3,4-¥¸¥¯¥í¥í-1-¥Ö¥Æ¥ó¤Î¥é¥Ã¥È¤òÍѤ¤¤ë
È¿Éü·Ð¸ýÅêÍ¿ÆÇÀ­¡¦À¸¿£È¯À¸ÆÇÀ­Ê»¹ç»î¸³

Combined Repeat Dose and Reproductive/Developmental
Toxicity Screening Test of 3,4-Dichloro-1-butene in Rats

Í×Ìó

¥×¥é¥¹¥Á¥Ã¥¯»º¶È¤Ç¹çÀ®¥Ý¥ê¥Þ¡¼¤ÎÀ½Â¤¤ËÍѤ¤¤é¤ì¤Æ¤¤¤ë¹âÀ¸»º´û¸²½³Øʪ¼Á 3,£´-¥¸¥¯¥í¥í-1-¥Ö¥Æ¥ó¤Ë¤Ä¤¤¤Æ¡¤È¿Éü·Ð¸ýÅêÍ¿ÆÇÀ­¡¦À¸¿£È¯À¸ÆÇÀ­Ê»¹ç»î¸³¤ò¡¤SD·Ï[Crj:CD(SD)]¥é¥Ã¥È¤òÍѤ¤¡¤0(ÂоÈ)¡¤0.4¡¤2¡¤10¤ª¤è¤Ó50 mg/kg/dayÍÑÎ̤Ǽ»ܤ·¤¿¡¥Æ°Êª¿ô¤Ï1·²»óͺ³Æ10ɤ¤È¤·¡¤È︳ʪ¼Á¤Ï¸òÇÛ³«»Ï14ÆüÁ°¤«¤é¡¤Íº¤Ï44Æü´Ö¡¤»ó¤ÏʬÊÚ¸åÓ®°é3Æü(41¡Á46Æü´Ö)¤Þ¤ÇÅêÍ¿¤·¤¿¡¥

1.¡¡È¿ÉüÅêÍ¿ÆÇÀ­

ͺ¿Æ¤Ë¤ª¤¤¤Æ¤Ï¡¤ÉÂÍýÁÈ¿¥³Ø¸¡ºº¤Ç¡¤´ÎºÙ˦¤ÎÈîÂ礪¤è¤Ó¿Õ¡¶á°ÌÇ¢ºÙ´É¾åÈé¤Î¾Ë»ÒÅ©¤ÎÁý²Ã¤¬ 10 mg/kg°Ê¾å¤Î·²¤Ëǧ¤á¤é¤ì¡¤´Î¡¤ª¤è¤Ó¿Õ¡½ÅÎ̤ÏÁý²Ã¤·¤¿¡¥¤µ¤é¤Ë¡¤50 mg/kg·²¤Ç¡¤¤¤¤º¤ì¤â°ì²áÀ­¤Î¼«È¯±¿Æ°Äã²¼¡¤Î®Þ·¤ª¤è¤ÓÀݱÂÎ̤θº¾¯¤¬¡¤ÅêÍ¿³«»ÏÆü¤Ëǧ¤á¤é¤ì¤¿¡¥·ì±ÕÀ¸²½³Ø¸¡ºº¤Ç¤Ï¡¤Áí¥¿¥ó¥Ñ¥¯¤ÎÁý²Ã¤ª¤è¤ÓÇ¢ÁÇÃâÁǤθº¾¯¤¬Ç§¤á¤é¤ì¤¿¡¥Âνš¤Ç¢¸¡ºº¤ª¤è¤Ó·ì±Õ³Ø¸¡ºº¤Ç¤Ï¡¤Í­°Õ¤ÊÊѲ½¤Ïǧ¤á¤é¤ì¤Ê¤«¤Ã¤¿¡¥°ìÊý¡¤»ó¿Æ¤Ë¤ª¤¤¤Æ¤â¡¤Íº¿Æ¤ÈƱÍͤˡ¤°ì²áÀ­¤Î°ìÈ̾õÂÖ¤ÎÊѲ½¤ª¤è¤ÓÀݱÂÎ̤θº¾¯·¹¸þ¤¬50 mg/kg·²¤Çǧ¤á¤é¤ì¡¤1ɤ¤ÏʬÊÚ¸åÓ®°é2Æü¤Ë»àË´¤·¤¿¡¥¤Þ¤¿¡¤Æ±·²¤Ç´ÎºÙ˦¤ÎÈîÂ礬¾¯¿ôÎã¤Ë¤ß¤é¤ì¤¿¤¬¡¤´Î¡½ÅÎ̤ˤÏÍ­°Õ¤ÊÊѲ½¤Ïǧ¤á¤é¤ì¤º¡¤¿Õ¡¤ÏÁêÂнÅÎ̤ΤßÁý²Ã¤·¤¿¤¬¡¤ÉÂÍýÁÈ¿¥³ØŪ¤Ë°Û¾ï¤Ïǧ¤á¤é¤ì¤Ê¤«¤Ã¤¿¡¥

°Ê¾å¤Î·ë²Ì¤«¤é¡¤ 3,4-¥¸¥¯¥í¥í-1-¥Ö¥Æ¥ó¤Î¥é¥Ã¥È¤Ø¤ÎÈ¿ÉüÅêÍ¿¤Ë¤è¤ê¡¤´Î¡¤ª¤è¤Ó¿Õ¡¤ËÂФ¹¤ë±Æ¶Á¤¬Ç§¤á¤é¤ì¡¤Ìµ±Æ¶ÁÎ̤Ïͺ2mg/kg/day¡¤»ó10 mg/kg/day¤È¿äÄꤵ¤ì¤¿¡¥

2.¡¡À¸¿£È¯À¸ÆÇÀ­

¿Æưʪ¤ÎÀ¸¿£¤Ë¤Ä¤¤¤Æ¡¤¸òÈøΨ¡¤¼õÂÛΨ¡¤Ç¥¿±´ü´Ö¡¤Ê¬ÊÚ¤ª¤è¤ÓÓ®°é¾õÂÖ¤ËÍ­°Õ¤ÊÊѲ½¤Ïǧ¤á¤é¤ì¤Ê¤«¤Ã¤¿¡¥¤Þ¤¿¡¤»ùưʪ¤ÎȯÀ¸¤Ë¤Ä¤¤¤Æ¤â¡¤½Ð»º»ù¿ô¡¤À¸Â¸»ù¿ô¡¤À­È桤À¸Â¸Î¨¡¤ÂνŤª¤è¤Ó·ÁÂ֤ˡ¤È︳ʪ¼Á¤ÎÅêÍ¿¤Ëµ¯°ø¤¹¤ëÊѲ½¤Ïǧ¤á¤é¤ì¤Ê¤«¤Ã¤¿¡¥¤·¤¿¤¬¤Ã¤Æ¡¤»óͺ¿Æưʪ¤ÎÀ¸¿£Ç½¤ª¤è¤Ó»ùưʪ¤ÎȯÀ¸¤ËÂФ¹¤ë̵±Æ¶ÁÎ̤ϡ¤¤¤¤º¤ì¤â 50 mg/kg/day¤È¿äÄꤵ¤ì¤¿¡¥

ÊýË¡

£±.¡¡È︳ʪ¼Á

3, 4-¥¸¥¯¥í¥í-1-¥Ö¥Æ¥ó¤Ï¡¤Ê¬»ÒÎÌ124.99¡¤Í»ÅÀ-61¡î¡¤Ê¨ÅÀ116¡î¤Î̵¿§Æ©ÌÀ¤Ê±ÕÂΤǡ¤¿å¤ËÍϤ±¤Ë¤¯¤¯¡¤¥¨¥¿¥Î¡¼¥ë¡¤¿¢ÊªÌý¤ËÍϤ±¤ä¤¹¤¯¡¤¥Ù¥ó¥¼¥ó¡¤¥¯¥í¥í¥Û¥ë¥à¤Ë¶Ë¤á¤ÆÍϤ±¤ä¤¹¤¤¡¥»î¸³¤Ë¤Ï¡¤Åìµþ²½À®¹©¶È(³ô)À½Â¤¤Î»îÌô(¥í¥Ã¥ÈÈÖ¹æFHD01¡¤½ãÅÙ99.7¡ó)¤òÆþ¼ê¤·¡¤Îä°Å½ê(4¡î)¤ÇÌ©ÀòÊݴɤ·¡¤»ÈÍѤ·¤¿¡¥ÅêÍ¿±Õ¤Ï¡¤¤³¤ì¤ò¶ÉÊý¥´¥ÞÌý(µÜß·ÌôÉÊ)¤ËÍϲò¤·¤ÆÄ´À½¤·¡¤»ÈÍÑ»þ¤Þ¤ÇÎä°Å¾ò·ï²¼¤ÇÌ©ÀòÊݴɤ·¤¿¡¥È︳ʪ¼Á¤Î¸¶ÂΤª¤è¤ÓÅêÍ¿±ÕÃæ¤ÎÈ︳ʪ¼Á¤òʬÀϤ·¡¤°ÂÄê¤Ç¤¢¤ë¤³¤È¤ò³Îǧ¤·¤¿¡¥

