ホ౯ሗ࿌᭩⤒⓶㟁Ẽ᢬ᢠヨ㦂ࢆ⏝࠸ࡓ⓶⭵⭉㣗ᛶヨ㦂௦᭰ἲ⓶⭵⭉㣗ᛶヨ㦂㈨ᩱ⦅⧩ጤဨ఍

ᖹᡂ 29 ᖺ㸦2017 ᖺ㸧2 ᭶ 24 ᪥

17ホ౯ጤဨ㧘ᶫ ♸ḟᅜ❧་⸆ရ㣗ရ⾨⏕◊✲ᡤ ẘᛶ㒊୰ᮧࡿࡾࡇ⊂❧⾜ᨻἲே 〇ရホ౯ᢏ⾡ᇶ┙ᶵᵓ ໬Ꮫ≀㉁⟶⌮ࢭࣥࢱ࣮㡲᪉ ╩ኵ

ఫ཭໬Ꮫᰴᘧ఍♫ ࣞࢫ࣏ࣥࢩࣈࣝࢣ࢔㒊㸦໬ᏛရᏳ඲ࢢ࣮ࣝࣉ㸧㸭᪥ᮏ໬Ꮫᕤᴗ༠఍ᑠᓥ ⫕ᅜ❧་⸆ရ㣗ရ⾨⏕◊✲ᡤ Ᏻ඲ᛶணホ౯㒊┠ḟ
1. ヨ㦂ἲࡢ⛉Ꮫⓗ࠾ࡼࡧつไ㠃࠿ࡽࡢጇᙜᛶ
2. ヨ㦂ࣉࣟࢺࢥࣝᵓᡂࡢጇᙜᛶ
3. 㛤Ⓨ࠾ࡼࡧホ౯࡟౑ࢃࢀࡓ≀㉁ࡢศ㢮ࠊ㑅ᢥ⌮⏤ࡢጇᙜᛶ
4. ヨ㦂ἲࡢṇ☜ᛶࢆホ౯ࡍࡿࡓࡵ࡟⏝࠸ࡽࢀࡓ≀㉁ࡢ in vitro ࠾ࡼࡧཧ↷ࢹ࣮ࢱࡢ᭷↓5. ヨ㦂ἲࡢṇ☜ᛶ㸦෌⌧ᛶ㸧
6. ヨ㦂ἲࡢಙ㢗ᛶ
7. ௚ࡢ⛉Ꮫⓗ࡞ሗ࿌࡜ࡢẚ㍑ࡢ᭷↓8. 㸱Rs ཎ๎࡬ࡢ㛵୚㸦ື≀⚟♴㠃࠿ࡽࡢጇᙜᛶ㸧
9. ヨ㦂ἲࡢ᭷⏝ᛶ࡜㝈⏺㸦ࢥࢫࢺࠊ᫬㛫࠿ࡽࡢጇᙜᛶ࡞࡝㸧10. ࡑࡢ௚㸦≉チࡢ᭷↓࡞࡝㸧
11. ⤖ㄽ
12. ᩥ⊩
AnnexAppendix
OECD Guidelines for the Testing of Chemicals, Test No. 430: In Vitro Skin Corrosion: Transcutaneous
Electrical Resistance Test Method (TER)

28せ᪨࢘ࢧࢠࢆ⏝࠸ࡿ⓶⭵⭉㣗ᛶヨ㦂ࡢື≀ᐇ㦂௦᭰ἲ㸦௦᭰ἲ㸧࡜ࡋ࡚ࠊ⤒῭༠ຊ㛤Ⓨᶵᵓ㸦OECD㸸
Organisation for Economic Co-operation and Development㸧࡟࡚ヨ㦂࢞࢖ࢻࣛ࢖ࣥ㸦TG: TestGuideline㸧430࡜ࡋ࡚ᢎㄆࡉࢀࡓࣛࢵࢺ᦬ฟ⓶⭵ࢆ⏝࠸ࡿ⤒⓶㟁Ẽ᢬ᢠヨ㦂㸦TER: Transcutaneous
Electrical Resistance㸧ࡢ᭷⏝ᛶࢆホ౯ࡋࡓࠋಙ㢗ᛶ࡜ጇᙜᛶ࡜࠸࠺どⅬ࡟࠾࠸࡚ࠊTERࢆホ౯ࡋࡓ⤖ᯝࠊ㐺⏝⠊ᅖ࡟㝈⏺ࡣ࠶ࡿࡶࡢࡢࠊᮏヨ㦂ἲ࡟ࡼࡾ⭉㣗ᛶࡢ᭷↓ࢆホ౯࡛ࡁࡿ࡜⪃࠼ࡽࢀࡓࠋ
ࡋ࠿ࡋࠊ⏕ࡁ࡚࠸ࡿࣛࢵࢺ࠿ࡽ᥇ྲྀࡋࡓ⓶⭵ࢆ⏝࠸ࡿࡇ࡜࠿ࡽ໬⢝ရ➼ࡢホ౯࡬ࡢᛂ⏝࡟ࡣၥ㢟ࡀ࠶ࡿࠋ39

