ホ౯఍㆟ሗ࿌᭩⤒⓶㟁Ẽ᢬ᢠヨ㦂ࢆ⏝࠸ࡓ⓶⭵⭉㣗ᛶヨ㦂௦᭰ἲ

JaCVAM ホ౯఍㆟

ᖹᡂ 29 ᖺ㸦2017 ᖺ㸧7 ᭶ 25 ᪥11JaCVAM ホ౯఍㆟኱ 㔝 Ὀ 㞝 㸦බ┈㈈ᅋἲே ᮌཎグᛕᶓ὾⏕࿨⛉Ꮫ᣺⯆㈈ᅋ㸧㸸ᗙ㛗㣤 ሯ ᑦ ᩥ 㸦⊂❧⾜ᨻἲே ་⸆ရ་⒪ᶵჾ⥲ྜᶵᵓ㸧*஬༑ᔒⰋ᫂ 㸦ᅜ❧་⸆ရ㣗ရ⾨⏕◊✲ᡤ ⏕ά⾨⏕໬Ꮫ㒊㸧▼ ஭ 㞝 ஧ 㸦ᅜ❧་⸆ရ㣗ရ⾨⏕◊✲ᡤ Ᏻ඲ᛶ⏕≀ヨ㦂◊✲ࢭࣥࢱ࣮㸧஭ ୖ ᬛ ᙲ 㸦᪥ᮏච␿ẘᛶᏛ఍㸧௒ ஭ ᩍ Ᏻ 㸦᪥ᮏື≀ᐇ㦂௦᭰ἲᏛ఍㸧ᒾ℩⿱⨾Ꮚ 㸦᪥ᮏ〇⸆ᕤᴗ༠఍㸧⠛ ⏣ ࿴ ಇ 㸦⊂❧⾜ᨻἲே ་⸆ရ་⒪ᶵჾ⥲ྜᶵᵓ㸧ᮡᒣ┿⌮Ꮚ 㸦᪥ᮏ໬⢝ရᕤᴗ㐃ྜ఍㸧௰ ஭ ಇ ྖ 㸦᪥ᮏ໬Ꮫᕤᴗ༠఍㸧୰ᮧࡿࡾࡇ 㸦⊂❧⾜ᨻἲே 〇ရホ౯ᢏ⾡ᇶ┙ᶵᵓ㸧す ᕝ ⛅ ె 㸦ᅜ❧་⸆ရ㣗ရ⾨⏕◊✲ᡤ Ᏻ඲ᛶ⏕≀ヨ㦂◊✲ࢭࣥࢱ࣮㸧἟ ⃝  ⪽ 㸦᪥ᮏẘᛶᏛ఍㸧㔝 ཱྀ ┿ ᕼ 㸦⊂❧⾜ᨻἲே ་⸆ရ་⒪ᶵჾ⥲ྜᶵᵓ㸧**᳃ ⏣  ೺ 㸦᪥ᮏ⎔ቃኚ␗ཎᏛ఍㸧ᶓ 㛵 ༤ 㞝 㸦᪥ᮏ⓶⭵࢔ࣞࣝࢠ࣮࣭᥋ゐ⓶⭵⅖Ꮫ఍㸧                ௵ᮇ㸸ᖹᡂ 28 ᖺ 4 ᭶ 1 ᪥㹼ᖹᡂ 30 ᖺ 3 ᭶ 31 ᪥*㸸ᖹᡂ 28 ᖺ 4 ᭶ 1 ᪥㹼ᖹᡂ 29 ᖺ 3 ᭶ 31 ᪥**㸸ᖹᡂ 29 ᖺ 4 ᭶ 1 ᪥㹼ᖹᡂ 30 ᖺ 3 ᭶ 31 ᪥22ࣛࢵࢺ᦬ฟ⓶⭵ࢆ⏝࠸ࡿ⤒⓶㟁Ẽ᢬ᢠヨ㦂㸦TER: Transcutaneous Electrical Resistance㸧ࡣࠊ࢘ࢧࢠࢆ⏝࠸ࡿ⓶⭵⭉㣗ᛶヨ㦂ࡢ௦᭰࡜ࡋ࡚㛤Ⓨࡉࢀࡓヨ㦂ἲ࡛࠶ࡿࠋᮏヨ㦂ἲ࡛ࡣࠊ⭉㣗ᛶ≀㉁ࡀゅ㉁ᒙ࡟྾཰