£².¡¡»ÈÍÑưʪ¤ª¤è¤Ó»ô°é¾ò·ï

ÆüËÜ¥Á¥ã¡¼¥ë¥¹¡¦¥ê¥Ð¡¼ (³ô)¤è¤êÈÂÆþ¤·¤¿SD·Ï[Crj: CD(SD)]¥é¥Ã¥È¤ò9Æü´Ö¸¡±Ö¡¦Æë²½»ô°é¤·¤¿¸å¡¤°ìÈ̾õÂ֤˰۾郎ǧ¤á¤é¤ì¤Ê¤«¤Ã¤¿¤â¤Î¤ò¡¤Íº¤Ï9½µÎð(343-384 g)¡¤»ó¤Ï8½µÎð(192-222 g)¤Ç¡¤1·²»óͺ³Æ10ɤ¤È¤·¤Æ»î¸³¤Ë¶¡¤·¤¿¡¥¥é¥Ã¥È¤Ï¡¤²¹ÅÙ22¡Þ3¡î¡¤¼¾ÅÙ55¡Þ10¡ó¡¤´¹µ¤²ó¿ô10²ó°Ê¾å/»þ¡¤¾ÈÌÀ12»þ´Ö(6-18»þ)¤ËÀßÄꤷ¤¿»ô°é¼¼¤Ç¶âÌÖ¥±¡¼¥¸¤Ë¸ÄÊ̤˼ýÍƤ·¡¤¸Ç·¿»ôÎÁ(¥é¥ÜMR¥¹¥È¥Ã¥¯¡¤ÆüËÜÇÀ»º¹©¶È(³ô))¤ª¤è¤Ó¿å¤ò¼«Í³¤ËÀݼ褵¤»¤¿¡¥¤¿¤À¤·¡¤¸òÈøÀ®Î©¸å¤Î»ó¤Ï¡¤Áãºî¤êºàÎÁ(¥Û¥ï¥¤¥È¥Õ¥ì¡¼¥¯¡¤ÆüËÜ¥Á¥ã¡¼¥ë¥¹¡¦¥ê¥Ð¡¼(³ô))¤òÆþ¤ì¤¿¥Ý¥ê¥«¡¼¥Ü¥Í¡¼¥ÈÀ½¥±¡¼¥¸¤Ë¼ýÍƤ·¤¿¡¥

3.¡¡ÅêÍ¿Î̤ª¤è¤ÓÅêÍ¿ÊýË¡

ÅêÍ¿ÎÌÀßÄê»î¸³¤È¤·¤Æ¡¤¥é¥Ã¥È¤ò 1·²»óͺ³Æ2ɤ¤È¤·¡¤3,4-¥¸¥¯¥í¥í-1-¥Ö¥Æ¥ó¤Î20¡¤60¡¤200¡¤600¤¢¤ë¤¤¤Ï2000 mg/kgÍÑÎ̤òñ²ó·Ð¸ýÅêÍ¿¤·¤¿¡¥2000 mg/kg·²¤Ç»óͺÁ´Î㤬»àË´¤·¤¿¡¥¥é¥Ã¥È¤ò1·²»óͺ³Æ4ɤ¤È¤·¡¤0¡¤3¡¤10¡¤30¡¤100¤¢¤ë¤¤¤Ï300 mg/kg/dayÍÑÎ̤ò¡¤14Æü´ÖÈ¿Éü·Ð¸ýÅêÍ¿¤·¤¿¡¥ÅêÍ¿7Æü¤ÎͼÊý¤«¤é¸òÇÛ¤¬À®Î©¤¹¤ë¤Þ¤Ç¡¤»óͺ³Æ1ɤ¤Å¤Ä¤òƱµï¤µ¤»¤¿¡¥¼«È¯±¿Æ°Äã²¼¡¤Î®Þ·¤Ê¤É¤Î¾É¾õ¡¤´Î¡¤ª¤è¤Ó¿Õ¡½ÅÎ̤ÎÁý²Ã¤¬¡¤30 mg/kg°Ê¾å¤Î»óͺ¤Ëǧ¤á¤é¤ì¤¿¡¥¸òÈø¤Ï¡¤³Æ·²¤ÎÁ´Îã¤ËÀ®Î©¤·¤¿¡¥¤½¤³¤Ç¡¤Ëܻ¤Ë¤ª¤±¤ëÅêÍ¿Î̤ϡ¤50 mg/kg¤òºÇ¹âÍÑÎ̤Ȥ·¡¤°Ê²¼10¡¤2¤ª¤è¤Ó0.4 mg/kg/day¤Î4ÍÑÎ̤òÀßÄꤷ¤¿¡¥ÅêÍ¿ÊýË¡¤Ï¡¤ÅêÍ¿±ÕÎ̤òÂνÅ100 gÅö¤¿¤ê0.5 ml¤È¤·¡¤°ß¥¾¥ó¥Ç¤òÁõÃ夷¤¿Ãí¼ÍÅû¤òÍѤ¤¤Æ¡¤1Æü1²ó(¸áÁ°Ãæ)¡¤¸òÇÛ³«»Ï14ÆüÁ°¤«¤éͺ¤Ï44Æü´Ö¡¤»ó¤ÏʬÊÚ¸åÓ®°é3Æü(41¡Á46Æü´Ö)¤Þ¤Ç¡¤·Ð¸ýÅêÍ¿¤·¤¿¡¥Âоȷ²¤Ë¤Ï¡¤¶ÉÊý¥´¥ÞÌý¤òƱÍͤËÅêÍ¿¤·¤¿¡¥

4.¡¡´Ñ»¡¤ª¤è¤Ó¸¡ºº

1)¡¡¿Æưʪ¤Ë´Ø¤¹¤ë¹àÌÜ

(1) °ìÈ̾õÂÖ´Ñ»¡

ÅêÍ¿´ü´ÖÃæËèÆü¡¤Æ°Êª¤ÎÀ¸»à¡¤³°´Ñ¡¤¹ÔÆ°Åù¤Ë¤Ä¤¤¤Æ´Ñ»¡¤·¤¿¡¥

(2) ÂνŤª¤è¤ÓÀݱÂÎ̬Äê

ÂνŤÎ¬Äê¤Ï¡¤ÅêÍ¿³«»ÏÆü (ÅêÍ¿³«»ÏľÁ°)¤ª¤è¤Ó¤½¤Î¸å¤Ï7Æü´Ö³Ö¤Ç¹Ô¤¤¡¤¤µ¤é¤ËºÇ½ªÅêÍ¿Æü¤ª¤è¤ÓÅË»¦Æü¤Ë¬Äꤷ¤¿¡¥¤¿¤À¤·¡¤»ó¤ÎÇ¥¿±¸å¤Ï¡¤Ç¥¿±0¡¤7¡¤14¤ª¤è¤Ó20Æü¡¤¤Ê¤é¤Ó¤ËÓ®°é0¤ª¤è¤Ó4Æü¤Ë¬Äꤷ¤¿¡¥ÀݱÂÎ̤ϡ¤ÂνŬÄêÆü¤Ë¹ç¤ï¤»¤Æ¡¤ÍâÆü¤Þ¤Ç¤Î24»þ´Ö¤Î»ôÎÁ¾ÃÈñÎ̤ò¬Äꤷ¤¿¡¥»ó¤ÎÓ®°é4Æü¤ÎÀݱÂÎ̤ϡ¤Á°Æü¤«¤é¤Î24»þ´Ö¾ÃÈñÎ̤ò¬Äꤷ¤¿¡¥

(3) ¸òÇÛ¤ª¤è¤ÓʬÊÚ¾õÂÖ´Ñ»¡

ÅêÍ¿ 14Æü¤Î¸á¸å¤Ë¡¤Íº¤Î¥±¡¼¥¸¤ËƱ°ì·²Æâ¤Î»ó¤òÆþ¤ì¤Æ1ÂÐ1¤ÎÂФòºî¤ê¡¤¸òÈø¤¬³Îǧ¤µ¤ì¤ë¤Þ¤Ç(5Æü´Ö¤ÇÁ´Îã¤Î¸òÈø¤ò³Îǧ)¡¤Ï¢Â³Æ±µï¤µ¤»¤¿¡¥¸òÈø¤Î³Îǧ¤ÏËèÄ«°ìÄê»þ¹ï(9:30ʬº¢)¤Ë¹Ô¤¤¡¤ç´Àò·ÁÀ®¤¢¤ë¤¤¤Ïç´¹¤Ãæ¤ËÀº»Ò¤¬³Îǧ¤µ¤ì¤¿Æü¤òÇ¥¿±0Æü¤È¤·¤¿¡¥Ê¬ÊÚ¾õÂ֤δѻ¡¤âƱ¤¸»þ¹ï¤Ë¹Ô¤¤¡¤1Ê¢¤´¤È¤ËÁ´Îã¤Î½Ð»º¤¬³Îǧ¤µ¤ì¤¿Æü¤òÓ®°é0Æü¤È¤·¤¿¡¥¸òÇÛ¤ª¤è¤ÓʬÊڤδѻ¡·ë²Ì¤«¤é¡¤³Æ·²¤Ë¤Ä¤¤¤Æ¸òÈøΨ¡Î(¸òÈøÀ®Î©Æ°Êª¿ô¡¿Æ±µïưʪ¿ô)¡ß100¡Ï¡¤¼õÂÛΨ¡Î(¼õÂÛ»ó¿ô¡¿¸òÈøÀ®Î©»ó¿ô)¡ß100¡Ï¤ª¤è¤Ó½Ð»ºÎ¨¡Î(À¸»ù½Ð»º»ó¿ô¡¿À¸Â¸Ç¥¿±»ó¿ô)¡ß100¡Ï¤Ê¤é¤Ó¤ËʬÊڤγÎǧ¤µ¤ì¤¿Îã¤Ë¤Ä¤¤¤ÆÇ¥¿±´ü´Ö(Ç¥¿±0Æü¤«¤éʬÊÚ¤¬³Îǧ¤µ¤ì¤¿Æü¤Þ¤Ç¤Î´ü´Ö)¤ò»»Äꤷ¤¿¡¥

