6bd2\u7406\u8d44\u6599\u4f5c\u4e3a\u53c2\u8003\uff0c\u53ef\u5bf9\u6bcf\u65e5\u5141\u8bb8\u66b4\u9732\u91cf\uff08PDE\uff09<\/span>\u8fdb\u884c\u4fee\u8ba2\u30021999 \u5e74\u5f62\u6210\u4e86\u4fee\u8ba2\u534f\u8bae\u5e76\u7ec4\u5efa\u4e86\u4fee\u8ba2\u4e13\u5bb6\u5de5\u4f5c\u7ec4\u3002\u8be5\u534f\u8bae\u5141\u8bb8\u5bf9\u5404\u79cd\u6eb6\u5242<\/span>\u7684 PDE \u8fdb\u884c\u518d\u5ba1\u8bae\uff0c\u5e76\u5141\u8bb8\u5bf9\u73b0\u6709\u6307\u5bfc\u539f\u5219\u548c PDE \u6570\u503c\u8fdb\u884c\u5fae\u5c0f\u53d8\u66f4\u3002\u6b64\u5916\uff0c\u534f\u8bae\u8fd8<\/span>\u5141\u8bb8\u57fa\u4e8e\u8db3\u591f\u7684\u6bd2\u6027\u8d44\u6599\u589e\u52a0\u65b0\u7684\u6eb6\u5242\u53ca PDE \u6570\u636e\u3002<\/span><\/p>\n

      \u53bb\u5e74\u5e95\u548c\u4eca\u5e74\u521d\uff0cEWG \u5ba1\u67e5\u4e86\u6eb6\u5242\u56db\u6c22\u544b\u5583\uff08THF\uff09\u7684\u65b0\u6bd2\u6027\u6570\u636e\u3002\u7efc\u8ff0\u4e2d\u7684\u6570<\/span>\u636e\u662f\u7f8e\u56fd\u56fd\u5bb6\u6bd2\u7406\u5b66\u9879\u76ee\uff08NTP\uff09\u5df2\u53d1\u8868\u7684\u4fe1\u606f\uff0c\u5305\u62ec\u51e0\u9879\u81f4\u7a81\u53d8\u8bd5\u9a8c\u548c 2 \u4e2a\u556e\u9f7f\u7c7b\u52a8<\/span>\u7269\u5438\u5165\u7ed9\u836f\u7684\u81f4\u764c\u8bd5\u9a8c\u5f97\u5230\u7684\u6570\u636e\u3002\u6570\u636e\u5df2\u53d1\u7ed9 EWG \u7684\u6210\u5458\u8fdb\u884c\u5206\u6790\u3002<\/span><\/p>\n

<\/mpcpc><\/span><\/p>\n

\u52a8\u7269\u6bd2\u6027<\/span><\/strong><\/p>\n

       \u7528\u9f20\u4f24\u5bd2\u6c99\u95e8\u6c0f\u83cc\u3001\u4e2d\u56fd\u4ed3\u9f20\u5375\u5de2\u7ec6\u80de\u3001\u9ed1\u8179\u679c\u8747\u3001\u5c0f\u9f20\u9aa8\u9ad3\u7ec6\u80de\u548c\u5c0f\u9f20\u5916\u5468\u8840\u7ec6<\/span>\u80de\u8fdb\u884c\u4e86\u9057\u4f20\u6bd2\u7406\u7814\u7a76\u3002\u5206\u522b\u5728\u6dfb\u52a0\u548c\u4e0d\u6dfb\u52a0\u8bf1\u5bfc\u7684 S9 \u809d\u836f\u9176\u5916\u6e90\u6027\u4ee3\u8c22\u6fc0\u6d3b\u7269\u7684\u60c5<\/span>\u51b5\u4e0b\u8fdb\u884c\u4e86\u4f53\u5916\u8bd5\u9a8c\u3002\u9664\u4e86\u96c4\u6027\u5c0f\u9f20\u7ea2\u7ec6\u80de\u4e0e\u57fa\u7ebf\u76f8\u6bd4\u7565\u5fae\u5c0f\u5e45\u589e\u52a0\u5916\uff0c\u9057\u4f20\u6bd2\u7406\u7814\u7a76<\/span>\u4e2d\u672a\u89c1\u5176\u4ed6\u9633\u6027\u53cd\u5e94\u3002<\/span><\/p>\n

      \u5206\u522b\u5c06 50 \u53ea\u96cc\u6027\u548c 50 \u53ea\u96c4\u6027\u5927\u9f20\u4ee5\u5438\u5165\u9014\u5f84\u66b4\u9732\u4e8e 0\u3001200\u3001600\u30011800 ppm \u6d53\u5ea6<\/span>\u7684\u56db\u6c22\u544b\u5583\uff0c\u4e3a\u671f 105 \u5468\uff0c\u6bcf\u5468 5 \u5929\uff0c\u6bcf\u5929 6 \u5c0f\u65f6\u3002\u540c\u6cd5\u5904\u7406 50 \u53ea\u96cc\u6027\u548c 50 \u53ea\u96c4\u6027\u5c0f<\/span>\u9f20\u3002\u5728\u8bd5\u9a8c\u6761\u4ef6\u4e0b\uff0c\u5bf9\u4e8e<\/span>\u96c4\u6027\u5927\u9f20\uff0cTHF \u6709\u4e00\u4e9b\u81f4\u764c\u8ff9\u8c61\uff0c\u8868\u73b0\u4e3a\u80be\u7624\u6216\/\u548c\u80be\u764c\u7684\u53d1\u751f\u7387\u589e\u52a0\u3002\u5bf9\u4e8e\u96cc\u6027\u5c0f\u9f20\uff0cTHF \u6709\u660e\u663e\u7684<\/span>\u81f4\u764c\u6d3b\u6027\uff0c\u8868\u73b0\u4e3a\u809d\u7ec6\u80de\u7624\u548c\u809d\u7ec6\u80de\u764c\u53d1\u751f<\/span>\u7387\u589e\u52a0\u3002\u5bf9\u4e8e\u96cc\u6027\u5927\u9f20\u548c\u96c4\u6027\u5c0f\u9f20\uff0c\u672a\u53d1\u73b0 THF \u6709\u81f4\u764c\u8ff9\u8c61\u3002<\/span>\u7528 THF \u5728\u6700\u654f\u611f\u79cd\u5c5e\u4e2d\u7684\u6700\u4f4e\u66b4\u9732\u91cf\uff0c\u5373\u96c4\u6027\u5927\u9f20 200 ppm \u6d53\u5ea6\u6765\u8ba1\u7b97 PDE\u3002<\/span><\/p>\n

\"\u300aICH<\/p>\n

\"\u300aICH<\/p>\n

\u7ed3\u8bba\uff1a<\/span><\/strong><\/p>\n

\u8be5\u6eb6\u5242\uff08THF\uff09\u539f PDE \u503c\u4e3a\u5927\u4e8e 50 mg\/\u5929\uff08121 mg\/\u5929\uff09\uff0c\u5c5e\u4e8e 3 \u7c7b\u3002\u57fa\u4e8e\u6162\u6027\u6bd2<\/span>\u6027\/\u81f4\u764c\u6027\u6570\u636e\uff0c\u65b0\u7b97\u51fa\u7684\u56db\u6c22\u544b\u5583 PDE \u662f 7.2 mg\/\u5929\uff0c\u56e0\u6b64\uff0c\u5efa\u8bae\u5c06\u56db\u6c22\u544b\u5583\u5f52\u5230 ICH<\/span>\u300a\u6742\u8d28\uff1a\u6b8b\u7559\u6eb6\u5242\u7684\u6307\u5bfc\u539f\u5219\u300b\u8868 2 \u7684 2 \u7c7b\u30022 \u7c7b\u6eb6\u5242\u5305\u62ec\u975e\u9057\u4f20\u6bd2\u6027\u81f4\u764c\u7269\u7684\u6eb6\u5242\uff0c<\/span>\u8bd5\u9a8c\u8bc1\u660e THF \u5bf9\u556e\u9f7f\u7c7b\u52a8\u7269\u4e3a\u975e\u9057\u4f20\u6bd2\u6027\u81f4\u764c\u7269\uff0c\u56e0\u6b64\u5c06\u5176\u5206\u4e3a 2 \u7c7b\u662f\u5408\u9002\u7684\u3002<\/span><\/p>\n

<\/mpcpc><\/p>\n

\u7b2c\u4e09\u90e8\u5206\uff1a<\/span><\/strong><\/p>\n

\u6742\u8d28\uff1a\u6b8b\u7559\u6eb6\u5242\uff08\u4fee\u8ba2\uff09<\/span><\/strong><\/p>\n

N-\u7532\u57fa\u5421\u54af\u70f7\u916e\uff08NMP\uff09\u7684 PDE<\/span><\/strong><\/p>\n