1. ヨ㦂ἲࡢ⛉Ꮫⓗ࠾ࡼࡧつไ㠃࠿ࡽࡢጇᙜᛶ⓶⭵⭉㣗ᛶヨ㦂ࡣ⓶⭵่⃭ᛶヨ㦂ࡢ୍⎔࡜ࡋ࡚⾜ࢃࢀࠊ࢞࢖ࢻࣛ࢖࡛ࣥࡣ Draize ࡽ࡟ࡼࡾᥦၐࡉࢀࡓ࢘ࢧࢠࢆ⏝࠸ࡿ᪉ἲࡀ᥎ዡࡉࢀ࡚࠸ࡿ 1)ࠋࡇࡢ᪉ἲࡣ⿕㦂≀㉁ࡢ่⃭ᛶࡸ⭉㣗ᛶࢆ᳨ฟࡍࡿヨ㦂ἲ࡜ࡋ࡚㛗ࡃ⏝࠸ࡽࢀ࡚ࡁࡓࡶࡢࡢࠊุᐃࢆ⫗║࡛⾜࠺ࡓࡵᐈほᛶ࡟ஈࡋࡃᐇ㦂㛫ࡸ᪋タ㛫࡛ࡢ෌⌧ᛶࡀஈࡋ࠸ࠊ᭦࡟ື≀࡟⃭ࡋ࠸③ࡳ࡜ࢫࢺࣞࢫࢆ୚࠼ࡿࡇ࡜ࡀ♫఍ⓗ࡟ၥ㢟࡜࡞ࡾࠊ௨๓ࡼࡾື≀ࢆ౑⏝ࡋ࡞࠸௦᭰ἲࡢ㛤Ⓨࡀษᮃࡉࢀ࡚࠸ࡓࠋࡇࡢື≀ᐇ㦂௦᭰ἲ㸦௨ୗࠊ௦᭰ἲ࡜グࡍ㸧࡜ࡋ࡚ࠊ⤒῭༠ຊ㛤Ⓨᶵᵓ㸦OECD㸸Organisation for Economic Co-operation and Development㸧࡟࡚ᢎㄆࡉࢀࡓヨ㦂࢞࢖ࢻࣛ࢖ࣥ㸦TG: Test Guideline㸧430 ࡟ࡣࠊ⤒⓶㟁Ẽ᢬ᢠヨ㦂㸦TER:Transcutaneous Electrical Resistance)ࡀグ㍕ࡉࢀ࡚࠸ࡿ 2㸧ࠋࡇࡢヨ㦂ἲࡣࠊ⭉㣗ᛶ≀㉁ࡀゅ㉁ᒙ࡟྾
཰ࡉࢀࡓᚋᣑᩓࡋࠊୗᒙࡢ⾲⓶⣽⬊ࢆയᐖࡍࡿࡇ࡜࡟ࡼࡾ⓶⭵ࡢࣂࣜ࢔࣮ᶵ⬟ࢆയᐖࡍࡿ࡜࠸࠺⪃࠼ࢆࡶ࡜࡟ࠊ⿕㦂≀㉁᭚㟢ᚋࡢ㟁Ẽ᢬ᢠ್ࢆᣦᶆ࡟⓶⭵⭉㣗ᛶࢆホ౯ࡋ࡚࠸ࡿࠋᮏヨ㦂ἲࡣḢᕞ௦᭰ἲホ౯ࢭࣥࢱ࣮(ECVAM㸸European Centre for the Validation of Alternative Methods㸧࡟ࡼࡿࣂࣜࢹ࣮ࢩࣙࣥ◊✲ࢆ⤒࡚ࠊḢᕞ࡛ࡣ໬Ꮫ≀㉁ࡢ⓶⭵⭉㣗ᛶホ౯ࢆ┠ⓗ࡜ࡋ࡚ᢎㄆࡉࢀࠊ໬Ꮫ≀㉁ࡢࣜࢫࢡ⾲♧ࡸ㆑ู➼࡟฼⏝ࡉࢀ࡚࠸ࡿࠋ≉࡟᫖௒࡛ࡣᅜ㐃໬Ꮫရࡢศ㢮࠾ࡼࡧ⾲♧࡟㛵ࡍࡿୡ⏺ㄪ࿴ࢩࢫࢸ࣒㸦UN GHS㸸United Nations Globally Harmonized System of Classification and Labellingof Chemicals㸧ศ㢮࡟ᚑࡗ࡚ホ౯ࡉࢀࡿࢣ࣮ࢫࡀቑ࠼࡚࠸ࡿࠋᡃࡀᅜ࡛᪤Ꮡࡢ໬Ꮫ≀㉁ࢆホ౯ࡍࡿሙྜࠊOECD ࡛ᢎㄆࡉࢀࡓヨ㦂᪉ἲ࡟ࡼࡿ⤖ᯝࢆ฼⏝ࡍࡿࡇ࡜ࡣྍ⬟࡛࠶ࡿࡀࠊ⌧ᅾࡲ࡛௦᭰ἲ࡛ࡢ⤖ᯝࢆࡶ࡜࡟⭉㣗ᛶࢆホ౯ࡉࢀࡓ౛ࡣከࡃ࡞࠸ࠋᏳ඲ᛶホ౯࡟࠾ࡅࡿ௦᭰ἲࡢᬑཬࡀษᮃࡉࢀ࡚࠸ࡿ⌧≧࡟࠾࠸࡚ࠊᡃࡀᅜ࡛ࡶ✚ᴟⓗ࡟ཷࡅධࢀࡿࡇ࡜ࡀᚲせ࡜࡞ࡗ࡚࠸ࡿࠋࡇࢀࡽࡢ≧ἣ࡟㚷ࡳࠊᮏホ౯᭩࡛ࡣࠊOECD TG430 ࡟ᥖ㍕ࡉࢀࡓ TER ࡢ⭉㣗ᛶホ౯࡟࠾ࡅࡿ᭷⏝ᛶࢆホ౯ࡋࡓ 2㸧ࠋ
2. ヨ㦂ࣉࣟࢺࢥࣝᵓᡂࡢጇᙜᛶ 2㸧1) ཎ⌮   ษ㝖ࡋࡓࣛࢵࢺ⓶⭵ࢆヨ㦂ࢩࢫࢸ࣒࡜ࡋ࡚౑⏝ࡋࠊࡑࡢ㟁Ẽ᢬ᢠࡢኚ໬ࢆ⓶⭵യᐖᛶࡢᣦᶆ࡜ࡍࡿࠋ2㸧᪉ἲ   ᦬ฟࡋࡓ┤ᚄ20 mm෇┙≧ࡢ⓶⭵㸦ࣛࢵࢺࠊ28-30᪥㱋࡯࡝㸧ࢆᅗ㸯࡟♧ࡍࡼ࠺࡟ࠊ
ࢸࣇࣟࣥ㸦࣏ࣜࢸࢺࣛࣇ࢚ࣝ࢜ࣟࢳࣞࣥ㸸PTFE㸧ࢳ࣮ࣗࣈࡢୗ㒊࡟⾲⓶㠃ࢆୖ࡟ࡋ࡚࠶࡚ࠊࢦ࣒〇ࡢOࣜࣥࢢ࡛ࡣࡉࡴࠋ⓶⭵ࡢࡘ࠸ࡓPTFEࢳ࣮ࣗࣈࢆ◲㓟࣐ࢢࢿࢩ࣒࢘㸦154mM㸧⁐ᾮ࡟ࡘࡅࠊ⿕㦂≀㉁⁐ᾮ150 ȝLࢆ⾲⓶㠃࡟ࠊ30Υ࡛24᫬㛫㐺⏝ࡍࡿࠋWheatstone㟁ᶫ⿦⨨࡟ప㟁ᅽࢆ࠿ࡅࠊ100 Hz࡟࠾ࡅࡿ㟁Ẽ᢬ᢠᗘࢆᐃࡍࡿࠋ     ࡉࡽ࡟ࠊ㟁Ẽ᢬ᢠࡀ 5 kȍ ௨ୗࡢሙྜ࡟ࡣࠊ10㸣ࢫ࣮ࣝ࣍ࣟࢲ࣑ࣥ㹀ᰁⰍᾮ࡟࡚ 2 ᫬㛫ᰁⰍࡋࠊ⓶⭵࡟྾╔ࡉࢀࡓⰍ⣲ࡢ㔞ࢆ྾ගᗘ࠿ࡽ⟬ฟࡍࡿࠋ     㟁Ẽ᢬ᢠᗘࡀ 5 kȍ ࡼࡾᑠࡉࡃࠊ᫂ࡽ࠿࡟ᦆയࡢ࠶ࡿሙྜࠊࡲࡓࡣᦆയࡀ࡞ࡃ࡚ࡶⰍ⣲㔞ࡀ㝧ᛶᑐ↷≀㉁࡛࠶ࡿ 10 M ሷ㓟௨ୖࡢሙྜࠊ⭉㣗ᛶ࡜ุ᩿ࡍࡿࠋ