(4) ͺ¤ÎÎ×¾²ÉÂÍý³Ø¸¡ºº

Ç¢¸¡ºº¡§ÅêÍ¿³«»Ï 38¤¢¤ë¤¤¤Ï40Æü¤Ë¡¤¥é¥Ã¥È¤òÂå¼Õ¥±¡¼¥¸¤ËÌó3»þ´Ö¼ýÍƤ·¤ÆºÎÇ¢¤·¡¤³°´Ñ¤Î´Ñ»¡¤Ê¤é¤Ó¤ËpH¡¤Àø·ì¡¤¥¿¥ó¥Ñ¥¯¡¤Åü¡¤¥±¥È¥óÂΡ¤¥Ó¥ê¥ë¥Ó¥ó¤ª¤è¤Ó¥¦¥í¥Ó¥ê¥Î¡¼¥²¥ó[°Ê¾å¡¤¥Þ¥¤¥ë¥¹¡¦»°¶¦(³ô)¡¤¥Þ¥ë¥Æ¥£¥¹¥Æ¥£¥Ã¥¯¥¹]¤ª¤è¤ÓÄÀÞÖ(URI-CELL±Õ¤ÇÀ÷¿§¡¤¥±¥ó¥Ö¥ê¥Ã¥¸¥±¥ß¥«¥ë¥×¥í¥À¥¯¥È¼Ò)¤ò¸¡ºº¤·¤¿¡¥

·ì±Õ³Ø¸¡ºº¡§¶¡»î·ì±Õ¤ÎºÎ¼è¤Ï¡¤ÅêÍ¿´ü´Ö½ªÎ»ÍâÆü¤Ë¤ª¤±¤ëÅË»¦Ë¶¸¡»þ¤Ë¹Ô¤Ã¤¿¡¥Æ°Êª¤ÏºÎ·ìÁ°Æü¤Î¸á¸å 5»þ¤è¤ê½ü±Â¤·¡¤¿å¤Î¤ß¤òµëÍ¿¤·¤¿¡¥ºÎ¼è¤·¤¿·ì±Õ¤Ï3ʬ³ä¤·¡¤¤½¤Î°ìÉô¤ÏEDTA-2K¤Ç¶Å¸ÇËɻ߽èÍý¤·¡¤Â¿¹àÌܼ«Æ°·ìµå·×¿ôÁõÃÖ[Åì°¡°åÍÑÅÅ»Ò(³ô)¡¤E-4000]¤Ë¤è¤ê¡¤ÀÖ·ìµå¿ô(Åŵ¤Äñ¹³¸¡½ÐÊý¼°)¡¤·ì¿§ÁÇÎÌ(¥é¥¦¥ê¥ëβ»À¥Ê¥È¥ê¥¦¥à-¥Ø¥â¥°¥í¥Ó¥óË¡)¡¤¥Ø¥Þ¥È¥¯¥ê¥Ã¥ÈÃÍ(¥Ñ¥ë¥¹¸¡½ÐÊý¼°)¡¤Ê¿¶ÑÀÖ·ìµåÍÆÀÑ¡¤Ê¿¶ÑÀÖ·ìµå·ì¿§ÁÇÎÌ¡¤Ê¿¶ÑÀÖ·ìµå·ì¿§ÁÇÇ»ÅÙ(°Ê¾å¡¤·×»»ÃÍ)¡¤Çò·ìµå¿ô¤ª¤è¤Ó·ì¾®ÈÄ¿ô(°Ê¾å¡¤Åŵ¤Äñ¹³¸¡½ÐÊý¼°)¤ò¡¤Evelyn-MalloyË¡¤ÎÊÑË¡1)¤Ë¤è¤ê¥á¥È¥Ø¥â¥°¥í¥Ó¥óÇ»ÅÙ¤ò¡¤¤Þ¤¿ÅÉËõɸËܤòºîÀ½¤·¤ÆÌÖ¾õÀÖ·ìµå¿ô(Brilliant cresyl blueÀ÷¿§)¤ª¤è¤ÓÇò·ìµåɴʬΨ(May-GiemsaÀ÷¿§)¤ò¬Äꤷ¤¿¡¥¤µ¤é¤Ë°ìÉô¤Ï3.8¡ó¥¯¥¨¥ó»À¥Ê¥È¥ê¥¦¥à±Õ¤Ç½èÍý¤·¤Æ·ìÞù¤òÆÀ¡¤·ì±Õ¶Å¸Ç¼«Æ°Â¬ÄêÁõÃÖ(¥¢¥á¥ë¥ó¥°¼Ò¡¤KC-10A)¤Ë¤è¤ê¡¤¥×¥í¥È¥í¥ó¥Ó¥ó»þ´Ö(Quick°ìÃÊË¡)¤ª¤è¤Ó³èÀ­²½Éôʬ¥È¥í¥ó¥Ü¥×¥é¥¹¥Á¥ó»þ´Ö(¥¨¥é¥¸¥ó»À³èÀ­²½Ë¡)¤ò¬Äꤷ¤¿¡¥

·ì±ÕÀ¸²½³Ø¸¡ºº¡§ºÎ¼è¤·¤¿·ì±Õ¤Î°ìÉô¤«¤é·ìÀ¶¤òʬΥ¤·¡¤À¸²½³Ø¼«Æ°Ê¬ÀÏÁõÃÖ [ÆüËÜÅÅ»Ò(³ô)¡¤JCA-VX-1000·¿¥¯¥ê¥Ê¥é¥¤¥¶¡¼]¤Ë¤è¤ê¡¤Áí¥¿¥ó¥Ñ¥¯(BiuretË¡)¡¤¥¢¥ë¥Ö¥ß¥ó(BCGË¡)¡¤A/GÈæ(·×»»ÃÍ)¡¤¥°¥ë¥³¡¼¥¹¡¤¥È¥ê¥°¥ê¥»¥é¥¤¥É¡¤Áí¥³¥ì¥¹¥Æ¥í¡¼¥ë(°Ê¾å¡¤¹ÚÁÇË¡)¡¤Áí¥Ó¥ê¥ë¥Ó¥ó(JendrassikË¡)¡¤Ç¢ÁÇÃâÁÇ(Urease-UVË¡)¡¤¥¯¥ì¥¢¥Á¥Ë¥ó(JaffË¡)¡¤GOT¡¤GPT¡¤¦Ã-GTP¡¤LDH(°Ê¾å¡¤SSCCË¡)¡¤¥¢¥ë¥«¥ê¥Û¥¹¥Õ¥¡¥¿¡¼¥¼(GSCCË¡)¡¤¥³¥ê¥ó¥¨¥¹¥Æ¥é¡¼¥¼(BTC-DTNBË¡)¡¤¥«¥ë¥·¥¦¥à(OCPCË¡)¤ª¤è¤Ó̵µ¡¥ê¥ó(¹ÚÁÇË¡)¤ò¡¤¤Þ¤¿ÅŲò¼Á¼«Æ°Ê¬ÀÏÁõÃÖ[Åì°¡ÅÅÇȹ©¶È(³ô)¡¤NAKL-1]¤Ë¤è¤ê¡¤¥Ê¥È¥ê¥¦¥à¡¤¥«¥ê¥¦¥à¤ª¤è¤Ó±öÁǤò¬Äꤷ¤¿¡¥