ICH \u534f\u8c03\u4e09\u65b9\u6307\u5bfc\u539f\u5219<\/span><\/strong><\/p>\n


<\/span><\/p>\n

\u5728 2002 \u5e74 9 \u6708 12 \u65e5\u7684 ICH \u6307\u5bfc\u59d4\u5458\u4f1a\u4f1a\u8bae\u4e0a\u8fdb\u5165 ICH \u8fdb\u7a0b\u7b2c\u56db\u9636\u6bb5\uff0c\u5e76\u5728 2005 \u5e7411 \u6708\u7eb3\u5165\u6838\u5fc3\u6307\u5bfc\u539f\u5219\uff0c\u5efa\u8bae ICH \u7684\u4e09\u65b9\u76d1\u7ba1\u673a\u6784\u91c7\u7eb3\u8be5\u6307\u5bfc\u539f\u5219<\/span><\/p>\n

\uff082002 \u5e74 10 \u6708 28 \u65e5\u6307\u51fa\u4e86\u7b2c\u4e00\u4e2a\u8ba1\u7b97\u516c\u5f0f\u6709 2 \u9879\u6587\u5b57\u9519\u8bef – \u672c\u7248\u672c\u4e2d\u5df2\u66f4\u6b63\uff09<\/span><\/p>\n


<\/span><\/p>\n

       ICH Q3C \u6307\u5bfc\u539f\u5219\u5728 1997 \u5e74 12 \u6708\u8fdb\u5165\u7b2c 5 \u9636\u6bb5\u3002\u4e13\u5bb6\u5de5\u4f5c\u7ec4\uff08EWG\uff09\u7684\u6210\u5458\u8fbe\u6210\u4e00\u81f4\u610f\u89c1\uff1a\u5982\u679c\u6709\u53ef\u9760\u7684\u548c\u66f4\u76f8\u5173\u7684\u6bd2\u7406\u8d44\u6599\u4f5c\u4e3a\u53c2\u8003\uff0c\u53ef\u5bf9\u6bcf\u65e5\u5141\u8bb8\u66b4\u9732\u91cf\uff08PDE\uff09\u8fdb\u884c\u4fee\u8ba2\u30021999 \u5e74\u5f62\u6210\u4e86\u4fee\u8ba2\u534f\u8bae\u5e76\u7ec4\u5efa\u4e86\u4fee\u8ba2\u4e13\u5bb6\u5de5\u4f5c\u7ec4\u3002\u8be5\u534f\u8bae\u5141\u8bb8\u5bf9\u5404\u79cd\u6eb6\u5242\u7684 PDE \u8fdb\u884c\u518d\u5ba1\u8bae\uff0c\u5e76\u5141\u8bb8\u5bf9\u73b0\u6709\u6307\u5bfc\u539f\u5219\u548c PDE \u6570\u503c\u8fdb\u884c\u5fae\u5c0f\u53d8\u66f4\u3002\u6b64\u5916\uff0c\u534f\u8bae\u8fd8\u5141\u8bb8\u57fa\u4e8e\u8db3\u591f\u7684\u6bd2\u6027\u8d44\u6599\u589e\u52a0\u65b0\u7684\u6eb6\u5242\u53ca PDE \u6570\u636e\u3002<\/span><\/p>\n

      \u4e13\u5bb6\u5de5\u4f5c\u7ec4\u5728\u53bb\u5e74\u5e74\u5e95\u6536\u5230\u4e86\u6eb6\u5242 N-\u7532\u57fa\u5421\u54af\u70f7\u916e\u7684\u65b0\u6bd2\u6027\u6570\u636e\u3002\u6b64\u5185\u5bb9\u5df2\u7531NMP \u4ea7\u4e1a\u96c6\u56e2\u63d0\u4ea4\u7ed9 FDA\u3002\u8fd9\u662f\u7531 E.I. Dupont de Nemours & Co.\u8fdb\u884c\u7684\u4e00\u9879\u4e3a\u671f 2 \u5e74\u7684\u5927\u9f20\u957f\u671f\u5582\u98df\u5b9e\u9a8c\uff08\u672a\u516c\u5f00\u53d1\u8868\uff09\u3002\u6570\u636e\u5df2\u53d1\u7ed9 EWG \u7684\u6210\u5458\u8fdb\u884c\u5206\u6790\u3002\u5728\u5f53\u65f6\u770b\u6765\uff0c\u6570\u636e\u8db3\u4ee5\u5411\u6307\u5bfc\u59d4\u5458\u4f1a\u5efa\u8bae\u66f4\u6539 NMP \u6bd2\u6027\u7c7b\u522b\u3002\u5728\u4e0a\u6b21 ICH \u4f1a\u8bae\u4e0a\uff082000 \u5e74 2 \u6708 28 \u65e5\u81f3 3 \u6708 2 \u65e5\uff09\uff0c\u4f5c\u8005\u5411\u6307\u5bfc\u59d4\u5458\u4f1a\u6c47\u62a5\u4e86 EWG \u5206\u6790\u7684\u7ed3\u679c\u53ca\u8fbe\u6210\u7684\u5171\u8bc6\u3002\u8be5\u5171\u8bc6\u662f\u5c06NMP \u4ece\u7b2c 2 \u7c7b\u6eb6\u5242\uff08PDE \u4e3a 48.4 mg\/\u5929\uff09\u6539\u4e3a\u7b2c 3 \u7c7b\u6eb6\u5242\uff08PDE \u4e3a 207 mg\/\u5929\uff09\u3002\u4f46\u4e0d\u4e45\uff0cEWG \u7684\u6210\u5458\u53c8\u63d0\u4f9b\u4e86\u5176\u4ed6\u610f\u89c1\u548c\u6570\u636e\uff0c\u7531\u6b64\u53ef\u786e\u5b9a\u66f4\u4f4e\u7684 PDE\u3002\u4ee5\u4e0b\u6bb5\u843d\u662f\u5bf9\u7528\u4e8e\u8ba1\u7b97\u65b0 PDE \u7684\u5408\u9002\u800c\u4e14\u66f4\u7075\u654f\u7684\u7814\u7a76\u8fdb\u884c\u7684\u5206\u6790\u3002<\/span><\/p>\n

\u52a8\u7269\u6bd2\u6027<\/span><\/p>\n

        \u4ee5 \u4e0b \u8bba \u6587 \u7528 \u4e8e \u8ba1 \u7b97 NMP \u7684 PDE \uff1a \u201cEffects Of Prenatal Exposure To <\/span>N-Methylpyrrolidone On Postnatal Development And Behaviour In Rats\u201d, Hass U. et al., <\/span>Neurotoxicol. Teratol.: 1994, 16, (3), 241-249.<\/span><\/p>\n

       \u53d6\u598a\u5a20\u7684 Wistar \u5927\u9f20\uff0c\u5728\u5b55\u671f\u7b2c 7\uff5e20 \u5929\u901a\u8fc7\u5438\u5165\u9014\u5f84\u66b4\u9732\u4e8e 150 ppm NMP\uff0c6\u5c0f\u65f6\/\u5929\uff0c\u7136\u540e\u8ba9\u5176\u4ea7\u4ed4\u3002\u7ed3\u679c\u672a\u68c0\u6d4b\u5230\u6bcd\u4f53\u6bd2\u6027\uff0c\u4ea7\u4ed4\u6570\u4e5f\u672a\u53d7\u7ed9\u836f\u5f71\u54cd\u3002\u672a\u89c2\u5bdf\u5230\u673a\u4f53\u5f02\u5e38\u3002\u51fa\u751f\u540e 5 \u5468\u5185\u5e7c\u4ed4\u4f53\u91cd\u4e0b\u964d\uff08\u5dee\u5f02\u6709\u7edf\u8ba1\u5b66\u610f\u4e49\uff09\u3002\u5e7c\u4ed4\u65ad\u4e73\u524d\u7684\u751f\u957f\u53d1\u80b2\u53d7\u5230\u5f71\u54cd\uff0c\u8868\u73b0\u4e3a\u89e3\u51b3\u56f0\u96be\u4efb\u52a1\u7684\u9ad8\u7ea7\u8ba4\u77e5\u80fd\u529b\u53d7\u635f\u3002\u4e2d\u67a2\u795e\u7ecf\u7cfb\u7edf\u7684\u57fa\u7840\u529f\u80fd\u6b63\u5e38\uff0c\u5b66\u4e60\u7b80\u5355\u4efb\u52a1\u7684\u80fd\u529b\u672a\u53d7\u5f71\u54cd\u3002\u672a\u786e\u7acb NOEL\u3002<\/span><\/p>\n