ࡉࢀࡓᚋᣑᩓࡋࠊୗᒙࡢ⾲⓶⣽⬊ࢆയᐖࡍࡿ࡜࠸࠺⪃࠼ࢆࡶ࡜࡟ࠊ⿕㦂≀㉁᭚㟢ᚋࡢ㟁Ẽ᢬ᢠ್ࢆᣦᶆ࡜ࡋ࡚⓶⭵⭉㣗ᛶࢆホ౯ࡍࡿࠋᮏヨ㦂ἲ࡟ࡘ࠸࡚ࡣࠊECVAM㸦European Centre for the Validation ofAlternative Methods㸸Ḣᕞ௦᭰ἲホ౯ࢭࣥࢱ࣮㸧࡛ࣂࣜࢹ࣮ࢩࣙࣥ◊✲ࡀᐇ᪋ࡉࢀࠊESAC㸦ECVAMScientific Advisory Committee㸸ECVAM ⛉Ꮫㅎၥ఍㆟㸧ࡸ 1,2,3) ICCVAM㸦Interagency Coordinating Committee
on the Validation of Alternative Methods㸸⡿ᅜ௦᭰ἲ࡟㛵ࡍࡿ┬ᗇ㛫㐃⤡఍㆟㸧4,5)࡟࠾࠸࡚ᮏヨ㦂ἲࡢಙ㢗ᛶ➼ࡀ☜ㄆࡉࢀࡓᚋࠊOECD㸦Organisation for Economic Co-operation and Development㸸⤒῭༠ຊ㛤Ⓨᶵᵓ㸧࡟࡚ࢸࢫࢺ࢞࢖ࢻࣛ࢖ࣥ㸦TG㸧430 ࡜ࡋ࡚ 2004 ᖺ࡟ᢎㄆࡉࢀ࡚࠸ࡿࠋࡇࡢ TG ࡣఱᗘ࠿ᨵゞࡉࢀ࡚࠾ࡾࠊ⌧ᅾࡣ 2015 ᖺ∧࡜࡞ࡗ࡚࠸ࡿ 6)ࠋ
JaCVAM ホ౯఍㆟ࡣࠊ⓶⭵⭉㣗ᛶヨ㦂㈨ᩱ⦅⧩ጤဨ఍࡟ࡼࡾసᡂࡉࢀࡓࠕ⤒⓶㟁Ẽ᢬ᢠヨ㦂ࢆ⏝࠸ࡓ⓶⭵⭉㣗ᛶヨ㦂௦᭰ἲࡢホ౯ሗ࿌᭩ࠖ7)ࢆ⏝࠸࡚ࠊᮏヨ㦂ἲࡢጇᙜᛶ࡟ࡘ࠸᳨࡚ウࡋࡓࠋ㸯㸬ヨ㦂ἲࡢᐃ⩏ྡ⛠㸸 ⤒⓶㟁Ẽ᢬ᢠヨ㦂ࢆ⏝࠸ࡓ⓶⭵⭉㣗ᛶヨ㦂௦᭰ἲ௦᭰ࡍࡿᑐ㇟ẘᛶヨ㦂㸸 ࢘ࢧࢠࢆ⏝࠸ࡿ⓶⭵⭉㣗ᛶヨ㦂ヨ㦂ἲࡢᴫ␎㸸ᮏヨ㦂ἲ࡛ࡣࠊࣛࢵࢺ㸦28-30 ᪥㱋࡯࡝㸧࠿ࡽษ㝖ࡋࡓ 20 mm ෇┙≧ࡢ⓶⭵ࢆヨ㦂ࢩࢫࢸ࣒࡜ࡋ࡚౑⏝ࡍࡿࠋ⿕㦂≀㉁ࢆ⾲⓶㠃࡟୍ᐃ᫬㛫㐺⏝ࡋࠊゅ㉁ᒙ࡟྾཰ࡉࢀࡓᚋ
