In vitro ⚻⊹ๆ෼⹜㛎㧔in vitro ⊹⤏ㅘㆊ⹜㛎㧕ߩ⹏ଔળ⼏ႎ๔ᦠ

JaCVAM ⹏ଔળ⼏ᐔᚑ 25 ᐕ 10 ᦬ 21 ᣣ

11
JaCVAM ⹏ଔળ⼏ศ↰ᱞ⟤㧔ᣣᧄᲥᕈቇળ㧕㧦ᐳ㐳ᵻ㊁ື⑲㧔ᣣᧄⅣႺᄌ⇣ේቇળ㧕੖ච፲⦟᣿ 㧔࿖┙ක⮎ຠ㘩ຠⴡ↢⎇ⓥᚲ ↢ᵴⴡ↢ൻቇㇱ㧕৻㝩 ീ㧔ᣣᧄൻቇᎿᬺදળ㧕*ᄢፉஜᐘ㧔ᣣᧄൻቇᎿᬺදળ㧕ᄢ㊁ᵏ㓶㧔ᐳ㐳ផ⮈㧕*ዊ═ේᒄ㆏ 㧔⁛┙ⴕ᡽ᴺੱ ක⮎ຠක≮ᯏེ✚วᯏ᭴㧕
ዊ㊁ኹඳᔒ 㧔⁛┙ⴕ᡽ᴺੱ ක⮎ຠක≮ᯏེ✚วᯏ᭴㧕㤥Ỉ ദ㧔ᣣᧄേ‛ታ㛎ઍᦧᴺቇળ㧕᧖ጊ⌀ℂሶ 㧔ᣣᧄൻ♆ຠᎿᬺㅪวળ㧕⼱↰ᥓሶ㧔⁛┙ⴕ᡽ᴺੱ ක⮎ຠක≮ᯏེ✚วᯏ᭴㧕*⷏Ꮉ⑺૫㧔࿖┙ක⮎ຠ㘩ຠⴡ↢⎇ⓥᚲ ቟ోᕈ↢‛⹜㛎⎇ⓥ࠮ࡦ࠲࡯㧕㐳⼱Ꮉ㓉৻ 㧔⁛┙ⴕ᡽ᴺੱ ⵾ຠ⹏ଔᛛⴚၮ⋚ᯏ᭴㧕’ ᩕੑ㧔ᣣᧄ఺∉Ქᕈቇળ㧕Ⴧ↰శノ㧔ᐳ㐳ផ⮈㧕ጊ↰㓉ᔒ㧔⁛┙ⴕ᡽ᴺੱ ⵾ຠ⹏ଔᛛⴚၮ⋚ᯏ᭴㧕*ᮮ㑐ඳ㓶㧔ᣣᧄ⊹⤏ࠕ࡟࡞ࠡ࡯࡮ធ⸅⊹⤏Ἳቇળ㧕ศ↰ ✛㧔࿖┙ක⮎ຠ㘩ຠⴡ↢⎇ⓥᚲ ቟ోᕈ↢‛⹜㛎⎇ⓥ࠮ࡦ࠲࡯ ∛ℂㇱ㧕ศ᧛ ഞ㧔ᐳ㐳ផ⮈㧕ᷰㇱ৻ੱ㧔ᣣᧄ⵾⮎Ꮏᬺදળ㧕                  છᦼ㧦ᐔᚑ 24 ᐕ 4 ᦬ 1 ᣣ㨪ᐔᚑ 26 ᐕ 3 ᦬ 31 ᣣ*㧦ᐔᚑ 25 ᐕ 4 ᦬ 1 ᣣ㨪ᐔᚑ 26 ᐕ 3 ᦬ 31 ᣣ