(5) ÉÂÍý³Ø¸¡ºº

Éλàưʪ¤Ïȯ¸«¸å®¤ä¤«¤Ë¡¤Íº¤Î·×²èÅË»¦Æ°Êª¤ÏºÎ·ì¤Ë³¤¤¤Æ¡¤¤Þ¤¿»ó¤Î·×²èÅË»¦Æ°Êª¤ÏÓ®°é 4Æü¤Î´Ñ»¡½ªÎ»¸å¤Ë¡¤Ê¬ÊÚͽÄêÆü¤ò²á¤®¤Æ¤âʬÊÚ¤¬Ç§¤á¤é¤ì¤Ê¤¤»ó¤Ë¤Ä¤¤¤Æ¤ÏʬÊÚͽÄê¤Î4Æü¸å¤Ë¡¤¤¤¤º¤ì¤â¥¨¡¼¥Æ¥ëËã¿ì²¼¤ÇÊü·ìÅË»¦¤·¤Æ˶¸¡¤·¡¤Ç¾¡¤¿´Â¡¡¤´Î¡¡¤¿Õ¡¡¤ç£Â¡¡¤Éû¿Õ¡¤¶»Á£¤Ê¤é¤Ó¤Ëͺ¤Ë¤Ä¤¤¤Æ¤Ï¤µ¤é¤ËÀºÁ㡤ÀºÁã¾åÂΤòÇéÎ̤·¤¿¡¥»ó¤Ë¤Ä¤¤¤Æ¤Ï¡¤ÍñÁã¤Î²«Âοô¤ª¤è¤Ó»ÒµÜ¤ÎÃå¾²¿ô¤òÄ´¤Ù¡¤Ã徲Ψ¡Î(Ãå¾²¿ô¡¿²«Âοô)¡ß100¡Ï¤ò»»Äꤷ¤¿¡¥ÉÂÍýÁÈ¿¥³Ø¸¡ºº¤Ï¡¤ºÎ¼è¤·¤¿´ï´±¤ò10¡óÃæÀ­¥ê¥ó»À´Ë¾×¥Û¥ë¥Þ¥ê¥ó±Õ(ÀºÁ㡤ÀºÁã¾åÂΤΤߥ֥¢¥ó±Õ)¤Ç¸ÇÄê¸å¡¤Âоȷ²¤ª¤è¤Ó50 mg/kg·²¤ÎÁ´Î㡤¤Ê¤é¤Ó¤Ë¾¤Î·²¤ÎÇ¥¿±¤ÎÀ®Î©¤·¤Ê¤«¤Ã¤¿ÂФÎǾ¡¤²¼¿âÂΡ¤´ãµå¡¤¹Ã¾õÁ£(¾åÈé¾®ÂΤò´Þ¤à)¡¤¶»Á£¡¤¿´Â¡¡¤ÇÙ¡¤´Î¡¡¤¿Õ¡¡¤Éû¿Õ¡¤ç£Â¡¡¤°ß¡¤¾®Ä²(½½Æó»ØIJ¡¦¶õIJ¡¦²óIJ)¡¤ÂçIJ(ÌÕIJ¡¦·ëIJ¡¦Ä¾Ä²)¡¤ç¹Â¡¡¤ç¯æù¡¤¹ü¿ñ¡¤¤µ¤é¤Ëͺ¤Ç¤ÏÀºÁ㡤ÀºÁã¾åÂΡ¤Á°Î©Á£¡¤ÀºÇ¹¡¤»ó¤Ç¤ÏÍñÁ㡤»ÒµÜ¡¤ç´¡¤ÆýÁ£¤Ë¤Ä¤¤¤Æ¡¤0.4¡¤2¤ª¤è¤Ó10 mg/kg·²¤ÎÇ¥¿±¤¬À®Î©¤·¤¿ÂФǤϡ¤50 mg/kg·²¤ÇÆÇÀ­±Æ¶Á¤È¹Í¤¨¤é¤ì¤ëÊѲ½¤Îǧ¤á¤é¤ì¤¿»óͺ¤Î´Î¡¤ª¤è¤Óͺ¤Î¿Õ¡¤Ë¤Ä¤¤¤Æ¡¤¾ïË¡¤Ë½¾¤¤¥Ñ¥é¥Õ¥£¥óÀÚÊÒ¤òºîÀ½¤·¡¤¥Ø¥Þ¥È¥­¥·¥ê¥ó¡¦¥¨¥ª¥¸¥óÀ÷¿§¤ò»Ü¤·¤Æ¶À¸¡¤·¤¿¡¥¤Þ¤¿¡¤ÄÀÃåʪ¤òƱÄꤹ¤ë¤¿¤á¡¤Íº¤Î¿Õ¡¤Ë¤Ä¤¤¤Æ¤ÏPASÀ÷¿§¡¤°ìÉô¤ÎÎã¤Î´Î¡¡¤¿Õ¡¡¤°ß¤ª¤è¤ÓIJ¤Ë¤Ä¤¤¤Æ¤Ï»éËÃÀ÷¿§(¥º¥À¥ó­·)¤â¹Ô¤Ã¤¿¡¥

2)¡¡¿·À¸»ù¤Ë´Ø¤¹¤ë¹àÌÜ

(1) »º»ù¿ô¤ª¤è¤ÓÀ­Èæ¤Î´Ñ»¡

ʬÊÚ´°Î»¤Î³Îǧ¸å³ÆÊ¢¤Î»º»ù¿ô (À¸Â¸»ù¤È»àË´»ù¤Î¹ç·×)¤òÄ´¤Ù¡¤Ê¬ÊÚΨ¡Î(Áí½Ð»º»ù¿ô¡¿Ãå¾²¿ô)¡ß100¡Ï¤ò»»Äꤷ¤¿¡¥À­Ê̤ÏæêÌç¤ÈÀ¸¿£Æ͵¯¤Îµ÷Î¥¤ÎĹû¤Ë¤è¤êȽÄꤷ¡¤·²¤´¤È¤ÎÀ­Èæ¤ò»»½Ð¤·¤¿¡¥

(2) ³°É½°Û¾ï¤ª¤è¤Ó°ìÈ̾õÂ֤δѻ¡

ʬÊÚ´°Î»¸å¡¤¸ý¹ÐÆâ¤ò´Þ¤à³°É½¤Î°Û¾ï¤ò´Ñ»¡¤·¤¿¡¥¤Þ¤¿¡¤ËèÆü°ìÈ̾õÂÖ¤ª¤è¤ÓÀ¸»à¤ò³Îǧ¤·¡¤½ÐÀ¸Î¨¡Î (½Ð»º³Îǧ»þÀ¸»ù¿ô¡¿Áí½Ð»º»ù¿ô)¡ß100¡Ï¤ª¤è¤Ó¿·À¸»ùÀ¸Â¸Î¨¡Î(Ó®°é4ÆüÀ¸»ù¿ô¡¿½Ð»º³Îǧ»þÀ¸»ù¿ô)¡ß100¡Ï¤òµá¤á¤¿¡¥

(3) ÂνŬÄê

Ó®°é 0Æü¤ª¤è¤Ó4Æü¤Ë¡¤»óͺÊ̤˳ÆÊ¢¤´¤È¤ÎÁíÂνŤò¬Äꤷ¡¤1ɤÅö¤¿¤ê¤ÎÊ¿¶ÑÂνŤò»»½Ð¤·¤¿¡¥

(4) ÉÂÍý³Ø¸¡ºº

»àË´Îã¤Ïȯ¸«»þ¤Ë¡¤À¸Â¸Îã¤Ï»ó¿Æ¤Î²ò˶»þ (Ó®°é4Æü)¤Ë¥¨¡¼¥Æ¥ë¡¦¥¯¥í¥í¥Û¥ë¥à¤ÇËã¿ì»à¤µ¤»¡¤¶»Ê¢Éô¤Ë¤ª¤±¤ë¼çÍ×´ï´±¤òÆù´ãŪ¤Ë´Ñ»¡¤·¤¿¡¥

5.¡¡Åý·×½èÍý

¥Ñ¥é¥á¥È¥ê¥Ã¥¯¥Ç¡¼¥¿¤Ï Bartlett¤Îʬ»¶¸¡Äê¤ò¹Ô¤¤¡¤Ê¬»¶¤¬°ìÍͤʾì¹ç¤Ï°ì¸µÇÛÃÖ¤Îʬ»¶Ê¬ÀϤò¹Ô¤Ã¤¿¡¥Ê¬»¶¤¬°ìÍͤǤʤ¤¾ì¹ç¤ª¤è¤Ó¥Î¥ó¥Ñ¥é¥á¥È¥ê¥Ã¥¯¥Ç¡¼¥¿¤ÏKruskal-Wallis¤Î½ç°Ì¸¡Äê¤ò¹Ô¤Ã¤¿¡¥¤½¤ì¤é¤Î·ë²ÌÍ­°Õº¹¤òǧ¤á¤¿¾ì¹ç¡¤DunnettË¡¤¢¤ë¤¤¤ÏScheffeË¡(·²¤ÎÂ礭¤µ¤¬°Û¤Ê¤ë¾ì¹ç)¤Ë¤è¤êÂоȷ²¤ËÂФ¹¤ë³Æ·²¤ÎÈæ³Ó¸¡Äê¤ò¹Ô¤Ã¤¿¡¥¥«¥Æ¥´¥ê¥«¥ë¥Ç¡¼¥¿¤Ï¡¤¦Ö^2¸¡Äê¤ò¹Ô¤Ã¤¿¡¥¤Ê¤ª¡¤¿·À¸»ù¤Ë´Ø¤¹¤ë¥Ç¡¼¥¿¤Ï¡¤1Ê¢Åö¤¿¤ê¤ÎÊ¿¶Ñ¤ò1ɸËܤȤ·¤¿¡¥