410ᅗ㸯㸬TER ᴫせᅗ 2㸧
3. 㛤Ⓨ࠾ࡼࡧホ౯࡟౑ࢃࢀࡓ≀㉁ࡢศ㢮ࠊ㑅ᢥ⌮⏤ࡢጇᙜᛶ
Botham ࡽ࡟ࡼࡾ TER ࡟ࡘ࠸࡚ࡣࠊ20 ࡢ⿕㦂≀㉁࡟ࡼࡾ᪋タෆ෌⌧ᛶ 3㸧ࠊ࠾ࡼࡧ 50 ࡢ⿕㦂≀㉁࡟ࡼࡾ᪋タ㛫෌⌧ᛶ࠾ࡼࡧணᛶࡀㄪ࡭ࡽࢀ࡚࠸ࡿ 4㸧ࠋࡑࢀࡽࡢ≀㉁ࣜࢫࢺ࡜ࡑࢀࡽࡢ≀⌮࣭໬ᏛᏛⓗᛶ≧ࢆ ANNEX 1 ࠾ࡼࡧ 2 ࡟♧ࡍࠋࡲࡓ Fentem ࡽ࡟ࡼࡾࠊ60 ≀㉁ࢆ⏝࠸࡚ࠊ෌⌧ᛶ࠾ࡼࡧணᛶࡀㄪ࡭ࡽࢀ࡚࠸ࡿ 5㸧ࠋࡑࢀࡽࡢ≀㉁ࣜࢫࢺࢆ⭉㣗ᛶࡸ pH, つไ≧ἣ࡜࡜ࡶ࡟ ANNEX 3࡟♧ࡍࠋࡑࢀࡽ࡛ࢃ࠿ࡿࡼ࠺࡟ࠊᮏヨ㦂ἲࡣᖜᗈ࠸ᛶ≧ࡢ໬Ꮫ≀㉁᳨࡛ウࡉࢀ࡚࠸ࡿࠋ
4. ヨ㦂ἲࡢṇ☜ᛶࢆホ౯ࡍࡿࡓࡵ࡟⏝࠸ࡽࢀࡓ≀㉁ࡢ in vitro ࠾ࡼࡧཧ↷ࢹ࣮ࢱࡢ᭷↓⿕㦂≀㉁ࡢከࡃࡣ ECVAM ࡢ⓶⭵⭉㣗ᛶヨ㦂ࣂࣜࢹ࣮ࢩ࡛ࣙࣥ౑⏝ࡉࢀࡓ≀㉁࡛࠶ࡾ 6)ࠊࡑࢀ
ࡽࡢ⭉㣗ᛶ࡟㛵ࡍࡿཧ↷ࢹ࣮ࢱࡀධᡭྍ⬟࡛࠶ࡿ
5. ヨ㦂ἲࡢṇ☜ᛶ㸦෌⌧ᛶ㸧 TER ࡢ᪋タෆ෌⌧ᛶࡣ 20 ࡢ⿕㦂≀㉁㸦6 ⭉㣗ᛶ≀㉁࠾ࡼࡧ 14 㠀⭉㣗ᛶ≀㉁㸧ࢆ⏝࠸ࠊ3 ᪋タ
511㛫࡛ ANOVA ゎᯒࢆ⏝࠸ࠊ᪋タ㛫࡟᭷ពᕪࡀ࡞࠸࡜ࡉࢀ࡚࠸ࡿ 3㸧ࠋ ୍᪉ࠊ᪋タ㛫෌⌧ᛶ࡛ࡣࠊ2 ᪋タࡀ 50 ࡢ⿕㦂≀㉁㸦25 ⭉㣗ᛶ≀㉁࠾ࡼࡧ 25 㠀⭉㣗ᛶ≀㉁㸧ࢆ⏝࠸ࠊ92㸣㸦࠸ࡎࢀࡢ≀㉁⩌ࡶ 23 ≀㉁࡛ࡢ⤖ᯝࡀ୍⮴ࡋࡓ㸧࡛࠶ࡿ࡜ࡉࢀ࡚࠸ࡿ 4㸧ࠋ௨ୖࡢ⤖ᯝ࠿ࡽࠊ෌⌧ᛶࡣ㧗࠸࡜ุ᩿ࡉࢀ࡚࠸ࡿࠋ60 ≀㉁ࢆ⏝࠸ࡓ 3 ᪋タ࡛ࡢ 2 way ࡢ ANOVA ゎᯒ࡟࠾࠸࡚ࠊ᪋タෆ࠾ࡼࡧ᪋タ㛫ࡢኚື࡟᭷ព࡞ᕪࡣ࡞࠸࡜ุ᩿ࡉࢀࡓ 5)ࠋࡲࡓࠊ60 ≀㉁㸦27 ⭉㣗ᛶ≀㉁࠾ࡼࡧ 33 㠀⭉㣗ᛶ≀㉁㸧ࡢ࠺ࡕࠊ37≀㉁ࡣ 3 ᪋タ࡜ࡶ᪋タෆ࠾ࡼࡧ᪋タ㛫෌⌧ᛶࡀㄆࡵࡽࢀࡓࠋṧࡿ 23 ≀㉁ࡢ࠺ࡕ 10 ≀㉁࡛᪋タෆ෌⌧ᛶࡀᝏ࠿ࡗࡓࠋࡇࡢࡼ࠺࡟ࠊ࠸ࡃࡘ࠿ࡢ≀㉁࡛෌⌧ᛶࡢ⤖ᯝࡀ␗࡞ࡗ࡚࠸ࡓࡀࠊECVAM ࡣᮏヨ㦂ἲࡢಙ㢗ᛶ࡜෌⌧ᛶࡣ㧗࠸࡜ุ᩿ࡋࡓࠋࡇࡢ⤖ㄽࡣࠊECVAM ⛉Ꮫㅎၥ఍㆟ (ESAC:ECVAM Scientific Advisory Committee)7㸧࠾ࡼࡧ⡿ᅜࡢ௦᭰ἲ࡟㛵ࡍࡿ┬ᗇ㛫㐃⤡఍㆟ (ICCVAM㸸
