ᐇ㦂ື≀࡛ࡢ▱ぢ .1 ᛴᛶẘᛶ

ᛴᛶẘᛶ

㸫23㸫

⾲3-1 ᛴᛶẘᛶヨ㦂⤖ᯝ

ື≀✀ ⤒㊰ LD50 ฟ඾

࢘ࢧࢠ ⤒⓶ >8 g/kg NIOSH 2014

ࣛࢵࢺ ⤒ཱྀ 810 mg/kg NIOSH 2014

࣐࢘ࢫ ⤒ཱྀ 6,800 mg/kg NIOSH 2014

࣐࢘ࢫ ⭡⭍ෆ 300 mg/kg NIOSH 2014

ࡑࡢ௚ࡢ༢ᅇᢞ୚ẘᛶ

࣭ࣛࢵࢺ࡟TDBPPࢆ50 mg/mLࡢ⏝㔞࡛⭡⭍ෆ༢ᅇᢞ୚ࡋࠊ24᫬㛫⵳ᒀ㔞ࢆ ᐃࡋ ࡓࠋTDBPP༢ᅇᢞ୚࡛2᪥ᚋ࡟ᒀ㔞ࡀ5ಸ࡟ቑຍࡋࠊ1㐌㛫ᚋ࡟ࡣᒀ㔞ࡣṇᖖ࡟ᡠࡗࡓ (Lynn et al. 1982)ࠋ

࣭Wistar⣔ࣛࢵࢺ࡟TDBPPࢆ 0ࠊ10ࠊ25ࠊ50ࠊ100ࠊ200 mg/kgయ㔜ࡢ⏝㔞࡛⭡⭍ෆ ༢ᅇᢞ୚ࡋࠊ48᫬㛫ᚋ࡟ᏳᴦṚࡉࡏࡓ (40᫬㛫ᚋ࡟ᏳᴦṚࡉࡏࡓ㧗⏝㔞⩌ࢆ㝖ࡃ)ࠋ⭈⮚

┦ᑐ㔜㔞ࡢ᭷ព࡞ቑຍࡀ200 mg/kg⩌࡛ぢࡽࢀࠊ⭈⮚ࡣ⭘኱࣭㏥Ⰽࡋ࡚Ỉ⭘≧࡛࠶ࡾࠊ⓶

㉁ෆഃ࡟㢧ⴭ࡞ቯṚᖏࡀほᐹࡉࢀࡓࠋ⤌⧊Ꮫⓗ࡟ࡣ100 mg/kg௨ୖࡢ⩌࡛ᒀ⣽⟶ቯṚࡀほ ᐹࡉࢀࡓࠋ⾑₢ࢡࣞ࢔ࢳࢽࣥࡢ᭷ព࡞ୖ᪼ࡀ50 mg/kg⩌࠿ࡽぢࡽࢀࡓ (Søderlund et al.

1982b)ࠋ

3.1.3.2 ่⃭ᛶཬࡧ⭉㣗ᛶ

⓶⭵่⃭ᛶ

࣭࢔ࣝࣅࣀ࢘ࢧࢠ (6༉) ࡢ೺ᖖ⓶⭵ཬࡧᦆയ⓶⭵࡟TDBPPࢆ1.1 gࡢ⏝㔞࡛ሬᕸࡋࠊ24

᫬㛫ᚋ࡟Ὑίࡋࡓࠋሬᕸᚋ24᫬㛫ཬࡧ72᫬㛫ᚋ࡟⣚ᩬཬࡧᾋ⭘ࢆほᐹࡋࡓࡀࠊ่⃭ᛶࡢ

཯ᛂࡣ࡞࠿ࡗࡓ (Kerst 1974)ࠋ

║่⃭ᛶ

࣭࢘ࢧࢠ (6༉) ࡢ║࡟TDBPPࢆ0.22 gࡢ⏝㔞࡛ᢞ୚ࡋࡓ⤖ᯝࠊ72᫬㛫ࡢほᐹᮇ㛫୰࡟

ゅ⭷ࠊ⹿ᙬཪࡣ║▛⤖⭷࡟☜ㄆࡋ࠺ࡿ่⃭ཪࡣᦆയࢆᘬࡁ㉳ࡇࡉ࡞࠿ࡗࡓ (Kerst 1974ࠊ US EPA 1976)ࠋ

3.1.3.3 ឤసᛶ

࣭ࣔࣝࣔࢵࢺ (5㹼10༉/⩌) ࢆ⏝࠸࡚ࠊࣛࣥࢻࢩࣗࢱ࢖ࢼ࣮ἲኚἲཬࡧ㊊㋲ἲ࡟ࡼࡾ

TDBPPࡢ⓶⭵ឤసᛶࢆヨ㦂ࡋࡓࠋ࠸ࡎࢀࡢ᪉ἲ࡟࠾࠸࡚ࡶឤసᛶࡣㄆࡵࡽࢀ࡞࠿ࡗࡓ (Morrow et al. 1976)ࠋ

3.1.3.4 ཯᚟ᢞ୚ẘᛶ

⤒⓶᭚㟢

㸫24㸫

࣭࢘ࢧࢠ࡟TDBPPࢆ2.2ࠊ4.4ࠊ8.8 g/kgయ㔜ࡢ⏝㔞࡛1᪥1ᅇࠊ4㐌㛫ሬᕸࡋࡓࠋࡑࡢ

⤖ᯝࠊ⾑ᾮཬࡧᒀ୰ࡢ⮯⣲ࡢቑຍࡀ⏝㔞౫Ꮡᛶ࡟ㄆࡵࡽࢀࠊࡍ࡭࡚ࡢ࢘ࢧࢠࡣ4㐌㛫௨ෆ

࡟Ṛஸࡋࡓࠋ ࡲࡓࠊ⭈⮚ཬࡧ⫢⮚࡟ⴭࡋ࠸ኚᛶᛶࡢኚ໬ࡀㄆࡵࡽࢀࡓࠋࢥ࢚ࣜࣥࢫࢸࣛ

࣮ࢮάᛶࡢ㍍ᗘ࡞ῶᑡࡶㄆࡵࡽࢀࡓ (Brieger et al. 1968)ࠋ

࣭࢘ࢧࢠ࡟TDBPPࢆ50ཪࡣ250 mg/kgయ㔜ࡢ⏝㔞࡛ሬᕸࡋࡓูࡢヨ㦂࡛ࡣ⾑ᾮཬࡧᒀ

୰ࡢ⮯⣲ࡢቑຍࡀㄆࡵࡽࢀࡓࡀࠊṚஸࡣ⏕ࡌ࡞࠿ࡗࡓ (Ulsamer et al. 1980)ࠋ

࣭New Zealand White࢘ࢧࢠ (12༉) ࡟TDBPPࢆ2.27 g/kgయ㔜ࡢ⏝㔞࡛㐌1ᅇ13㐌 㛫ࠊ⫼㒊೺ᖖ⓶⭵ (6༉) ཪࡣ⫼㒊ᦆയ⓶⭵ (6༉) ࡟ሬᕸࡋࡓࠋࡑࡢ⤖ᯝࠊᦆയࡢ᭷↓࡟