·ë²Ì

1.¡¡È¿ÉüÅêÍ¿ÆÇÀ­

1)¡¡»àË´¤ª¤è¤Ó°ìÈ̾õÂÖ

»àË´¤Ë¤Ä¤¤¤Æ¤Ï¡¤ 50 mg/kg·²¤Ç¡¤Ê¬ÊÚ¸åÓ®°é2Æü¤Ë»ó¤Î1ɤ¤¬Éλà¾õÂ֤Ȥʤ俤Τǡ¤ÀÚÇ÷ÅË»¦¤·¤¿¡¥¤³¤Î1ɤ°Ê³°¡¤»àË´¤Ïǧ¤á¤é¤ì¤Ê¤«¤Ã¤¿¡¥°ìÈ̾õÂ֤ˤĤ¤¤Æ¤Ï¡¤Íº¤Ë¤ª¤¤¤Æ¡¤ÅêÍ¿1Æü¤Ë¡¤¼«È¯±¿Æ°Äã²¼¤ª¤è¤Óή޷¤¬50 mg/kg·²¤Î¤Û¤ÜÁ´Îã¤Ëǧ¤á¤é¤ì¤¿¡¥ÅêÍ¿2Æü°Ê¹ß¤Ï¡¤¼«È¯±¿Æ°¤ÎÄã²¼¤¬ÅêÍ¿5¡Á12Æü¤Ë¤«¤±¤Æ1ɤ¤Ëǧ¤á¤é¤ì¤¿°Ê³°¡¤°Û¾ï¤Ïǧ¤á¤é¤ì¤Ê¤«¤Ã¤¿¡¥»ó¤Ë¤ª¤¤¤Æ¤â¡¤50 mg/kg·²¤ÇÅêÍ¿1Æü¤Ë¼«È¯±¿Æ°Äã²¼¤¬Á´Îã¤Ë¡¤Î®Þ·¤¬ÌóȾ¿ô¤Ëǧ¤á¤é¤ì¤¿¡¥¤Þ¤¿¡¤Ó®°é2Æü¤ËÀÚÇ÷ÅË»¦¤·¤¿Îã¤Ç¤Ï¡¤Ç¥¿±Ëö´ü¤ÎÅêÍ¿39Æü°Ê¹ß¤Ë¤ª¤¤¤Æ¼«È¯±¿Æ°¤¬Ãø¤·¤¯Äã²¼¤·¡¤¿¼Âç¸ÆµÛ¡¤´ãâÛ²¼¿â¤Ê¤É¤¬Ç§¤á¤é¤ì¤¿¡¥¤½¤Î¸åʬÊڤϤ·¤¿¤¬¡¤°ìÈ̾õÂ֤Ϥµ¤é¤Ë°­²½¤·¡¤Ó®°é¹ÔÆ°¤ò¤È¤é¤º¡¤ÈéÉæ¤ÏÁóÇò¤ÇÉλà¾õÂ֤Ȥʤä¿¡¥

2)¡¡ÂνÅ(Fig. 1¡¤2)

»óͺ¤È¤â¡¤ÂνŤËÍ­°Õ¤ÊÊѲ½¤Ïǧ¤á¤é¤ì¤Ê¤«¤Ã¤¿¡¥ 50 mg/kg·²¤ÎÂνŤϡ¤»óͺ¤È¤âÂоȷ²¤ò¤ä¤ä²¼²ó¤Ã¤Æ¿ä°Ü¤·¡¤Íº¤ÎÅêÍ¿´ü´ÖÃæ¤ÎÂνÅÁý²ÃÎÌ¡¤»ó¤Î¸òÇÛÁ°¡¤Ç¥¿±´ü´Ö¤ª¤è¤ÓÓ®°é´ü´ÖÃæ¤ÎÂνÅÁý²ÃÎ̤Ϥ¤¤º¤ì¤âÂоȷ²¤ËÈæ¤Ù¤Æ¾¯¤Ê¤«¤Ã¤¿¤¬¡¤Åý·×³ØŪͭ°Õº¹¤Ïǧ¤á¤é¤ì¤Ê¤«¤Ã¤¿¡¥

3)¡¡ÀݱÂÎÌ(Fig. 3¡¤4)

»óͺ¤È¤â¡¤ 50 mg/kg·²¤Ç¡¤ÅêÍ¿1Æü¤ÎÀݱÂÎ̤ÏÂоȷ²¤ËÈæ¤Ù¤ÆÍ­°Õ¤Ë¾¯¤Ê¤«¤Ã¤¿¡¥ÅêÍ¿8Æü°Ê¹ß¤Ï¡¤Í­°Õ¤ÊÊѲ½¤Ïǧ¤á¤é¤ì¤Ê¤«¤Ã¤¿¡¥

4)¡¡Íº¤ÎÇ¢½ê¸«¡¤·ì±Õ³Ø½ê¸«¤ª¤è¤Ó·ì±ÕÀ¸²½³Ø½ê¸«(Table 1)

Ç¢¤ª¤è¤Ó·ì±Õ³Ø½ê¸«¤Ç¤Ï¡¤³Æ¸¡ºº¹àÌܤËÍ­°Õ¤ÊÊѲ½¤Ïǧ¤á¤é¤ì¤Ê¤«¤Ã¤¿¡¥·ì±ÕÀ¸²½³Ø½ê¸«¤Ç¤Ï¡¤Í­°Õ¤ÊÁí¥¿¥ó¥Ñ¥¯¤ÎÁý²Ã¤ª¤è¤ÓÇ¢ÁÇÃâÁǤθº¾¯¤¬¡¤ 50 mg/kg·²¤Çǧ¤á¤é¤ì¤¿¡¥

5)¡¡Ë¶¸¡½ê¸«

À¸Â¸Æ°Êª¤Ë¤ª¤¤¤Æ¡¤Íº¤Ï´Î¡¤Î¼ðÂ礬 50 mg/kg·²¤Î2ɤ¡¤¿Õ¡¤Î¼ðÂ礬10 mg/kg·²¤Î1ɤ¤ª¤è¤Ó50 mg/kg¤Î3ɤ¤Ëǧ¤á¤é¤ì¤¿¡¥»ó¤Ï´Î¡¤Î¼ðÂ礬¡¤50 mg/kg·²¤Î1ɤ¤Ëǧ¤á¤é¤ì¤¿¡¥»ó¤Î50 mg/kg·²¤ÎÀÚÇ÷ÅË»¦Æ°Êª¤Ë¤Ï¡¤´Î¡¤ª¤è¤Ó¿Õ¡¤ÎÂ࿧¡¤Éû¿Õ¤ÎÈîÂ硦Â࿧¡¤¶»Á£¤ª¤è¤Óç£Â¡¤Î°à½Ì¤¬Ç§¤á¤é¤ì¤¿¡¥¤³¤ì¤é¤Î½ê¸«°Ê³°¤Ë¤â¡¤³Æ·²¤ËÊѲ½¤¬Ç§¤á¤é¤ì¤¿¤¬¡¤»¶È¯Åª¤Ç¡¤È︳ʪ¼ÁÅêÍ¿¤È¤Î´ØÏ¢À­¤Ï¤ß¤é¤ì¤Ê¤«¤Ã¤¿¡¥

6)¡¡´ï´±½ÅÎÌ(Table 2)

ͺ¤Ë¤ª¤¤¤Æ¡¤¤¤¤º¤ì¤âÍ­°Õ¤Ê´Î¡¤ÎÀäÂФª¤è¤ÓÁêÂнÅÎ̤ÎÁý²Ã¤¬ 50 mg/kg·²¤Ë¡¤¿Õ¡¤ÎÀäÂнÅÎ̤ÎÁý²Ã¤¬10 mg/kg·²¡¤ÀäÂФª¤è¤ÓÁêÂнÅÎ̤ÎÁý²Ã¤¬50 mg/kg·²¤Ëǧ¤á¤é¤ì¤¿¡¥»ó¤Ë¤ª¤¤¤Æ¤â¡¤´Î¡¤ª¤è¤Ó¿Õ¡½ÅÎ̤ÎÁý²Ã·¹¸þ¤¬50 mg/kg·²¤Ç¤ß¤é¤ì¤¿¤¬¡¤Í­°Õº¹¤Ï¿Õ¡¤ÎÁêÂнÅÎ̤ˤΤßǧ¤á¤é¤ì¤¿¡¥

7)¡¡ÉÂÍýÁÈ¿¥³Ø½ê¸«(Table 3)

È︳ʪ¼Á¤ÎÅêÍ¿¤Ëµ¯°ø¤¹¤ë¤È¹Í¤¨¤é¤ì¤ëÊѲ½¤¬¡¤´Î¡¤ª¤è¤Ó¿Õ¡¤Ëǧ¤á¤é¤ì¤¿¡¥Ç¥¿±¤òÀ®Î©¤µ¤»¤¿Íº¤Ë¤ª¤¤¤Æ¡¤´ÎºÙ˦¤Î¾®ÍÕÃæ¿´À­ÈîÂ礬 50 mg/kg·²¤Î9ɤÃæ4ɤ¤Ëǧ¤á¤é¤ì¤¿¡¥¿Õ¡¤Ç¤Ï¡¤¶á°ÌÇ¢ºÙ´É¾åÈé¤ËPASÍÛÀ­¾Ë»ÒÅ©¤¬Âоȷ²¤Ë¤âǧ¤á¤é¤ì¤¿¤¬¡¤10 mg/kg·²¤Î10ɤÃæ5ɤ¤ª¤è¤Ó50 mg/kg·²¤Î9ɤÁ´Îã¤Ç¤Ï¡¤¤½¤Î¿ô¤ª¤è¤ÓÂ礭¤µ¤¬ÌÀ¤é¤«¤ËÁý²Ã¤·¤Æ¤¤¤¿¡¥¤Þ¤¿¡¤¤ä¤ä°à½Ì¤·¡¤Â¿³Ë¤Ç¡¤¾ã³²¸å¤ÎºÆÀ¸Áü¤È¹Í¤¨¤é¤ì¤ë¹¥±ö´ðÀ­Ç¢ºÙ´É¤ÎÌÜΩ¤ÄÎ㤬¡¤50 mg/kg·²¤Î2ɤ¤Ëǧ¤á¤é¤ì¤¿¡¥Ê¬ÊÚ¤·¡¤Ó®°é¤â½çÄ´¤Ç¤¢¤Ã¤¿»ó¤Ë¤ª¤¤¤Æ¤Ï¡¤´ÎºÙ˦¤ÎÈîÂ礬50 mg/kg·²¤Î8ɤÃæ3ɤ¤Ëǧ¤á¤é¤ì¤¿¡¥Ç¥¿±¤¬À®Î©¤·¤Ê¤«¤Ã¤¿ÂФˤª¤¤¤Æ¤Ï¡¤50 mg/kg·²¤Î1ÂФÎͺ¤Î´Î¡¤ª¤è¤Ó¿Õ¡¤Ë¡¤Ç¥¿±¤òÀ®Î©¤µ¤»¤¿Íº¤ÈƱÍͤÎÊѲ½¤¬¤ß¤é¤ì¤¿¤¬¡¤»óͺ¤È¤â²¼¿âÂΤäÀ¸¿£´ï·Ï´ï´±¤Ë°Û¾ï¤Ïǧ¤á¤é¤ì¤Ê¤«¤Ã¤¿¡¥50 mg/kg·²¤Î»ó¤ÎÀÚÇ÷ÅË»¦Æ°Êª¤Ë¤ª¤¤¤Æ¤Ï¡¤´ÎºÙ˦¡¤¿Õ¡¤Î¶á°ÌÇ¢ºÙ´É¾åÈé¤Ê¤é¤Ó¤Ë°ß¤ª¤è¤Ó¾®Ä²Ç´ËìɽÁؾåÈé¤Î»éËÃÊÑÀ­¡¤¿Õ¡¤Î¹¥±ö´ðÀ­Ç¢ºÙ´É¤ÎÁý²Ã¤ª¤è¤Ó±ó°ÌÇ¢ºÙ´É¤Î³ÈÄ¥¡¤ç£Â¡¤ª¤è¤Ó¶»Á£¤Î°à½Ì¡¤¹ü¿ñ¤Î¤·ì¸º¾¯¤Ê¤É¤Î½ê¸«¤¬Ç§¤á¤é¤ì¤¿¡¥°Ê¾å¤ÎÊѲ½°Ê³°¤Ë¤â¸¡ºº¤·¤¿´ï´±¤Ë°Û¾ï¤¬Ç§¤á¤é¤ì¤¿¤¬¡¤»¶È¯Åª¤¢¤ë¤¤¤ÏÍÑḬ̂͸À­·¹¸þ¤Î¤Ê¤¤½ê¸«¤Ç¤¢¤Ã¤¿¡¥

