║่⃭ᛶヨ㦂௦᭰ἲࡢホ౯఍㆟ሗ࿌᭩

2013 ᖺᨵゞ OECD TG 438 ࢽ࣡ࢺࣜࡢ᦬ฟ║⌫ࢆ⏝࠸ࡓ║่⃭ᛶヨ㦂(ICE ἲ:Isolated Chicken Eye Test)

JaCVAM ホ౯఍㆟

ᖹᡂ 26 ᖺ㸦2014 ᖺ㸧10 ᭶ 28 ᪥11JaCVAM ホ౯఍㆟኱㔝Ὀ㞝  㸦㐠Ⴀጤဨ఍᥎⸀㸧㸸ᗙ㛗஬༑ᔒⰋ᫂ 㸦ᅜ❧་⸆ရ㣗ရ⾨⏕◊✲ᡤ ⏕ά⾨⏕໬Ꮫ㒊㸧୍㨣 ຮ㸦᪥ᮏ໬Ꮫᕤᴗ༠఍㸧⠛⏣࿴ಇ㸦⊂❧⾜ᨻἲே ་⸆ရ་⒪ᶵჾ⥲ྜᶵᵓ㸧ᮡᒣ┿⌮Ꮚ 㸦᪥ᮏ໬⢝ရᕤᴗ㐃ྜ఍㸧㇂ᕝᾈᏊ㸦᪥ᮏື≀ᐇ㦂௦᭰ἲᏛ఍㸧すᕝ⛅ె㸦ᅜ❧་⸆ရ㣗ရ⾨⏕◊✲ᡤ Ᏻ඲ᛶ⏕≀ヨ㦂◊✲ࢭࣥࢱ࣮㸧ᖹ㈡⚽᫂㸦⊂❧⾜ᨻἲே ་⸆ရ་⒪ᶵჾ⥲ྜᶵᵓ㸧∾ ᰤ஧㸦᪥ᮏච␿ẘᛶᏛ఍㸧ቑ⏣ග㍤㸦ᗙ㛗᥎⸀㸧᳃⏣ ೺㸦᪥ᮏ⎔ቃኚ␗ཎᏛ఍㸧ᒣ⏣㝯ᚿ㸦⊂❧⾜ᨻἲே 〇ရホ౯ᢏ⾡ᇶ┙ᶵᵓ㸧ᶓ㛵༤㞝㸦᪥ᮏ⓶⭵࢔ࣞࣝࢠ࣮࣭᥋ゐ⓶⭵⅖Ꮫ఍㸧ྜྷ⏣Ṋ⨾㸦᪥ᮏẘᛶᏛ఍㸧ྜྷ⏣ ⥳ 㸦ᅜ❧་⸆ရ㣗ရ⾨⏕◊✲ᡤ Ᏻ඲ᛶ⏕≀ヨ㦂◊✲ࢭࣥࢱ࣮ ⑓⌮㒊㸧ྜྷᮧ ຌ㸦ᗙ㛗᥎⸀㸧Ώ㒊୍ே㸦᪥ᮏ〇⸆ᕤᴗ༠఍㸧                  ௵ᮇ㸸ᖹᡂ 26 ᖺ 4 ᭶ 1 ᪥㹼ᖹᡂ 28 ᖺ 3 ᭶ 31 ᪥22ࢽ࣡ࢺࣜࡢ᦬ฟ║⌫ࢆ⏝࠸ࡓ║่⃭ᛶヨ㦂(Isolated Chicken Eye Testࠊ௨ୗ ICE ἲ)ࡣࠊ࢘ࢧࢠࢆ⏝࠸ࡓ Draize ║่⃭ᛶヨ㦂(௨ୗࠊDraize ἲ)ࡢ௦᭰ヨ㦂ἲ࡛࠶ࡿࠋ2003 ᖺ࠿ࡽ 2006 ᖺ࡟࠿ࡅ࡚ࠊࢺࢵࣉࢲ࢘ࣥ᪉ᘧ࡟࠾ࡅࡿ㔜⠜࡞║ࡢയᐖࢆᘬࡁ㉳ࡇࡍ໬Ꮫ≀㉁(UN GHS ༊ศ 1 ≀㉁)ࢆྠᐃࡍࡿࡓ
ࡵࡢヨ㦂ἲ࡜ࡋ࡚ࠊ