࠿࠿ࢃࡽࡎTDBPPᢞ୚⩌࡟࠾࠸࡚ࠊ⤫ィᏛⓗ࡟᭷ព࡞⫢⮚┦ᑐ㔜㔞ࡢቑຍࡀㄆࡵࡽࢀࠊ ࡉࡽ࡟⢭ᕢ㔜㔞ࡢ᭷ព࡞ῶᑡࡀほᐹࡉࢀࡓࠋ⑓⌮⤌⧊Ꮫⓗ᳨ᰝ࡛ࠊ㞝8༉୰6༉࡟៏ᛶ㛫

㉁ᛶ⭈⅖ࡀࠊ㞝8༉୰7༉࡟⢭ᕢⴎ⦰ཬࡧ⢭ᏊᙧᡂࡢḞዴ (⢭⣽⟶࡟⢭♽⣽⬊ࡣᏑᅾࡋࠊ

஧ḟ⢭ẕ⣽⬊ࡶᏑᅾࡍࡿࡀ⢭ᏊࡣᏑᅾࡋ࡞࠸) ࡀほᐹࡉࢀࡓࠋ㞤࡛ࡣ᭷ᐖ཯ᛂࡣㄆࡵࡽࢀ

࡞࠿ࡗࡓࠋ⫢⮚࡟⤌⧊Ꮫⓗኚ໬ࡣㄆࡵࡽࢀ࡞࠿ࡗࡓ (Osterberg et al. 1977ࠊ1978)ࠋ

⤒ཱྀᢞ୚

࣭Sprague-Dawleyࣛࢵࢺ (㞤10༉/⩌) ࡟TDBPPࢆ0ࠊ100ࠊ150ࠊ500ࠊ1,000 mg/kgయ㔜 /᪥ࡢ⏝㔞࡛10᪥㛫ᙉไ⤒ཱྀᢞ୚ࡋࡓ⤖ᯝࠊṚஸ⋡ࡣ0ࠊ0ࠊ0ࠊ70ࠊ100%࡛࠶ࡗࡓ (Seabaugh et al. 1981)ࠋ

࣭㞝ࣛࢵࢺ (⣔⤫࡯࠿୙᫂) ࡟TDBPPࢆ㣫ᩱ୰0ࠊ100ࠊ1,000 mg/kgࡢ⃰ᗘ࡛28᪥㛫ΰ㣵 ᢞ୚ࡋࡓ⤖ᯝࠊ1,000 mg/kg ⩌࡛㣫ᩱຠ⋡ཬࡧయ㔜ቑຍࡢᢚไࠊᚰ⮚ࠊ⫢⮚ࠊ⭁⮚ࠊ⭈⮚

ཬࡧ⢭ᕢࡢ┦ᑐ㔜㔞ࡢ᭷ព࡞ῶᑡࢆㄆࡵࡓࡀࠊ⾑ᾮࠊᒀཬࡧ⑓⌮⤌⧊ࡢྛ᳨ᰝ࡛␗ᖖࡣ࡞

࠿ࡗࡓࠋ⮯⣲࡜ࡋ࡚ ᐃࡋࡓ⬡⫫ࠊ⫢⮚ཬࡧ➽⫗ࡢ⤌⧊୰⃰ᗘࡣᢞ୚4㐌㛫࡛40㹼50ಸ࡟

ቑຍࡋࡓ (Kerst 1974)ࠋࡲࡓࠊྠࡌヨ㦂ࢆ⎔ቃ┬ࡢ໬Ꮫ≀㉁ࡢ⎔ቃࣜࢫࢡึᮇホ౯࡛ࡣࠊ

⏝㔞ࢆ%⾲♧ࡢ0ࠊ0.01ࠊ0.1%࡜ࡋࠊNOAELࢆ0.1% (90 mg/kg/᪥⛬ᗘ) ࡜ሗ࿌ࡋ࡚࠸ࡿ

(⎔ቃ┬ 2004)ࠋ

࣭㞤㞝ࣛࢵࢺ (⣔⤫࡯࠿୙᫂) ࡟TDBPPࢆ0ࠊ10ࠊ50ࠊ100 mg/kg/᪥ࡢ⏝㔞࡛4㐌㛫ᙉไ

⤒ཱྀᢞ୚ࡋࠊ༙ᩘࢆ4㐌㛫࡛ࠊṧࡾࢆ6㐌㛫࡛ᏳᴦṚࡉࡏࡓ⤖ᯝࠊ⾑୰࡛⮯⣲⃰ᗘࡢቑຍࢆ

ㄆࡵࡓ௨እ࡟ࡣࠊᢞ୚࡟㛵㐃ࡋࡓᙳ㡪ࡣ࡞࠿ࡗࡓ (Brieger et al. 1968)ࠋࡲࡓࠊྠࡌヨ㦂

ࢆ⎔ቃ┬ࡢ໬Ꮫ≀㉁ࡢ⎔ቃࣜࢫࢡึᮇホ౯࡛ࡣࠊNOAELࢆ100 mg/kg/᪥࡜ሗ࿌ࡋ࡚࠸ࡿ

(⎔ቃ┬ 2004)ࠋ

࣭Osborne-Mendelࣛࢵࢺ (48༉/⩌) ࡟TDBPPࢆ0ࠊ25ࠊ100ࠊ250 mg/kg య㔜/᪥ࡢ⏝㔞

࡛ࣉࣟࣆࣞࣥࢢࣜࢥ࣮ࣝ࡟ῧຍࡋ࡚90᪥㛫ᙉไ⤒ཱྀᢞ୚ࡋࡓ⤖ᯝࠊ25 mg/kg௨ୖࡢ⩌࡛↓

ฎ⨨ᑐ↷⩌࠶ࡿ࠸ࡣ⏕⌮㣗ሷỈᢞ୚ᑐ↷⩌࡜ẚ㍑ࡋ࡚ࠊయ㔜ቑຍࡢᢚไࠊ⭈⮚┦ᑐ㔜㔞ࡢ ῶᑡ࡟᭷ព࡞ᕪࢆㄆࡵࡓࠋࡲࡓࠊ㞤㞝25 mg/kg⩌࡛⫢⮚┦ᑐ㔜㔞ࡢῶᑡࠊ㞤250 mg/kg⩌