Interagency Coordinating Committee on the Validation of Alternative Methods)8㸧࡛ࡢホ౯࡟࠾࠸࡚ࡶ☜ㄆࡉࢀࡓࠋ
6. ヨ㦂ἲࡢಙ㢗ᛶ Botham et al (1996)࡜Fentem et al (1998)ࡢ᳨ウ⤖ᯝ࠾ࡼࡧࡑࢀࡽࢆྜ⟬ࡋࡓICCVAMࡢ㞟ィ⤖ᯝ6)ࢆ⾲㸯࡟♧ࡍࠋࡑࡢ⤖ᯝ࡜ࡑࢀࡒࢀࡢㄽᩥࡢṇ☜ᗘࠊឤᗘࠊ≉␗ᗘ࡟኱ࡁ࡞ᕪࡣ࡞ࡃࠊṇ☜ᗘࡣ
⣙81㸣ࠊឤᗘࡣ⣙94㸣ࠊ≉␗ᗘࡣ⣙71㸣࡛࠶ࡗࡓࠋഇ㝜ᛶࡣ6㸣ࠊ3≀㉁ㄆࡵࡽࢀࠊࡇࢀࡽࡣ
MethacroleinࠊGlycol bromoacetate (85%)࠾ࡼࡧ1,2-Benzisothiazolin-3-one (33%) in aqueous propylene
glycol࡛࠶ࡗࡓࠋMethacrolein࠾ࡼࡧGlycol bromoacetate (85%)ࡣUNࡢ⭉㣗ᛶࡢ⣽ศ㢮࡛࠸ࡎࢀࡶᙉ
ࡃ࡞࠸ࡶࡢ(1B/1C)࡟ᒓࡍࡿࡶࡢ࡛࠶ࡾࠊ1,2-Benzisothiazolin-3-one (19.3%)࡟࠾࠸࡚ࡣ⓶⭵่⃭ᛶࡶ࡞࠸࡜໬Ꮫ≀㉁➼Ᏻ඲ࢹ࣮ࢱࢩ࣮ࢺ (MSDS㸸Material Safety Data Sheet) ࡟グ㍕ࡀ࠶ࡿ㸦ᮍῧ௜㈨ᩱ㸧ࠋ௨ୖࡢ⤖ᯝ࠿ࡽࠊୖグഇ㝜ᛶ࡜࡞ࡗࡓ3≀㉁ࡢ⭉㣗ᛶࡣᙉࡃ࡞࠸࡜ุ᩿࡛ࡁࡿࠋ✀ࠎࡢ໬Ꮫ≀㉁ศ㢮࡟ࡼࡿᕪࡣ࡞ࡃࠊTER ࡣ⭉㣗ᛶ࠾ࡼࡧ㠀⭉㣗ᛶࢆศ㢮ࡍࡿࡓࡵࡢ௦᭰ἲ࡜
ࡋ࡚᭷⏝࡛࠶ࡿࠋࡓࡔࡋࠊࡑࢀ௨ୖࡢ⣽ศ㢮࡟ࡘ࠸࡚ࡣ᳨ウࡀ୙༑ศ࡛࠶ࡿ࡜ࡉࢀ࡚࠸ࡿࠋ
⾲㸯. TER ࡢணᛶFentem et al. (1998) 5㸧