࡟ᣑᩓࡋࠊୗᒙࡢ⾲⓶⣽⬊࡟ᑐࡋയᐖࡍࡿ⛬ᗘࢆࠊ⤒⓶㟁Ẽ᢬ᢠࢆᣦᶆ࡜ࡋ࡚ᐃࡍࡿࡇ࡜࡟ࡼࡾ⓶⭵⭉㣗ᛶࢆホ౯ࡍࡿࠋࡉࡽ࡟ࠊ㟁Ẽ᢬ᢠࡀ 5 kȍ ௨ୗࡢሙྜ࡟ࡣࠊ10㸣ࢫ࣮ࣝ࣍ࣟࢲ࣑ࣥ㹀ᰁⰍᾮ࡟࡚ᰁⰍࡋࠊ⓶⭵࡟྾╔ࡉࢀࡓⰍ⣲ࡢ㔞ࢆ྾ගᗘ࠿ࡽ⟬ฟࡍࡿࠋࡇࡢ⤖ᯝࠊ⤒⓶㟁Ẽ᢬ᢠࡀ 5㹩Ȑࡼࡾᑠࡉࡃࠊ᫂ࡽ࠿࡟ᦆയࡢ࠶ࡿሙྜ㸦౛࠼ࡤ✸Ꮝ㸧ࠊࡲࡓࡣࠊ᫂ࡽ࠿࡞ᦆയࡀ࡞ࡃ࡚ࡶⰍ⣲㔞ࡀ㝧ᛶᑐ↷≀㉁㸦10㹋ሷ㓟㸧ࡢ⤖ᯝ௨ୖࡢሙྜࠊ⓶⭵⭉㣗ᛶ࡜ุᐃࡍࡿࠋ㸰㸬ホ౯࡟⏝࠸ࡓ㈨ᩱཬࡧホ౯ෆᐜࡢ⛉Ꮫⓗጇᙜᛶᮏヨ㦂ἲࡣࠊECVAM ࡟ࡼࡿᗈ࠸⠊ᅖࡢ⿕㦂≀㉁ࢆ⏝࠸ࡓࣂࣜࢹ࣮ࢩࣙࣥ◊✲࡟ࡼࡾࠊጇᙜᛶࡀ᳨ドࡉࢀࠊESAC ࡟ࡼࡾಙ㢗ᛶ࡜෌⌧ᛶࡣ㧗࠸࡜ホ౯ࡉࢀ࡚࠸ࡿ 1,2,3)ࠋࡇࡢ⤖ㄽࡣࠊICCVAM ࡟࠾࠸࡚ࡶ☜ㄆࡉࢀ࡚࠸ࡿࠋࡇࢀࡽࡢ⤖ᯝࡣබ⾲ࡉࢀ࡚࠾ࡾࠊ㏱࡛᫂⊂❧࡞⛉Ꮫⓗホ౯ࡀ⾜ࢃࢀ࡚࠸ࡿ࡜⪃࠼ࡿ 4,5)ࠋ
ᮏヨ㦂ἲࡣࠊOECD ࡟ࡼࡾヨ㦂ἲ࢞࢖ࢻࣛ࢖ࣥ࡟᥇ᢥࡉࢀࡓ㸦TG 430㸧6)ࠋᮏ㑥࡟࠾࠸࡚ࡣࠊJaCVAM ⓶⭵⭉㣗ᛶヨ㦂㈨ᩱ⦅⧩ጤဨ఍ࡀࠊࡇࢀࡽࡢ㈨ᩱࢆ⏝࠸࡚ᮏヨ㦂ἲࢆホ౯ࡋ࡚࠸ࡿ 7)ࠋࡲࡓࠊᮏヨ㦂ἲࡣࠊ⭉㣗ᛶ≀㉁ࡀゅ㉁ᒙࢆ㏱㐣࣭ᣑᩓࡋࡓࡢࡕ࡟⾲⓶⣽⬊ࢆയᐖࡋࠊ⓶⭵ࡢࣂࣜ࢔ᶵ⬟ࢆയᐖࡍࡿ࡜࠸࠺⓶33⭵യᐖᶵᵓࢆᶍೌࡋ࡚࠾ࡾࠊ⓶⭵ࣂࣜ࢔ᶵ⬟ࡢᣦᶆ࡜ࡋ࡚⤒⓶㟁Ẽ᢬ᢠࢆホ౯ࡋ࡚࠾ࡾࠊ⓶⭵⭉㣗ᛶⓎ⌧ᶵᗎࡀ⪃៖ࡉࢀ࡚࠸ࡿࠋ௨ୖࡢⅬ࠿ࡽࠊᮏヨ㦂ἲࡢホ౯࡟⏝࠸ࡓ㈨ᩱ࡞ࡽࡧ࡟ホ౯ෆᐜ࡟ࡘ࠸࡚ࡣࠊ⓶⭵⭉㣗ᛶࢆホ౯ࡍࡿ᪉ἲ࡜ࡋ࡚⛉Ꮫⓗጇᙜᛶࡀ࠶ࡿ࡜⪃࠼ࡿࠋ㸱㸬ᮏヨ㦂ἲࡢ᭷⏝ᛶ࡜㐺⏝㝈⏺
ᮏヨ㦂ἲ࡟ᑐࡍࡿ Botham1,8)࡜ Fentem3)ࡢண

