ホ౯఍㆟ሗ࿌᭩
ARE-Nrf2 Luciferase Test Method㸦ゅ໬⣽⬊ᰴ࣏࣮ࣞࢱ࣮࢔ࢵࢭ࢖㸧

JaCVAM ホ౯఍㆟

ᖹᡂ 27 ᖺ㸦2015 ᖺ㸧4 ᭶ 30 ᪥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㒊㸧㔠Ꮚ࿴ᘯ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᳃⏣ ೺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ゅ໬⣽⬊ᰴ࣏࣮ࣞࢱ࣮࢔ࢵࢭ࢖㸸Antioxidant response element (ARE)-Nrf21 Luciferase TestMethod㸦௨ୗࠊᮏヨ㦂ἲ࡜グࡍ㸧ࡣࠊ໬Ꮫ≀㉁ࡢ⓶⭵ឤసᛶࢆணࡍࡿヨ㦂ἲ࡛࠶ࡾࠊᚑ

᮶ࡢࣔࣝࣔࢵࢺࢆ⏝࠸ࡿ⓶⭵ឤసᛶヨ㦂㸦OECD TG406㸧
ࠊ࣐࢘ࢫࢆ⏝࠸ࡿᒁᡤࣜࣥࣃ⠇ヨ㦂㸦Local Lymph Node Assay (LLNA)ࠊOECD TG429㸧࠾ࡼࡧ LLNA ࡢኚἲ࡛࠶ࡿ LLNA:DA(OECD TG442A)࡞ࡽࡧ࡟ LLNA:BrdU-ELISA (OECD TG442B)࡜ẚ࡭ࠊື≀ࢆ⏝࠸࡞࠸࡜࠸࠺≉ᚩࢆ᭷ࡍࡿࠋᮏヨ㦂ἲࡣࠊ⓶⭵ឤసᛶࢆ᭷ࡍࡿከࡃࡢ໬Ꮫ≀㉁ࡀ ARE ࡟ࡼࡾไᚚࡉࢀ࡚࠸ࡿ㑇ఏᏊࡢⓎ⌧ࢆㄏᑟࡍࡿࡇ࡜࠿ࡽࠊࡇࡢㄏᑟάᛶࢆᇵ㣴⣽⬊ࢆ⏝࠸࡚࡟ࡼࡾࠊ⓶⭵ឤసᛶࡢ᭷↓ࢆணᐃࡍࡿࡇ࡜ࡍࡿヨ㦂ἲ࡛࠶ࡿࠋᮏヨ㦂ἲࡢࣂࣜࢹ࣮ࢩࣙࣥ◊✲ࡢ⤖ᯝ࡟ࡘ࠸࡚ࡣࠊEuropean