ホ౯ሗ࿌᭩In vitro ⭷ࣂࣜ࢔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ᛶ7. ௚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. ᩥ⊩
Annex
Appendix
OECD Guidelines for the Testing of Chemicals, Test No. 435: In Vitro Membrane Barrier Test Method
for Skin Corrosion

28せ᪨࢘ࢧࢠࢆ⏝࠸ࡿ⓶⭵⭉㣗ᛶヨ㦂ࡢື≀ᐇ㦂௦᭰ἲ㸦௦᭰ἲ㸧࡜ࡋ࡚⤒῭༠ຊ㛤Ⓨᶵᵓ㸦OECD㸸

Organisation for Economic Co-operation and Development㸧࡟࡚ヨ㦂࢞࢖ࢻࣛ࢖ࣥ㸦TG: TestGuideline㸧435 ࡜ࡋ࡚ᢎㄆࡉࢀࡓ in vitro ⭷ࣂࣜ࢔ヨ㦂ࡢ᭷⏝ᛶࢆホ౯ࡋࡓࠋಙ㢗ᛶ࡜ጇᙜᛶ࡜࠸࠺どⅬ࡟࠾࠸࡚ࠊin vitro ⭷ࣂࣜ࢔ヨ㦂࡜ࡋ࡚ Corrositex ࢆホ౯ࡋࡓ⤖ᯝࠊᮏヨ㦂ἲࡣ୍㒊ࡢ≀㉁࡟࠾࠸࡚⭉㣗ᛶࡢ᭷↓ࢆホ౯࡛ࡁࡿ࡜⪃࠼ࡽࢀࡓࡀࠊࡑࡢ㐺⏝⠊ᅖࡣ⊃ࡃࠊࡲࡓࠊ㐺⏝ྍ⬟≀㉁ࡢศ㢮ࡀ୙᫂☜࡛࠶ࡿࡓࡵࠊ⭉㣗ᛶࡢホ౯࡟⏝࠸ࡿࡇ࡜ࡣᅔ㞴࡛࠶ࡿ࡜ุ᩿ࡋࡓࠋ39