ᛶࡢ᳨ウ⤖ᯝ࠾ࡼࡧ ICCVAM ࡟ࡼࡿ㞟ィ⤖ᯝࢆ⾲㸯࡟♧ࡋࡓࠋ୧⪅ࡢ⤖ᯝࢆྜࢃࡏࡓ⤖ᯝ࡜ࡑࢀࡒࢀࡢㄽᩥࡢṇ☜ᗘࠊឤᗘࠊ≉␗ᗘ࡟኱ࡁ࡞ᕪࡣ࡞ࡃࠊṇ☜ᗘࡣ⣙ 81㸣ࠊឤᗘࡣ⣙ 94㸣ࠊ≉␗ᗘࡣ⣙ 71㸣࡛࠶ࡗࡓࠋࡇࡢ୰࡛ࠊഇ㝜ᛶࡣ 3 ≀㉁ (6㸣) ࡟ࡘ࠸࡚ㄆࡵࡽࢀ࡚࠸ࡿࡶࡢࡢࠊࡇࢀࡽ 3 ≀㉁ࡢ⭉㣗ᛶࡢ UN GHS1⣽ศ㢮ࡣ࠸ࡎࢀࡶᙉᗘࡀᙅ࠸ഃࡢࣞ࣋ࣝ࡟࠶ࡿ
(UN GHS ༊ศ 1A ࡟ࡣ┦ᙜࡋ࡞࠸)࡜᥎ᐹࡉࢀࡿࡓࡵࠊࠕ⭉㣗ᛶࡣᙉࡃ࡞࠸࡜ุ᩿࡛ࡁࡿ 7)ࠖ࡜࠸࠺㈨ᩱ
⦅⧩ጤဨ఍ࡢุ᩿ࡣᨭᣢ࡛ࡁࡿࠋ