࡛⫢⮚┦ᑐ㔜㔞ࡢቑຍࡀぢࡽࢀࠊ25 mg/kg௨ୖࡢ⩌࡛⢭ᕢ┦ᑐ㔜㔞ࡢ᭷ព࡞ῶᑡࠊᒀ⣽⟶

ୖ⓶ࡢ෌⏕ࠊ⫧ཌཬࡧ␗ᙧᡂࢆకࡗࡓ៏ᛶ⭈⅖ࡢⓎ⏕⋡ࡢቑຍཬࡧ⑕≧ࡢᝏ໬ࢆㄆࡵࡓ

㸫25㸫

(Osterberg et al. 1978)ࠋࡲࡓࠊྠࡌヨ㦂ࢆ⎔ቃ┬ࡢ໬Ꮫ≀㉁ࡢ⎔ቃࣜࢫࢡึᮇホ౯࡛ࡣࠊ LOAELࢆ25 mg/kgయ㔜/᪥࡜ሗ࿌ࡋ࡚࠸ࡿ (⎔ቃ┬ 2004)ࠋ

࣭࢖ࢾ࡟TDBPPࢆ50ཪࡣ100 mg/kgయ㔜ࡢ⏝㔞࡛4㐌㛫ΰ㣵ᢞ୚ࡋࡓࠋయ㔜ࡢῶᑡ࡜

⾑୰⮯⣲⃰ᗘࡢୖ᪼ࡀほᐹࡉࢀࡓ (Brieger et al. 1968)ࠋ

3.1.3.5 ⏕ṪⓎ⏕ẘᛶ

⤒⓶᭚㟢

࣭New Zealand White࢘ࢧࢠ (12༉) ࡟TDBPPࢆ2.27 g/kgయ㔜ࡢ⏝㔞࡛㐌1ᅇ13㐌 㛫ࠊ⫼㒊೺ᖖ⓶⭵ཬࡧ⫼㒊ᦆയ⓶⭵࡟ሬᕸࡋࡓࠋࡑࡢ⤖ᯝࠊ⢭ᕢ㔜㔞ࡢ᭷ព࡞ῶᑡࡀほᐹ ࡉࢀࠊ⑓⌮⤌⧊Ꮫⓗ᳨ᰝ࡛㞝8༉୰7༉࡟⢭ᕢⴎ⦰ཬࡧ⢭ᏊᙧᡂࡢḞዴ (⢭⣽⟶࡟⢭♽⣽

⬊ࡣᏑᅾࡋࠊ஧ḟ⢭ẕ⣽⬊ࡶᏑᅾࡍࡿࡀ⢭ᏊࡣᏑᅾࡋ࡞࠸) ࡀほᐹࡉࢀࡓ (Osterberg et al. 1977ࠊ1978)ࠋ

⤒ཱྀᢞ୚

࣭Sprague-Dawleyࣛࢵࢺ (10༉/⩌) ࡟TDBPPࢆ0ࠊ250ࠊ1,000 mg/kgయ㔜ࡢ⏝㔞࡛

ዷፎ6㹼15᪥࡟ᙉไ⤒ཱྀᢞ୚ࡋࡓࠋࡑࡢ⤖ᯝࠊẕື≀Ṛஸ⋡ࡢቑຍࡀぢࡽࢀࠊྛ⩌ࡢṚஸ

⋡ࡣࡑࢀࡒࢀ0ࠊ10ࠊ100%࡛࠶ࡾࠊ1,000 mg/kg⩌࡛ࡣዷፎ9㹼11᪥┠࡟Ṛஸࡋࡓ (Seabaugh et al. 1981)ࠋ

࣭Sprague-Dawleyࣛࢵࢺ (30༉/⩌) ࡟TDBPPࢆ0ࠊ5ࠊ25ࠊ125 mg/kgయ㔜/᪥ࡢ⏝㔞࡛ዷ ፎ6㹼15᪥ࡲ࡛ᙉไ⤒ཱྀᢞ୚ࡋࡓ⤖ᯝࠊ125 mg/kg⩌ࡢẕື≀࡛᭷ព࡞య㔜ቑຍࡢᢚไࢆㄆ

ࡵࡓࡀࠊ㯤యᩘࠊ╔ᗋᩘࠊ⫾ඣࡢ᪩ᮇ࣭ᚋᮇṚஸࠊ⫾ඣయ㔜ࠊ㢌Ẋ㛗࡟ᙳ㡪ࡣぢࡽࢀࡎࠊ ࡉࡽ࡟྾཰⬇ࢆ♧ࡍẕື≀ࡢⓎ⏕⋡ࠊ⏕Ꮡඣᩘࠊ྾཰⬇ࡢⓎ⏕⋡ࠊ╔ᗋ๓⬇ᦆኻ⋡ࡶᢞ୚

࡟㛵㐃ࡋࡓኚ໬ࢆ♧ࡉ࡞࠿ࡗࡓࠋࡲࡓࠊ⫾ඣࡢෆ⮚ཬࡧ㦵᱁࡛ኚ␗ࡀぢࡽࢀࡓࡶࡢࡢࠊ⏝

㔞౫Ꮡᛶࡣ࡞ࡃࠊ᭷ព࡞ᕪࡶㄆࡵ࡞࠿ࡗࡓࠋࡇࡢヨ㦂࡟࠾࠸࡚TBBPP࡟ࡣദወᙧᛶࡣㄆࡵ

ࡽࢀ࡞࠸࡜⤖ㄽࡉࢀࡓ (Seabaugh et al. 1981)ࠋࡲࡓࠊྠࡌヨ㦂ࢆ⎔ቃ┬ࡢ໬Ꮫ≀㉁ࡢ⎔

ቃࣜࢫࢡึᮇホ౯࡛ࡣࠊNOAELࢆ125 mg/kg/᪥࡜ሗ࿌ࡋ࡚࠸ࡿ (⎔ቃ┬ 2004)ࠋ

࣭Wistar⣔ࣛࢵࢺ࡟TDBPPࢆ0ࠊ25ࠊ50ࠊ100ࠊ200 mg/kgయ㔜/᪥ࡢ⏝㔞࡛ዷፎ7㹼15᪥

ࡲ࡛ᙉไ⤒ཱྀᢞ୚ࡋࡓ⤖ᯝࠊ200 mg/kg⩌ࡢ⫾ඣ࡛㦵᱁ኚ␗ࡢ᭷ព࡞ቑຍࢆㄆࡵࡓࡀࠊ⫗

║ⓗཬࡧෆ⮚ወᙧࡣㄆࡵࡽࢀ࡞࠿ࡗࡓࠋࡲࡓࠊ50ཬࡧ100 mg/kg⩌࡛⏕⫱⋡ࡢ᭷ព࡞పୗ

ࢆㄆࡵࡓࡀࠊ࠸ࡎࢀࡢ⩌࡟࠾࠸࡚ࡶ့⫱⋡ཬࡧ10㐌᫬ࡢ⏕Ꮡ⋡࡟ᙳ㡪ࡣ࡞࠿ࡗࡓࠋẕື≀

࡛ࡣ200 mg/kg⩌࡛ⴭࡋ࠸య㔜ቑຍࡸᦤ㣵㔞ࡢᢚไࡀぢࡽࢀࡓࠋ200 mg/kgࡣẕື≀࡟ẘ ᛶࢆ♧ࡍ⏝㔞࡛࠶ࡿࡇ࡜࠿ࡽࠊⴭ⪅ࡽࡣࠊTDBPPࡣദወᙧᛶࢆᣢࡓ࡞࠸࡜⤖ㄽࡋ࡚࠸ࡿ