\"\u300aICH<\/p>\n

<\/span>
<\/p>\n

\"\u300aICH<\/p>\n

\u7ed3\u8bba\uff1a<\/span><\/strong><\/p>\n

       \u9009\u62e9\u8fd9\u9879\u7814\u7a76\u662f\u56e0\u4e3a\u53d1\u73b0\u4e86\u6bd2\u6027\u7ec8\u70b9\uff0c\u5373 NMP \u5bf9\u5b50\u5bab\u5185\u53d1\u80b2\u4e2d\u7684\u795e\u7ecf\u7cfb\u7edf\u7684\u529f\u80fd<\/span>\u6709\u5f71\u54cd\u3002\u8fd9\u662f\u6f5c\u5728\u7684\u4e25\u91cd\u6bd2\u6027\uff0c\u76ee\u524d\u4e0d\u77e5\u9053\u8fd9\u79cd\u5f71\u54cd\u662f\u6c38\u4e45\u7684\u8fd8\u662f\u53ef\u9006\u7684\u3002\u540c\u65f6\u4e5f\u4e0d\u80fd<\/span>\u786e\u5b9a\u8fd9\u79cd\u53d1\u80b2\u7684\u5ef6\u8fdf\u662f\u5426\u662f\u7531\u5e7c\u4ed4\u4f53\u91cd\u504f\u4f4e\u6240\u81f4\u3002\u7136\u800c\uff0c\u4e13\u5bb6\u5de5\u4f5c\u7ec4\u51b3\u5b9a\u5728\u5176\u89e3\u91ca\u548c\u5b89<\/span>\u5168\u6027\u51b3\u5b9a\u4e2d\u6301\u8c28\u614e\u6001\u5ea6\u3002<\/span><\/p>\n

       EWG \u6210\u5458\u5efa\u8bae\u5c06 NMP(N-\u7532\u57fa\u5421\u54af\u70f7\u916e\uff09\u4fdd\u7559\u4e3a ICH\u300a\u6742\u8d28\uff1a\u6b8b\u7559\u6eb6\u5242\u7684\u6307\u5bfc\u539f<\/span>\u5219\u300b\u8868 2 \u7684\u7b2c 2 \u7c7b\u6eb6\u5242\u3002\u8fd8\u4e5f\u5e94\u5ba3\u5e03\u8be5\u6eb6\u5242\u7684\u4e0a\u8ff0\u65b0 PDE \u548c\u9650\u5ea6\u3002\u7b2c 2 \u7c7b\u6eb6\u5242\u5305\u62ec\u6709<\/span>\u795e\u7ecf\u6bd2\u6027\u3001\u975e\u9057\u4f20\u6bd2\u6027\u81f4\u764c\u6027\u548c\u81f4\u7578\u6027\u7b49\u91cd\u5927\u6bd2\u6027\u7684\u6eb6\u5242\uff0c\u5176\u4f7f\u7528\u91cf\u5e94\u9650\u5236\u5728\u8868\u4e2d\u7684<\/span>PDE \u8303\u56f4\u5185\u3002<\/span><\/p>\n


<\/p>\n

\u7b2c\u56db\u90e8\u5206\uff1a<\/span><\/strong><\/p>\n

\u6742\u8d28\uff1a\u6b8b\u7559\u6eb6\u5242\uff08\u4fee\u8ba2\uff09<\/span><\/strong><\/p>\n

\u5f02\u4e19\u57fa\u82ef\u7684 PDE<\/span><\/strong><\/p>\n

ICH \u534f\u8c03\u4e09\u65b9\u6307\u5bfc\u539f\u5219<\/span><\/strong><\/p>\n


<\/span><\/p>\n

\u5df2\u8fdb\u5165 ICH \u8fdb\u7a0b\u7b2c\u56db\u9636\u6bb5\uff0c\u4e8e 2011 \u5e74 2 \u6708 4 \u65e5\u7eb3\u5165\u4e86\u6838\u5fc3\u6307\u5bfc\u539f\u5219\uff0c\u5e76\u5efa\u8bae ICH \u7684\u4e09<\/span><\/p>\n

\u65b9\u76d1\u7ba1\u673a\u6784\u91c7\u7eb3\u8be5\u6307\u5bfc\u539f\u5219<\/span><\/p>\n


<\/span><\/p>\n

\u5f15\u8a00<\/span><\/strong><\/p>\n

       \u5f02\u4e19\u57fa\u82ef[\u522b\u540d\uff1aCumol\uff1bisopropylbenzene\uff1bisopropylbenzol\uff1b(1-methyl\/ethyl)benzene\uff1b<\/span>2-phenylpropane]\u6536\u5f55\u5728 ICH \u6307\u5bfc\u539f\u5219 Q3C \u4e2d\uff0c\u5c5e\u4e8e 3 \u7c7b\u6eb6\u5242\uff0c\u5373\u4f4e\u6bd2\u6027\u7684\u6eb6\u5242\u3002\u5728 1996<\/span>\u5e74 11 \u6708\u7b2c\u4e8c\u9636\u6bb5 ICH Q3C \u6307\u5bfc\u539f\u5219\u7b2c 2 \u9636\u6bb5\u7b7e\u7f72\u65f6\u4e13\u5bb6\u5de5\u4f5c\u7ec4\u7528\u4e8e\u5efa\u7acb\u5f02\u4e19\u57fa\u82ef\u7684\u5141<\/span>\u65e5\u66b4\u9732\u91cf\uff08PDE\uff09\u503c\u7684\u6bd2\u6027\u6570\u636e\u6458\u8981\u53d1\u8868\u4e8e Connelly \u7b49\u4eba\u7684\u6587\u7ae0\u4e2d\uff081\uff09\u3002<\/span><\/p>\n

        \u6839\u636e EWG \u7684\u8fd9\u4efd\u62a5\u544a\uff0c\u672a\u5f97\u5230\u5f02\u4e19\u57fa\u82ef\u81f4\u764c\u6027\u7814\u7a76\u7684\u6570\u636e\u3002\u81f3\u4e8e\u9057\u4f20\u6bd2\u6027\u6570\u636e\uff0c<\/span>\u5f02\u4e19\u57fa\u82ef\u5728 Ames \u548c\u917f\u9152\u9175\u6bcd\u8bd5\u9a8c\u4e2d\u5448\u9634\u6027\uff0c\u5728\u4f53\u5916 UDS \u548c\u7528\u5c0f\u9f20\u80da\u80ce\u7ec6\u80de\u8fdb\u884c\u7684\u7ec6<\/span>\u80de\u8f6c\u5316\u8bd5\u9a8c\u4e2d\u5448\u9633\u6027\u3002PDE \u503c\u7684\u8ba1\u7b97\u57fa\u4e8e 1956 \u5e74\u53d1\u8868\u7684\u5927\u9f20\u6bd2\u6027\u7814\u7a76\u3002\u7ba1\u9972\u7ed9\u4e88\u96cc\u6027<\/span>Wistar \u5927\u9f20\u5f02\u4e19\u57fa\u82ef\uff0c\u5242\u91cf\u4e3a 154\u3001462 \u548c 769 mg\/kg\uff0c5 \u5929\/\u5468\uff0c\u4e3a\u671f 6 \u4e2a\u6708\u3002\u5728 2 \u4e2a\u8f83<\/span>\u9ad8\u5242\u91cf\u4e0b\u6ca1\u6709\u7ec4\u7ec7\u75c5\u7406\u5b66\u53d8\u5316\uff0c\u4f46\u80be\u810f\u91cd\u91cf\u7565\u6709\u589e\u52a0\uff0c\u8868\u660e NOEL \u4e3a 154 mg\/kg\u3002\u5f97\u51fa<\/span>\u7684\u7ed3\u8bba\u662f\u5f02\u4e19\u57fa\u82ef\u7684 PDE \u662f 55.0 mg\/\u5929\uff0c\u5373\u5f02\u4e19\u57fa\u82ef\u662f\u4f4e\u6bd2\u6027\u6eb6\u5242\uff0c\u5e94\u5217\u4e3a 3 \u7c7b\u3002\uff081\uff09<\/span>\u540c\u65f6\u5df2\u516c\u5e03\u65b0\u7684\u6bd2\u6027\u6570\u636e\uff0c\u5305\u62ec\u4e3a\u671f 2 \u5e74\u7684 NTP \u5438\u5165\u7814\u7a76\u7684\u7ed3\u679c\uff0c\u5176\u8868\u660e\u5f02\u4e19\u57fa<\/span>\u82ef\u5bf9\u556e\u9f7f\u7c7b\u52a8\u7269\u5177\u6709\u81f4\u764c\u4f5c\u7528\u3002\uff082\uff09\u56e0\u6b64\u6839\u636e 1999 \u5e74\u7684\u4fee\u8ba2\u534f\u8bae\uff0c\u542f\u52a8\u4e86\u5bf9\u5f02\u4e19\u57fa\u82ef<\/span>PDE \u503c\u7684\u91cd\u65b0\u8bc4\u4ef7\u3002\u4e3a\u4e86\u5236\u5b9a\u672c\u6587\u4ef6\u4e2d\u4fee\u8ba2\u7684 PDE \u503c\uff0c\u91c7\u7528\u4e86 Connelly \u7b49\u4eba\u7684\u6587\u732e\uff081\uff09<\/span>\u4e2d\u8be6\u8ff0\u7684\u6807\u51c6\u65b9\u6cd5\uff08\u6821\u6b63\u56e0\u5b50\u3001\u6d53\u5ea6\u4ece ppm \u6362\u7b97\u81f3 mg\/L\u3001\u751f\u7406\u7cfb\u6570\u503c\uff09\u3002<\/span><\/p>\n