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㸧ࠋࡇࡢ᪉ἲࡣ⿕㦂≀㉁ࡢ่⃭ᛶࡸ⭉㣗ᛶࢆ᳨ฟࡍࡿヨ㦂ἲ࡜ࡋ࡚㛗ࡃ౑⏝ࡉࢀ࡚ࡁࡓࡶࡢࡢࠊุᐃࢆ⫗║࡛⾜࠺ࡓࡵᐈほᛶ࡟ஈࡋࡃᐇ㦂㛫ࡸ᪋タ㛫࡛ࡢ෌⌧ᛶࡀஈࡋ࠸ࠊ᭦࡟ື≀࡟⃭ࡋ࠸③ࡳ࡜ࢫࢺࣞࢫࢆ୚࠼ࡿࡇ࡜ࡀ♫఍ⓗ࡟ၥ㢟࡜࡞ࡾࠊ௨๓ࡼࡾື≀ࢆ౑⏝ࡋ࡞࠸ື≀ᐇ㦂௦᭰ἲ㸦௨ୗࠊ௦᭰ἲ࡜グࡍ㸧ࡢ㛤Ⓨࡀษᮃࡉࢀ࡚࠸ࡓࠋࡇࡢ௦᭰ἲ࡜ࡋ࡚ࠊ⤒῭༠ຊ㛤Ⓨᶵᵓ㸦OECD㸸Organisation for Economic Co-operation andDevelopment㸧࡟࡚ヨ㦂࢞࢖ࢻࣛ࢖ࣥ㸦TG: Test Guideline㸧435ࠊin vitro ⭷ࣂࣜ࢔ヨ㦂࡜ࡋ࡚ᢎㄆࡉࢀ࡚࠸ࡿ 2㸧ࠋࡇࡢヨ㦂ἲࡣࠊ㐺⏝ࡉࢀࡓ⭉㣗ᛶ≀㉁࡟ࡼࡾᘬࡁ㉳ࡇࡉࢀࡿ⭷ࣂࣜ࢔㞀ᐖࢆ᳨ฟࡍࡿࡇ࡜ࢆᣦᶆ࡟⓶⭵⭉㣗ᛶࢆホ౯ࡋ࡚࠸ࡿࠋᮏヨ㦂ἲࡣࣂࣜࢹ࣮ࢩࣙࣥヨ㦂ࡀᐇ᪋ࡉࢀࠊḢᕞ࡛ࡣ໬Ꮫ≀㉁ࡢ⓶⭵⭉㣗ᛶホ౯ࢆ┠ⓗ࡜ࡋ࡚ᢎㄆࡉࢀࠊ໬Ꮫ≀㉁ࡢࣜࢫࢡ⾲♧㆑ู➼࡟฼⏝ࡉࢀ࡚࠸ࡿࠋ≉࡟᫖௒࡛ࡣᅜ㐃໬Ꮫရࡢศ㢮࠾ࡼࡧ⾲♧࡟㛵ࡍࡿୡ⏺ㄪ࿴ࢩࢫࢸ࣒㸦UN GHS㸸United
Nations Globally Harmonized System of Classification and Labelling of Chemicals㸧ศ㢮࡟ᚑࡗ࡚ホ౯ࡉࢀࡿࢣ࣮ࢫࡀቑ࠼࡚࠸ࡿࠋᡃࡀᅜ࡛᪤Ꮡࡢ໬Ꮫ≀㉁ࢆホ౯ࡍࡿሙྜࠊOECD ࡛ᢎㄆࡉࢀࡓヨ㦂᪉ἲ࡟ࡼࡿ⤖ᯝࡣࠊ୍⯡ⓗ࡟⾜ᨻⓗ࡟ཷࡅධࢀࡽࢀࡿࡀࠊ⌧ᅾࡲ࡛௦᭰ἲ࡛ࡢ⤖ᯝࢆࡶ࡜࡟⾜ᨻⓗ࡟ホ౯ࡉࢀࡓ౛ࡣከࡃ࡞