(Kawashima et al. 1983ࠊ⎔ቃ┬ 2004)ࠋࡲࡓࠊྠࡌヨ㦂ࢆ⎔ቃ┬ࡢ໬Ꮫ≀㉁ࡢ⎔ቃࣜࢫ ࢡึᮇホ౯࡛ࡣࠊNOAELࢆ100 mg/kg/᪥࡜ሗ࿌ࡋ࡚࠸ࡿ (⎔ቃ┬ 2004)ࠋ

ࡑࡢ௚ࡢᢞ୚⤒㊰

㸫26㸫

࣭Sprague-Dawleyࣛࢵࢺ (㞝6 ༉/⩌) ࡟0ࠊ0.4ࠊ0.9ࠊ1.8ࠊ3.5ࠊ7.1ࠊ14.2ࠊ28.4ࠊ 56.8ࠊ113.5 mgࡢTDBPPࢆ72᪥㛫 (3ᅇ/㐌) ⭡⭍ෆᢞ୚ࡋࡓ⤖ᯝࠊ28.4 mg௨ୖࡢ⩌࡛⏝

㔞౫Ꮡᛶࡢ⢭ᕢࠊ⢭ᕢୖయࠊ๓❧⭢ཬࡧ⢭ᄞ㔜㔞ࡢ᭷ព࡞ῶᑡࢆㄆࡵࠊ⢭ᕢ࡛ࡢ⢭Ꮚᙧ ᡂࠊ⢭ᕢୖయ࡛ࡢ⢭Ꮚ㈓ⶶཬࡧ⢭Ꮚࡢ㐠ືᛶ࡟ῶᑡࡀぢࡽࢀࠊ⢭ᕢࡢ⤌⧊Ꮫⓗ᳨ᰝ࡛⢭⣽

⟶࡬ࡢᙳ㡪ࢆㄆࡵࡓࠋᙳ㡪ࡢぢࡽࢀࡓ⢭⣽⟶࡟ࡣ⏕Ṫ⣽⬊ࡀ࡯࡜ࢇ࡝࡞ࡃࠊ⢭ᕢࡢ㛫㉁࡛

ࡣ㈎㣗స⏝ࡢάᛶ໬ࢆ♧ࡍ࣐ࢡࣟࣇ࢓࣮ࢪࡀほᐹࡉࢀࡓࠋࣛ࢖ࢹ࢕ࢵࣄ⣽⬊ࡣṇᖖ࡛࠶ࡗ ࡓࠋ࡞࠾ࠊTDBPPࡣࢸࢫࢺࢫࢸࣟࣥࡢ⾑Ύ୰⃰ᗘࡸin vitro࡛ࡢ⢭ᕢࡢࢸࢫࢺࢫࢸࣟࣥศ Ἢ⬟࡟᭷ព࡞ᙳ㡪ࢆ♧ࡉ࡞࠿ࡗࡓ (Cochran & Wiedow 1986)ࠋ

࣭B6C3F1࣐࢘ࢫ (㞝12㹼15 ༉/⩌) ࡟TDBPPࢆ0ࠊ⣙200ࠊ400ࠊ600ࠊ800ࠊ1,000 mg/kgయ㔜/᪥ࡢ⏝㔞࡛5᪥㛫⭡⭍ෆᢞ୚ࡋࡓ⤖ᯝࠊTDBPPᢞ୚⩌࡛⢭Ꮚ㢌㒊ወᙧࡢⓎ⏕⋡

࡟᭷ព࡞ቑຍࢆㄆࡵࠊ800 mg/kg௨ୖࡢ⩌࡛ⴭࡋ࠿ࡗࡓ (Salamone & Katz 1981)ࠋ

3.1.3.6 㑇ఏẘᛶ

࣭ከࡃࡢヨ㦂ࡀᐇ᪋ࡉࢀࠊ㝧ᛶ⤖ᯝࡀከࡃሗ࿌ࡉࢀ࡚࠸ࡿ (ୗ⾲㸹IPCS 1995)ࠋ

࣭ࡑࡢ௚࡟ࡶin vivo ヨ㦂⣔࡛ࡣࠊࢺࣛࣥࢫࢪ࢙ࢽࢵࢡ࣐࢘ࢫࡢ⭈⮚࡛㑇ఏᏊ✺↛ኚ␗

(De Boer et al. 1996)ࠊࢩࣙ࢘ࢪࣙ࢘ࣂ࢚࡛య⣽⬊ኚ᥮ (Vogel & Nivard 1993)ࠊࣛࢵࢺ⫢

⣽⬊࡛ᑠ᰾ࠊࢩࣙ࢘ࢪࣙ࢘ࣂ࢚࡛⎔≧XᰁⰍయḞᦆཬࡧకᛶຎᛶ⮴Ṛ✺↛ኚ␗ (Van Beerendonk et al. 1994) ࢆㄏⓎࡋࡓࠋ

⾲3-2 In vitroヨ㦂⤖ᯝ (IPCS 1995)

ヨ㦂✀ ヨ㦂⣔/⃰ᗘ ⤖ᯝ¹⁾ 㸫S9 㸩S9 ฟ඾

᚟ᖐ✺↛

ኚ␗

ࢿࢬ࣑ࢳࣇࢫ⳦ TA100

0.05 mmol/L 㸫 㸩 Holme et al. 1983

ࢿࢬ࣑ࢳࣇࢫ⳦ TA100ࠊ TA1535

0.0110 PL/ࣉ࣮ࣞࢺ

ࢿࢬ࣑ࢳࣇࢫ⳦ TA1537ࠊ TA1538

0.0110 PL/ࣉ࣮ࣞࢺ

㸩

㸫

㸩

㸫

Blum & Ames 1977 Brusick et al. 1978 Prival et al. 1977

ࢿࢬ࣑ࢳࣇࢫ⳦ TA1535 0.1ࠊ1.0 PL/ࣉ࣮ࣞࢺ

ࢿࢬ࣑ࢳࣇࢫ⳦ TA1538 0.1ࠊ1.0 PL/ࣉ࣮ࣞࢺ

(㸩)

㸫

㸩

㸫

Carr & Rosenkranz 1978

㸫27㸫

ヨ㦂✀ ヨ㦂⣔/⃰ᗘ ⤖ᯝ¹⁾ 㸫S9 㸩S9 ฟ඾

ࢿࢬ࣑ࢳࣇࢫ⳦ TA100ࠊ TA98ࠊTA1535 10㹼1,000 Pg/ࣉ࣮ࣞࢺ

ࢿࢬ࣑ࢳࣇࢫ⳦ TA1537 10㹼1,000 Pg/ࣉ࣮ࣞࢺ

㸫

㸫

㸩

㸫

MacGregor et al.