એ਄

22

ᒰ⹥⹜㛎ᴺߪ‫ޔ‬એਅߩㅢ⍮߿ࠟࠗ࠼࡜ࠗࡦߦⷙቯߐࠇࠆࡅ࠻߹ߚߪታ㛎േ‛߆ࠄ៰಴ߒߚ⊹⤏ࠍ↪޿ߚൻቇ‛⾰ߩ⊹⤏ㅘㆊᕈࠍ᷹ቯߔࠆ⹜㛎ᴺߢ޽ࠆ‫ޕ‬ኻᔕߔࠆᓥ᧪⹜㛎ߪ‫ߪߚ߹࠻ࡅޔ‬ታ㛎േ‛ߩ⊹⤏ߦൻቇ‛⾰ࠍ⋥ធႣᏓ෶ߪ⾍ઃߒߡߘߩⴊਛỚᐲࠍ᷹ቯߔࠆ⹜㛎ߢ޽ࠆ߇‫․ޔ‬ቯߩࡊࡠ࠻ࠦ࡞ࠍⷙቯߒߚ
⹜㛎ᴺߢߪߥ޿‫ޕ‬৻ᣇ‫ߦ⤏⊹ߩ࠻࠶࡜ޔ‬᡼኿ᕈ࡜ࡌ࡞ߒߚൻቇ‛⾰ࠍ⋥ធႣᏓ෶ߪ⾍ઃߒߡⴊਛ‫ޔ❱⚵ޔ‬ዩਛߩ᡼኿ᵴ
ᕈࠍ᷹ቯߔࠆ⹜㛎ᴺߪ OECD TG 427 (Skin Absorption: In Vivo Method)ߣߒߡⷙቯߐࠇߡ޿ࠆ߇‫ޔ‬ൻቇ‛⾰ߩઍ⻢‛߽฽ࠎߛ᷹ቯߢ޽ࠆߚ߼‫ޔ‬ᒰ⹥⹜㛎ᴺߦኻᔕߔࠆᓥ᧪⹜㛎ᴺߦߪ⹥ᒰߒߥ޿‫ޕ‬Ԙ Opinion on Basic Criteria for the in vitro assessment of dermal absorption of cosmetic
ingredients - updated March 2006 (Adopted by the SCCP during the 7th plenary of 28 March2006)
ԙ Test guideline 428: OECD Guideline for the Testing of chemicals: Skin Absorption: in vitro
Method (Adopted 13 April, 2004)
Ԛ COLIPA GUIDELINES: Guidelines for percutaneous Absorption㧛Penetration (Edition of1997) ੹࿁‫ࠆߥ⇣ޔ‬ᯏ㑐߆ࠄ␜ߐࠇߡ޿ࠆ਄⸥ߩ⊹⤏ㅘㆊᕈ⹜㛎ᴺߦߟ޿ߡ‫⤏⊹ޟ‬ㅘㆊ⹜㛎⹏ଔᆔຬળ‫ޠ‬߇ߣࠅ߹ߣ߼ߚႎ๔㧝㧕‫ޔ‬㧞㧕ࠍฃߌ‫ޔ‬એਅߩ 10 㗄⋡ߦߟ޿ߡ⹏ଔߒߚߩߢႎ๔ߔࠆ‫ޕ‬㧨ክ⼏ౝኈ㧪1㧚ᒰ⹥⹜㛎ᴺߪ‫ߥ߁ࠃߩߤޔ‬ᓥ᧪⹜㛎ᴺࠍઍᦧߔࠆ߽ߩ߆‫ߥ߁ࠃߩߤޔߪߚ߹ޕ‬Ქᕈࠍ⹏ଔ޽ࠆ޿ߪ੍᷹ߔࠆ߽ߩ߆‫ޕ‬ᒰ⹥⹜㛎ᴺߪ‫ޔ‬ࡅ࠻߹ߚߪታ㛎േ‛ߩ⊹⤏ߦൻቇ‛⾰ࠍ⋥ធႣᏓ෶ߪ⾍ઃߒߡోりᦑ㔺㊂ࠍᛠីߔࠆᓥ᧪ߩ in vivo ߦࠃࠆ㧔⊹⤏߆ࠄߩๆ෼㊂ࠍ᷹ቯߔࠆ㧕ᣇᴺࠍઍᦧߔࠆ߽ߩߢ޽ࠆ‫ޕ‬ᒰ⹥⹜㛎ᴺߪൻቇ‛⾰ߩ⊹⤏ࠍ੺ߔࠆㅘㆊᕈࠍ᷹ቯߔࠆ߽ߩߢ޽ࠅ‫ޔ‬Ქᕈࠍ⹏ଔ޽ࠆ޿ߪ੍᷹ߔࠆ߽ߩߢߪߥ޿‫ޕ‬
2. ᒰ⹥⹜㛎ᴺߣᓥ᧪⹜㛎ᴺߩ㑆ߦߤߩࠃ߁ߥ⑼ቇ⊛ߥߟߥ߇ࠅ߇޽ࠆ߆㧫ᒰ⹥⹜㛎ᴺߪࡅ࠻߹ߚߪታ㛎േ‛߆ࠄ៰಴ߒߚ⊹⤏ࠍ↪޿ߡൻቇ‛⾰ߩ⊹⤏ㅘㆊ㊂ࠍ⹏ଔߔࠆ invitro ߩࡕ࠺࡞♽ߢ޽ࠅ‫⤏⊹ޔ‬ㅘㆊ㊂߆ࠄోりᦑ㔺㊂ߩផቯ߇น⢻ߢ޽ࠆ‫ޕ‬ᓥ᧪ߩ⹜㛎ߪࡅ࠻߹ߚߪታ㛎േ‛ߩ⊹⤏ߦൻቇ‛⾰ࠍႣᏓ߹ߚߪ⾍ઃߒ‫ޔ‬ๆ෼ߐࠇߚൻቇ‛⾰ߩ㊂ ⴊਛỚᐲ ࠍ᷹ቯߔࠆ KPXKXQ ⹜㛎ߢ޽ࠆ‫ޕ‬ਔ⹜㛎ߣ߽ߦ‫ߩࠄ߆⤏⊹ޔ‬ൻቇ‛⾰ߩๆ෼ߦኻߔࠆਥⷐߥࡃ࡝ࠕߣߥࠆⷺ⾰ጀࠍ᦭ߔࠆὐߢ⑼ቇ
⊛ߟߥ߇ࠅ߇޽ࠆ‫ޕ‬33