࠸ࠋᏳ඲ᛶホ౯࡟࠾ࡅࡿ௦᭰ἲࡢᬑཬࡀษᮃࡉࢀ࡚࠸ࡿ⌧≧࡟࠾࠸࡚ࠊᡃࡀᅜ࡛ࡶ⛉Ꮫⓗ࡟ጇᙜ࡜ࡉࢀࡓࡶࡢࡣ✚ᴟⓗ࡟ཷࡅධࢀࡿࡇ࡜ࡀᚲせ࡜࡞ࡗ࡚࠸ࡿࠋࡇࢀࡽࡢ≧ἣ࡟㚷ࡳࠊᮏホ౯᭩࡛ࡣࠊOECD TG435 ࡟ᢎㄆࡉࢀࡓ in vitro ⭷ࣂࣜ࢔ヨ㦂࡜ࡋ࡚ࠊ
Corrositex ࡢ⭉㣗ᛶホ౯࡟࠾ࡅࡿ᭷⏝ᛶࢆホ౯ࡋࡓ 2㸧ࠋ
2. ヨ㦂ࣉࣟࢺࢥࣝᵓᡂࡢጇᙜᛶOECD ࢞࢖ࢻࣛ࢖ࣥ 435ࠕin vitro ⭷ࣂࣜ࢔ヨ㦂ࠖ2㸧ࡢཎ⌮࠾ࡼࡧ᪉ἲ࡟ࡘ࠸࡚㏙࡭ࡿࠋ㸯㸧ཎ⌮  㧗ศᏊ࡛ᵓᡂࡉࢀࡿ⭷ࣂࣜ࢔࠾ࡼࡧ໬Ꮫ≀㉁᳨▱ࢩࢫࢸ࣒㸦Chemical Detection
System㸸CDS㸧࠿ࡽ࡞ࡿࠋࡇࡢ᪉ἲࡢཎ⌮ࡣࠊ໬Ꮫ≀㉁࡟ࡼࡿ⓶⭵⭉㣗ᛶⓎ⌧ᶵᵓࡢ㔜せ࡞ࢫࢸࢵࣉ࡛࠶ࡿ⓶⭵ࡢࣂࣜ࢔ᶵ⬟ࡢ㞀ᐖࢆ᳨ฟࡍࡿࡶࡢ࡛࠶ࡿࠋၟᴗⓗ࡟ࡣᅗ㸯࡟♧ࡍࡼ࠺࡟Corrositex࡜ࡋ࡚㈍኎ࡉࢀ࡚࠸ࡿ2)ࠋ
2㸧᪉ἲ ⿕㦂≀㉁ࡢ㐺⏝࡟ࡼࡿ⭷ࣂࣜ࢔ࡢୗࡢ pH ࡢኚ໬ࡲࡓࡣ࢖ࣥࢪࢣ࣮ࢱ࣮ᾮࡢ≉ᛶࢆྵࡴከᩘࡢⰍࡢኚ໬ࢆ᳨ฟࡋࠊ᭚㟢᫬㛫࡜ほᐹᮇ㛫࡜ࡢ㛵ಀ࡟࠾࠸࡚ㄪ࡭ࡿࡇ࡜࡟ࡼࡾࠊ⭉㣗ᛶࡢ⛬ᗘࢆุᐃࡍࡿࡶࡢ࡛࠶ࡿࠋ ⭷ࣂࣜ࢔ࢆ⏝࠸ࡿᮏヨ㦂ࡣࠊ౑⏝┠ⓗ࡜᝿ᐃࡋ࡚࠸ࡿ⿕㦂≀㉁࡟㐺ྜࡋ࡚࠸ࡿࡇ࡜ࢆணࡵ☜ㄆࡋ࡚࠾࠿ࡡࡤ࡞ࡽ࡞࠸ࠋ⭷ࣂࣜ࢔ヨ㦂ࢆ⾜࠺๓࡟㐺ྜᛶヨ㦂ࢆᐇ᪋ࡋ࡚ࠊ⿕㦂≀㉁ࢆCDS࡟ࡼࡗ᳨࡚ฟྍ⬟࠿ุ᩿ࡍࡿࠋCDSࡀ⿕㦂≀㉁ࢆ᳨ฟ࡛ࡁ࡞࠸ሙྜࠊ⭷ࣂࣜ࢔ヨ㦂ἲࡣࡑࡢ⿕㦂≀㉁ࡢ
⭉㣗ᛶࡢ᭷↓ࢆホ౯ࡍࡿ࡟ࡩࡉࢃࡋࡃ࡞࠸ࡢ࡛ࠊ␗࡞ࡿヨ㦂ἲࢆ⏝࠸ࡿࠋ