2.¡¡À¸¿£È¯À¸ÆÇÀ­

1)¡¡¿Æưʪ¤ËµÚ¤Ü¤¹±Æ¶Á(Table 4)

(1) ¸òÈøΨ¤ª¤è¤Ó¼õÂÛΨ

¸òÈø¤Ï¡¤Æ±µï³«»Ï 5Æü°ÊÆâ¤Ë¡¤Âоȷ²¤ª¤è¤ÓÈ︳ʪ¼ÁÅêÍ¿³Æ·²¤ÎÁ´Îã¤ËÀ®Î©¤·¤¿¡¥¼õÂÛΨ¤â¡¤Âоȷ²¤Î90¡ó¤ËÂФ·¡¤È︳ʪ¼ÁÅêÍ¿³Æ·²¤Ç¤Ï80¡Á100¡ó¤ÎÈϰϤˤ¢¤ê¡¤Í­°Õ¤ÊÊѲ½¤Ïǧ¤á¤é¤ì¤Ê¤«¤Ã¤¿¡¥

(2) ²«Âοô¡¤Ãå¾²¿ô¤ª¤è¤ÓÃ徲Ψ

Âоȷ²¤Î²«Âοô¤Ï 18.3¡¤Ãå¾²¿ô¤Ï17.6¡¤Ã徲Ψ¤Ï95.6¡ó¤Ç¤¢¤Ã¤¿¡¥È︳ʪ¼ÁÅêÍ¿³Æ·²¤Î²«Âοô¡¤Ãå¾²¿ô¡¤Ã徲Ψ¤È¤âÂоȷ²¤ÈÎà»÷¤·¤¿Ãͤò¼¨¤·¡¤Í­°Õ¤ÊÊѲ½¤Ïǧ¤á¤é¤ì¤Ê¤«¤Ã¤¿¡¥

(3) ½Ð»ºÎ¨¤ª¤è¤ÓÇ¥¿±´ü´Ö

½Ð»ºÎ¨¤Ï¡¤Âоȷ²¤ª¤è¤ÓÈ︳ʪ¼ÁÅêÍ¿³Æ·²¤È¤â 100¡ó¤Ç¤¢¤Ã¤¿¡¥Ç¥¿±´ü´Ö¤Ï¡¤Âоȷ²¤Î22.6Æü¤ËÂФ·¡¤È︳ʪ¼ÁÅêÍ¿³Æ·²¤Ç¤Ï22.3¡Á22.5Æü¤ÎÈϰϤˤ¢¤ê¡¤Í­°Õ¤ÊÊѲ½¤Ïǧ¤á¤é¤ì¤Ê¤«¤Ã¤¿¡¥

(4) ʬÊÚ¤ª¤è¤ÓÓ®°é¾õÂÖ

50 mg/kg·²¤ÎÀÚÇ÷ÅË»¦¤·¤¿1ɤ¤ò½ü¤¤¤Æ¡¤¤¤¤º¤ì¤Îưʪ¤Ë¤âʬÊÚ¤ª¤è¤ÓÓ®°é¾õÂ֤˰۾ï¤Ïǧ¤á¤é¤ì¤Ê¤«¤Ã¤¿¡¥ÀÚÇ÷ÅË»¦Îã¤ÏÇ¥¿±Ëö´ü¤«¤é°ìÈ̾õÂÖ¤¬°­²½¤·¡¤¼«Á³Ê¬ÊÚ¤·¤¿¤¬Ê¬ÊÚ³Îǧ»þ¤Ë¤ª¤¤¤Æ16ɤÃæ9ɤ¤Î»ùưʪ¤Ï»àË´¤·¤Æ¤¤¤¿¡¥¿Æưʪ¤ÏʬÊÚ¸å°ìÈ̾õÂÖ¤¬¤µ¤é¤Ë°­²½¤·¡¤Ó®°é¹ÔÆ°¤ò¼è¤é¤º¡¤Ó®°é2Æü¤Þ¤Ç¤Ë»Ä¤ê¤Î»ùưʪ¤âÁ´Î㤬»àË´¤·¤¿¡¥Á´»ù¤¬»àË´¤·¤¿»þÅÀ¤Ç¡¤¿Æưʪ¤ÏÉλà¾õÂ֤Ǥ¢¤Ã¤¿¡¥

2)¡¡¿·À¸»ù¤ËµÚ¤Ü¤¹±Æ¶Á(Table 5)

(1) À¸Â¸À­

Âоȷ²¤Î 1Ê¢Åö¤¿¤êÁí½Ð»º»ù¿ô¤Ï16.7ɤ¡¤Ê¬ÊÚΨ¤Ï95.0¡ó¤Ç¤¢¤Ã¤¿¡¥¤Þ¤¿¡¤¿·À¸»ù¿ô¤Ï16.3ɤ¡¤½ÐÀ¸Î¨¤Ï98.0¡ó¡¤À­Èæ¤Ï0.88¡¤Ó®°é4ÆüÀ¸Â¸Î¨¤Ï99.3¡ó¤Ç¤¢¤Ã¤¿¡¥10 mg/kg°Ê²¼¤Î·²¤Ç¤Ï¡¤¤³¤ì¤é¤Î»Øɸ¤ÏÂоȷ²¤ÈÎà»÷¤·¤¿Ãͤò¼¨¤·¤¿¡¥50 mg/kg·²¤Ë¤ª¤¤¤Æ¤â¡¤¾å½Ò¤ÎÀÚÇ÷ÅË»¦¤·¤¿1ɤ¤Î»ó¿Æ¤ÇÁ´»ù¤¬»àË´¤·¤¿¤¿¤á¡¤Ó®°é4ÆüÀ¸Â¸Î¨¤¬Âоȷ²¤ËÈæ¤Ù¤Æ¤ä¤äÄãÃͤò¼¨¤·¤¿¤¬¡¤Í­°Õ¤ÊÊѲ½¤Ç¤Ï¤Ê¤«¤Ã¤¿¡¥À¸Â¸¤·¤¿¿·À¸»ù¤Î°ìÈ̾õÂ֤ˡ¤°Û¾ï¤Ïǧ¤á¤é¤ì¤Ê¤«¤Ã¤¿¡¥

(2) ÂνÅ

Âоȷ²¤ÎÓ®°é 0Æü¤Ë¤ª¤±¤ëÂνŤÏͺ7.1 g¡¤»ó6.7 g¤ËÂФ·¡¤È︳ʪ¼ÁÅêÍ¿³Æ·²¤Ïͺ6.7¡Á7.0¡¤»ó6.3¡Á6.6 g¤ÎÈϰϤˤ¢¤Ã¤¿¡¥¤Þ¤¿Ó®°é4Æü¤Ë¤ª¤±¤ëÂνŤÏÂоȷ²¤Îͺ11.2 g¡¤»ó10.9 g¤ËÂФ·¡¤È︳ʪ¼ÁÅêÍ¿³Æ·²¤Ïͺ10.7¡Á11.3 g¡¤»ó10.2¡Á10.5 g¤ÎÈϰϤˤ¢¤ê¡¤¤¤¤º¤ì¤âÍ­°Õ¤ÊÊѲ½¤Ïǧ¤á¤é¤ì¤Ê¤«¤Ã¤¿¡¥