3㧚ᒰ⹥⹜㛎ᴺߣߘߩ࠺࡯࠲ߪ‫ޔ‬ㅘ᣿ߢ⁛┙ߥ⑼ቇ⊛⹏ଔࠍฃߌߡ޿ࠆ߆‫ޕ‬
ᒰ⹥⹜㛎ᴺߪ‫ޔࠇߙࠇߘޔ‬EU‫ޔ‬OECD ߅ࠃ᰷߮Ꮊൻ♆ຠදળ߆ࠄ⊒ⴕߐࠇߚ߽ߩߢ‫ߪ࠲࡯࠺ޔ‬ㅘ᣿ᕈ߇޽ࠅ⁛┙ߒߚ⹏ଔ߇ⴕࠊࠇߡ޿ࠆ‫ޕ‬ᬌ⸛ኻ⽎ߩ 3 ⹜㛎ᴺߦ㑐ߔࠆ౏ᑼߩᬌ⸽ߪߥߐࠇߡ޿ߥ޿߇‫ޔ‬OECD ߩኾ㐷ኅߪ OECD TG 428
ࠍᡰᜬߔࠆߦචಽߥ࠺࡯࠲ߩ޽ࠆߎߣߦวᗧߒߡ޿ࠆ㧟㧕‫ޕ‬
4. ᒰ⹥⹜㛎ᴺߪ‫ޔ‬ᓥ᧪⹜㛎ᴺߩઍᦧᴺߣߒߡ‫⾰‛ߥ߁ࠃߩߤޔ‬෶ߪ⵾ຠࠍ⹏ଔߔࠆߎߣࠍ⋡⊛ߣߒߡ޿ࠆ߆‫ޕ‬ᓥ᧪⹜㛎ᴺߪ⊹⤏ߦㆡ↪෶ߪᦑ㔺ߒߚൻቇ‛⾰ߩⴊਛỚᐲ̅ᤨ㑆ᦛ✢ਅ㕙Ⓧ㧔AUC㧕ࠍ᳞߼ࠆᣇᴺߢ޽ࠆߩߦኻߒ‫ޔ‬ᒰ⹥⹜㛎ᴺߪ⊹⤏ㆡ↪෶ߪᦑ㔺ߒߚൻቇ‛⾰ߩ⊹⤏ࠍ੺ߔࠆๆ෼㊂ࠍ᳞߼ࠆ⹜㛎ߢ޽ࠆ‫ޕ‬ᒰ⹥⹜㛎ᴺߪ‫⥸৻ޔ‬ൻቇ‛⾰ߩ⊹⤏ㅘㆊᕈࠍᛠីߔࠆ߶߆‫ޔ‬ൻ♆ຠ‫⤏⊹ޔ‬ㆡ↪ߩᄖ↪ක⮎ຠ㧔⾍ઃ೷㧕߅ࠃ߮ක⮎ㇱᄖຠ╬‫ޔ‬෶ߪߘࠇࠄ⵾ຠߦ฽߹ࠇࠆᣂⷙේᢱ‛⾰ߩߚ߼ߦ‫ో⊛⊹⚻ޔ‬りᦑ㔺ࠍ⹏ଔߔࠆᓥ᧪⹜㛎ߩઍᦧᴺߣߒߡ೑↪߇น⢻ߢ޽ࠆ‫ޕ‬
5㧚ᒰ⹥⹜㛎ᴺߪ‫⹏࠼࡯ࠩࡂޔ‬ଔ޽ࠆ޿ߪ࡝ࠬࠢ⹏ଔߩߤߜࠄߦ᦭↪ߢ޽ࠆ߆‫ޕ‬ᒰ⹥⹜㛎ᴺߪ‫⹜ᧄޔ‬㛎⚿ᨐ߆ࠄᓧࠄࠇࠆൻቇ‛⾰ߩ⊹⤏ㅘㆊ㊂ߦၮߠ߈‫ޔ‬in vivo ߢߩ⚻⊹ᛩਈߦࠃࠆోりᦑ㔺㊂ࠍផቯߔࠆߎߣ߇น⢻ߢ޽ࠆߩߢ‫ޔ‬ᒰ⹥ൻቇ‛⾰ߩ࡝ࠬࠢ⹏ଔߦ᦭↪ߢ޽ࠆ‫ޕ‬