410ᅗ㸯㸬TER ᴫせᅗ                  ᅗ㸯㸬Corrositex2㸧             3. 㛤Ⓨ࠾ࡼࡧホ౯࡟౑ࢃࢀࡓ≀㉁ࡢศ㢮ࠊ㑅ᢥ⌮⏤ࡢጇᙜᛶCorrositex ࡢ෌⌧ᛶࡣ Botham et al ࡢㄽᩥ࡟ࡼࢀࡤ 3)ࠊࣉࣞࣂࣜࢹ࣮ࢩࣙࣥ࡟࡚ᵝࠎ࡞࢝ࢸࢦࣜ
࣮ࡢ໬Ꮫ≀㉁ࢆྵࡴ 50 ࡢ⿕㦂≀㉁࡟ࡼࡾ᪋タ㛫෌⌧ᛶ࠾ࡼࡧணᛶࡀㄪ࡭ࡽࢀ࡚࠸ࡿࠋࡑࢀࡽࡢ≀㉁ࣜࢫࢺࢆ ANNEX 1 ࡟♧ࡍࠋࡲࡓࠊFentem et al ࡢࣂࣜࢹ࣮ࢩࣙࣥ࡟࡚ 60 ≀㉁ࢆ⏝࠸࡚ࠊ෌⌧ᛶ࠾ࡼࡧண