ᅇ㢳ⓗࣂࣜࢹ࣮ࢩࣙࣥࡀ NICEATM/ICCVAM ࡟ࡼࡾ࡞ࡉࢀࠊ2009 ᖺ࡟ OECD TG
438 (௨ୗࠊTG438(2009)1))࡜ࡋ࡚᥇ᢥࡉࢀࡓࠋ
ࡇࢀ࡜ࡣู࡟ NICEATM/ICCVAM ࡣࠊECVAM ࠾ࡼࡧ JaCVAM ࡢ༠ຊࡢୗࠊ2006 ᖺ࠿ࡽ 2010ᖺ࡟࠿ࡅ࡚ࠊ࣎ࢺ࣒࢔ࢵࣉ᪉ᘧ࡟࠾ࡅࡿ༊ศእ≀㉁ࡢྠᐃἲ࡜ࡋ࡚ࡢ㐺⏝ᛶ࡟㛵ࡍࡿᅇ㢳ⓗࣂࣜࢹ࣮ࢩࣙࣥࢆ᪂ࡓ࡟⾜ࡗࡓࠋࣂࣜࢹ࣮ࢩࣙࣥ࡟ࡣࠊึᅇ࡟౑⏝ࡉࢀࡓ ICCVAM ࢹ࣮ࢱ(2006)2)ࡀࡑࡢ
ࡲࡲ⏝࠸ࡽࢀ࡚ゎᯒࡀ࡞ࡉࢀࡓࡀࠊICE ἲᣑ኱㐺⏝ࡢᥦゝ࡟ࡣ⮳ࡽ࡞࠿ࡗࡓࠋ
ࡑࡢᚋࠊ2012 ᖺࠊOECD ᑓ㛛ጤဨ఍࡟ࡼࡾ UN GHS ༊ศୗ࡟࠾࠸࡚෌ホ౯ࡀᐇ᪋ࡉࢀࡓࠋ
ึᅇ࡟౑⏝ࡉࢀࡓࢹ࣮ࢱ࣮࣋ࢫ࡟࠾ࡅࡿ in vivo ࠾ࡼࡧ in vitro ୧᪉ࡢࢹ࣮ࢱࡀぢ┤ࡉࢀࡓ࡯࠿ࠊinvitro ࡢ༊ศእᇶ‽ࡀṇᘧ࡟タᐃࡉࢀࡓࠋࡑࡇ࡛ᨵࡵ࡚ホ౯ࡀ⾜ࢃࢀࡓ⤖ᯝࠊICE ἲࡣࢺࢵࣉࢲ࢘ࣥ᪉ᘧ࡟࠾ࡅࡿ UN GHS ༊ศ 1 ≀㉁ࡢྠᐃࡢࡳ࡞ࡽࡎࠊ࣎ࢺ࣒࢔ࢵࣉ᪉ᘧ࡟࠾ࡅࡿ༊ศእ≀㉁ࡢྠᐃ
ἲ࡜ࡋ࡚౑⏝ࡍࡿࡇ࡜ࡀྍ⬟࡛࠶ࡿ࡜ุ᩿ࡉࢀࠊ2013 ᖺ 7 ᭶ 26 ᪥௜ࡅ࡛ 2013 ᖺᨵゞ TG 438(௨ୗࠊTG438(2013)3))࡜ࡋ࡚᥇ᢥࡉࢀࡓࠋ
TG 438(2013)࡟࠾ࡅࡿ୺࡞ᨵゞⅬࡣࠊ1) ࣎ࢺ࣒࢔ࢵࣉ᪉ᘧ࡟ࡼࡿ UN GHS ༊ศእ≀㉁ྠᐃ࡬ࡢ㐺⏝࠾ࡼࡧ 2) 㐺⏝㝈⏺ࠊ࡛࠶ࡿࠋJaCVAM ホ౯఍㆟ࡣࠊࡇࡢᨵゞࡢጇᙜᛶ࡟ࡘ࠸᳨࡚ウࡋࡓࠋ㸯㸬ヨ㦂ἲࡢᐃ⩏ྡ⛠㸸 2013 ᖺᨵゞ OECD TG 