1980

ࢿࢬ࣑ࢳࣇࢫ⳦ TA100ࠊ TA1535

0.3㹼100 Pmol/ࣉ࣮ࣞࢺ

㸩 㸩 Nakamura et al.

1979

ࢿࢬ࣑ࢳࣇࢫ⳦ TA100

up to 100 Pg/ࣉ࣮ࣞࢺ グ㍕↓ࡋ 㸩 McCann & Ames

1977

ࢿࢬ࣑ࢳࣇࢫ⳦ TA100 112ࠊ224 Pg/ࣉ࣮ࣞࢺ 2,240ࠊ4,480ࠊ11,200 Pg/ࣉࣞ

࣮ࢺ

グ㍕࡞ࡋ 㸩

㸩 㸩

Salamone & Katz 1981

ࢿࢬ࣑ࢳࣇࢫ⳦ TA100

50 Pg/ࣉ࣮ࣞࢺ௨ୖ 㸩 Brusick et al. 1980

ࢿࢬ࣑ࢳࣇࢫ⳦ TA100

>1 PL/ࣉ࣮ࣞࢺࠊ 0.01 PL/ࣉ࣮ࣞࢺ

㸩 グ㍕࡞ࡋ

グ㍕࡞ࡋ 㸩

Prival et al. 1977

๓㐍✺↛

ኚ␗

࣐࢘ࢫࣜࣥࣃ⭘L5178Y⣽⬊

5 mg/L

㸩 (sS9㸸୙᫂)

Brusick et al. 1978 Ulsamer et al. 1980

㑇ఏᏊ✺

↛ኚ␗

ࢳࣕ࢖ࢽ࣮ࢬࣁ࣒ࢫࢱ࣮V79⣽

⬊ 0.02 mmol/L

グ㍕࡞ࡋ 㸩

Holme et al. 1983 Søderlund et al.

1985 ࢳࣕ࢖ࢽ࣮ࢬࣁ࣒ࢫࢱ࣮V79⣽

⬊

up to 150 Pg/mL

㸫 㸫 Sala et al. 1982

ᰁⰍయ

␗ᖖ

࣐࢘ࢫࣜࣥࣃ⭘L5178Y⣽⬊

0.01 PL/mL

㸩

(sS9㸸୙᫂) Brusick et al. 1980 ࢳࣕ࢖ࢽ࣮ࢬࣁ࣒ࢫࢱ࣮V79⣽

⬊

⏝㔞୙᫂

㸫 (sS9㸸୙᫂)

Furukawa et al.

1978

㸫28㸫

ヨ㦂✀ ヨ㦂⣔/⃰ᗘ ⤖ᯝ¹⁾ 㸫S9 㸩S9 ฟ඾

ࢳࣕ࢖ࢽ࣮ࢬࣁ࣒ࢫࢱ࣮⫵⥺⥔

ⱆ⣽⬊⏤᮶CHL⣽⬊

0.25 mg/mL

グ㍕࡞ࡋ 㸩 Ishidate et al. 1981

஧ಸయࣄࢺ⥺⥔ⱆ⣽⬊HE2144 (10㐌㱋㞝⬇⏤᮶)

0.035ࠊ0.070ࠊ0.349 mg/mL

㸫 グ㍕࡞ࡋ Sasaki et al. 1980

ጜጒᰁⰍ ศయ஺᥮

ࢳࣕ࢖ࢽ࣮ࢬࣁ࣒ࢫࢱ࣮V79⣽

⬊

⏝㔞୙᫂

㸩 (sS9㸸୙᫂)

Furukawa et al.

1978 ࢳࣕ࢖ࢽ࣮ࢬࣁ࣒ࢫࢱ࣮V79⣽

⬊

35ࠊ50ࠊ100ࠊ200 Pg/mL 50 Pg/mL

㸩 グ㍕࡞ࡋ

グ㍕࡞ࡋ 㸩

Sala et al. 1982

࣐࢘ࢫࣜࣥࣃ⭘L5178Y⣽⬊

0.005 PL/mL

㸩

(sS9㸸୙᫂) Brusick et al. 1980

஧ಸయࣄࢺ⥺⥔ⱆ⣽⬊HE2144 (10㐌㱋㞝⬇⏤᮶)

0.070 mg/mL

㸩 グ㍕࡞ࡋ Sasaki et al. 1980

୙ᐃᮇ DNAྜᡂ

༢ᒙᇵ㣴ࣛࢵࢺ⫢⣽⬊

0.01㹼0.1 mmol/Lࠊ18㹼19᫬

㛫᭚㟢

㸩

Holme et al. 1983 Holme & Søderlund,

1984 Gordon et al. 1985

Søderlund et al.

1985

୙ᐃᮇ DNAྜᡂ DNAᦆയ

༢ᒙᇵ㣴ࣄࢺ (KB) ⣽⬊

2 PL/mLࠊ4.5᫬㛫᭚㟢

㸩 (sS9㸸୙᫂)

Gutter &

Rosenkranz 1977 Blum & Ames 1977

୙ ᐃ ᮇ DNAྜᡂ

ࣉ࣮ࣝࡋࡓໟ⓶ୖ⓶⣽⬊

10㹼99 Pg/mL࡜100㹼400 Pg/mL

㸫

(sS9㸸୙᫂) Lake et al. 1978

DNAᦆയ

ᇵ㣴Reuberࣛࢵࢺ࣊ࣃࢺ࣮࣐⣽

⬊

᭚㟢㔞୙᫂

㸫 グ㍕↓ࡋ Gordon et al. 1985

㸫29㸫

ヨ㦂✀ ヨ㦂⣔/⃰ᗘ ⤖ᯝ¹⁾ 㸫S9 㸩S9 ฟ඾

ศ㞳ࣛࢵࢺ⫢⣽⬊

5 Pmol/L 㸩 Søderlund et al.

1992 ࢥࣟࢽ࣮

ᙧᡂ㜼ᐖ

ࢳࣕ࢖ࢽ࣮ࢬࣁ࣒ࢫࢱ࣮V79⣽

⬊

⏝㔞୙᫂

㸩 (sS9㸸୙᫂)

Furukawa et al.