ᛶࡀㄪ࡭ࡽࢀ࡚࠸ࡿ 4㸧ࠋࡑࡢࣜࢫࢺࢆ ANNEX 2 ࡟♧ࡍࠋࡇࢀࡽࡢ୰࡛ࠊ㐺ྜᛶヨ㦂࡛ホ౯ྍ⬟࡜ุ᩿ࡉࢀࠊホ౯࡟౑ࢃࢀࡓ≀㉁ࡣ 45 ≀㉁࡛࠶ࡿࠋ⡿ᅜࡢ௦᭰ἲ࡟㛵ࡍࡿ┬ᗇ㛫㐃⤡఍㆟㸦ICCVAM㸸Interagency Coordinating Committee on the Validation of Alternative Methods)ࡢ➨୕⪅ホ౯࡛ࡣࠊࡇࡢ 45 ≀㉁࡟ຍ࠼ࠊ〇㐀ඖࡢ IVI ♫࠿ࡽᥦ౪ࡉࢀ 118 ≀㉁ࠊྜィ 163 ≀㉁ࡢࢹ࣮
ࢱࡀ౑⏝ࡉࢀࡓ 5㸧ࠋ
4. ヨ㦂ἲࡢṇ☜ᛶࢆホ౯ࡍࡿࡓࡵ࡟⏝࠸ࡽࢀࡓ≀㉁ࡢ in vitro ࠾ࡼࡧཧ↷ࢹ࣮ࢱࡢ᭷↓ࣂࣜࢹ࣮ࢩ࡛ࣙࣥ⏝࠸ࡽࢀࡓ⿕㦂≀㉁ࡢከࡃࡣࠊḢᕞ௦᭰ἲホ౯ࢭࣥࢱ࣮(ECVAM㸸European
Centre for the Validation of Alternative Methods㸧ࡢ⓶⭵⭉㣗ᛶヨ㦂ࣂࣜࢹ࣮ࢩ࡛ࣙࣥ౑⏝ࡉࢀࡓ≀㉁࡛࠶ࡾࠊࡑࢀࡽࡢཧ↷ࢹ࣮ࢱࡣධᡭ࡛ࡁࡿࠋ୍᪉ࠊIVI ♫࠿ࡽᥦ౪ࡉࢀࡓ 118 ≀㉁ࡢࢹ࣮ࢱࡢᐈ
ほᛶࡣ☜ㄆ࡛ࡁ࡞࠿ࡗࡓࠋ
5. ヨ㦂ἲࡢṇ☜ᛶ㸦෌⌧ᛶ㸧 Botham et al (1995)ࡢࣂࣜࢹ࣮ࢩࣙࣥ࡟࠾ࡅࡿ᪋タ㛫෌⌧ᛶ࡛ࡣࠊ2 ᪋タࡀ 50 ࡢཧ↷≀㉁㸦25⭉㣗ᛶ≀㉁࠾ࡼࡧ 25 㠀⭉㣗ᛶ≀㉁㸧ࢆ⏝࠸࡚ホ౯ࡋࡓ 3)ࠋLab. A ࡛ホ౯࡛ࡁࡓ≀㉁ࡀ 38ࠊࡑࡢ
511࠺ࡕṇ☜ᗘࡣ 74% (28/38)ࠊLab. B ࡛ホ౯࡛ࡁࡓ≀㉁ࡀ 35ࠊࡑࡢ࠺ࡕṇ☜ᗘࡣ 80% (28/35)࡛࠶ࡿ
࡜ࡉࢀ࡚࠾ࡾࠊ᪋タ㛫ࡢ෌⌧ᛶࡣ㧗࠸࡜ุ᩿ࡉࢀ࡚࠸ࡿࠋ
Fentem et al (1998)ࡢࣂࣜࢹ࣮ࢩࣙࣥ࡟࠾ࡅࡿ 60 ≀㉁ࡢ࠺ࡕࠊ20 ≀㉁࡛᪋タෆ࠾ࡼࡧ᪋タ㛫ࡢኚືࡀホ౯ࡉࢀࠊࡑࢀࡽࡢ㛫࡟᭷ព࡞ᕪࡣ࡞࠸࡜ุ᩿ࡉࢀࡓ 4)ࠋ࠸ࡃࡘ࠿ࡢ≀㉁ࡢ⤖ᯝࡀ᪋タ㛫࡛␗࡞ࡗ࡚࠸ࡓࡀࠊECVAM ࡣᮏヨ㦂ἲࡢಙ㢗ᛶ࡜෌⌧ᛶࡣ㧗࠸࡜ุ᩿ࡋࡓࠋࡇࡢ⤖ㄽࡣࠊECVAM⛉Ꮫㅎၥጤဨ఍(ESAC: ECVAM Scientific Advisory Committee, 2001㸧࡛ࡢホ౯ᚋ 6)ࠊICCVAM ࡟࠾࠸࡚ࡶ☜ㄆࡉࢀࡓ 7㸧ࠋ