6㧚ᒰ⹥⹜㛎ᴺߪ‫⾰‛ࠆߔߣ⊛⋡ޔ‬෶ߪ⵾ຠߩᲥᕈࠍ⹏ଔߢ߈ࠆ߆‫ߩߘޕ‬႐ว‫ޔ‬ᒰ⹥⹜㛎ᴺߩㆡ↪᧦ઙ߇᣿⏕ߦߥߞߡ޿ࠆ߆‫ޕ‬ᒰ⹥⹜㛎ᴺߪ‫ޔ‬ኻ⽎ߣߔࠆൻቇ‛⾰෶ߪ⵾ຠߩోりᦑ㔺ߦࠃࠆๆ෼㊂ࠍផቯ⹏ଔߔࠆ߽ߩߢ‫ޔ‬Ქᕈ⹏ଔࠍ⋥ធ⋡⊛ߣߔࠆ߽ߩߢߪߥ޿‫ޕ‬ߥ߅‫ޔ‬ኻ⽎ߣߔࠆൻቇ‛⾰ߩ‛ᕈߦᔕߓߚᒰ⹥⹜㛎ᴺߩㆡ↪᧦ઙ╬ߪ᣿⏕ߦߥߞߡ޿ࠆ‫ޕ‬㧣㧚ᒰ⹥⹜㛎ᴺߪࡊࡠ࠻ࠦ࡞ߩᓸ⚦ߥᄌᦝߦኻߒߡචಽ㗎ஜߢ޽ࠆ߆‫ޕ‬ࡊࡠ࠻ࠦ࡞ߩᓸ⚦ߥᄌᦝߦߪ㗎ஜߢ޽ࠆ߇‫⹜ޔ‬㛎ߦ↪޿ࠆ៰಴⊹⤏ߩㇱ૏߿ᕈ⁁ߦᔕߓߡ‫⚿ޔ‬ᨐߩ⸃㉼ࠍᘕ㊀ߦⴕ߁ᔅⷐ߇޽ࠆ㧔ᣂ㞲⊹⤏߆ಓ⚿⊹⤏߆‫ޔ‬Ძⓣߩ᦭ήઁ㧕‫ޕ‬8㧚ᒰ⹥⹜㛎ᴺߩᛛⴚ⠌ᓧߪ‫ޔ‬ㆡಾߥ⸠✵ߣ⚻㛎ࠍ⚻ߡ޿ࠆᜂᒰ⠪ߦߣߞߡኈᤃߥ߽ߩߢ޽ࠆ߆‫⹜ޕ‬㛎
ᴺߩታᣉߦ․ᱶߥ⸳஻߇ᔅⷐ߆‫ޕ‬ᒰ⹥⹜㛎ߦ↪޿ࠆ៰಴⊹⤏ߪ‫ޔ‬㉂⚛߿ᾲ߅ࠃ߮ൻቇಣℂ╬ߦࠃࠅ೸㔌ߒߚ⴫⊹‫ߪ޿ࠆ޽ޔ‬ෘߐ 200
㨪400 Ǎm ߦ⭯ಾߒߚ⊹⤏⚵❱ߢ޽ࠆ‫ޕ‬Ꮢ⽼ߩᮡຠࠍ↪޿ࠆ㒢ࠅ‫ߩߘޔ‬ᓟߩၭ㙃߿⹜㛎ᚻᛛ╬ߩᛛⴚ⠌ᓧߪኈᤃߥ߽ߩߢ޽ࠆ߇‫⭯ࠍ⤏⊹ߢࡓ࡯࠻ࡑ࡯࠳ޔ‬ಾߒߡ⹜㛎ᮡຠࠍ⥄ࠄ૞⵾ߔࠆᛛⴚߪᾫ✵ࠍⷐߔࠆ‫ޕ‬߹ߚ‫⤏⊹ޔ‬ᮡຠࠍ⥄ࠄ૞⵾ߔࠆ႐วߦߪ࠳࡯ࡑ࠻࡯ࡓ߇ᔅⷐߣߥࠆ‫ࡓ࠙࠴࡝࠻ޕ‬᳓ࠍ↪޿ߚ⊹⤏ࡃ࡝ࠕߩஜోᕈߩ⏕⹺㧔Integrity ᷹ቯ㧕߅ࠃ߮ᮡ⼂ߐࠇߚⵍ㛎‛⾰ࠍ↪޿ࠆ႐วߦߪ RI ⸳஻߇ᔅⷐߣߥࠆ‫ޕ‬44