1978 ᙧ㉁㌿᥮ ࣐࢘ࢫBALB/3T3⣽⬊

⏝㔞୙᫂

㸩 (sS9㸸୙᫂)

Brusick et al. 1978 Ulsamer et al. 1980 C3H/10T1/2⣽⬊ࠊ

0.16ࠊ20 Pg/mL

㸫

(sS9㸸୙᫂) Dunkel et al. 1988 C3H/10T1/2⣽⬊ࠊ

40 Pg/mL 80 Pg/mL

㸫 㸫

㸫 ᮍᐇ᪋

Sala et al. 1982

1) 㸫㸸㝜ᛶࠊ㸩㸸㝧ᛶࠊ (㸩)㸸ᙅ࠸㝧ᛶ

⾲3-3In vivoヨ㦂⤖ᯝ (IPCS 1995)

ヨ㦂᪉ἲ ື≀✀/⏝㔞 ⤖ᯝ¹⁾ ฟ඾

ᑠ᰾

㞤㞝ࢳࣕ࢖ࢽ࣮ࢬࣁ࣒ࢫࢱ࣮

200 mg/kg య㔜 400ࠊ800 mg/kg య㔜

⭡⭍ෆᢞ୚ࠊ㦵㧊⣽⬊

㸫

㸩 Sala et al. 1982

B6C3F1࣐࢘ࢫ

204ࠊ408ࠊ612ࠊ816ࠊ1,020ࠊ1,275ࠊ 1,530 mg/kg య㔜ࠊ

2ᅇ⭡⭍ෆᢞ୚ࠊ㦵㧊⣽⬊

(㸩) Salamone & Katz 1981

ᰁⰍయ

␗ᖖ

ࣛࢵࢺ

25ࠊ250ࠊ2,500 mg/kg య㔜ࠊ ༢ᅇཪࡣ5ᅇ/㐌/13㐌ᙉไ⤒ཱྀᢞ୚ࠊ㦵㧊

⣽⬊

㸫

Osterberg 1977 Nakanishi &

Schneider 1979

DNAᦆയ

Wistar⣔㞝ࣛࢵࢺ

250 mg/kg య㔜 (350 Pmol/kg య㔜)ࠊ ༢ᅇ⭡⭍ෆᢞ୚2᫬㛫ᚋࠊ✀ࠎࡢჾᐁ (⫢

⮚ࠊ⭈⮚ࠊᑠ⭠௚)

㸩

Holme et al. 1983 Søderlund et al.

1992

㸫30㸫

ヨ㦂᪉ἲ ື≀✀/⏝㔞 ⤖ᯝ¹⁾ ฟ඾

ື≀✀୙᫂

25 mg/kg య㔜 (36 Pmol/kg య㔜)ࠊ ༢ᅇ⭡⭍ෆᢞ୚20ศᚋࠊ⭈⮚

㸩 Pearson et al. 1993b

1) 㸫㸸㝜ᛶࠊ㸩㸸㝧ᛶࠊ (㸩)㸸ᙅ࠸㝧ᛶ

3.1.3.7 Ⓨࡀࢇᛶ

⤒⓶᭚㟢

࣭ICR/Ha Swiss࣐࢘ࢫ (㞤29ཪࡣ30༉/⩌) ࡟TDBPPࢆ0ࠊ10ࠊ30 mg/ື≀ࡢ⏝㔞࡛

㐌3ᅇࠊ๋ẟࡋࡓ⓶⭵࡟10 mg⩌࡛ࡣ496᪥ཪࡣ30 mg⩌࡛ࡣ474᪥㛫ሬᕸࡋࡓࠋ

TDBPP⩌࡟࠾࠸࡚ࠊ⓶⭵⭘⒆ (ங㢌⭘ࠊ⒴ཪࡣ/ཬࡧ⫗⭘) ࡢ᭷ព࡞ቑຍ࡟ຍ࠼ࠊᢞ୚⓶

⭵࠿ࡽ㞳ࢀࡓ㒊఩࡟࠿࡞ࡾࡢᩘࡢ⭘⒆ࠊ౛࠼ࡤࠊ⯉ࡸཱྀ⭍㡿ᇦࡢᡥᖹୖ⓶⒴ࠊ๓⫶ࡢங㢌

⭘ཬࡧ⒴ࡀㄆࡵࡽࢀࡓ (Van Duuren et al. 1978)ࠋ

⾲3-4 ࣐࢘ࢫࡢⓎࡀࢇᛶヨ㦂⤖ᯝ (Van Duuren et al. 1978)

ᢞ୚㔞 (mg/ື≀) ⭘⒆ࢆᣢࡘື≀ᩘ/๗᳨ື≀ᩘ^a

0 10 30

(㛤ጞ᫬ື≀ᩘ) ๓⫶㸸ங㢌⭘/⒴

⫵㸸ங㢌≧⭘⒆

⓶⭵㸸ங㢌⭘/⒴/⫗⭘

ཱྀ⭍㸸ங㢌⭘/ᡥᖹୖ⓶⒴

(29) 1/29 7/29 0/29 0/29

(29) 10/29 26/29 2/29 2/29

(30) 20/30 28/30 5/30 4/30 a㸸ᢞ୚⩌ࡢ๓⫶ࠊ⫵ࠊ⓶⭵ཬࡧཱྀ⭍ࡢ⭘⒆Ⓨ⏕ᩘࡢቑຍࡣᑐ↷⩌࡜ẚ㍑ࡋ࡚⤫ィⓗ࡟᭷

ព࡛࠶ࡗࡓ (࢝࢖஧஌᳨ᐃ㸸p<0.05)

⤒ཱྀᢞ୚

࣭Fischer 344ࣛࢵࢺ (㞤㞝ྛ55༉/⩌) ࡟TDBPPࢆ㣫ᩱ୰0ࠊ50ࠊ100 mg/kgࡢ⃰ᗘ࡛103 㐌㛫ΰ㣵ᢞ୚ࡋࡓ⤖ᯝࠊ㞝ࡢ50 mg/kg௨ୖࡢ⩌ཬࡧ㞤ࡢ100 mg/kg⩌࡛ࠊᒀ⣽⟶⭢⭘ཬࡧ

⭢⒴ࡢⓎ⏕⋡࡟᭷ព࡞ቑຍࢆㄆࡵࡓࠋࡲࡓࠊ⭈⮚ࡢ๓ࡀࢇ⑓ኚ࡛࠶ࡿ␗ᙧᡂཬࡧ㐣ᙧᡂࡢ

Ⓨ⏕⋡ࡣࠊᑐ↷⩌ (㞤㞝ྜィ) ࡛0/105༉ࠊ㞤50 mg/kg⩌࡛25/54༉ࠊ㞝50 mg/kg⩌࡛

53/54༉ࠊ㞤100 mg/kg⩌࡛46/54༉ࠊ㞝100 mg/kg⩌࡛39/54༉࡛࠶ࡗࡓ (US NCI 1978ࠊ IARC 1979ࠊReznik et al. 1979)ࠋ

⾲3-5 ࣛࢵࢺࡢⓎࡀࢇᛶヨ㦂⤖ᯝ1 (US NCI 1978ࠊIARC 1979ࠊReznik et al.