ICCVAM (1999) ࡢBotham et al. (1992 and⥲ィ 6㸧1996)3,4㸧ṇ☜ᗘ

81% (99/122)

82% (53/65)

81% (47/58)

ឤᗘ94%(51/54)

96%(27/28)

93%(25/27)≉␗ᗘ71%(48/68)

70%(26/37)

71%(22/31)

7. ௚ࡢ⛉Ꮫⓗ࡞ሗ࿌࡜ࡢẚ㍑ࡢ᭷↓ OECD ࡢ⭉㣗ᛶヨ㦂௦᭰ἲ࢞࢖ࢻࣛ࢖ࣥ࡜ࡋ࡚ࠊ௚࡟ࠕTG431 ࣄࢺ⾲⓶ࣔࢹࣝヨ㦂ࠖ9)࠾ࡼࡧ
ࠕTG435 in vitro ⭷ࣂࣜ࢔ヨ㦂ࠖ10㸧ࡀᢎㄆࡉࢀ࡚࠸ࡿࠋࡇࢀࡽࡣ࠸ࡎࢀࡶࣂࣜࢹ࣮ࢩࣙࣥ◊✲ࡀᐇ᪋ࡉࢀࠊICCVAM ࡣࡇࢀࡽࡢヨ㦂ἲ(Rat Skin TER, EpiSkin™, EpiDerm™࠾ࡼࡧ Corrositex®)ࡢṇ☜ᗘࠊឤᗘࠊ≉␗ᗘࠊ࡟ࡘ࠸࡚ẚ㍑ࡋࡓ⤖ᯝࢆ⾲ 2 ࡟♧ࡍࠋヨ㦂≀㉁ࡢᩘ㔞ࡸ㑅ᢥ≀㉁ࡢ✀㢮ࡀ␗࡞ࡗ࡚࠸ࡿࡓࡵ⤖ᯝࡢุᐃࡔࡅࢆࡶࡗ࡚ࠊ༢⣧࡟ᙜヱヨ㦂ἲࡢඃ㉺ᛶࢆホ౯ࡍࡿࡇ࡜ࡣᅔ㞴࡛࠶ࡿࡀࠊᙜヱヨ㦂ἲࡣ௚ࡢヨ㦂ἲ࡜ྠ➼ࡢண࡜ᛮࢃࢀࡿࠋ
126ᛶࢆ᭷ࡍࡿ