Union Reference Laboratory for Alternatives to Animal Testing (EURLECVAM)࡟ࡼࡿ➨୕⪅ホ౯ࡀ⤊஢ࡋ࡚࠸ࡿ㸯㸧ࠋJaCVAM ホ౯఍㆟ࡣࠊ⓶⭵ឤసᛶヨ㦂㈨ᩱ⦅
⧩ጤဨ఍࡟ࡼࡾసᡂࡉࢀࡓ⓶⭵ឤసᛶヨ㦂 ゅ໬⣽⬊ᰴ࣏࣮ࣞࢱ࣮࢔ࢵࢭ࢖ࡢホ౯ሗ࿌᭩ࢆᇶ࡟ᮏヨ㦂ἲࡢጇᙜᛶ࡟ࡘ࠸᳨࡚ウࡋࡓࠋ㸯㸬ヨ㦂ἲࡢᐃ⩏ྡ⛠㸸 ゅ໬⣽⬊ᰴ࣏࣮ࣞࢱ࣮࢔ࢵࢭ࢖㸸ARE-Nrf2 Luciferase Test Method௦᭰ࡍࡿᑐ㇟ẘᛶヨ㦂㸸 ࣔࣝࣔࢵࢺࢆ⏝࠸ࡿ⓶⭵ឤసᛶヨ㦂㸦OECD TG406㸧࠾ࡼࡧ࣐࢘ࢫ ࢆ ⏝ ࠸ ࡿ ᒁ ᡤ ࣜ ࣥ ࣃ ⠇ ヨ 㦂 [LLNA (OECD TG429) ࠊ LLNA:DA (OECD TG442A) ࠊLLNA:BrdU-ELISA (OECD TG442B)]
ヨ㦂ἲࡢᴫ␎㸸  ᮏヨ㦂ἲࡣࠊNrf2-Keap12-ARE pathway ࢆ฼⏝ࡋࠊࢣࣛࢳࣀࢧ࢖ࢺ⏤᮶
ARE-Nrf2 ࣝࢩࣇ࢙࣮ࣛࢮ࣏࣮ࣞࢱ࣮㑇ఏᏊࢆ⏝࠸ࡓ࣏࣮ࣞࢱ࣮࢔ࢵࢭ࢖࡛࠶ࡿ 1)ࠋ
 Nrf2-Keap1-ARE pathway ࡣࠊ㌿෗ᅉᏊ Nrf2ࠊNrf2 ࡢᢚไᅉᏊ Keap1 ࠾ࡼࡧ ARE ࡀ㛵ಀࡍࡿ㑇ఏᏊⓎ⌧⤒㊰࡛࠶ࡿࠋNrf2 ࡣ Keap1 ࡜⤖ྜࡋࠊARE ࡟౫Ꮡࡋ࡚Ⓨ⌧ࡍࡿ㑇ఏᏊ⩌ࡢⓎ⌧㔞ࢆไᚚࡋ࡚࠸ࡿࠋKeap1 ࡢࢩࢫࢸ࢖ࣥṧᇶ࡟ồ㟁Ꮚᛶࡢ໬Ꮫ≀㉁ࡀ⤖ྜࡍࡿ࡜ࠊNrf2