1979)

㸫31㸫

ᢞ୚㔞 (㣫ᩱ୰mg/kg) ⭘⒆ࢆᣢࡘື≀ᩘ/᳨ᰝື≀ᩘ

0 50 100

㞝 (㛤ጞ᫬ື≀ᩘ)

⭈⮚¹⁾㸸ᒀ⣽⟶⭢⭘/⭢⒴

(55) 0/53

(55) 30/54**

(55) 30/54**

㞤 (㛤ጞ᫬ື≀ᩘ)

⭈⮚¹⁾㸸ᒀ⣽⟶⭢⭘/⭢⒴

(55) 0/52

(55) 4/54

(55) 13/54**

1) Reznik et al. 1979ࠊFisher᳨ᐃ㸸 **㸹p<0.01

࣭F344ࣛࢵࢺ࡟TDBPPࢆ0 ཪࡣ100 mg/kgయ㔜/᪥ࡢ⏝㔞࡛ࠊ㐌5᪥4㐌ཪࡣ52㐌㛫 ᙉไ⤒ཱྀᢞ୚ࡋࡓࠋ1ࠊ5ࠊ10ࠊ20ࠊ50ࠊ75ཬࡧ260ᅇࡢᢞ୚ᚋ࡟2ࠥ9༉ࡢື≀ࢆᏳᴦ Ṛࡉࡏࠊ⭈⮚ࡢ⤌⧊ᙧែཬࡧ㉸ᚤ⣽ᵓ㐀ࢆほᐹࡋࡓࠋTDBPPᢞ୚24᫬㛫ᚋࠊ⓶㧊ቃ⏺㒊 ࡢୖ⓶⣽⬊ࡣ᰾/⣽⬊㉁ẚࠊᕧ኱⣽⬊ࠊ᰾ࡢ✵⬊໬ཬࡧከᙧᛶࡀቑຍࡋࡓࠋࡇࢀࡽࡢኚ໬

ࡣࠊᢞ୚ࡀ⥅⥆ࡍࡿ࡟ࡘࢀ࡚㔜⑕ᗘࡀቑࡋࠊ52㐌㛫ࡲ࡛࡟⓶㉁඲యࡲ࡛ᣑ኱ࡋࡓࠋ

TDBPPᢞ୚52㐌ᚋ࡟ࠊ5༉୰3༉ࡢ⭈⮚࡟ᒀ⣽⟶ࡢᑠᆺࡢங㢌≧㐣ᙧᡂࡀࠊ1༉ࡢ⭈⮚

࡟⭢⒴ࡀほᐹࡉࢀࡓ௚ࠊ3༉࡟ୗ⾜⤖⭠ࡢ࣏࣮ࣜࣉ≧⭢⭘ࡀㄆࡵࡽࢀࡓࠋ⭈⮚ࡢ㟁Ꮚ㢧ᚤ 㙾᳨ᰝ࡛ࡣࠊ㏆఩ᒀ⣽⟶᭤㒊ࡢୖ⓶࡟࠾ࡅࡿᚤ⤧ẟཬࡧᴟᛶࡢᾘኻࡀほࡽࢀࠊ⭘⒆⣽⬊࡛

ࡣࠊ⣽⬊㉁ࡣศ໬ᗘࡀపࡃࠊከࡃࡢ㡿ᇦ࡟࠾࠸࡚ࠊ⣽⬊ࡢ⾲㠃ࡣᚤ⤧ẟ࡟ࡼࡗ࡚そࢃࢀ࡚

࠸ࡓࠋᢞ୚4㐌㛫ᚋ ࠿ࡽ52㐌ࡲ࡛ࢆ᳜≀Ἔᢞ୚࡟ษࡾ᭰࠼ࡓື≀࡛ࡣࠊᚎࠎ࡟ࠊ୙᏶඲

࡛ࡣ࠶ࡿࡀࠊ࡯ࡰṇᖖ࡞ᙧែࡢᒀ⣽⟶ୖ⓶࡬ࡢಟ᚟ࡀほᐹࡉࢀࡓࠋ⣽⬊㉁ࡢ␗ᖖࡀᾘኻࡋ ࡓᚋࡶ᰾ࡢኚ໬ࡣṧᏑࡋࡓ (Reznik et al. 1981)ࠋ

࣭B6C3F1࣐࢘ࢫ (㞤㞝ྛ50༉/⩌) ࡟TDBPPࢆ㣫ᩱ୰0ࠊ500ࠊ1,000 mg/kgࡢ⃰ᗘ࡛103 㐌㛫ΰ㣵ᢞ୚ࡋࡓ⤖ᯝࠊ㞝࡛ࡣ500 mg/kg௨ୖࡢ⩌࡛๓⫶ࡢᡥᖹୖ⓶ங㢌⭘ཬࡧᡥᖹୖ⓶

⒴ࠊ⫵ࡢ⭢⭘ཬࡧ⒴ࠊ1,000 mg/kg⩌࡛ᒀ⣽⟶⭢⭘ཬࡧ⭢⒴ࡢⓎ⏕⋡࡟᭷ព࡞ቑຍࢆㄆ

ࡵࠊ㞤࡛ࡣ500 mg/kg௨ୖࡢ⩌࡛๓⫶ࡢᡥᖹୖ⓶ங㢌⭘ཬࡧᡥᖹୖ⓶⒴ࠊ⫢⮚ࡢ⭢⭘ཬࡧ

⒴ࠊ1,000 mg/kg⩌࡛⫵ࡢ⭢⭘ཬࡧ⒴ࡢⓎ⏕⋡࡟᭷ព࡞ቑຍࢆㄆࡵࡓࠋࡲࡓࠊ⭈⮚ࡢ๓ࡀ

ࢇ⑓ኚ࡛࠶ࡿ␗ᙧᡂཬࡧ㐣ᙧᡂࡢⓎ⏕⋡ࡣࠊᑐ↷⩌ (㞤㞝ྜィ) ࡛0/109༉ࠊ㞤500 mg/kg

⩌࡛20/50༉ࠊ㞝500 mg/kg⩌࡛46/50༉ࠊ㞤1,000 mg/kg⩌࡛40/46༉ࠊ㞝1,000 mg/kg⩌

࡛49/50༉࡛࠶ࡗࡓ (US NCI 1978ࠊReznik et al. 1979ࠊIARC 1979)ࠋ

⾲ 3-6 ࣐࢘ࢫࡢⓎࡀࢇᛶヨ㦂⤖ᯝ 2 (US NCI 1978ࠊReznik et al. 1979ࠊIARC 1979)