⾲ 2㸬ヨ㦂ἲࡢẚ㍑⤖ᯝ 6,8㸧TEREpiSkinEpiDermCorrositex≀㉁ᩘ

12260

24163

ṇ☜ᗘ81% (99/122)

83% (50/60)

92% (22/24)

79% (128/163)

ឤᗘ

94%(51/54)

82%(23/28)

92%(11/12)

85%(76/89)≉␗ᗘ71%(48/68)

84%(27/32)

83%(10/12)

72%(52/74)

8. 㸱Rs ཎ๎࡬ࡢ㛵୚㸦ື≀⚟♴㠃࠿ࡽࡢጇᙜᛶ㸧 ᮏヨ㦂ἲࡣࠊࣛࢵࢺࡢ᦬ฟ⓶⭵ࢆ⏝࠸࡚࠸ࡿࡓࡵ᏶඲࡞⨨ࡁ᥮࠼ヨ㦂࡜ࡣ࡞ࡽ࡞࠸ࠋࡋ࠿ࡋࠊ
Ᏻᴦẅ࡟ࡼࡾ⓶⭵ࢆ᦬ฟࡍࡿࡇ࡜ࠊ1 ༉࠿ࡽᚓࡽࢀࡿ⓶⭵࡛」ᩘࡢヨ㦂ࡀᐇ᪋ྍ⬟࡛࠶ࡿࠋࡋࡓࡀࡗ࡚ࠊື≀ᩘࡢ๐ῶࡀྍ⬟࡛࠶ࡾࠊࡲࡓࠊ⭉㣗ᛶ≀㉁࡟ࡼࡿື≀࡬ࡢࢫࢺࣞࢫࢆ୚࠼ࡿࡇ࡜ࡣ
↓ࡃࠊື≀ᐇ㦂௦᭰ἲ࡜ࡋ࡚㸱Rs ࡢཎ๎࡟㐺ࡗࡓヨ㦂ἲ࡛࠶ࡿࠋ
9. ヨ㦂ἲࡢ᭷⏝ᛶ࡜㝈⏺
 ᮏヨ㦂ἲࡣ✀ࠎࡢ✀㢮ࡢ໬Ꮫ≀㉁࡟ᑐࡋ࡚㐺⏝࡛ࡁࡿࡀࠊࣉࣟࢺࢥࣝ࠿ࡽ㢮᥎ࡋ࡚ࠊ㞴Ỉ⁐ᛶࡢᅛయࡸ⢓ᛶࡢ㧗࠸≀㉁ࡣ㐺ษ࡟ホ౯࡛ࡁ࡞࠸ྍ⬟ᛶࡀ࠶ࡿࠋ⭉㣗ᛶࡢ⣽ศ㢮㸦UN GHS ࡟ࡼࡿ㸧࡟ࡣ౑⏝࡛ࡁ࡞࠸࡜ゝࢃࢀ࡚࠸ࡿ 2㸧ࠋ⾲ 3 ࡟♧ࡍ⩦⇍ᗘ☜ㄆ≀㉁ࢆ⏝࠸ࡿࡇ࡜࡟ࡼࡾᑓ㛛ᢏ⾡ࡢ⩦⇍࡟ࡘ࠸࡚☜ㄆࡍࡿࡇ࡜ࡀ࡛ࡁࡿ 2)ࠋ
10. ࡑࡢ௚㸦≉チࡢ᭷↓࡞࡝㸧 ≉チ࡟ࡘ࠸࡚ࡣ♧ࡉࢀ࡚࠸࡞࠸ࠋ
11. ⤖ㄽ
ಙ㢗ᛶ࡜ጇᙜᛶ࡜࠸࠺どⅬ࡟࠾࠸࡚ࠊࣛࢵࢺ᦬ฟ⓶⭵ࢆ⏝࠸ࡿ⤒⓶㟁Ẽ᢬ᢠヨ㦂㸦TER㸧ࢆホ౯ࡋࡓ⤖ᯝࠊᮏጤဨ఍ࡣᙜヱヨ㦂ἲࢆ⏝࠸ࢀࡤࠊ⭉㣗ᛶࡢ᭷↓ࢆホ౯࡛ࡁࡿ࡜⪃࠼ࡓࠋ