ࡣ Keap1 ࠿ࡽゎ㞳ࡋࠊ᰾ෆ࡬⛣⾜ࡋ࡚ DNA ୖࡢ ARE ࡟⤖ྜࡍࡿࠋࡑࡢ⤖ᯝࠊୗὶࡢ㑇ఏᏊ⩌ࡢⓎ⌧ࡀㄏᑟࡉࢀࠊ໬Ꮫ≀㉁࡟ࡼࡿ㞀ᐖ࠿ࡽ⣽⬊ࢆಖㆤࡍࡿࡓࡵ࡟ᶵ⬟ࡍࡿࠋ⓶⭵ឤసᛶࢆ᭷ࡍࡿከࡃࡢ໬Ꮫ≀㉁ࡀ Nrf2-Keap1-ARE pathway ࢆάᛶ໬ࡍࡿࡇ࡜ࡀ▱ࡽࢀ࡚࠸ࡿࠋᮏヨ㦂ἲ࡛ࡣࠊAKR1C2 㑇ఏᏊ㸦ᶞ≧⣽⬊࡟࠾࠸࡚⓶⭵ឤసᛶ≀㉁࡟ࡼࡾⓎ⌧ㄏᑟࡉࢀࡿ㑇ఏᏊࡢ 1 ࡘ㸧ࡢ ARE ࢆ⼥ྜࡉࡏࡓ SV40 ࣉ࣮ࣟࣔࢱ࣮ࢆ᭷ࡍࡿࣝࢩࣇ࢙࣮ࣛࢮ㑇ఏᏊࡢࣉࣛࢫ࣑ࢻࢆᏳᐃⓗ࡟ᑟධࡋࡓ HaCaT ⣽⬊㸦ࣄࢺࢣࣛࢳࣀࢧ࢖ࢺ⏤᮶ᇵ㣴⣽⬊ᰴ㸧ࢆ⏝࠸ࡿࠋ໬Ꮫ≀㉁࡟ࡼࡾ Nrf2-Keap1-ARE pathway ࡀάᛶ໬ࡉࢀࡿ࡜ࣝࢩࣇ࢙࣮ࣛࢮ㑇ఏᏊࡀⓎ⌧ࡍࡿࠋᇶ㉁ࢆῧຍࡋ࡚ࣝࢩࣇ࢙࣮ࣛࢮࡀゐ፹ࡍࡿ཯ᛂࡢⓎගᙉᗘࢆᐃࡍࡿࡇ࡜࡟ࡼࡾࠊ໬Ꮫ≀㉁ࡢ⓶⭵ឤసᛶࡀホ౯ࡉࢀࡿࠋ
12

Nrf2㸸Nuclear factor (erythroid-derived 2)-like 2
Keap1: Kelch-like ECH-associated protein 133㸰㸬ホ౯࡟⏝࠸ࡓ㈨ᩱ࠾ࡼࡧホ౯ෆᐜࡢ⛉Ꮫⓗጇᙜᛶᮏヨ㦂ἲࡣࠊKeratinoSensTM3 ࢆ⏝࠸࡚ᐇ᪋ࡉࢀࡓࣂࣜࢹ࣮ࢩࣙࣥ◊✲ 2-5)࡜ࡑࢀ࡟⥆ࡃ
EURL ECVAM Scientific Advisory Committee ࡟ࡼࡾ⊂❧ࡋࡓ➨୕⪅ホ౯ࡀᐇ᪋ࡉࢀ 1)ࠊ⓶⭵ឤసᛶヨ㦂ࡢ௦᭰ἲ࡜ࡋ࡚⛉Ꮫⓗ࡟ጇᙜ࡛࠶ࡿ࡜ሗ࿌ࡉࢀ࡚࠸ࡿࠋᮏ㑥࡟࠾࠸࡚ࡣࠊJaCVAM ⓶⭵ឤసᛶヨ㦂㈨ᩱ⦅⧩ጤဨ఍ࡀࠊᮏヨ㦂ἲࡢ⓶⭵ឤసᛶヨ㦂௦᭰ἲ࡜ࡋ࡚ࡢ⛉Ꮫⓗጇᙜᛶ࡟ࡘ࠸࡚ࠊබ㛤ࡉࢀ࡚࠸ࡿ᝟ሗ 