<\/span><\/p>\n

\u9057\u4f20\u6bd2\u6027<\/span><\/strong><\/p>\n

\u5f53\u6dfb\u52a0\u548c\u4e0d\u6dfb\u52a0\u809d S9 \u6fc0\u6d3b\u9176\u8fdb\u884c\u8bd5\u9a8c\u65f6\uff0c\u5f02\u4e19\u57fa\u82ef\u5728\u9f20\u4f24\u5bd2\u6c99\u95e8\u6c0f\u83cc\u83cc\u682a TA97\u3001<\/span>TA98\u3001TA100 \u6216 TA1535 \u4e2d\u5747\u65e0\u81f4\u7a81\u53d8\u4f5c\u7528\u3002\u5bf9\u4e8e\u7ecf\u8179\u819c\u5185\u6ce8\u5c04\u5904\u7406\u7684\u96c4\u6027\u5927\u9f20\uff0c\u5f02<\/span>\u4e19\u57fa\u82ef\u8bf1\u5bfc\u9aa8\u9ad3\u5fae\u6838\u7ea2\u7ec6\u80de\u51fa\u73b0\u8f83\u5c0f\u4f46\u663e\u8457\u7684\u589e\u52a0\u3002\u76f8\u53cd\uff0c\u5bf9\u4e8e\u5438\u5165\u9014\u5f84\u66b4\u9732\u4e8e\u5f02\u4e19\u57fa<\/span>\u82ef\u957f\u8fbe 3 \u4e2a\u6708\u7684\u96c4\u6027\uff08\u9ad8\u8fbe 1000 ppm\uff09\u6216\u96cc\u6027\uff08\u9ad8\u8fbe 500 ppm\uff09\u5c0f\u9f20\uff0c\u672a\u89c1\u5916\u5468\u8840\u4e2d\u5fae<\/span>\u6838\u7ea2\u7ec6\u80de\u6570\u589e\u52a0\u3002\uff082\uff09<\/span><\/p>\n

p53 \u548c K-ras \u7a81\u53d8\u5206\u522b\u89c1\u4e8e\u66b4\u9732\u540e\u5c0f\u9f20\u80ba\u80bf\u7624\u4e2d\u7684 52 %\u548c 87 %\uff0c\u800c\u5bf9\u7167\u7ec4\u8be5\u6bd4\u4f8b<\/span>\u5206\u522b\u4e3a 0 %\u548c 14 %\u3002\u5728\u80ba\u80bf\u7624\u53d1\u73b0\u7684\u8fd9\u79cd\u7a81\u53d8\u6a21\u5f0f\u8868\u660e\uff0cDNA \u635f\u4f24\u548c\u57fa\u56e0\u7ec4\u4e0d\u7a33\u5b9a\u53ef<\/span>\u80fd\u662f\u5bfc\u81f4\u5c0f\u9f20\u80ba\u764c\u7684\u5f71\u54cd\u56e0\u7d20\u3002\uff083\uff09\u4f46\u603b\u4f53\u9057\u4f20\u6bd2\u6027\u5e76\u672a\u5145\u5206\u8bc1\u660e\u5f02\u4e19\u57fa\u82ef\u6216\u5176\u4ee3\u8c22<\/span>\u7269\u7684\u76f4\u63a5\u81f4\u7a81\u53d8\u4f5c\u7528\u65b9\u5f0f\u662f\u80bf\u7624\u53d1\u751f\u7684\u4e3b\u8981\u539f\u56e0\u3002\uff082\uff09<\/span><\/p>\n


<\/span><\/p>\n

\u81f4\u764c\u6027<\/span><\/strong><\/p>\n

F344 \u5927\u9f20\u4ee5\u5438\u5165\u9014\u5f84\u66b4\u9732\u5728\u5f02\u4e19\u57fa\u82ef\u6d53\u5ea6\u4e3a 250\u3001500 \u6216 1000 ppm \u7684\u7a7a\u6c14\u4e2d\uff0c6<\/span>\u5c0f\u65f6\/\u5929\uff0c5 \u5929\/\u5468\uff0c\u4e3a\u671f 2 \u5e74\u3002\u5728\u6240\u6709\u5242\u91cf\u6c34\u5e73\uff0c\u96c4\u6027\u52a8\u7269\u9f3b\u547c\u5438\u9053\u4e0a\u76ae\u817a\u7624\u3001\u80be\u5c0f\u7ba1<\/span>\u817a\u7624\u6216\u764c\uff08\u7ec4\u5408\uff09\u7684\u53d1\u751f\u7387\u5747\u589e\u52a0\u3002\u5728\u6240\u6709\u5242\u91cf\u6c34\u5e73\u4e0b\uff0c\u96cc\u6027\u52a8\u7269\u9f3b\u547c\u5438\u9053\u4e0a\u76ae\u817a\u7624\u53d1<\/span>\u75c5\u7387\u589e\u52a0\u3002\uff082\uff09<\/span><\/p>\n

\u5f02\u4e19\u57fa\u82ef\u7684\u5206\u5b50\u91cf\uff1a120.19<\/span><\/p>\n


<\/span><\/p>\n

\"\u300aICH<\/p>\n

F1 = 5<\/span>\uff0c\u4ece\u5927\u9f20\u5916\u63a8\u5230\u4eba<\/span><\/p>\n

F2 = 10\uff0c\u8003\u8651\u4eba\u7684\u4e2a\u4f53\u5dee\u5f02<\/span><\/p>\n

F3 = 1\uff0c\u56e0\u4e3a\u6cbb\u7597\u7684\u6301\u7eed\u65f6\u95f4\u8f83\u957f\uff08105 \u5468\uff09<\/span><\/p>\n

F4 = 10\uff0c\u56e0\u4e3a\u6709\u81f4\u764c\u4f5c\u7528\u62a5\u9053<\/span><\/p>\n

F5 = 10\uff0c\u56e0\u4e3a\u672a\u5236\u5b9a NOEL<\/span><\/p>\n

\"\u300aICH<\/p>\n

B6C3F1 \u5c0f\u9f20\u4ee5\u5438\u5165\u9014\u5f84\u66b4\u9732\u5728\u5f02\u4e19\u57fa\u82ef\u6d53\u5ea6\u4e3a 125\u3001250 \u6216 500 ppm\uff08\u96cc\u6027\uff09\u6216<\/span>250\u3001500 \u6216 1000 ppm\uff08\u96c4\u6027\uff09\u7684\u7a7a\u6c14\u4e2d\uff0c6 \u5c0f\u65f6\/\u5929\uff0c5 \u5929\/\u5468\uff0c\u4e3a\u671f 2 \u5e74\u3002\u5728\u6240\u6709\u5242\u91cf<\/span>\u6c34\u5e73\uff0c\u96c4\u6027\u548c\u96cc\u6027\u7684\u80ba\u6ce1\/\u652f\u6c14\u7ba1\u80bf\u7624\u53d1\u751f\u7387\u5747\u589e\u52a0\u3002\u7ed3\u679c\u663e\u793a\uff0c\u5728\u96cc\u6027\u5c0f\u9f20\u4e2d\uff0c\u809d\u7ec6<\/span>\u80de\u817a\u7624\u6216\u764c\uff08\u7ec4\u5408\uff09\u7684\u53d1\u751f\u7387\u5448\u5242\u91cf\u76f8\u5173\u6027\u589e\u52a0\u3002\uff082\uff09<\/span><\/p>\n

LOEL \u4e3a 125 ppm\uff08\u96cc\u6027\u5c0f\u9f20\uff09<\/span><\/p>\n

\"\u300aICH<\/p>\n

\"\u300aICH<\/p>\n

F1 = 12\uff0c\u4ece\u5c0f\u9f20\u5916\u63a8\u5230\u4eba<\/span><\/p>\n

F2 = 10\uff0c\u8003\u8651<\/span>\u4eba\u7684\u4e2a\u4f53\u5dee\u5f02<\/span><\/p>\n

F3 = 1\uff0c\u56e0\u4e3a\u6cbb\u7597\u7684\u6301\u7eed\u65f6\u95f4\u8f83\u957f\uff08105 \u5468\uff09<\/span><\/p>\n

F4 = 10\uff0c\u56e0\u4e3a\u6709\u81f4\u764c<\/span>\u4f5c\u7528\u62a5\u9053<\/span><\/p>\n