713

⾲ 3 ⩦⇍ᗘ☜ㄆ୍ぴ⾲ 2)
໬Ꮫ≀㉁1

CASRNUN GHS ༊ศ 3

VRM ༊ศ4

In vivo ヨ㦂⤖ᯝ࡟ᇶ࡙ࡃIn vivo ࡟࠾ࡅࡿ⭉㣗ᛶ≀㉁

In vitro ヨ㦂⤖ᯝ࡟ᇶ࡙ࡃ໬Ꮫ≀㉁
2
ࢡࣛࢫ

≀⌮
ⓗ≧
ែ

pH5

N,N’- ࢪ࣓ࢳ ࣝ ࢪ ࣉࣟࣆࣞࣥࢺࣜ࢔࣑ࣥ

10563-29-8

᭷ᶵሷᇶ

1A6×⭉㣗ᛶᾮయ

8.3

1,2-ࢪ࢔࣑ࣀࣉࣟࣃࣥ

78-90-0᭷ᶵሷᇶ

1A6×⭉㣗ᛶᾮయ

8.3◲㓟㸦10%㸧

7664-93-9↓ᶵ㓟(1A/)1B/1C5×⭉㣗ᛶ
1×㠀⭉㣗ᛶ

ᾮయ

1.2

1310-58-3↓ᶵሷᇶ(1A/)1B/1C6×⭉㣗ᛶ

ᾮయ

13.2

124-07-2

᭷ᶵ㓟

1B/1C

4×⭉㣗ᛶ
2×㠀⭉㣗ᛶ

ᾮయ

3.6

88-18-6

ࣇ࢙ࣀ࣮ࣝ

1B/1C4×⭉㣗ᛶ
2×㠀⭉㣗ᛶ

ᾮయ

3.9Ỉ㓟໬࣒࢝ࣜ࢘
㸦10㸣aq㸧㸧࢜ࢡࢱࣥ㓟㸦࢝ࣉࣜࣝ 㓟㸧2-tert- ࣈࢳ ࣝ ࣇ࢙ ࣀ࣮ࣝIn vivo ࡟࠾ࡅࡿ㠀⭉㣗ᛶ≀㉁࢖ࢯࢫࢸ࢔ࣜࣥ㓟2724-58-5

᭷ᶵ㓟

㠀⭉㣗ᛶ

6×㠀⭉㣗ᛶ

ᾮయ

3.6

4- ࢔࣑ ࣀ -1,2,4- ࢺࣜ࢔ ࢰ࣮ࣝ

584-13-4

᭷ᶵሷᇶ

㠀⭉㣗ᛶ

6×㠀⭉㣗ᛶ

ᅛయ

5.5⮯໬ࣇ࢙ࢿࢳࣝ

103-63-9

ồ㟁Ꮚ≀㉁

㠀⭉㣗ᛶ

6×㠀⭉㣗ᛶ

ᾮయ

3.64-㸦࣓ࢳࣝࢳ࢜㸧-࣋ࣥࢬ࢔ࣝࢹࣄࢻ

3446-89-7 ồ㟁Ꮚ≀㉁㠀⭉㣗ᛶ

6×㠀⭉㣗ᛶ

ᾮయ

6.8

1,9-ࢹ࢝ࢪ࢚ࣥ

1647-16-1

୰ᛶ᭷ᶵ
≀ ㉁

㠀⭉㣗ᛶ

6×㠀⭉㣗ᛶ

ᾮయ

3.9ࢸࢺࣛࢡ࢚ࣟࣟࢳࣞࣥ

127-18-4

୰ᛶ᭷ᶵ
≀ ㉁

㠀⭉㣗ᛶ

6×㠀⭉㣗ᛶ

ᾮయ

4.5

␎ㄒ㸸aq.=Ỉ⁐ᾮࠊCASRN=CAS Ⓩ㘓␒ྕࠊUN GHS=ᅜ㐃໬Ꮫရࡢศ㢮࠾ࡼࡧ⾲♧࡟㛵ࡍࡿୡ⏺ㄪ࿴ࢩࢫࢸ࣒(1)ࠊ VRM=ࣂࣜࢹ࣮ࢩࣙࣥ῭ࡳཧ↷ヨ㦂ἲ1㸸ࡇࢀࡽࡢ≀㉁ࡣࠊ᭱ึ࡟⭉㣗ᛶ≀㉁࡜㠀⭉㣗ᛶ≀㉁ࠊḟ࡟⭉㣗ᛶࡢ⣽༊ศࠊࡉࡽ࡟໬Ꮫ≀㉁ࢡࣛࢫ
ࡢ㡰࡛ศ㢮ࡉࢀࠊḢᕞ௦᭰ἲホ౯ࢭࣥࢱ࣮㸦ECVAM㸧࡟ࡼࡿࣛࢵࢺ TERᐃἲࡢࣂࣜࢹ࣮ࢩࣙࣥ