6. ヨ㦂ἲࡢಙ㢗ᛶ Botham et al (1995)ࠊFentem et al (1998)࠾ࡼࡧICCVAM (1999)ࡢ㞟ィ⤖ᯝࢆ⾲1࡟♧ࡍ3,4,5㸧ࠋࡑࢀࡒࢀࡢሗ࿌࡟グ㍕ࡉࢀࡓṇ☜ᗘࠊឤᗘ࠾ࡼࡧ≉␗ᗘࡣࠊ73-80㸣ࠊ⣙71-89㸣ࠊ65-76㸣࡛࠶ࡾࠊヨ㦂㛫࡛ᕪࡀ኱ࡁ࠿ࡗࡓࠋࡶࡗ࡜ࡶ኱ࡁ࡞ၥ㢟Ⅼࡣࠊࣂࣜࢹ࣮ࢩࣙࣥ◊✲࡛㑅ᢥࡉࢀࡓ≀㉁ࡢ୰࡛ࠊ
CDSࢆ⏝࠸ࡿ㐺ྜᛶヨ㦂࡟ࡼࡾBotham et al (1995)࡛ࡣ70-76%ࠊFentem et al (1998)࡛ࡣ64%ࡢ≀㉁࡛ࡋ࠿ヨ㦂ࢆᐇ᪋࡛ࡁ࡞࠿ࡗࡓ࡜࠸࠺⤖ᯝ࡛࠶ࡿࠋ౛࠼ࡤࠊpH ࡀ 4.5~8.5 ࡢ⠊ᅖࡢỈ⁐ᛶ≀㉁ࡣከࡃࡢሙྜࠊヨ㦂࡟㐺⏝࡛ࡁ࡞࠿ࡗࡓ㸦ࡇࢀࡲ᳨࡛ᰝࡉࢀࡓࡇࡢ pH ⠊ᅖࡢ໬Ꮫ≀㉁ࡢ 85%
ࡣࠊື≀ヨ㦂࡟࡚㠀⭉㣗ᛶ࡛࠶ࡗࡓ㸧ࠋᅛయ(Ỉ⁐ᛶ/㠀Ỉ⁐ᛶ)ࠊᾮయ(Ỉ⁐ᾮ/㠀Ỉ⁐ᾮ)࠾ࡼࡧங
๣࡟㐺⏝࡛ࡁࡿ࡜ࡉࢀ࡚࠸ࡿࡀࠊࣂࣜࢹ࣮ࢩࣙࣥヨ㦂࡟࠾ࡅࡿ㐺ྜヨ㦂࡟࠾࠸࡚ࠊ᳨ฟྍ⬟࡞ኚ໬ࡣ⏕ࡌ࡞࠿ࡗࡓ(ࡍ࡞ࢃࡕࠊࣂࣜࢹ࣮ࢩࣙࣥヨ㦂ἲࡢCDS࡛Ⰽࡢኚ໬ࢆ♧ࡉ࡞࠿ࡗࡓሙྜࡣ㐺⏝࡜ࡳ࡞ࡉࢀ࡞࠸)ࠋࡇࡢ⤖ᯝ࠿ࡽࠊᮏヨ㦂ἲࡣ୍㒊ࡢ⿕㦂≀㉁࡜ΰྜ≀ࡢ⭉㣗ᛶホ౯࡟ࡋ࠿㐺⏝࡛ࡁࡎࠊ௚ࡢ᪉ἲ࡜ྜࢃࡏ࡚฼⏝ࡉࢀࡡࡤ࡞ࡽ࡞࠸ࠋࡲࡓࠊࣂࣜࢹ࣮ࢩࣙࣥ⤖ᯝ࡜࣓࣮࣮࢝ࡢ⤖ᯝࢆྵࡴICCVAMࡢ㞟ィ⤖ᯝࡣࠊ㐺ྜྍ⬟࡞163≀㉁ࡢヲ⣽ࡸ㑅ᐃ⌮⏤ࡀ㈨ᩱ࡟᫂グࡉࢀ࡚࠾ࡽࡎࠊ㐺ษ࡞ホ౯ࡀ୙ྍ⬟࡛࠶ࡗࡓࠋࡼࡗ࡚ࠊᮏጤဨ఍ࡣࠊ⾲1ࡢ୰࡛ࠊFentem et al (1998)ࡢ⤖ᯝࡀࣂࣜࢹ࣮ࢩࣙࣥ⤖ᯝ࡜ࡋ࡚ጇᙜ࡞⤖ᯝ࡜ุ᩿ࡋࠊࡑࡢឤᗘࡀ71%࡛࠶ࡿࡇ࡜࠿ࡽᮏヨ㦂ἲࡢணᛶࡣ㧗ࡃ࡞࠸࡜ุ᩿ࡋࡓࠋホ౯࡛ࡁࡿ≀㉁ࡢ⠊ᅖࡣ᭷ᶵ㓟ࠊ↓ᶵ㓟ࠊ㓟↓Ỉศゎ≀㸦໬Ꮫ≀㉁࠿ࡽ┤᥋ࡲࡓࡣಟ㣭ࡶࡋࡃࡣ㒊ศⓗ࡞⨨᥮࡟ࡼࡗ࡚సࡾฟࡉࢀࡿ㓟࡜ᖜᗈࡃᐃ⩏ࡉࢀࡿࠋࡇࡢࢡࣛࢫ࡟ࡣࠊ↓Ỉ≀ࠊࣁࣟ㓟ࠊሷ㢮ࡀྵࡲࢀࡿ㸧ࠊ࠾ࡼࡧ ሷᇶ࡞࡝࡟㝈ᐃࡉࢀࡿ࡜グ㍕ࡉࢀ࡚࠸ࡿࠋࣉࣟࢺࢥࣝ࡟ࡼࢀࡤࠊ㝈ᐃࡉࢀࡓ≀㉁ศ㢮ࡢ⠊ᅖ࡛ࠊGHS⣽ศ㢮ࡶྍ⬟࡛࠶ࡿࡇ࡜ࢆᛕ㢌࡟⨨࠸࡚౑⏝ࡍ࡭ࡁ࡛࠶ࡿ࡜ࡉࢀ࡚࠸ࡿࡀࠊ⤖ᯝ࠿ࡽࡑࡢጇᙜᛶࢆㄞࡳྲྀࢀ࡞࠿ࡗࡓࠋ