438㸦TG438㸦2013㸧3㸧㸧ࢽ࣡ࢺࣜࡢ᦬ฟ║⌫ࢆ⏝࠸ࡓ║่⃭ᛶヨ㦂 (ICE ἲ: Isolated Chicken Eye Test)௦᭰ࡍࡿᑐ㇟ẘᛶヨ㦂㸸 Draize ἲヨ㦂ἲࡢᴫ␎㸸 ICE ἲࡣࠊࢽ࣡ࢺࣜ࠿ࡽ᦬ฟࡋࡓ║⌫࡟⿕㦂≀㉁ࢆ᭚㟢ࡋࠊࡑࡢ⤖ᯝࠊ║⌫࡟⏕ࡌࡿゅ⭷ࡢኚᛶࢆࠊゅ⭷ࡢ⭘⬽ࠊΰ⃮ᗘ࠾ࡼࡧࣇࣝ࢜ࣞࢭ࢖ࣥᰁⰍᛶࡢኚ໬࡜ࡋ࡚࡜ࡽ࠼ࡿࠋࡇࢀࡽ 3 ホ౯㡯┠ࡢኚ໬ࢆࡑࢀࡒࢀಶูࡢࢫࢥ࢔࡟ኚ᥮ࡋ࡚ᚓࡽࢀࡿ⥲ྜホ౯ࢆࡶ࡜࡟ in vivo ࡛ࡢ║่⃭ᛶࢆணࡍࡿࠋྛホ౯㡯┠ࡢኚ໬ࡣࠊA)ゅ⭷ࡢ⭘⬽㸸ගᏛⓗཌᗘィࢆ⿦╔ࡋࡓ⣽㝽ⅉ㢧ᚤ㙾࡟࡚ゅ⭷ࡢཌࡉࢆᐃࡋࠊ᭚㟢 240 ศᚋࡲ࡛ࡢ⤒᫬ⓗ࡞ኚ໬⋡ࢆᐃ㔞ⓗ࡟ồࡵࡿࠋB)ゅ⭷ࡢΰ⃮ᗘ㸸⣽㝽ⅉ㢧ᚤ㙾࡟࡚ゅ⭷ΰ⃮ᗘࡢ⤒᫬ⓗ࡞ኚ໬ࢆ᭚㟢 240 ศᚋࡲ࡛ほᐹࡍࡿࠋC)ࣇࣝ࢜ࣞࢭ࢖ࣥᰁⰍᛶ㸸⣽㝽ⅉ㢧ᚤ㙾࡟࡚᭚㟢 30 ศᚋࡢゅ⭷⾲㠃ࡢࣇࣝ࢜ࣞࢭ࢖ࣥᰁⰍᛶࢆㄪ࡭ࡿࠋྛ㡯┠ࡢ⤖ᯝࢆയᐖࡢ⛬33ᗘ࡟ࡼࡾࠊ║่⃭ᛶࡢ᭱ࡶᙅ࠸ࢡࣛࢫ I ࠿ࡽ᭱ࡶᙉ࠸ࢡࣛࢫ IV ࡢ 4 ẁ㝵࡟ศ㢮ࡋࠊࡑࢀࡽࡢศ㢮⤖ᯝࢆ⥲ྜࡋ࡚ࠊ⿕㦂≀㉁ࡢ║่⃭ᛶࢆุᐃࡍࡿࠋ㸰㸬ホ౯࡟⏝࠸ࡓ㈨ᩱ࠾ࡼࡧホ౯ෆᐜࡢ⛉Ꮫⓗጇᙜᛶ
NICEATM/ICCVAM ࡟ࡼࡿᅇ㢳ⓗࣂࣜࢹ࣮ࢩࣙࣥࢆ⤒࡚ OECD ࡟࡚ TG 438(2009)࡜ࡋ࡚᥇ᢥࡉ
ࢀࡓᚋࠊ2012 ᖺ࡟ OECD ᑓ㛛ጤဨ఍࡟ࡼࡾ UN GHS ༊ศୗ࡟࠾࠸࡚෌ホ౯ࡀᐇ᪋ࡉࢀࠊ2013 ᖺ࡟ࡣ TG 438(2013)࡜ࡋ࡚᥇ᢥࡉࢀ࡚࠾ࡾࠊࡑࡢホ౯࡟⏝࠸ࡓ㈨ᩱ 1-5)࡜ホ౯ෆᐜ࡟⛉Ꮫⓗጇᙜᛶࡀ࠶ࡿࠋࡲࡓࠊ௒ᅇࡢᨵゞ࡟ඛ❧ࡕ OECD ᑓ㛛ጤဨ఍࡟ࡼࡾࠊ๓ᅇホ౯ࢆ⾜ࡗࡓ ICCVAM(2006)ࣂࣜࢹ