11㸧ヨ㦂࡟⏝࠸ࡽࢀࡿ≀㉁࠿ࡽ㑅ᢥࡉࢀࡓࡶࡢ࡛࠶ࡿ㸦Barratt et al 1998

, Fentem et al 19985㸧㸧ࠋ≉࡟᩿ࡾࡀ࡞࠸㝈ࡾࠊᥖ㍕ࡋࡓ≀㉁ࡣᕷ㈍ရ㉎ධ᫬ࡢ⣧ᗘ࡛ヨ㦂ࢆ⾜ࡗࡓ㸦Barratt et al 199811㸧㸧ࠋྍ⬟࡞㝈ࡾࠊḟࡢᇶ‽ࢆ‶ࡓࡍ≀㉁ࢆ㑅ᢥࡋࡓࠋ(i)VRM ࡟ࡼࡿᐃࡲࡓࡣணࢆ⾜࠼ࡿ⭉㣗ᛶ཯ᛂࡢ⠊ᅖࢆ௦⾲ࡍࡿ≀㉁࡛࠶ࡿࡇ࡜㸦౛࠼ࡤࠊ㠀⭉㣗ᛶ≀㉁ࠊ⭉㣗ᛶ≀㉁ࡢ࠺ࡕ཯ᛂࡀᙅ࠸≀㉁࠿ࡽᙉ࠸≀㉁ࡲ࡛㸧
ࠋ(ii)ࣂࣜࢹ࣮ࢩࣙࣥヨ㦂࡟⏝࠸ࡽࢀࡓ໬Ꮫ≀㉁ࢡࣛࢫࢆ௦⾲ࡍࡿ≀㉁࡛࠶ࡿࡇ࡜ࠋ(iii)VRM ࡢᛶ⬟≉ᛶࢆ཯ᫎࡍࡿ≀㉁࡛࠶ࡿࡇ࡜ࠋ(iv)᫂☜࡟ᐃ⩏ࡉࢀࡓ໬Ꮫᵓ㐀ࢆᣢࡘ≀㉁࡛࠶ࡿࡇ࡜ࠋ(v) Invivo ࡟࠾ࡅࡿཧ↷ヨ㦂ἲ࡛᫂☜࡞⤖ᯝࢆᑟࡃ≀㉁࡛࠶ࡿࡇ࡜ࠋ(vi)ᕷ㈍ရ࡛࠶ࡿࡇ࡜ࠋ(vii)ᴟ➃࡟㧗㢠࡞ᗫᲠ㈝⏝ࢆకࢃ࡞࠸≀㉁࡛࠶ࡿࡇ࡜ࠋ
2㸸Barratt et al㸦199811㸧㸧࡟ࡼࡾᣦᐃࡉࢀࡓ໬Ꮫ≀㉁ࢡࣛࢫ࡜ࡋࡓࠋ
3㸸UN GHS ࡢ 1Aࠊ1Bࠊ1C ࡟┦ᙜࡍࡿᅜ㐃ᐜჾ➼⣭ࡣࡑࢀࡒࢀ IࠊIIࠊIII ࡛࠶ࡿࠋ4㸸ࣂࣜࢹ࣮ࢩࣙࣥ࡟࡚᪋タ㛫෌⌧ᛶ⤖ᯝࢆグ㍕ࡋ࡚࠸ࡿࠋ⅊Ⰽ㒊ศࡣ 6 ᐇ㦂ࡢุᐃ⤖ᯝࡀ␗࡞ࡿࡇ࡜

148

ࢆព࿡ࡍࡿࠋ
5㸸pH ್ࡣ Fentem et al5㸧 ࠾ࡼࡧ Barratt et al11㸧 ࡢᩥ⊩࠿ࡽᚓࡓࠋ

12.ᩥ⊩1) OECD (2015) Guideline for the testing of chemicals. 404, Acute Dermal Irritation/Corrosion.
2) OECD (2015) Guideline for the testing of chemicals. 430, in vitro Skin Corrosion: Transcutaneouselectrical resistance test (TER).
3) Botham, P.A. et al.㸦1992㸧The skin corrosivity test in vitro. Results of an inter-laboratory trial. Toxicol
In Vitro, 6:191-44) 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
5) Fentem, J.H. et al. (1998) The ECVAM International Validation Study on in vitro tests for skincorrosivity. 2. Results and evaluation by the management team. Toxicology in Vitro, 12, 483-524
6) ICCVAM (1999) NIH Publication No.99-4495. Corrositex: An in vitro test method for assessing dermalcorrosivity potential of chemicals.
7) EC-ECVAM (1998) Statement on the Scientific Validity of the Rat Skin Transcutaneos ElectricalResistance (TER) Test (an In Vitro Test for Skin Corrosivity), Issued by the ECVAM ScientificAdvisory Committee (ESAC10), 3 April 1998. Available at: [http://www.ecvam.jrc.ec.europa.eu.html].
8) 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 forassessing dermal corrosivity potential of chemicals.
9) OECD (2016) Guideline for the testing of chemicals. 431, in vitro Skin Corrosion: Human skin modeltest.
10) OECD (2015) Guideline for the testing of chemicals. 435, in vitro membrane barrier test method for
Skin Corrosion.
11) Barratt, M.D. et al. (1998) The ECVAM international validation study on in vitro tests for skincorrosivity. 1. Selection and distribution of the test chemicals. Toxicology in Vitro, 12, 471-482

915

ANNEX1: Botham 1992 ࡢࣂࣜࢹ࣮ࢩ࡛ࣙࣥ౑ࢃࢀࡓ 20 ≀㉁   Code No. 1㹼6 ࡀ⭉㣗ᛶ≀㉁ࠊࡑࡢ௚ࡣ㠀⭉㣗ᛶ≀㉁1016

ANNEX 2: Botham 1996 ࡢࣂࣜࢹ࣮ࢩ࡛ࣙࣥ౑ࢃࢀࡓ 50 ≀㉁

1117

1218

1319

ANNEX 3: Fentem 1998 ࡢࣂࣜࢹ࣮ࢩ࡛ࣙࣥ౑ࢃࢀࡓ 60 ≀㉁2014