F5 = 10\uff0c\u56e0\u4e3a\u672a\u5236\u5b9a NOEL<\/span><\/p>\n

\"\u300aICH<\/p>\n

\u7ed3\u8bba<\/span><\/strong><\/p>\n

\u556e\u9f7f\u7c7b\u52a8\u7269\u7814\u7a76\u4e2d\u7684\u4e3b\u8981\u81f4\u764c\u4f5c\u7528\u4e0e\u5438\u5165\u7ed9\u836f\u9014\u5f84\uff08\u547c\u5438\u9053\u548c\u55c5\u89c9\u7684\u7ec4\u7ec7\uff09\u76f8\u5173\uff0c<\/span>\u56e0\u6b64\u53ef\u80fd\u4e0e\u7ecf\u53e3\uff08\u4e3b\u8981\uff09\u7ed9\u836f\u836f\u7269\u7684\u6b8b\u7559\u6eb6\u5242\u4e0d\u76f8\u5173\u3002\u7136\u800c\uff0c\u8fd8\u62a5\u9053\u4e86\u5168\u8eab\u81f4\u764c\u53cd\u5e94\uff08\u96c4<\/span>\u6027\u5927\u9f20\u7684\u80be\u810f\uff0c\u96cc\u6027\u5c0f\u9f20\u7684\u809d\u810f\uff09\uff0c\u56e0\u6b64\u8ba4\u4e3a\u9002\u5408\u7528 NTP \u7814\u7a76\u6570\u636e\u6765\u8ba1\u7b97 PDE\u3002<\/span>\u5f02\u4e19\u57fa\u82ef\u539f PDE \u5927\u4e8e 50 mg\/\u5929\uff0855 mg\/\u5929\uff09\uff0c\u5c5e\u4e8e 3 \u7c7b\u3002\u57fa\u4e8e\u81f4\u764c\u6027\u6570\u636e\uff0c\u65b0\u7b97<\/span>\u51fa\u7684\u5f02\u4e19\u57fa\u82ef PDE \u662f 0.7 mg\/\u5929\uff0c\u56e0\u6b64\uff0c\u5efa\u8bae\u5c06\u5f02\u4e19\u57fa\u82ef\u5f52\u5230 ICH\u300a\u6742\u8d28\uff1a\u6b8b\u7559\u6eb6\u5242\u7684<\/span>\u6307\u5bfc\u539f\u5219\u300b\u8868 2 \u7684 2 \u7c7b\u3002<\/span><\/p>\n


<\/span><\/p>\n

\"\u300aICH<\/p>\n


<\/span><\/p>\n

\u7b2c\u4e94\u90e8\u5206\uff1a<\/span><\/strong><\/p>\n

\u6742\u8d28\uff1a\u6b8b\u7559\u6eb6\u5242\uff08\u4fee\u8ba2\uff09<\/span><\/strong><\/p>\n

\u4e09\u4e59\u80fa\u7684 PDE \u548c\u7532\u57fa\u5f02\u4e01\u57fa\u916e\u7684 PDE<\/span><\/strong><\/p>\n

ICH \u534f\u8c03\u7684\u6307\u5bfc\u539f\u5219<\/span><\/strong><\/p>\n

\u5df2\u8fbe\u5230 ICH \u8fdb\u7a0b\u7b2c\u56db\u9636\u6bb5\uff0c\u4e8e 2016 \u5e74 11 \u6708 9 \u65e5\u7eb3\u5165\u4e86\u6838\u5fc3\u6307\u5bfc\u539f\u5219\uff0c\u5e76\u5efa\u8bae ICH \u76d1<\/span><\/p>\n

\u7ba1\u65b9\u91c7\u7eb3\u8be5\u6307\u5bfc\u539f\u5219<\/span><\/p>\n

\u4e09\u4e59\u80fa<\/span><\/strong><\/p>\n

\u5f15\u8a00<\/span><\/strong><\/p>\n

\u4e09\u4e59\u80fa\uff08TEA\uff09\u5728\u5316\u5b66\u5408\u6210\u4e2d\u7528\u4f5c\u50ac\u5316\u6eb6\u5242\uff081\u30012\uff09\u3002\u5176\u4e3a\u65e0\u8272\u6db2\u4f53\uff0c\u53ef\u6eb6\u4e8e\u6c34\u3001<\/span>\u4e59\u9187\u3001\u56db\u6c2f\u5316\u78b3\u3001\u4e59\u919a\uff0c\u6781\u6613\u6eb6\u4e8e\u4e19\u916e\u3001\u82ef\u548c\u6c2f\u4eff\u3002TEA \u5728 20 \u00b0C \u4e0b\u7684\u84b8\u6c7d\u538b\u4e3a 54 mmHg\uff0c<\/span>\u636e\u62a5\u9053\uff0c\u5176\u5bf9\u80ba\u548c\u9f3b\u9053\u6709\u523a\u6fc0\u6027\uff0c\u6709\u5f88\u5f3a\u7684\u6c28\u6c14\u5473\uff082\u30013\uff09\u3002<\/span>\u4eba\u7c7b\u7814\u7a76\u7684\u6570\u636e\u663e\u793a\uff0cTEA \u6613\u7ecf\u53e3\u670d\u6216\u5438\u5165\u9014\u5f84\u5438\u6536\uff0c\u5e76\u8fc5\u901f\u6392\u51fa\uff0c\u4e3b\u8981\u4ee5\u539f\u578b<\/span>\u5316\u5408\u7269\u548c\/\u6216\u5176 N-\u6c27\u5316\u7269\u5f62\u5f0f\u5728\u5c3f\u4e2d\u6392\u51fa\uff084\uff5e6\uff09\u3002<\/span>\u5728\u4eba\u7c7b\u5fd7\u613f\u8005\u7684\u7814\u7a76\u4e2d\uff0c\u66b4\u9732\u91cf\u5927\u4e8e 2.5 ppm\uff0810 mg\/m3\uff09\u65f6\u5c40\u90e8\u8bf1\u5bfc\u7684\u89d2\u819c\u80bf\u80c0<\/span>\u9020\u6210\u4e86\u4e00\u8fc7\u6027\u89c6\u89c9\u5e72\u6270\uff084\u30017\uff09\uff1b\u5728\u51fa\u73b0\u89d2\u819c\u5f71\u54cd\u7684\u66b4\u9732\u6c34\u5e73\u672a\u68c0\u51fa\u5168\u8eab\u53cd\u5e94\u3002\u6c14\u5473\u9608<\/span>\u503c\u4ecb\u4e8e 0.0022 \u81f3 0.48 mg\/m3\uff088\uff5e10\uff09\u3002<\/span><\/p>\n

\u9057\u4f20\u6bd2\u6027<\/span><\/strong><\/p>\n

\u5728 Ames \u8bd5\u9a8c\u4e2d\uff0c\u5728\u6709\u6216\u65e0\u4ee3\u8c22\u6d3b\u5316\u7684\u6761\u4ef6\u4e0b\uff0cTEA \u672a\u8bf1\u5bfc\u6807\u51c6\u6c99\u95e8\u6c0f\u83cc\u83cc\u682a\u7a81\u53d8<\/span>\uff0811\uff09\u3002\u5728\u6709\u6216\u65e0\u4ee3\u8c22\u6d3b\u5316\u7684\u6761\u4ef6\u4e0b\uff0cTEA \u672a\u8bf1\u5bfc\u4e2d\u56fd\u4ed3\u9f20\u5375\u5de2\u7ec6\u80de\u53d1\u751f\u59d0\u59b9\u67d3\u8272\u5355<\/span>\u4f53\u4ea4\u6362\uff0812\uff09\u3002\u5728\u4f53\u5185\u7814\u7a76\u4e2d\uff0c\u5927\u9f20\u66b4\u9732\u4e8e 1 mg\/m3\uff080.25 ppm\uff09\u548c 10 mg\/m3\uff082.5 ppm\uff09<\/span>\u7684 TEA\uff0c\u8fde\u7eed\u5438\u5165 30 \u5929\u6216 90 \u5929\uff0c\u7ed3\u679c TEA \u8bf1\u5bfc\u4e86\u975e\u6574\u500d\u4f53\uff0c\u4f46\u5bf9\u9aa8\u9ad3\u6ca1\u6709\u81f4\u7578\u4f5c\u7528<\/span>\uff0813\uff09\u3002\u53ea\u5728\u4f4e\u5242\u91cf\u548c\u65e9\u671f\u65f6\u95f4\u70b9\u68c0\u51fa\u4e86\u5f31\u7684\u7ec6\u80de\u9057\u4f20\u6bd2\u6027\uff1b\u7531\u4e8e\u7814\u7a76\u5b58\u5728\u4e0d\u8db3\u4e4b\u5904\uff0c<\/span>\u8be5\u7ed3\u679c\u7684\u610f\u4e49\u975e\u5e38\u503c\u5f97\u6000\u7591\u3002\u603b\u4f53\u800c\u8a00\uff0c\u73b0\u6709\u6570\u636e\u672a\u8bc1\u660e TEA \u76f8\u5173\u7684\u6f5c\u5728\u9057\u4f20\u6bd2\u6027\u3002<\/span>\u81f4\u764c\u6027<\/span><\/strong><\/p>\n