9㧚ᒰ⹥⹜㛎ᴺߪ‫ޔ‬ᓥ᧪⹜㛎ᴺߣᲧߴߡᤨ㑆⊛⚻⾌⊛ߦఝࠇߡ޿ࠆ߆‫ޕ‬
ᒰ⹥⹜㛎ᴺߢߪ‫ޔ‬േ‛ታ㛎ߦ઻߁⚻⾌߇೥ᷫߢ߈‫ߦ⊛⾌⚻ޔ‬ఝࠇߡ޿ࠆ‫ޔߒߛߚޕ‬RI ࠍ૶↪ߔࠆ႐วߪ⚻⾌⊛ߦഠࠆ‫ޕ‬ ৻ᣇ‫ᤨޔ‬㑆⊛ߥఝ૏ᕈߦ㑐ߒߡߩᬌ⸛ߪߥߐࠇߡ޿ߥ޿‫ޕ‬10. ᒰ⹥⹜㛎ᴺߪ‫ޔ‬േ‛⑔␩ߩⷰὐ෸߮⑼ቇ⊛⷗࿾߆ࠄ‫⾰‛ࠆߔߣ⊛⋡ޔ‬෶ߪ⵾ຠߩᲥᕈࠍ⹏ଔߔࠆઍᦧᴺߣߒߡ‫ⴕޔ‬᡽਄೑↪ߔࠆߎߣߪน⢻߆‫ޕ‬ᒰ⹥⹜㛎ᴺߪേ‛⑔␩ߩ 3R ߩⷰὐ߆ࠄផᅑߐࠇ‫ޔ‬᰷☨ߢߪ৻⥸⊛ߦ૶ࠊࠇ‫ޔ‬ᚒ߇࿖ߢ߽⚻⊹ๆ෼⹜㛎ߦᐢߊ↪޿ࠄࠇߡ޿ࠆ‫ޕ‬ᒰ⹥⹜㛎ᴺߪ‫ޔ‬ൻቇ‛⾰ߩ⊹⤏߆ࠄߩㅘㆊᕈࠍ᷹ቯߔࠆ߽ߩߢ޽ࠅ‫ޔ‬Ქᕈࠍ⹏ଔ޽ࠆ޿ߪ੍᷹ߔࠆ߽ߩߢߪߥ޿߇‫⾰‛ࠆߔߣ⊛⋡ޔ‬෶ߪ⵾ຠߩోりᦑ㔺㊂ࠍផቯߔࠆઍᦧ⹜㛎ᴺߣߒߡ‫ⴕޔ‬᡽਄೑↪ߔࠆߎߣߪน⢻ߢ޽ࠆ‫ޕ‬ෳ⠨ᢥ₂㧝㧕‫ޟ‬In vitro⚻⊹ๆ෼⹜㛎㧔in vitro ⊹⤏ㅘㆊ⹜㛎㧕‫⤏⊹ ޠ‬ㅘㆊ⹜㛎⹏ଔᆔຬળ✬㧞㧕‫ޟ‬In vitro ⊹⤏ㅘㆊᕈ⹜㛎ᴺߩ⏕┙ߩ⚻✲‫⤏⊹ ޠ‬ㅘㆊ⹜㛎⹏ଔᆔຬળ✬㧟㧕 OECD (2000). Report of the Meeting of the OECD Extended Steering Committee for

Percutaneous Absorption Testing, Annex 1 to ENV/JM/TG(2000)5. OECD, Paris.

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6