࣮ࢩࣙࣥࢹ࣮ࢱ࣮࣋ࢫࡢ 175 ≀㉁࡟ࡘ࠸࡚ࠊin vivo ࠾ࡼࡧ in vitro ࡢಶࠎࡢࢹ࣮ࢱ࡟ࡘ࠸࡚෌ホ౯ࡉࢀࡓࡀࠊ᭱⤊ⓗ࡟࣎ࢺ࣒࢔ࢵࣉ᪉ᘧࡢホ౯࡟ࡣ 175 ≀㉁୰ 152 ≀㉁㸦༢୍≀㉁㸸72ࠊΰྜ≀㉁㸸
80㸧ࡀࠊࢺࢵࣉࢲ࢘ࣥ᪉ᘧࡢホ౯࡟ࡣ 140 ≀㉁㸦༢୍≀㉁㸸65ࠊΰྜ≀㉁㸸75㸧ࡀ⏝࠸ࡽࢀࠊ༑ศ࡞ᩘࢆ⏝࠸࡚ホ౯ࡉࢀ࡚࠸ࡿࠋ㸱㸬ᮏヨ㦂ἲࡢ᭷⏝ᛶ࡜㐺⏝㝈⏺
➨୕⪅ホ౯ሗ࿌᭩(ICCVAM 20064)ࠊ➨୕⪅ホ౯ሗ࿌᭩ 20126))࡛ሗ࿌ࡉࢀ࡚࠸ࡿ࡜࠾ࡾࠊࢺࢵࣉࢲ
࢘ࣥ᪉ᘧ࠾ࡼࡧ࣎ࢺ࣒࢔ࢵࣉ᪉ᘧ࡟࠾ࡅࡿ᪋タෆ࣭᪋タ㛫෌⌧ᛶࡣ㧗࠸ࠋࡲࡓࠊ㐺⏝㝈⏺࡟㛵ࡋ࡚ࡣࠊ㜵ở᭷ᶵ⁐፹ྵ᭷ሬᩱࠊᅛయ≀㉁ࠊ⏺㠃άᛶ๣࠾ࡼࡧ࢔ࣝࢥ࣮ࣝ㢮࡟ࡘ࠸࡚ࡣࠊ㧗࠸ഇ㝜ᛶ⋡࠶ࡿ࠸ࡣഇ㝧ᛶ⋡ࡀ♧ࡉࢀࡓࡀࠊ௨ୗࡢ⌮⏤࠿ࡽࡇࢀࡽࡢ໬Ꮫ≀㉁࡟ࡶ ICE ἲࢆ㐺⏝ࡍࡿࡇ࡜ࡀ࡛ࡁࡿ࡜ሗ࿌ࡉࢀࡓࠋ࣎ࢺ࣒࢔ࢵࣉ᪉ᘧ㸸࣭㜵ở᭷ᶵ⁐፹ྵ᭷ሬᩱ࡛㝧ᛶ 2 ≀㉁ࡢ࠺ࡕࠊ1 ≀㉁㸦TNO-94㸧ࡀഇ㝜ᛶ࡛࠶ࡗࡓࡀࠊ⏝㏵ࡢ㢮ఝࡋࡓ໬ྜ≀㸦TNO-93㸧ࡣ㝧ᛶ࡛࠶ࡗࡓࠋᚑࡗ࡚ࠊICE ἲ࡬ࡢ㐺⏝㡿ᇦ࠿ࡽ㝖እࡍࡿ࡟ࡣ᰿ᣐࡀ୙༑ศ࡛࠶ࡾࠊ㜵ở᭷ᶵ⁐፹ྵ᭷ሬᩱࢆ㐺⏝㡿ᇦ࠿ࡽ㝖እࡍࡿᚲせࡣ࡞࠸ࠋ࣭༢୍≀㉁ࠊΰྜ≀㉁ࠊᾮయࠊᅛయ➼࡟࠾ࡅࡿഇ㝜ᛶ⋡ࡣ 5㸣௨ୗ࡜ప࠸ࠋഇ㝧ᛶ⋡࡟ࡘ࠸࡚ࡣࠊICE ἲ࡛ࡣ 33%࡜௚ࡢヨ㦂ἲ࡟ẚ࡭ప࠸ࡇ࡜ࡀ♧ࡉࢀࡓ㸦BCOP㸦Bovine Corneal Opacity andPermeability㸧ἲ; 69㸣ࠊCM (Cytosensor