\u65e0\u6570\u636e\u53ef\u7528\u3002<\/span><\/p>\n

\u751f\u6b96\u6bd2\u6027<\/span><\/strong><\/p>\n

\u6ca1\u6709\u53ef\u9760\u7684\u751f\u6b96\u6bd2\u6027\u4fe1\u606f\u53ef\u7528\u3002\u5728\u7f8e\u56fd\u73af\u5883\u4fdd\u62a4\u5c40\uff08US EPA\uff09\u7efc\u5408\u98ce\u9669\u4fe1\u606f\u7cfb\u7edf<\/span>\u8bc4\u4f30\u5ba1\u67e5\uff0814\uff09\u4e2d\u5f15\u7528\u4e86\u4e09\u4ee3\u751f\u6b96\u7814\u7a76\uff0c\u5176\u4e2d\uff0c\u4ee5 0\u30012 \u6216 200 ppm\uff08\u7ea6 0\u30010.14 \u6216 14 mg\/kg\/<\/span>\u5929\uff09\u7684\u5242\u91cf\uff08TEA \u6eb6\u4e8e\u996e\u7528\u6c34\uff09\u5bf9\u5927\u9f20\uff0810 \u53ea\/\u6027\u522b\/\u7ec4\uff09\u7ed9\u836f\u3002\u7531\u4e8e\u672a\u89c2\u5bdf\u5230\u75c7\u72b6\uff0c\u5728<\/span>\u7b2c\u4e09\u4ee3\u5c06\u9ad8\u5242\u91cf\u63d0\u9ad8\u5230\u4e86 500 ppm\u3002\u7ecf 2 \u4ee3\u7ed9\u836f\uff0c\u5728 200 ppm \u7684\u5242\u91cf\u4e0b\u672a\u53d1\u73b0\u660e\u663e\u4f5c\u7528\u3002<\/span>\u7136\u800c\uff0c\u7531\u4e8e\u6d4b\u5b9a\u7684\u7ec8\u70b9\u6709\u7f3a\u9677\uff0c\u7814\u7a76\u6570\u636e\u4e0d\u7528\u4e8e\u786e\u5b9a\u6bcf\u65e5\u5141\u8bb8\u66b4\u9732\u91cf\uff08PDE\uff09\u3002<\/span><\/p>\n

\u591a\u6b21\u7ed9\u836f\u6bd2\u6027<\/span><\/strong><\/p>\n

\u8ba4\u4e3a\u5728\u5927\u9f20\u4e2d\u8fdb\u884c\u7684\u4e9a\u6162\u6027\u5438\u5165\u7814\u7a76\uff08\u4e0e\u7ecf\u6d4e\u5408\u4f5c\u4e0e\u53d1\u5c55\u7ec4\u7ec7[OECD]\u8bd5\u9a8c\u6307\u5bfc\u539f\u5219 413 \u548c 452 \u76f8\u4f3c\uff09\u662f\u53d1\u8868\u7684\u7528\u4e8e\u8ba1\u7b97 PDE \u7684\u6700\u76f8\u5173\u52a8\u7269\u7814\u7a76\u3002F344 \u5927\u9f20\uff0850 \u53ea\/\u7ec4\/<\/span>\u6027\u522b\uff09\u7ecf\u5168\u8eab\u5438\u5165\u66b4\u9732\u4e8e 0\u300125 \u6216 247 ppm\uff080\u30010.10 \u6216 1.02 mg\/L\uff09\u7684 TEA\uff0c6 \u5c0f\u65f6\/<\/span>\u5929\uff0c5 \u5929\/\u5468\uff0c\u4e3a\u671f 28 \u5468\uff0815\uff09\u3002\u5728\u6240\u6709\u5242\u91cf\u7ec4\u4e2d\uff0c\u672a\u89c2\u5bdf\u5230\u6709\u7edf\u8ba1\u5b66\u663e\u8457\u6027\u7684\u6cbb\u7597\u76f8\u5173\u7684\u7cfb\u7edf\u6027\u5f71\u54cd\u3002\u867d\u7136\u68c0\u51fa\u96c4\u6027\u5927\u9f20\u7684\u4f53\u91cd\u51fa\u73b0\u7565\u5fae\u5242\u91cf\u76f8\u5173\u6027\u4e0b\u964d\uff0c\u4f46\u4f53\u91cd\u589e\u52a0\u65e0\u7edf\u8ba1\u5b66\u5f71\u54cd\u3002\u8fd9\u9879\u7814\u7a76\u7684\u672a\u89c2\u5bdf\u5230\u4f5c\u7528\u6c34\u5e73\uff08NOEL\uff09\u4e3a 247 ppm\u3002TEA \u7684\u5206\u5b50\u91cf\uff1a101.19 g\/mol<\/span><\/p>\n

NOEL 247 ppm\u3002<\/span><\/p>\n

\"\u300aICH<\/p>\n

F1 = 5\uff0c\u4ece\u5927\u9f20\u5916\u63a8\u5230\u4eba<\/span><\/p>\n

F2 = 10\uff0c\u8003\u8651\u4eba\u7684\u4e2a\u4f53\u5dee\u5f02<\/span><\/p>\n

F3 = 2\uff0c\u56e0\u4e3a\u6cbb\u7597\u7684\u6301\u7eed\u65f6\u95f4\u8f83\u957f\uff0828 \u5468\uff09<\/span><\/p>\n

F4 = 1\uff0c\u56e0\u4e3a\u672a\u89c2\u5bdf\u5230\u4e25\u91cd\u7684\u53cd\u5e94<\/span><\/p>\n

F5 = 1\uff0c\u56e0\u4e3a\u5236\u5b9a\u4e86 NOEL<\/span><\/p>\n

\"\u300aICH<\/p>\n

\u7531\u4e8e\u7814\u7a76\u5b58\u5728\u660e\u663e\u7684\u7f3a\u9677\uff0c\u5176\u4ed6\u53d1\u8868\u7684\u52a8\u7269\u6bd2\u6027\u6570\u636e\u4e0d\u7528\u4e8e\u786e\u5b9a PDE\u3002<\/span><\/p>\n

\u7ed3\u8bba<\/span><\/strong><\/p>\n

\u6839\u636e\u5927\u9f20\u4e9a\u6162\u6027\u5438\u5165\u7814\u7a76\u7684 NOEL\uff0c\u7b97\u51fa TEA \u7684 PDE \u662f 62.5 mg\/\u5929\u3002\u7531\u4e8e\u63d0\u51fa\u7684<\/span>PDE \u5927\u4e8e 50 mg\/\u5929\uff0c\u5efa\u8bae\u5c06 TEA \u5f52\u5230 ICH\u300a\u6742\u8d28\uff1a\u6b8b\u7559\u6eb6\u5242\u7684\u6307\u5bfc\u539f\u5219\u300b\u8868 3 \u7684 3 \u7c7b<\/span>\uff08\u201c\u4f4e\u6f5c\u5728\u6bd2\u6027\u7684\u6eb6\u5242\u201d\uff09\u3002<\/span><\/p>\n


<\/span><\/p>\n

\u53c2\u8003\u6587\u732e<\/p>\n

\"\u300aICH<\/p>\n

\"\u300aICH<\/p>\n

\"\u300aICH<\/p>\n

\"\u300aICH<\/p>\n


<\/p>\n

\u7532\u57fa\u5f02\u4e01\u57fa\u916e<\/span><\/strong><\/p>\n

\u5f15\u8a00<\/span><\/strong><\/p>\n

\u7532\u57fa\u5f02\u4e01\u57fa\u916e\uff08MIBK\uff09\u5728 1997 \u5e74\u7684 ICH Q3C \u6bcd\u6307\u5bfc\u539f\u5219\u4e2d\u5c5e\u4e8e 3 \u7c7b\u6eb6\u5242\uff0c\u5373\uff0c<\/span>\u57fa\u4e8e\u5f53\u65f6\u5f97\u5230\u7684\u6bd2\u6027\u6570\u636e\u8bc4\u4ef7\u7ed3\u679c\uff08MIBK \u7684\u6bcf\u65e5\u5141\u8bb8\u66b4\u9732\u91cf\uff08PDE\uff09\u503c\u4e3a 100 mg\/\u5929\uff09\uff0c<\/span>\u4e3a\u4f4e\u6bd2\u6027\u6eb6\u5242\uff081\uff09\u3002\u7531\u4e8e\u5f97\u5230\u4e86\u65b0\u7684\u6bd2\u6027\u6570\u636e\uff0c\u5305\u62ec\u6765\u81ea\u7f8e\u56fd\u56fd\u5bb6\u6bd2\u7406\u5b66\u8ba1\u5212\uff08NTP\uff09<\/span>\u6240\u5f97 2 \u5e74\u7684\u5927\u9f20\u548c\u5c0f\u9f20\u5438\u5165\u81f4\u764c\u4f5c\u7528\u7684\u7ed3\u679c\uff0c\u4ee5\u53ca\u5df2\u53d1\u8868\u7684\u6709\u5173\u751f\u6b96\u548c\u53d1\u80b2\u6bd2\u6027\u7684\u7814<\/span>\u7a76\uff0c\u4e13\u5bb6\u5de5\u4f5c\u7ec4\u91cd\u65b0\u8bc4\u4f30\u4e86 MIBK \u7684 PDE \u503c\u3002<\/span><\/p>\n