(3) ·ÁÂÖ

È︳ʪ¼Á¤ÎÅêÍ¿¤Ëµ¯°ø¤¹¤ë¤È¹Í¤¨¤é¤ì¤ë³°É½¤ª¤è¤ÓÆ⡤ΰ۾ï¤Ïǧ¤á¤é¤ì¤Ê¤«¤Ã¤¿¡¥³°É½°Û¾ï¤Ë¤Ä¤¤¤Æ¤Ï¡¤ 10 mg/kg·²¤ÇĹɡ¡¤´ãµå¤ª¤è¤Ó²¼³Ü¤Î·ç»¡¤¾®¼ª¡¤¿°Îö¤Ê¤É´éÌ̤ÎÊ£¹ç°Û¾ï¤òÍ­¤¹¤ë1ɤ¤¬Ç§¤á¤é¤ì¤¿¡¥¤³¤ÎÎã¤ÏʬÊÚ³Îǧ»þ¤Ë»àË´¤·¤Æ¤¤¤¿¡¥Æâ¡°Û¾ï¤Ï¡¤¤¤¤º¤ì¤Î»ùưʪ¤Ë¤âǧ¤á¤é¤ì¤Ê¤«¤Ã¤¿¡¥Æâ¡ÊѰۤˤĤ¤¤Æ¤Ï¡¤¶»Á£¤Î·ÛÉô»Äα¡¤º¸çÁÆ°Ì®°ä»Ä¤¢¤ë¤¤¤ÏÇ¢´É¤Î³ÈÄ¥¡¦¶þ¶Ê¤¬Áí·×Âоȷ²¤Ç2ɤ(1.3¡ó)¡¤0.4 mg/kg·²¤Ç4ɤ(2.9¡ó)¡¤2 mg/kg·²¤Ç1ɤ(0.5¡ó)¡¤10 mg/kg·²¤Ç1ɤ(0.6¡ó)¤ª¤è¤Ó50 mg/kg·²¤Ç5ɤ(3.6¡ó)ǧ¤á¤é¤ì¤¿¡¥¤·¤«¤·¡¤¤³¤ì¤é¤Îȯ¸½Î¨¤Ë¤Ï·²´Ö¤Ë¡¤Í­°Õ¤Êº¹¤Ïǧ¤á¤é¤ì¤Ê¤«¤Ã¤¿¡¥

¹Í»¡¤ª¤è¤Ó·ëÏÀ

1.¡¡È¿ÉüÅêÍ¿ÆÇÀ­

ͺ¿Æ¤Ë¤Ä¤¤¤Æ¡¤ÅêÍ¿½éÆü¤ÎÅêÍ¿¸å¡¤¼«È¯±¿Æ°Äã²¼¤ª¤è¤Óή޷¤¬¤Û¤ÜÁ´Îã¤Ëǧ¤á¤é¤ì¡¤ÀݱÂÎ̤⸺¾¯¤·¤¿¡¥¤·¤«¤·¡¤¤³¤ì¤é¤ÎÊѲ½¤Ï°ì²áÀ­¤Ç¡¤ÂçÉôʬ¤ÎÎã¤Ç¤ÏÅêÍ¿ 2Æü°Ê¹ß¾É¾õ¤Ï¾Ã¼º¤·¡¤ÀݱÂÎ̤âÅêÍ¿8Æü°Ê¹ßÂоȷ²¤ÈÈæ¤Ù¤Æº¹¤Ï¤Ê¤¯¡¤ÂνŤËÂФ·¤ÆÍ­°Õ¤ÊÊѲ½¤Ïǧ¤á¤é¤ì¤Ê¤«¤Ã¤¿¡¥ÉÂÍý³Ø¸¡ºº¤Ë¤ª¤¤¤Æ¡¤´Î¡½ÅÎ̤ÎÁý²Ã¤ª¤è¤Ó´Î¡¤ÎÆù´ãŪ¼ðÂçÎ㤬50 mg/kg·²¤Ëǧ¤á¤é¤ì¡¤ÁÈ¿¥³ØŪ¤Ë¤Ï´ÎºÙ˦¤ÎÈîÂ礬´Ñ»¡¤µ¤ì¤¿¡¥·ì±ÕÀ¸²½³Ø¸¡ºº¤Çǧ¤á¤é¤ì¤¿Áí¥¿¥ó¥Ñ¥¯¤ÎÁý²Ã¤Ï¡¤¤³¤Î´Î¡¤Î·ÁÂÖŪÊѲ½¤È´ØÏ¢¤¹¤ë½ê¸«¤È¹Í¤¨¤é¤ì¡¤´Îµ¡Ç½¤ËÂФ·¤Æ¤Ï¤à¤·¤íж¿ÊŪ¤Ê±Æ¶Á¤¬¤¦¤«¤¬¤ï¤ì¤¿¡¥¤·¤«¤·¤Ê¤¬¤é¡¤14Æü´Ö¤ÎÅêÍ¿ÎÌÀßÄê»î¸³¤Ë¤ª¤¤¤Æ¤Ï¡¤100 mg/kg°Ê¾å¤Ç¥°¥ë¥³¡¼¥¹¤Î¸º¾¯¡¤300 mg/kg¤ÇGOT¡¤GPT¡¤¦Ã-GTP¡¤Áí¥Ó¥ê¥ë¥Ó¥ó¤ÎÁý²Ã¤ª¤è¤Ó¥×¥í¥È¥í¥ó¥Ó¥ó»þ´Ö¤Î±äŤ¬Ç§¤á¤é¤ì¤Æ¤¤¤ë¡¥¤·¤¿¤¬¤Ã¤Æ¡¤¤è¤ê¹âÍÑÎ̤ÎÅêÍ¿¤Ç¤Ï¡¤´Î¡¤ËÂФ·¾ã³²Åª¤Ë±Æ¶Á¤¹¤ë¤È¿ä»¡¤µ¤ì¤ë¡¥

¿Õ¡¤Ë¤ª¤¤¤Æ¤Ï¡¤ 10 mg/kg°Ê¾å¤Î·²¤Ç¶á°ÌÇ¢ºÙ´É¾åÈé¤Ë¤ª¤±¤ëPASÍÛÀ­¾Ë»ÒÅ©¤ÎÁý²Ã¤¬Ç§¤á¤é¤ì¡¤¿Õ¡½ÅÎ̤ÏÁý²Ã¤·¡¤Æù´ãŪ¤Ë¤â¿Õ¡¤¬¼ðÂ礹¤ëÎ㤬¤¢¤Ã¤¿¡¥

Ç¢ºÙ´É¾åÈé¤Î¾Ë»ÒÅ©¤Ï¡¤Â¿¤¯¤Î²½³Øʪ¼Á¤Çͺ¥é¥Ã¥È¤Ø¤ÎÅêÍ¿¤Ë¤è¤êÁý²Ã¤¹¤ë¤³¤È¤¬ÃΤé¤ì¤Æ¤ª¤ê 2, 3, 4)¡¤¤³¤ì¤Ï¦Á2u-¥°¥í¥Ö¥ê¥ó¤ÎÄÀÃåÁü¤Ç¡¤¶á°ÌÇ¢ºÙ´É¾åÈé¤Ë¤ª¤±¤ë¥¿¥ó¥Ñ¥¯¤ÎºÆµÛ¼ý¤¢¤ë¤¤¤Ï¤½¤ÎÂå¼Õ²áÄø¤ËÂФ¹¤ë²¿¤é¤«¤Î¾ã³²¤Ë¤è¤ë¤â¤Î¤È¹Í¤¨¤é¤ì¤Æ¤¤¤ë4)¡¥

¤·¤«¤·¤Ê¤¬¤é¡¤Ç¢¸¡ºº¤ª¤è¤Ó·ì±ÕÀ¸²½³Ø¸¡ºº¤Ë¤ª¤¤¤Æ¤Ï¡¤¿Õµ¡Ç½¤Î°Û¾ï¤ò¼¨º¶¤¹¤ë½ê¸«¤Ïǧ¤á¤é¤ì¤º¡¤¿Õ¡¤ËÂФ¹¤ë±Æ¶Á¤È¤·¤Æ¤Ï¡¤·ÚÅ٤ʤâ¤Î¤ÈȽÃǤµ¤ì¤ë¡¥

°ìÊý¡¤»ó¿Æ¤Ë¤ª¤¤¤Æ¤â¡¤Íº¿Æ¤ÈƱÍͤ˰ìÈ̾õÂÖ¤ª¤è¤ÓÀݱÂÎ̤ËÂФ¹¤ë°ì²áÀ­¤Î±Æ¶Á¤¬ 50 mg/kg·²¤Çǧ¤á¤é¤ì¤¿¡¥

´Î¡¤Ç¤Ï¡¤´ÎºÙ˦¤ÎÈîÂ礬 50 mg/kg·²¤Î¾¯¿ô¤Ë¤ß¤é¤ì¤¿¤¬¡¤´Î¡½ÅÎ̤ˤÏÍ­°Õ¤ÊÊѲ½¤Ïǧ¤á¤é¤ì¤Ê¤«¤Ã¤¿¡¥¤Þ¤¿¡¤¿Õ¡¤Ë¤ª¤¤¤Æ¤â¡¤ÁêÂнÅÎ̤ΤߤÎÁý²Ã¤¬50 mg/kg·²¤Ç¤ß¤é¤ì¤¿¤¬¡¤ÉÂÍýÁÈ¿¥³ØŪ¤Ë¤ÏÊѲ½¤Ïǧ¤á¤é¤ì¤Ê¤«¤Ã¤¿¡¥¤·¤¿¤¬¤Ã¤Æ¡¤´Î¡¤ª¤è¤Ó¿Õ¡¤ËÂФ¹¤ë±Æ¶Á¤Ï¡¤Íº¿Æ¤ËÈæ¤Ù¤Æ¤è¤ê·ÚÅ٤ʤâ¤Î¤È¹Í¤¨¤é¤ì¤¿¡¥