1-5)ࢆᇶ࡟ホ౯ࡋࡓࠋホ౯ࡢ⤖ᯝࠊᮏヨ㦂ἲࡣࠊ⓶⭵ឤసᛶࢆ᭷ࡍࡿከࡃࡢ໬Ꮫ≀㉁ࡀ ARE ࡟ࡼࡾไᚚࡉࢀ࡚࠸ࡿ㑇ఏᏊࡢⓎ⌧ࢆㄏᑟࡍࡿ࡜࠸࠺⓶⭵ឤసᛶⓎ⌧ᶵᗎ࡟࠾ࡅࡿ㔜せ࡞࢖࣋ࣥࢺࢆ᳨ฟࡋ࡚࠾ࡾࠊ⓶⭵ឤసᛶヨ㦂ࡢ௦᭰
ヨ㦂ἲ࡜ࡋ࡚ཎ⌮ⓗጇᙜᛶࡀ࠶ࡿ࡜⪃࠼ࡽࢀࡓ 6)ࠋ
࡞࠾ࠊ෌⌧ᛶࢆ᳨ウࡋࡓࣂࣜࢹ࣮ࢩࣙࣥヨ㦂࡟࠾࠸࡚⿕㦂≀㉁㑅ᢥ࡟೫ࡾࡀ࠶ࡾࠊ᪋タෆ࣭᪋タ㛫෌⌧ᛶ࡟ࡣ␃ពࡍ࡭ࡁ࡛࠶ࡿ࡜ホ౯఍㆟ࡣุ᩿ࡋࡓࠋ㸱㸬ᮏヨ㦂ἲࡢ᭷⏝ᛶ࡜㐺⏝㝈⏺
ᮏヨ㦂ἲࡣࠊࣄࢺࢣࣛࢳࣀࢧ࢖ࢺ⏤᮶ᇵ㣴⣽⬊ᰴࢆ⏝࠸ࡿ in vitro ヨ㦂ἲ࡛ࠊ3Rs ࡢ⢭⚄࡟ྜ⮴ࡋ࡚࠸ࡿࠋࡲࡓࠊ㸯⿕㦂≀㉁ᙜࡓࡾࡢࣛࣥࢽࣥࢢࢥࢫࢺࡶࠊ࣐࢘ࢫࢆ⏝࠸ࡿ LLNA
࡜ẚ㍑ࡋ࡚ 1/7 ⛬ᗘ࡛ᐇ᪋ྍ⬟࡛࠶ࡾࠊヨ㦂ᮇ㛫ࡶ LLNA ࡼࡾ▷ᮇ㛫࡛࠶ࡿࡇ࡜࠿ࡽࠊᮏヨ㦂ἲࡣ⡆౽ᛶ࠾ࡼࡧ⤒῭ᛶࡢ㠃࠿ࡽ᭷⏝࡜࠸࠼ࡿࠋ᭦࡟ࠊ⓶⭵ឤసᛶࢆ᭷ࡍࡿከࡃࡢ໬Ꮫ≀㉁ࡀ ARE ࡟ࡼࡾไᚚࡉࢀ࡚࠸ࡿ㑇ఏᏊࡢⓎ⌧ࢆㄏᑟࡍࡿࡇ࡜࠿ࡽࠊᮏヨ㦂ἲࡣࠊࡇࡢㄏᑟάᛶࢆᇵ㣴⣽⬊ࢆ⏝࠸࡚ᐃࡍࡿࡇ࡜࡟ࡼࡾࠊ⓶⭵ឤసᛶࡢ᭷↓ࢆணࡍࡿࡶࡢ࡛࠶ࡾࠊ໬Ꮫ≀㉁ࡢឤసᛶࢆุ᩿ࡍࡿୖ࡛㔜せ࡞᝟ሗࢆ୚࠼ࡿࠋࡋ࠿ࡋ࡞ࡀࡽࠊ⌧᫬Ⅼ࡛ࡇࡢヨ㦂࡟౑⏝࡛ࡁࡿ⣽⬊⣔ࡣ KeratinoSensTM ࡢࡳ࡛࠶ࡾࠊ౑⏝࡟ࡣ⣽⬊⣔ࢆᶞ❧ࡋࡓ Givaudan ♫࠿ࡽࣛ࢖ࢭࣥࢫࢆྲྀᚓࡍࡿࡇ࡜ࡀᚲせ࡛࠶ࡾࠊ㈝⏝ࡶྵࡵ࡚฼⏝ྍ⬟࡞᮲௳ࡢヲ⣽ࡣ୙࡛᫂࠶ࡿࠋ୍᪉ࠊKeratinoSensTM ࢆ౑⏝ࡋ࡞࠸ሙྜࡣࠊOECDసᡂࡢᮏヨ㦂ἲ࡟㛵ࡍࡿ Performance Standard㸦᱌㸧7)࡟ᚑ࠸ࠊጇᙜᛶࢆ♧ࡉ࡞ࡅࢀࡤ࡞ࡽ࡞