⾲ 1. Corrositex ࡢணᛶ 3,4,5,7)

ICCVAM ࡢ⥲ィ

Botham et al. (1995)
Lab.A

Lab.B

Fentem et al.㸦1998㸧ṇ☜ᗘ

79% (128/163)

74% (28/38)

80% (28/35)

73%

ឤᗘ

85% (76/89)

81% (17/21)

89% (16/18)

71%

≉␗ᗘ

70% (52/74)

65% (11/17)

71% (12/17)

76%ホ౯ᩘ

163

35/50

38/50

38/60

7. ௚ࡢ⛉Ꮫⓗ࡞ሗ࿌࡜ࡢẚ㍑ࡢ᭷↓12 OECD ࡢ⭉㣗ᛶヨ㦂௦᭰ἲ࢞࢖ࢻࣛ࢖ࣥ࡜ࡋ࡚ࠊ௚࡟ࠕTG430 ⤒⓶㟁Ẽ᢬ᢠヨ㦂ࠖ8㸧࠾ࡼࡧ
6ࠕTG431 ࣄࢺ⾲⓶ࣔࢹࣝヨ㦂ࠖ9㸧ࡀᢎㄆࡉࢀ࡚࠸ࡿࠋࡇࢀࡽࡣ࠸ࡎࢀࡶࣂࣜࢹ࣮ࢩࣙࣥ◊✲ࡀᐇ᪋ࡉࢀࠊICCVAM ࡣࡇࢀࡽࡢヨ㦂ἲ(Rat Skin TER, EpiSkin™࠾ࡼࡧ TER)ࡢṇ☜ᗘࠊឤᗘ࠾ࡼࡧ
≉␗ᗘ࡟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㞴࡛࠶ࡿࡀࠊ㐺⏝ྍ⬟≀㉁࡛࠶ࢀࡤࠊᮏࣔࢹࣝࡣ௚ࡢヨ㦂ἲ࡜ྠ➼ࡢணᛶࢆ᭷ࡍࡿ࡜⪃࠼ࡽࢀࡿࠋ ホ౯ྍ⬟࡞໬Ꮫ≀㉁ࡣ௚ࡢヨ㦂ἲ࡜ẚ࡭࡚㝈ᐃⓗ࡛࠶ࡿࠋ௚ࡢヨ㦂ἲ࡜ẚ㍑ࡋ࡚ឤᗘࡀపࡃࠊ
ഇ㝜ᛶࡀከ࠸ࠋ

⾲ 2㸬ヨ㦂ἲࡢẚ㍑⤖ᯝ
EpiSkinTM(OECD,TER(ICCVAM,10㸧5㸧

CORROSITEX(Fentem,2015)1999)

1998)4㸧

ṇ☜ᗘ

89.6%

81%

73%

ឤᗘ98.5%94%

71%≉␗ᗘ79.3%

71%

76%

8. 㸱Rs ཎ๎࡬ࡢ㛵୚㸦ື≀⚟♴㠃࠿ࡽࡢጇᙜᛶ㸧 ື≀ࢆ౑⏝ࡋ࡚࠾ࡽࡎࠊື≀⚟♴㠃࠿ࡽ௦᭰ἲ࡜ࡋ࡚ጇᙜ࡛࠶ࡿࠋ9. ヨ㦂ἲࡢ᭷⏝ᛶ࡜㝈⏺
 6㸬ヨ㦂ἲࡢಙ㢗ᛶ࡟ࡶグࡋࡓ㐺⏝㝈⏺࠿ࡽࠊከࡃࡢ໬Ꮫ≀㉁࠾ࡼࡧΰྜ≀࡟㐺⏝࡛ࡁ࡞࠸ྍ⬟ᛶࡀ࠶ࡿࠋุᐃࡶ⭉㣗ᛶࡢ᭷↓࡟㝈ࡽࢀ࡚࠾ࡾࠊࡑࡢ㝈⏺ࢆ༑ศ࡟ᢕᥱࡋ࡚౑⏝ࡍ࡭ࡁ࡛࠶ࡿࠋ
⾲ 3 ࡟♧ࡍ⩦⇍ᗘ☜ㄆ≀㉁ࢆṇࡋࡃศ㢮ࡍࡿࡇ࡜࡟ࡼࡾᑓ㛛ᢏ⾡ࡢ⩦⇍࡟ࡘ࠸࡚☜ㄆࡍࡿࡇ࡜
ࡀ࡛ࡁࡿ࡜ TG435 ࡟ࡣグ㍕ࡀ࠶ࡿࠋ