⾲㸯. TER ࡢணᛶICCVAM ࡟ࡼࡿ㞟

Botham et al. (1992 andFentem et al. (1998)ィ⤖ᯝ1996)ឤᗘ

94% (51/54)

96% (27/28)

93% (25/27)≉␗ᗘ

71% (48/68)

70% (26/37)

71% (22/31)ṇ☜ᗘ

81% (99/122)

82% (53/65)

81% (47/58)

OECD ࡢ in vitro ⭉㣗ᛶヨ㦂࢞࢖ࢻࣛ࢖ࣥ࡜ࡋ࡚ࠊ௚࡟ࠕTG431 ࣄࢺ⾲⓶ࣔࢹࣝヨ㦂ࠖ࠾ࡼࡧࠕTG435
in vitro ⭷ࣂࣜ࢔ヨ㦂ࠖࡀ࠶ࡾࠊICCVAM ࡛ࡣᮏヨ㦂ἲ࡜ࡇࢀࡽࡢヨ㦂ἲ (EpiSkinτ, EpiDermτ࠾ࡼࡧ
Corrositex®)࡟ࡘ࠸࡚≉␗ᛶࠊឤᗘࠊṇ☜ᛶ➼ࡢࣂࣜࢹ࣮ࢩࣙࣥ◊✲ࡀẚ㍑ࡉࢀ࡚࠸ࡿ 5,9,10)ࠋࡇࡢ⤖ᯝࠊᮏヨ㦂ἲࡣ௚ࡢヨ㦂ἲ࡜ྠ➼ࡢணᛶࢆ᭷ࡍࡿ࡜ホ౯ࡉࢀ࡚࠸ࡿࠋ௨ୖࡢⅬ࠿ࡽࠊᮏヨ㦂ἲࡣ✀ࠎࡢ໬Ꮫ≀㉁࡟ᑐࡋ࡚㐺⏝࡛ࡁࠊࡍ࡭࡚ࡢࢱ࢖ࣉࡢ⭉㣗ᛶ࠾ࡼࡧ㠀⭉㣗ᛶࢆศ㢮ࡍࡿࡓࡵࡢ௦᭰ἲ࡜ࡋ࡚᭷⏝࡛࠶ࡿ࡜⪃࠼ࡿࠋࡓࡔࡋࠊࣉࣟࢺࢥࣝ࠿ࡽ㢮᥎ࡋ࡚ࠊ㞴Ỉ⁐ᛶࡢᅛయࡸ⢓ᛶࡢ㧗࠸≀㉁ࡣ㐺ษ࡟ホ౯࡛ࡁ࡞࠸ྍ⬟ᛶࡀ࠶ࡿࠋࡲࡓࠊUN GHS ࡟ࡼࡿ⭉㣗ᛶࡢ⣽ศ㢮࡬ࡢ㐺⏝࡟ࡣ᳨ウࡀ୙༑ศ࡛࠶ࡾࠊ᭷⏝ᛶࢆホ౯࡛ࡁ࡞࠸ࠋ࡞࠾ࠊᮏ㑥࡟࠾ࡅࡿ⾜ᨻⓗ࡞ཷࡅධࢀ࡟࠾࠸࡚
ࡣࠊUN GHS ༊ศ㸯ࡢ⣽༊ศࢆồࡵࡽࢀ࡚࠸࡞࠸ࠋ