࠸ࠋࡲࡓࠊLogP ࡀ 7 ௨ୖࡢᙉ␯Ỉᛶ≀㉁ࡣࠊDMSO ࡜Ỉ࡬ࡢ⁐ゎ≉ᛶ࠿ࡽヨ㦂࡟㐺⏝࡛ࡁ࡞࠸ࠋ㓟↓Ỉ≀ࡣࠊࣜࢪࣥṧᇶ࡜཯ᛂᛶࢆ♧ࡍ≉ᚩࡀ࠶ࡾࠊࢩࢫࢸ࢖ࣥᇶ࡜ࡢ཯ᛂࡀᚲせ࡞ Nrf2 pathway ࢆㄏᑟࡋ࡞࠸ࡓࡵࠊഇ㝜ᛶ࡜ุᐃࡉࢀࡿྍ⬟ᛶࡀ࠶ࡿࠋࣝࢩࣇ࢙࣮ࣛࢮ㓝⣲࡟ᖸ΅ࡍࡿ໬Ꮫ≀㉁࡛ࡣࠊࣝࢩࣇ࢙࣮ࣛࢮάᛶࢆṇࡋࡃᐃࡍࡿࡇ࡜ࡀ࡛ࡁ࡞࠸ࡓࡵὀពࡀᚲせ࡛࠶ࡿࠋ㓟໬཯ᛂࡸ㓟໬ⓗ⬺࢔࣑ࣀ཯ᛂࢆᚲせ࡜ࡍࡿከࡃࡢࣉࣞࣁࣉࢸࣥࡣṇࡋࡃุᐃࡉࢀࡿࡀࠊࢩࢺࢡ࣒ࣟ P450 ࡟ࡼࡿάᛶ໬ࢆᚲせ࡜ࡍࡿࣉࣟࣁࣉࢸࣥࡣ᳨ฟ࡛ࡁ࡞࠸ࠋᇵ㣴⣽⬊ࢆ⏝࠸ࡿヨ㦂⣔ࡢࡓࡵࠊ⣽⬊ẘᛶࡢᙉ࠸≀㉁ࡣ㐺ษ࡞⃰ᗘ࡛ヨ㦂ࡀ࡛ࡁ࡞࠸ሙྜ
ࡀ࠶ࡿࠋ100 ≀㉁௨ୖࢆホ౯ࡋࡓሗ࿌ 4,5)࡟࠾ࡅࡿᮏヨ㦂ἲࡢឤᗘࡣࠊ76.7%࡜ 77%࡛࠶ࡿࡓࡵࠊ㝜ᛶࡢ⤖ᯝࡀᚓࡽࢀ࡚ࡶഇ㝜ᛶࡢྍ⬟ᛶࢆ⪃៖ࡍࡿᚲせࡀ࠶ࡿࠋࡲࡓࠊ≉␗ᗘࡶࠊ82.1%
3

KeratinoSensTM㸸Givaudan ♫࡟ࡼࡗ࡚ᶞ❧ࡉࢀࡓࢣࣛࢳࣀࢧ࢖ࢺ⏤᮶ ARE-Nrf2 ࣝࢩࣇ࢙࣮ࣛࢮ࣏࣮ࣞࢱ࣮㑇ఏᏊࡢࣉࣛࢫ࣑ࢻࢆᏳᐃⓗ࡟ᑟධࡋࡓࣄࢺࢣࣛࢳࣀࢧ࢖ࢺ⏤᮶ᇵ㣴⣽⬊ᰴ44࡜ 79%࡛࠶ࡿࡇ࡜࠿ࡽࠊ㝧ᛶࡢ⤖ᯝࡀᚓࡽࢀࡓሙྜ࡟ࡶࠊഇ㝧ᛶࡢྍ⬟ᛶࡀ࠶ࡿࡇ࡜࡟␃ពࡋ࡞ࡅࢀࡤ࡞ࡽ࡞࠸ࠋ㸲㸬┠ⓗ࡜ࡍࡿ≀㉁ཪࡣ〇ရࡢẘᛶࢆホ౯ࡍࡿヨ㦂ἲ࡜ࡋ࡚ࡢࠊ♫఍ⓗཷࡅධࢀᛶ࠾ࡼࡧ⾜ᨻୖࡢ฼⏝ࡢྍ⬟ᛶ ♫఍ⓗཷࡅධࢀᛶ㸸 ᮏヨ㦂ἲࡣࠊ⣽⬊ᇵ㣴ᢏ⾡࠾ࡼࡧ 96 ✰ࣉ࣮ࣞࢺ⏝࣑ࣝࣀ࣓࣮ࢱ࣮᧯సᢏ⾡ࢆಟᚓࡋ࡚࠸ࢀࡤᐜ᫆࡟ᐇ᪋࡛ࡁࡿヨ㦂࡛࠶ࡿࠋࡓࡔࠊ⌧᫬Ⅼ࡛౑⏝࡛ࡁࡿ⣽⬊⣔ࡣ KeratinoSensTM ࡢࡳ