713

⾲ 3 ⩦⇍ᗘ☜ㄆ୍ぴ⾲ 2㸧
1,2UN GHS ༊ศ 3

VRM ༊ศ3CASRN໬Ꮫ≀㉁ࢡࣛࢫ

In vivo ヨ㦂⤖ᯝ࡟ᇶ࡙ࡃIn vitro ヨ㦂⤖ᯝ࡟ᇶ࡙ࡃ࡯࠺⣲ࣇࣝ࢜ࣜࢻ஧Ỉ࿴≀

13319-75-0

↓ᶵ㓟

1A

1A

◪㓟

7697-37-2

↓ᶵ㓟

1A

1A

஬ሷ໬ࣜࣥ

10026-13-8 ↓ᶵ㓟ࡢ๓㥑≀㉁

1A

1A

ࣂࣞࣜࣝ㓟

638-29-9㓟ࢡࣟࣛ࢖ࢻ

1B

1B

Ỉ㓟໬ࢼࢺ࣒ࣜ࢘

1310-73-2

↓ᶵሷᇶ

1B

1B

1-(2-࢔࣑ࣀ࢚ࢳࣝ)ࣆ࣌ࣛࢪࣥ

140-31-8⬡⫫᪘࢔࣑ࣥ

1B

1B࣋ࣥࢮࣥࢫࣝ࣍ࣥ㓟ࢡࣟࣛ࢖ࢻ

98-09-9㓟ࢡࣟࣛ࢖ࢻ

1C

1CN,N-ࢪ࣓ࢳࣝ࣋ࣥࢪࣝ࢔࣑ࣥ

103-83-3

࢔ࢽࣜࣥ

1C1C

ࢸࢺ࢚ࣛࢳࣞࣥ࣌ࣥࢱ࣑ࣥ

112-57-2⬡⫫᪘࢔࣑ࣥ

1C1C

࢜࢖ࢤࣀ࣮ࣝ

97-53-0ࣇ࢙ࣀ࣮ࣝ㢮㠀⭉㣗ᛶ㠀⭉㣗ᛶ࢔ࢡࣜࣝ㓟ࣀࢽࣝ

2664-55-3

࢔ࢡࣜࣝ㓟㸭࣓ࢱࢡࣜࣝ㓟㠀⭉㣗ᛶ㠀⭉㣗ᛶⅣ㓟Ỉ⣲ࢼࢺ࣒ࣜ࢘

144-55-8↓ᶵሷᇶ㠀⭉㣗ᛶ㠀⭉㣗ᛶ  ໬Ꮫ≀㉁

1㸸ୖ࡟グ㍕ࡋࡓ12ࡢ໬Ꮫ≀㉁ࡣࠊ⓶⭵⭉㣗ᛶ≀㉁࡟㛵ࡍࡿGHS ⣽༊ศࡢࡑࢀࡒࢀ࠿ࡽ3≀㉁ࡎ
ࡘ࡜㠀⭉㣗ᛶࡢ3≀㉁࡛࠶ࡿࠋࡇࢀࡽࡣ᳨ド῭ࡳཧ↷ヨ㦂ἲ࡜ᵓ㐀ⓗ࡟ࡶᶵ⬟ⓗ࡟ࡶ㢮ఝࡢヨ㦂ἲ࡟ࡘ࠸࡚ࠊࡑࡢ⢭ᗘ࡜ಙ㢗ᛶࢆ♧ࡍ┠ⓗ࡟౑⏝ࡉࢀࡿࡼ࠺≉ᐃࡉࢀ࡚࠸ࡿࠊ໬Ꮫ≀㉁᭱ᑠ
ࣜࢫࢺࡢ୰࡛ཧ↷໬Ꮫ≀㉁࡜ࡋ࡚ิᣲࡉࢀ࡚࠸ࡿ40ࡢ୰࠿ࡽ㑅ᢥࡋࡓ5,11)ࠋࡇࢀࡽࡢ໬Ꮫ≀㉁ࡣ
ᕷ㈍ᴗ⪅࠿ࡽᐜ᫆࡟㉎ධ࡛ࡁࠊUN GHS ⣽༊ศࡣ㧗ရ㉁ࡢin vivo ヨ㦂ࡢ⤖ᯝ࡟ᇶ࡙࠸࡚࠸ࡿ11)ࠋ
2㸸⣧ᗘࡣ90㸣௨ୖ
3㸸UN GHS ⣽༊ศ1A, 1B ࠾ࡼࡧ1C ࡟ࡣUN ໟ⿦➼⣭IࠊII ࠾ࡼࡧIII ࡀࡑࢀࡒࢀᑐᛂࡍࡿࠋNC; 㠀⭉㣗ᛶ10. ࡑࡢ௚㸦≉チࡢ᭷↓࡞࡝㸧 ≉チ࡟ࡘ࠸࡚ࡣ♧ࡉࢀ࡚࠸࡞࠸ࠋ
11. ⤖ㄽಙ㢗ᛶ࡜ጇᙜᛶ࡜࠸࠺どⅬ࡟࠾࠸࡚ࠊin vitro ⭷ࣂࣜ࢔ヨ㦂࡛࠶ࡿ Corrositex ࢆホ౯ࡋࡓ⤖ᯝࠊᙜヱヨ㦂ἲࡣ௚ࡢヨ㦂ἲ࡜ẚ࡭࡚ࠊホ౯ྍ⬟࡞໬ྜ≀ࡀ㝈ᐃࡉࢀࠊഇ㝜ᛶࡀከࡃ☜ㄆࡉࢀࡓࠋᙜヱヨ㦂ἲ୍㒊ࡢ≀㉁࡟࠾࠸࡚⭉㣗ᛶࡢ᭷↓ࢆホ౯࡛ࡁࡿ࡜⪃࠼ࡽࢀࡓࡀࠊࡑࡢ㐺⏝⠊ᅖࡣ⊃ࡃࠊ814ࡲࡓࠊ㐺⏝ྍ⬟≀㉁ࡢࢡࣛࢫࡀ୙᫂☜࡛࠶ࡿࡓࡵࠊᮏጤဨ఍ࡣࠊᙜヱヨ㦂ἲࢆ⾜ᨻ┠ⓗࡢࡓࡵࡢ⭉㣗ᛶホ౯࡟⏝࠸ࡿࡇ࡜ࡣᅔ㞴࡛࠶ࡿ࡜ุ᩿ࡋࡓࠋ

12. ᩥ⊩
1) OECD (2015) Guideline for the testing of chemicals. 404, Acute Dermal Irritation/Corrosion
2) OECD (2006) Guidelines for the Testing of Chemicals, Test No. 435: In Vitro membrane barrier test
method3) Botham, P.A. et al. (1995) A prevalidation study on in vitro skin corrosivity testing: The report andrecommendations of ECVAM workshop 6. ATLA, 23, 219-255
4) 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
5) ICCVAM (1999) NIH Publication No.99-4495. Corrositex: An in vitro test method for assessing dermal
corrosivity potential of chemicals.
6) ECVAM (2001) Statement on the Application of the CORROSITEX Assay for Skin Corrosivity Testing.
15th Meeting of ECVAM Scientific Advisory Committee (ESAC), Ispra, Italy. ATLA 29, 96-97.
7) 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.
8) OECD (2015) Guideline for the testing of chemicals. 430, in vitro Skin Corrosion: Transcutaneouselectrical resistance test (TER).
9) OECD (2016) Guideline for the testing of chemicals. 431, in vitro Skin Corrosion: Human skin modeltest.
10) OECD (2015) Series on Testing & Assessment No. 219, Performance Standards for the assessment ofproposed similar or modified in vitro reconstructed human epidermis (RhE) test methods for skincorrosion testing as described in TG 43111) ICCVAM (2004) ICCVAM Recommended Performance Standards for In Vitro Test Methods for Skin
Corrosion. NIEHS, NIH Publication No. 04-4510. Available at:[http://www.ntp.niehs.nih.gov/iccvam/docs/dermal_docs/ps/ps044510.pdf].

915

ANNEX 1: Botham 1995 ࡢࣂࣜࢹ࣮ࢩ࡛ࣙࣥ౑ࢃࢀࡓ 50 ≀㉁

1016

1117

1218

ANNEX 2: Fentem 1998 ࡢࣂࣜࢹ࣮ࢩ࡛ࣙࣥ౑ࢃࢀࡓ 60 ≀㉁1319