\u9057\u4f20\u6bd2\u6027<\/span><\/strong><\/p>\n

\u81ea\u4ece 1997 \u5e74\u8fdb\u884c\u4e0a\u6b21\u8bc4\u4f30\u4ee5\u6765\uff0c\u6ca1\u6709\u62a5\u9053\u5173\u4e8e\u9057\u4f20\u6bd2\u6027\u7684\u5176\u4ed6\u4fe1\u606f\u3002\u73b0\u6709\u6570\u636e\u8868<\/span>\u660e\uff0cMIBK \u6ca1\u6709\u9057\u4f20\u6bd2\u6027\u3002<\/span><\/p>\n

\u81f4\u764c\u6027<\/span><\/strong><\/p>\n

NTP \u5df2\u5728\u4e3a\u671f 2 \u5e74\u7684\u5927\u9f20\u548c\u5c0f\u9f20\u5438\u5165\u7814\u7a76\u4e2d\u5bf9 MIBK \u8fdb\u884c\u4e86\u7814\u7a76\u3002F344\/N \u5927\u9f20\u548c<\/span>B6C3F1 \u5c0f\u9f20\uff0850 \u53ea\/\u6027\u522b\/\u7ec4\uff09\u7ecf\u5438\u5165\u66b4\u9732\u4e8e\u6d53\u5ea6\u4e3a 0\u3001450\u3001900 \u6216 1800 ppm \u7684 MIBK\uff0c<\/span>\u6bcf\u5929 6 \u5c0f\u65f6\uff0c\u6bcf\u5468 5 \u5929\uff0c\u4e3a\u671f 2 \u5e74\u3002\u5728 1800 ppm \u7684\u6d53\u5ea6\u4e0b\uff0c\u96c4\u6027\u5927\u9f20\u7684\u5b58\u6d3b\u51cf\u5c11\uff084\uff09\u3002<\/span>\u5bf9\u4e8e 900 \u548c 1800 ppm \u6d53\u5ea6\u4e0b\u7684\u96c4\u6027\u5927\u9f20\u548c 1800 ppm \u6d53\u5ea6\u4e0b\u7684\u96cc\u6027\u5c0f\u9f20\uff0c\u5176\u4f53\u91cd\u6da8\u5e45\u4e0b<\/span>\u964d\u3002MIBK \u6bd2\u6027\u548c\u81f4\u764c\u6027\u7684\u4e3b\u8981\u9776\u5668\u5b98\u662f\u5927\u9f20\u80be\u810f\u548c\u5c0f\u9f20\u809d\u810f\u3002\u8be5 NTP \u6280\u672f\u62a5\u544a\u7684\u7ed3<\/span>\u8bba\u662f\uff0c\u5bf9\u4e8e\u5927\u9f20\u548c\u5c0f\u9f20\uff0cMIBK \u6709\u4e00\u4e9b\u81f4\u764c\u6027\u8ff9\u8c61\uff084\u30015\uff09\u3002\u57fa\u4e8e\u8fd9\u4e9b NTP \u6570\u636e\uff0cIARC<\/span>\u5df2\u5c06 MIBK \u5f52\u5230 2B \u81f4\u764c\u7269\u7ec4\uff08\u201c\u53ef\u80fd\u5bf9\u4eba\u7c7b\u81f4\u764c\u201d\uff09\uff086\uff09\u3002<\/span>\u5728\u5927\u9f20 NTP \u7814\u7a76\u4e2d\uff0cMIBK \u5f15\u8d77\u6162\u6027\u8fdb\u884c\u6027\u80be\u75c5\uff08CPN\uff09\u589e\u52a0\uff0c\u5728\u6700\u9ad8\u5242\u91cf\u4e0b\uff0c<\/span>\u96c4\u6027\u5927\u9f20\u80be\u5c0f\u7ba1\u817a\u7624\u548c\u764c\u7684\u53d1\u75c5\u7387\u7565\u6709\u589e\u52a0\u3002\u8fdb\u4e00\u6b65\u7684\u673a\u5236\u7814\u7a76\u660e\u786e\u8868\u660e\uff0c\u96c4\u6027\u5927\u9f20\u7684<\/span>\u80be\u5c0f\u7ba1\u7624\u6700\u6709\u53ef\u80fd\u7531\u5e7f\u4e3a\u4eba\u77e5\u7684\u96c4\u6027\u5927\u9f20\u7279\u6709 \u03b12u-\u80be\u75c5\u4ecb\u5bfc\u7684\u4f5c\u7528\u65b9\u5f0f\u6240\u5f15\u8d77\uff0c\u8ba4\u4e3a\u5176<\/span>\u4e0e\u4eba\u7c7b\u6ca1\u6709\u76f8\u5173\u6027\uff087\uff09\u3002\u96cc\u6027\u5927\u9f20\u4e2d\u4e5f\u68c0\u51fa\u4e86 CPN \u52a0\u5267\uff08\u5728\u6240\u6709\u66b4\u9732\u6d53\u5ea6\u4e0b\uff0cCPN<\/span>\u7684\u53d1\u751f\u7387\u90fd\u589e\u52a0\uff0c\u5728 1800 ppm \u6d53\u5ea6\u4e0b\u4e25\u91cd\u6027\u589e\u52a0\uff09\uff0c\u5176\u4e0e\u4eba\u7684\u76f8\u5173\u6027\u76ee\u524d\u4e0d\u8be6\u3002\u5728<\/span>1800 ppm \u7684\u6d53\u5ea6\u4e0b\uff0c\u96c4\u6027\u5927\u9f20\u7684\u5355\u6838\u7ec6\u80de\u767d\u8840\u75c5\u589e\u52a0\uff0c\u540c\u6837\u5728\u8be5\u6d53\u5ea6\u4e0b\uff0c\u96cc\u6027\u5927\u9f20\u51fa<\/span>\u73b0\u4e86 2 \u4e2a\u80be\u95f4\u8d28\u80bf\u7624\uff08\u975e\u5e38\u7f55\u89c1\u7684\u80bf\u7624\uff0c\u5e76\u672a\u89c1\u4e8e NTP \u7684\u5386\u53f2\u5bf9\u7167\u52a8\u7269\u4e2d\uff09\uff0c\u5176\u4e0e MIBK<\/span>\u66b4\u9732\u7684\u5173\u7cfb\u5c1a\u4e0d\u786e\u5b9a\uff085\uff09\u3002<\/span>\u6839\u636e MIBK \u7684\u5927\u9f20\u81f4\u764c\u6027\u7814\u7a76\u7ed3\u679c\uff0cPDE \u7684\u8ba1\u7b97\u57fa\u4e8e 2 \u79cd\u4e0d\u540c\u7684\u60c5\u51b5\uff1a<\/span><\/p>\n

\uff08i\uff09\u96c4\u6027\u548c\u96cc\u6027\u5927\u9f20\u7684\u80bf\u7624\u7814\u7a76\u7ed3\u679c\u4e0e\u6cbb\u7597\u4e0d\u76f8\u5173\u548c\/\u6216\u4e0e\u4eba\u7c7b\u4e0d\u76f8\u5173\uff0c\u56e0\u6b64\uff0c\u7528<\/span>\u68c0\u51fa\u96cc\u6027\u5927\u9f20 CPN \u7684\u6700\u4f4e\u5242\u91cf\uff08LOEL 6= 450 ppm\uff09\u8ba1\u7b97 PDE\u3002<\/span><\/p>\n

\u6216<\/span><\/p>\n

\uff08ii\uff09 \u4e0d\u80fd\u6392\u9664\u4e0e MIBK \u66b4\u9732\u7684\u5173\u7cfb\uff0c\u4ee5\u53ca 1800 ppm \u4e0b\u96c4\u6027\u5927\u9f20\uff08\u5355\u6838\u7ec6\u80de\u767d\u8840<\/span>\u75c5\uff09\u548c\/\u6216\u96cc\u6027\u5927\u9f20\uff08\u80be\u95f4\u5145\u8d28\u80bf\u7624\uff09\u7684\u80bf\u7624\u53d1\u73b0\u4e0e\u4eba\u7c7b\u7684\u76f8\u5173\u6027\uff1b\u7528\u80bf\u7624NOEL\uff08900 ppm\uff09<\/span><\/p>\n

\u8ba1\u7b97 PDE\u3002<\/span>MIBK \u7684\u5206\u5b50\u91cf\uff1a100.16 g\/mol<\/span><\/p>\n