Microphysiometer)ἲ㸸68%5㸧㸧ࠋ༢୍≀㉁࠾ࡼࡧ⏺㠃άᛶ๣࡟ࡘ࠸࡚ࡢഇ㝧ᛶ⋡ࡣ㧗࠸ࡀࠊ࣎ࢺ࣒࢔ࢵࣉ᪉ᘧ࡟࠾࠸࡚㝧ᛶ࡜ุ᩿ࡉࢀࡓሙྜ࡟ࡣࠊ௚ࡢ㐺ษ࡞ヨ㦂ἲ࡟ࡼࡿ☜ㄆࡀᚲせ࡜ࡉࢀ࡚࠸ࡿࡇ࡜࠿ࡽࠊࡇࢀࡽࡢ໬Ꮫ≀㉁ࢆ㐺⏝㡿ᇦ࠿ࡽ㝖እࡍࡿᚲせࡣ࡞࠸ࠋࢺࢵࣉࢲ࢘ࣥ᪉ᘧ㸸

44࣭ഇ㝜ᛶ⋡ࡣᅛయ≀㉁࠾ࡼࡧ⏺㠃άᛶ๣࡟࠾࠸࡚㧗ࡃࠊഇ㝧ᛶ⋡ࡣ࢔ࣝࢥ࣮ࣝ㢮࡟࠾࠸࡚㧗࠿ࡗࡓࠋࡋ࠿ࡋࠊࡇࢀࡽࡢศ㢮࡟࠾࠸࡚ࡶ║่⃭ᛶࡀṇ☜࡟ணࡉࢀࡓ≀㉁ࡀ࠶ࡿࡇ࡜ࠊࡉࡽ࡟ࢺࢵࣉࢲ

࢘ࣥ᪉ᘧ࡟࠾࠸࡚㝜ᛶ࡜ุ᩿ࡉࢀࡓሙྜ࡟ࡣ௚ࡢ㐺ษ࡞ヨ㦂ἲ࡟ࡼࡿ☜ㄆࡀᚲせ࡜ࡉࢀ࡚࠸ࡿࡇ࡜࠿ࡽࠊᅛయ≀㉁࠾ࡼࡧ⏺㠃άᛶ๣ࢆ㐺⏝㡿ᇦ࠿ࡽ㝖እࡍࡿᚲせࡣ࡞࠸ࠋࡓࡔࡋࠊ࢔ࣝࢥ࣮ࣝ㢮࡛㝧ᛶ⤖ᯝࡀᚓࡽࢀࡓሙྜࡣࠊ⤖ᯝࡢゎ㔘ࡣៅ㔜࡟ࡍ࡭ࡁ࡛࠶ࡿࠋ ௨ୖ࠿ࡽࠊICE ἲࡣ࣎ࢺ࣒࢔ࢵࣉ᪉ᘧ࡛ࡢ༊ศእ≀㉁࠾ࡼࡧࢺࢵࣉࢲ࢘ࣥ᪉ᘧ࡛ࡢ UN GHS ༊ศ1 ≀㉁ࡢྠᐃἲ࡜ࡋ࡚ࠊࡍ࡭࡚ࡢ✀㢮ࡢ໬Ꮫ≀㉁࡟㐺⏝࡛ࡁࡿ࡜ࡉࢀࡓࠋ㸲㸬┠ⓗ࡜ࡍࡿ≀㉁ཪࡣ〇ရࡢẘᛶࢆホ౯ࡍࡿヨ㦂ἲ࡜ࡋ࡚ࡢࠊ⾜ᨻୖ฼⏝ཬࡧ♫఍ⓗཷࡅධࢀࡢྍ⬟ᛶ ♫఍ⓗཷࡅධࢀᛶ㸸
ICE ἲ࡛ࡣࠊ㣗⏝࡜ࡋ࡚ᒕẅࡉࢀࡓࢽ࣡ࢺࣜࡢ║⌫ࢆ⏝࠸ࡿࡓࡵ Draize ἲࡼࡾࡶ♫఍ⓗཷࡅධࢀᛶࡣ㧗࠸ࠋ௒ᅇࡢᨵゞ࡟࠾࠸࡚ࡣࠊື≀⚟♴ࡢほⅬ࠿ࡽࡢኚ᭦ࡀ࡞࠸ࡇ࡜࠿ࡽࠊᮏᨵゞἲࡢ♫఍ⓗཷࡅධࢀᛶࡣࠊᨵゞ๓࡜ኚࢃࡽ࡞࠸ࠋ ⾜ᨻୖࡢ฼⏝ᛶ㸸  TG 438㸦2013㸧ࡣࠊ໬Ꮫ≀㉁࡟ࡼࡿ║่⃭ᛶࢆホ౯࡛ࡁࠊࢺࢵࣉࢲ࢘ࣥ᪉ᘧ࡟࠾࠸࡚UN GHS༊ศ㸯≀㉁㸦㔜⠜࡞║ࡢയᐖࢆᘬࡁ㉳ࡇࡍ≀㉁㸧࡞ࡽࡧ࡟࣎ࢺ࣒࢔ࢵࣉ᪉ᘧ࡟࠾ࡅࡿUN GHS༊ศእ≀㉁㸦║่⃭ᛶ≀㉁࡜ࡋ࡚ศ㢮ࡉࢀ࡞࠸㸧ࡢ⠊ᅖ࡟࠾࠸࡚⾜ᨻⓗ฼⏝ࡣྍ⬟࡛࠶ࡿ࡜⪃࠼ࡿࠋཧ⪃ᩥ⊩1㸧 OECD Guidelines for The Testing of Chemicals, Isolated Chicken Eye Test forIdentifying Ocular Corrosives and Severe Irritants, TG438 (Adopted 7 September 2009)2㸧 ICCVAM, ICCVAM Test Method Evaluation Report: Current Validation Status of In Vitro TestMethods Proposed for Identifying Eye Injury Hazard Potential of Chemicals and Products. NIH
Publication No. 10-7553. Volume 1 and Volume 2 (2010).
3)

OECD Guidelines for The Testing of Chemicals, Isolated Chicken Eye Test for
Identifying Ocular Corrosives and Severe Irritants, TG438 (Adopted 26 July 2013)4㸧 Streamlined Summary Document Supporting OECD Test Guideline 438 on the Isolated Chicken
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