࡛࠶ࡾࠊ㈍኎ඖ࡛࠶ࡿ Givaudan ♫࠿ࡽࣛ࢖ࢭࣥࢫࢆྲྀᚓࡍࡿᚲせࡀ࠶ࡿࠋᮏヨ㦂ἲࡢᐇ᪋࡜⤖ᯝࡢゎ㔘࡟ᙜࡓࡗ࡚ࡣࠊ໬Ꮫ≀㉁ࡢᛶ㉁࡜ࡑࡢ㐺⏝㝈⏺ࢆぢᴟࡵࡿᚲせࡀ࠶ࡿࠋࡋ࠿ࡋࠊᮏヨ㦂ἲࡣࠊ⓶⭵ឤసᛶࢆ᭷ࡍࡿከࡃࡢ໬Ꮫ≀㉁ࡀ ARE ࡟ࡼࡾไᚚࡉࢀ࡚࠸ࡿ㑇ఏᏊࡢⓎ⌧ࢆㄏᑟࡍࡿ࡜࠸࠺⓶⭵ឤసᛶⓎ⌧ᶵᗎ࡟࠾ࡅࡿ㔜せ࡞࢖࣋ࣥࢺࢆ᳨ฟࡋ࡚࠾ࡾࠊ໬Ꮫ≀㉁ࡢ⓶⭵ឤసᛶࢆ⪃࠼ࡿୖ࡛㔜せ࡞᝟ሗࢆ୚࠼ࡿࡇ࡜࠿ࡽࠊᮏヨ㦂ἲࡢ♫఍ⓗཷࡅධࢀᛶࡣ㧗࠸ࡶࡢ࡜⪃࠼ࡿࠋ ⾜ᨻୖࡢ฼⏝ᛶ㸸 ᮏヨ㦂ἲ࡛㝧ᛶࡢ⤖ᯝࡀᚓࡽࢀࡓሙྜࠊࡑࡢ໬Ꮫ≀㉁ࢆᙉ࠸ឤసᛶ≀㉁࡛࠶ࡿ
GHS(Globally Harmonized System of Classification and Labelling of Chemicals)༊ศ㸯࡟ศ㢮ࡍࡿࡇ࡜ࡣ⾜ᨻୖྍ⬟࡛࠶ࡿࠋࡋ࠿ࡋ࡞ࡀࡽࠊ⛥࡟ഇ㝧ᛶࡢ⤖ᯝࡀ⏕ࡌࡿࡇ࡜࡟␃ពࡋ࡞ࡅࢀࡤ࡞ࡽ࡞࠸ࠋ୍᪉ࠊᮏヨ㦂ἲ࡛㝜ᛶࡢ⤖ᯝࡀᚓࡽࢀࡓሙྜࠊࡑࡢ໬Ꮫ≀㉁ࡢ⓶⭵ឤసᛶࡣഇ㝜ᛶࡢྍ⬟ᛶࡀ࠶ࡾࠊᮏヨ㦂ἲ༢⊂࡛ࡑࡢ⓶⭵ឤసᛶࢆุᐃࡍࡿࡇ࡜ࡣ㞴ࡋ࠸ࠋᮏヨ㦂ἲࡣࠊࡑࡢ≉ᛶࢆ༑ศ࡟⌮ゎࡋࡓୖ࡛ࠊIATA (Integrated Approaches to Testing and Assessment) ࢆᵓᡂࡍࡿࡑࡢ௚ࡢ᝟ሗ※࡜⤌ࡳྜࢃࡏ࡚㐺ษ࡟ホ౯ࡍࡿࡇ࡜ࡀࠊ⾜ᨻⓗ࡞ཷࡅධࢀ࡟ᚲせ࡛࠶ࡿ࡜⪃࠼ࡿࠋ55