50mg/kg·²¤Î»ó¿Æ¤Î1ɤ¤ÏÇ¥¿±Ëö´ü¤«¤é°ìÈ̾õÂÖ¤¬°­²½¤·¡¤Ó®°é2Æü¤ËÉλà¾õÂ֤Ȥʤ俤ΤÇÀÚÇ÷ÅË»¦¤·¤¿¡¥¤³¤ÎÎã¤ÎÉÂÍýÁÈ¿¥³Ø¸¡ºº¤Ç¤Ï¡¤ÆÃħŪ¤ÊÊѲ½¤È¤·¤Æ¡¤´ÎºÙ˦¡¤¿Õ¡ǢºÙ´É¾åÈé¤Ê¤é¤Ó¤Ë°ß¤ª¤è¤Ó¾®Ä²Ç´Ëì¤ÎɽÁؾåÈé¤Ë»éËÃÊÑÀ­¤¬Ç§¤á¤é¤ì¡¤Á´¿ÈŪ¤Ê»é¼ÁÂå¼Õ¤Î°Û¾ï¤¬¤¦¤«¤¬¤ï¤ì¤¿¡¥¤·¤«¤·¤Ê¤¬¤é¡¤¤³¤ÎÊѲ½¤ÏÀ¸Â¸Æ°Êª¤Ë¤Ïǧ¤á¤é¤ì¤º¡¤¤Þ¤¿¡¤¤è¤ê¹âÍÑÎÌÅêÍ¿¤·¤¿ÅêÍ¿ÎÌÀßÄê»î¸³¤Ë¤ª¤¤¤Æ¤â¡¤ÁÈ¿¥¤Î»éËÃÊÑÀ­¤ò¤¦¤«¤¬¤ï¤»¤ë´ï´±¤ÎÆù´ãŪÊѲ½¤Ïǧ¤á¤é¤ì¤Æ¤¤¤Ê¤¤¤³¤È¤«¤é¡¤È︳ʪ¼Á¤Ë¤è¤ëľÀÜŪ¤ÊÆÇÀ­±Æ¶Á¤È¹Í¤¨¤ë¤Î¤Ïº¤Æñ¤Ç¤¢¤Ã¤¿¡¥

°Ê¾å¤Î·ë²Ì¤«¤é¡¤ 3,4-¥¸¥¯¥í¥í-1-¥Ö¥Æ¥ó¤Î¥é¥Ã¥È¤Ø¤ÎÈ¿ÉüÅêÍ¿¤Ë¤è¤ê¡¤´Î¡¤ª¤è¤Ó¿Õ¡¤ËÂФ¹¤ë±Æ¶Á¤¬Ç§¤á¤é¤ì¤¿¡¥Ìµ±Æ¶ÁÎ̤ϡ¤Íº2 mg/kg/day¡¤»ó10 mg/kg/day¤È¿äÄꤵ¤ì¤¿¡¥

2.¡¡À¸¿£È¯À¸ÆÇÀ­

ͺ¿Æ¤ª¤è¤Ó»ó¿Æ¤ÎÀ¸¿£¤ËÂФ·¤Æ¤Ï¡¤´Ñ»¡¤·¤¿³Æ»Øɸ¤È¤âÂоȷ²¤È¤Î´Ö¤ËÍ­°Õ¤Êº¹¤Ïǧ¤á¤é¤ì¤Ê¤«¤Ã¤¿¡¥¤Þ¤¿¡¤»ùưʪ¤ÎȯÀ¸¤ËÂФ·¤Æ¤â¡¤Í­°Õ¤Ê±Æ¶Á¤Ïǧ¤á¤é¤ì¤Ê¤«¤Ã¤¿¡¥

50 mg/kg·²¤Ç¡¤Ê¬ÊÚ¸åÓ®°é¹ÔÆ°¤¬Ç§¤á¤é¤ì¤º¡¤Á´»ù¤¬»àË´¤·¤¿»ó¿Æ¤¬Ç§¤á¤é¤ì¤¿¤¬¡¤¤³¤ÎÎã¤ÏÇ¥¿±Ëö´ü¤«¤é°ìÈ̾õÂÖ¤¬°­²½¤·¡¤Ó®°é2Æü¤ËÉλà¾õÂ֤Ȥʤ俤³¤È¡¤¤ª¤è¤Ó²¼¿âÂΤäÀ¸¿£´ï·Ï´ï´±¤Ë¤Ï°Û¾ï¤Ïǧ¤á¤é¤ì¤Ê¤«¤Ã¤¿¤³¤È¤«¤é¡¤½ÅÅ٤ʰìÈÌÆÇÀ­³ØŪ±Æ¶Á¤Ëȼ¤¦½ê¸«¤ÈȽÃǤµ¤ì¤ë¡¥

¤Þ¤¿¡¤¸òÈø¤¬³Îǧ¤µ¤ì¤¿¤Ë¤â¤«¤«¤ï¤é¤ºÇ¥¿±¤·¤Ê¤«¤Ã¤¿ÂФ¬¡¤ÅêÍ¿Î̤ȤÏ̵´Ø·¸¤Ë»¶È¯¤·¤¿¤¬¡¤¤¤¤º¤ì¤ÎÂФˤâÀ¸¿£Ç½¤Î°Û¾ï¤ò¼¨º¶¤¹¤ëÉÂÍý³ØŪ¤Ê°Û¾ï¤Ïǧ¤á¤é¤ì¤º¡¤¶öȯŪ¤Ê¤â¤Î¤È¹Í¤¨¤é¤ì¤¿¡¥

ËÜÈ︳ʪ¼Á¤Î°ÛÀ­ÂΤǤ¢¤ë 1,4-¥¸¥¯¥í¥í-2-¥Ö¥Æ¥ó¤Ë¤Ä¤¤¤Æ¡¤Ç¥¿±¥é¥Ã¥È¤Ø¤ÎµÛÆþÅêÍ¿¤Ë¤è¤ê¡¤æõ¤Î³Ë»À¤ª¤è¤ÓÅüÂå¼Õ¤Ë±Æ¶Á¤¬¤ß¤é¤ì¡¤Ãå¾²¸å¤Îæõ¤Î»à˴Ψ¤¬Áý²Ã¤¹¤ë¤È¤ÎÊó¹ð5)¤¬¤¢¤ë¡¥¤·¤«¤·¡¤3,4-¥¸¥¯¥í¥í-1-¥Ö¥Æ¥ó¤Î¥é¥Ã¥È¤Ø¤Î·Ð¸ýÅêÍ¿¤Ë¤ª¤¤¤Æ¤Ï¡¤Ãå¾²¸å¤Îæõ¤ËÂФ¹¤ë±Æ¶Á¤ò¼¨º¶¤¹¤ëÊѲ½¤Ïǧ¤á¤é¤ì¤Ê¤«¤Ã¤¿¡¥

°Ê¾å¤Î·ë²Ì¤«¤é¡¤»óͺ¿Æưʪ¤ÎÀ¸¿£Ç½¤ª¤è¤Ó»ùưʪ¤ÎȯÀ¸¤ËÂФ¹¤ë±Æ¶Á¤Ï¡¤ 50 mg/kg/dayÅêÍ¿¤Ë¤è¤Ã¤Æ¤âǧ¤á¤é¤ì¤º¡¤Ìµ±Æ¶ÁÎ̤Ϥ¤¤º¤ì¤â¡¤50 mg/kg/day¤È¿äÄꤵ¤ì¤¿¡¥

ʸ¸¥

1)E. J. van Kampen, W. G. Zijlstra, Adv. Clin. Chem., 8, 141(1965).
2)C. A. Halder, C. E. Holdsworth, B. Y. Cockrell, V. J. Piccirillo, Toxicol. Indust. Health, 1, 67(1985)¡¥
3)M. Charbonneau, J. Strasser, E. A. Lock, M. J. Tumer, J. A. Swenberg, Toxicol. Appl. Pharmacol., 99, 122(1989)¡¥
4)S. J. Broghoff, B. G. Shrt, J. A. Swenberg, Annu. Rev. Pharmacol. Toxicol., 30, 349(1990)¡¥
5)F. R. Petronsyan, Zh. Arm., 35(5), 830(1982).

Ï¢ÍíÀè
»î¸³ÀÕǤ¼Ô¡§°ËÆ£µÁɧ
»î¸³Ã´Åö¼Ô¡§»³Ëܾù¡¤ÀÖÌÚÇ²¼Ê¿ÍµÆó¡¤
Ê¡ÅÄÉÄÈþ¡¤ÈÍ·ª½ï
¡Êºâ¡ËÃÜ»ºÀ¸Êª²Ê³Ø°ÂÁ´¸¦µæ½ê
¢©229-11¡¡¿ÀÆàÀÁêÌϸ¶»Ô¶¶ËÜÂæ3-7-11
Tel 0427-62-2775Fax 0427-62-7979

Correspondence
Authors:Yoshihiko Ito (Study director)
Yuzuru Yamamoto, Hiroshi Akagi, Yuuji Shimodaira,
Naemi Fukuda, Cleo Pan
Research Institute for Animal Science in Biochemistry and Toxicology
3-7-11 Hashimotodai, Sagamihara-shi, Kanagawa, 229-11, Japan
Tel +81-427-62-2775Fax +81-427-62-7979