1ᅜ㐃 ໬Ꮫရࡢศ㢮࠾ࡼࡧ⾲♧࡟㛵ࡍࡿୡ⏺ㄪ࿴ࢩࢫࢸ࣒㸦UN GHS㸸United Nations GloballyHarmonized System of Classification and Labelling of Chemicals㸧
44㸲㸬┠ⓗ࡜ࡍࡿ≀㉁ཪࡣ〇ရࡢẘᛶࢆホ౯ࡍࡿヨ㦂ἲ࡜ࡋ࡚ࡢࠊ♫఍ⓗཷࡅධࢀᛶཬࡧ⾜ᨻୖࡢ฼⏝ࡢྍ⬟ᛶ ♫఍ⓗཷࡅධࢀᛶ㸸ᮏヨ㦂ἲࡣࠊࣛࢵࢺࡢ᦬ฟ⓶⭵ࢆ⏝࠸࡚࠸ࡿࡓࡵ᏶඲࡞⨨ࡁ᥮࠼ヨ㦂࡛ࡣ࡞࠸ࠋࡋ࠿ࡋ࡞ࡀࡽࠊᮏヨ㦂ἲࢆ⏝࠸ࡿࡇ࡜࡛ື≀ᩘࡢ๐ῶࡀྍ⬟࡛࠶ࡾࠊࡲࡓࠊ⭉㣗ᛶ≀㉁࡟ࡼࡿື≀࡬ࡢࢫࢺࣞࢫࢆ୚࠼ࡿࡇ࡜ࡣ↓࠸ࡇ࡜࠿ࡽࠊື≀ᐇ㦂௦᭰ἲࡢ㸱Rs ࡢཎ๎࡟㐺ࡗࡓヨ㦂ἲ࡛࠶ࡿࠋᮏヨ㦂ἲࡣࠊᚲせ࡞ᢏ⾡ࡀ」㞧࡛ࡣ࡞ࡃࠊ㐺ษ࡞カ⦎࡟ࡼࡗ࡚ᐜ᫆࡟⩦ᚓ࡛ࡁࡿ࡜⪃࠼ࡽࢀࡿࠋ௨ୖࡢほⅬ࠿ࡽࠊᮏヨ㦂ἲࡣ♫఍ⓗ࡟ཷࡅධࢀࡽࢀࡿࡶࡢ࡛࠶ࡿ࡜ุ᩿ࡍࡿࠋ ⾜ᨻୖࡢ฼⏝ᛶ㸸ᮏヨ㦂ἲࡣࠊ✀ࠎࡢ໬Ꮫ≀㉁࡟㐺⏝࡛ࡁࠊ⭉㣗ᛶ࠾ࡼࡧ㠀⭉㣗ᛶࢆศ㢮ࡍࡿࡓࡵࡢ௦᭰ἲ࡜ࡋ࡚ࠊ⾜ᨻⓗ฼⏝ࡀྍ⬟࡛࠶ࡿ࡜⪃࠼ࡿࠋࡓࡔࡋࠊEU ࡛ࡣື≀ᐇ㦂ࢆ⾜ࡗࡓ໬⢝ရ➼ࡢ㈍኎ࢆ⚗Ṇࡋ࡚࠸ࡿࡇ࡜࠿ࡽࠊ໬⢝ရ➼ࡢホ౯࡬ࡢᮏヨ㦂᪉ἲࡢ㐺⏝ࡣၥ㢟ࡀ⏕ࡌࡿᠱᛕࡀ࠶ࡿࠋཧ⪃ᩥ⊩1)

Botham, P.A. et al. (1996) A prevalidation study on in vitro skin corrosivity testing: The report andrecommendations of ECVAM workshop 6. ATLA, 23, 219-255

2)

Barratt, M.D. et al. (1998) The ECVAM international validation study on in vitro tests for skin corrosivity. 1.
Selection and distribution of the test chemicals. Toxicology in Vitro, 12, 471-482

3)Fentem, J.H. et al. (1998) The ECVAM International Validation Study on in vitro tests for skin corrosivity. 2.
Results and evaluation by the management team. Toxicology in Vitro, 12, 483-524

4)

ICCVAM (1999) NIH Publication No.99-4495. Corrositex: An in vitro test method for assessing dermalcorrosivity potential of chemicals.

5)

ICCVAM (2002) NIH Publication No.02-4502. ICCVAM Evaluation of EPISKIN, and EpiDerm (EPI-200)
and rat skin transcutaneous electrical resistance (TER) assay: in vitro test method for assessing dermal
corrosivity potential of chemicals.

6)OECD (2015) Guideline for the testing of chemicals. 430, In Vitro Skin Corrosion: Transcutaneous Electrical
Resistance Test Method (TER).

7)

JaCVAM ⓶⭵⭉㣗ᛶ㈨ᩱ⦅⧩ጤဨ఍㸸⓶⭵⭉㣗ᛶヨ㦂ホ౯ሗ࿌᭩ ⤒⓶㟁Ẽ᢬ᢠヨ㦂ࢆ⏝࠸ࡓ⓶⭵⭉㣗ᛶヨ㦂௦᭰ἲࡢホ౯ሗ࿌᭩㸦2017 ᖺ 2 ᭶ 24 ᪥㸧㸬8)

Botham, P.A. et al.㸦1992㸧The skin corrosivity test in vitro. Results of an inter-laboratory trial. Toxicol InVitro. 6(3):191-4

9)ICCVAM (1999) NIH Publication No.99-4495. Corrositex: An in vitro test method for assessing dermal
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