\"\u300aICH<\/p>\n

F1 = 5\uff0c\u4ece\u5927\u9f20\u5916\u63a8\u5230\u4eba<\/span><\/p>\n

F2 = 10\uff0c\u8003\u8651\u4eba\u7684\u4e2a\u4f53\u5dee\u5f02<\/span><\/p>\n

F3 = 1\uff0c\u56e0\u4e3a\u6cbb\u7597\u7684\u6301\u7eed\u65f6\u95f4\u957f\uff082 \u5e74\uff09<\/span><\/p>\n

F4 = 1\uff0c\u53cd\u5e94\uff08\u96cc\u6027\u7684 CPN\uff09\u7684\u4e25\u91cd\u6027\u8f83\u4f4e\uff0c\u4e0e\u4eba\u7c7b\u7684\u76f8\u5173\u6027\u4e0d\u660e\u786e\u3002<\/span><\/p>\n

F5 = 5\uff0c\u56e0\u4e3a CPN \u7684 NOEL \u5c1a\u672a\u5236\u5b9a<\/span><\/p>\n

\"\u300aICH<\/p>\n

\"\u300aICH<\/p>\n

\u5728\u5c0f\u9f20\u7814\u7a76\u4e2d\uff0cMIBK \u589e\u52a0\u4e86\u66b4\u9732\u4e8e 1800 ppm \u7684\u96c4\u6027\u548c\u96cc\u6027\u5c0f\u9f20\u809d\u7ec6\u80de\u817a\u7624\u3001\u817a<\/span>\u7624\u6216\u764c\u7684\u53d1\u75c5\u7387\uff08\u7ec4\u5408\uff09\u3002\u8fdb\u4e00\u6b65\u7684\u673a\u5236\u7814\u7a76\u4e3a\u5c0f\u9f20\u809d\u810f\u80bf\u7624\u7684\u7ec4\u6210\u6027\u96c4\u6fc0\u7d20\u53d7\u4f53\uff08CAR\uff09<\/span>\u4ecb\u5bfc\u7684\u4f5c\u7528\u65b9\u5f0f\uff08MOA\uff09\u63d0\u4f9b\u4e86\u660e\u786e\u8bc1\u636e\uff088\uff09\u3002\u7531\u4e8e\u5df2\u786e\u5b9a\u8be5 MOA \u4e3a\u4e0e\u4eba\u7c7b\u4e0d\u76f8\u5173\uff0c<\/span>\u6545\u672a\u6839\u636e\u5c0f\u9f20\u4e3a\u671f 2 \u5e74\u7684\u7814\u7a76\u6570\u636e\uff089\uff09\u8ba1\u7b97 PDE\u3002<\/span><\/p>\n

\u751f\u6b96\u548c\u53d1\u80b2\u6bd2\u6027<\/span><\/strong><\/p>\n

\u5728\u53d1\u80b2\u6bd2\u6027\u7814\u7a76\u4e2d\uff0c\u598a\u5a20\u7684 F-344 \u5927\u9f20\u5728\u598a\u5a20\u7684\u7b2c 6 \u5230\u7b2c 15 \u5929\u5438\u5165\u5242\u91cf\u4e3a 0\u3001300\u3001<\/span><\/p>\n

1000 \u6216 3000 ppm \u7684 MIBK\uff0c6 \u5c0f\u65f6\/\u5929\u3002\u5728 3000 ppm \u7684\u5242\u91cf\u4e0b\u53d1\u73b0\u4e86\u4e00\u4e9b\u80ce\u513f\u6bd2\u6027\uff08\u80ce<\/span>\u513f\u4f53\u91cd\u964d\u4f4e\u548c\u9aa8\u9abc\u808c\u9aa8\u5316\u51cf\u5c11\uff09\uff0c\u8ba4\u4e3a\u5176\u7ee7\u53d1\u4e8e\u6bcd\u4f53\u6bd2\u6027\u3002\u5728 1000 ppm \u4e0b\uff0c\u6ca1\u6709\u6bcd\u4f53\u3001<\/span>\u80da\u80ce\u6216\u80ce\u513f\u6bd2\u6027\uff082\uff09\u3002<\/span>\u5728 2 \u4ee3\u751f\u6b96\u7814\u7a76\u4e2d\uff0c\u4f7f SD \u5927\u9f20\u4ee5\u5438\u5165\u5f62\u5f0f\u5168\u8eab\u66b4\u9732\u5728\u6d53\u5ea6\u4e3a 0\u3001500\u30011000 \u6216<\/span>2000 ppm \u7684 MIBK \u4e2d\uff0c6 \u5c0f\u65f6\/\u5929\uff0c\u4e3a\u671f 70 \u5929\uff0c\u6db5\u76d6 F0 \u4ee3\u7684\u4ea4\u914d\u524d\u671f\u5230 F2 \u4ee3\u7684\u54fa\u4e73\u671f\u3002<\/span>\u751f\u6b96\u53cd\u5e94\u7684 NOEL \u4e3a 2000 ppm\uff0c\u8fd9\u662f\u8bd5\u9a8c\u7684\u6700\u9ad8\u6d53\u5ea6\uff1b\u6839\u636e\u6025\u6027\u4e2d\u67a2\u795e\u7ecf\u7cfb\u7edf\u6291\u5236\u4f5c<\/span>\u7528\uff0c\u65b0\u751f\u513f\u6bd2\u6027\u7684 NOEL \u4e3a 1000 ppm\uff083\uff09\u3002<\/span><\/p>\n

\u7ed3\u8bba<\/span><\/strong><\/p>\n

MIBK \u539f PDE \u5927\u4e8e 50 mg\/\u5929\uff08100 mg\/\u5929\uff09\uff0c\u5c5e\u4e8e 3 \u7c7b\u6eb6\u5242\u3002\u65b0\u7b97\u51fa\u7684 MIBK \u7684 PDE<\/span><\/p>\n

\u662f\u57fa\u4e8e\u4e3a\u671f 2 \u5e74\u7684 NTP \u5438\u5165\u7814\u7a76\u4e2d\u96c4\u6027\u53ca\u96cc\u6027\u5927\u9f20\u7684\u80bf\u7624 NOEL\uff0c\u4ee5\u53ca\u96cc\u6027\u5927\u9f20\u6162\u6027<\/span><\/p>\n

\u8fdb\u5c55\u6027\u80be\u75c5\u7684 LOEL\uff1b\u5728\u8fd9 2 \u79cd\u60c5\u51b5\u4e0b\uff0c\u7b97\u51fa\u7684 PDE \u4e3a 45 mg\/\u5929\u3002\u56e0\u6b64\uff0c\u5efa\u8bae\u5c06 MIBK<\/span><\/p>\n

\u5f52\u5230 ICH\u300a\u6742\u8d28\uff1a\u6b8b\u7559\u6eb6\u5242\u7684\u6307\u5bfc\u539f\u5219\u300b\u8868 2 \u7684\u7b2c 2 \u7c7b\u6eb6\u5242\u3002<\/span><\/p>\n


<\/span><\/p>\n

\u53c2\u8003\u6587\u732e<\/span><\/strong><\/p>\n

1. Connelly JC, Hasegawa R, McArdle JV, Tucker ML. ICH Guideline ResidualSolvents. Pharmeuropa 1997;Suppl 9:5<\/span><\/p>\n

\"\u300aICH<\/p>\n

\n

<\/span><\/p>\n

<\/mpcps><\/section>\n


<\/p>\n<\/p><\/div>\n","protected":false},"excerpt":{"rendered":"

\u7eed20190120\u63a8\u9001\uff1a \u7b2c\u4e8c\u90e8\u5206\uff1a \u6742\u8d28\uff1a\u6b8b\u7559\u6eb6\u5242\uff08\u4fee\u8ba2\uff09 \u56db\u6c22\u544b\u5583\u7684 PDE ICH \u534f\u8c03\u4e09\u65b9\u6307\u5bfc\u539f\u5219 \u5728 […]<\/p>\n","protected":false},"author":1,"featured_media":80468,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":[],"categories":[2],"tags":[],"_links":{"self":[{"href":"https:\/\/www.05921.net\/index.php\/wp-json\/wp\/v2\/posts\/80467"}],"collection":[{"href":"https:\/\/www.05921.net\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.05921.net\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.05921.net\/index.php\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/www.05921.net\/index.php\/wp-json\/wp\/v2\/comments?post=80467"}],"version-history":[{"count":1,"href":"https:\/\/www.05921.net\/index.php\/wp-json\/wp\/v2\/posts\/80467\/revisions"}],"predecessor-version":[{"id":80489,"href":"https:\/\/www.05921.net\/index.php\/wp-json\/wp\/v2\/posts\/80467\/revisions\/80489"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.05921.net\/index.php\/wp-json\/wp\/v2\/media\/80468"}],"wp:attachment":[{"href":"https:\/\/www.05921.net\/index.php\/wp-json\/wp\/v2\/media?parent=80467"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.05921.net\/index.php\/wp-json\/wp\/v2\/categories?post=80467"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.05921.net\/index.php\/wp-json\/wp\/v2\/tags?post=80467"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}