㸫32㸫

ᢞ୚㔞 (㣫ᩱ୰mg/kg) ⭘⒆ࢆᣢࡘື≀ᩘ/᳨ᰝື≀ᩘ

0 500 1,000

㞝 (㛤ጞ᫬ື≀ᩘ) ๓⫶¹⁾㸸ᡥᖹୖ⓶⒴/ங㢌⭘

⫵¹⁾㸸⭢⭘/⒴

⭈⮚²⁾㸸ᒀ⣽⟶⭢⭘/⭢⒴

⫢⮚¹⁾㸸⭢⭘/⒴

(55) 0/51 12/54

0/54 28/54

(50) 10/47**^a

18/44*

6/50 31/49

(50) 13/48**

25/50**

17/49**

23/49 㞤 (㛤ጞ᫬ື≀ᩘ)

๓⫶¹⁾㸸ᡥᖹୖ⓶⒴/ங㢌⭘

⫵¹⁾㸸⭢⭘/⒴

⭈⮚²⁾㸸ᒀ⣽⟶⭢⭘/⭢⒴

⫢⮚¹⁾㸸⭢⭘/⒴

(55) 2/53 4/55 0/55 11/54

(50) 14/48**

9/50 3/50 23/50**

(50) 22/44**

17/50**

3/46 35/49**

1)US NCI 1978ࠊ2) Reznik et al. 1979ࠊFisher᳨ᐃ㸸*㸹p<0.05ࠊ**㸹p<0.01ࠊ a㸸ங㢌⭘ࡢࡳ

3.1.3.8 ࡑࡢ௚ࡢヨ㦂

⭈ẘᛶ

࣭ࣛࢵࢺࢆ⏝࠸ࡓ90᪥㛫ᙉไ⤒ཱྀᢞ୚ヨ㦂࡟࠾࠸࡚TDBPP 25 mg/kg⩌௨ୖ࡛៏ᛶ⭈⅖ ࡢⓎ⏕⋡ཬࡧ㔜⑕ᗘࡢቑຍࡀㄆࡵࡽࢀࡓ (Osterberg et al. 1978)ࠋࠕ㸱㸬㸱㸬㸲 ཯᚟ᢞ

୚ẘᛶࠖࡢ㡯ࡶཧ↷ࠋ

࣭TDBPPࡣࣛࢵࢺ࡟࠾࠸࡚⾑Ύࢡࣞ࢔ࢳࢽࣥཬࡧᒀ⣲ࡢୖ᪼ࠊ୪ࡧ࡟᭷ᶵ࢔ࢽ࢜ࣥཬࡧ

࢝ࢳ࢜ࣥ㍺㏦ࡢపୗࢆక࠺㏆఩ᒀ⣽⟶㞀ᐖཬࡧᛴᛶ⭈୙඲ࢆᘬࡁ㉳ࡇࡋࡓ (Søderlund et al. 1980ࠊElliott et al. 1982ࠊLynn et al. 1982)ࠋTDBPPࡣ⭷㏱㐣ᛶࡢቑ኱ࢆ≉ᚩ࡜ࡍࡿ

ึᮇࡢ㞀ᐖ࡟ࡼࡗ࡚⭈⣽⬊㉁㓝⣲ࡢᒀ୰᤼ἥࢆᘬࡁ㉳ࡇࡋࠊ⥆࠸࡚⣽⬊ᑠჾᐁ㛵㐃㓝⣲ࡢ

᤼ἥࡀ㉳ࡇࡾ⭈ᒀ⣽⟶ୖ⓶ࡢቯṚࢆᣍ᮶ࡍࡿ (Nomiyama et al. 1974ࠊEmanuelli et al.

1979ࠊFukuoka et al. 1987ࠊ 1988aࠊ1988b㸧ࠋTDBPPࡣࡲࡓࠊࢼࢺ࣒ࣜ࢘ඹ㍺㏦⣔࡟

ࡼࡗ࡚ๅᏊ⦕⭷ࢆ㏻ࡋ࡚⥔ᣢࡉࢀ࡚࠸ࡿࠊ௦ㅰࡢ⇞ᩱ࡜࡞ࡿங㓟ࠊࢢࣝࢥ࣮ࢫཬࡧࢡ࢚ࣥ

㓟ࡢ෌྾཰⬟࡟㞀ᐖࢆ㉳ࡇࡋࡓ (Kurokawa et al. 1985ࠊPitts 1987)ࠋ

࣭Wistar⣔ࣛࢵࢺ (㞝15ཪࡣ56༉) ࡟TDBPPࢆ0ཪࡣ286.8 Pmol/kgࡢ⏝㔞࡛༢ᅇ⤒

ཱྀᢞ୚ࡋࠊ10᪥㛫࡟ࢃࡓࡾẖ᪥ᏳᴦṚࡉࡏࠊTDBPP࡟ࡼࡿ⭈ẘᛶࢆホ౯ࡋࡓࠋࡑࡢ⤖

ᯝࠊ1᪥┠࡟⭈ᒀ⣽⟶ୖ⓶⣽⬊ࡢ᰾⃰⦰ࡀࠊ2᪥┠࡟ቯṚࡀࠊ3᪥┠࠿ࡽ෌⏕ࡀࠊཬࡧ4᪥

┠࠿ࡽᕧ኱᰾ᙧᡂࡀㄆࡵࡽࢀࡓࠋࡲࡓࠊ¹³C-NMRࢫ࣌ࢡࢺࣝ࡟ࡼࡾࠊࢩ࢔ࣝ㓟ཬࡧ࢖ࣀ

ࢩࢺ࣮ࣝࡀ࣐࣮࣮࡛࢝࠶ࡿࡇ࡜ࡀุ᫂ࡋࠊTDBPP࡟ࡼࡿ⑓ኚࡣࠊ⭈⮚ᡂศཬࡧ㓝⣲άᛶ ࡢኚ໬࡟ࡼࡗ࡚≉ᚩ௜ࡅࡽࢀࡓࠋࡍ࡞ࢃࡕࠊ 1᪥┠࡟ୖ⓶⣽⬊⭷ࡢ◚ቯࢆ♧၀ࡍࡿ⭈⮚ࡢ ࢩ࢔ࣝ㓟ྵ㔞ࡢቑຍࡀほᐹࡉࢀࠊ5᪥┠࡟ࠊ࢖ࣀࢩࢺ࣮ࣝྵ㔞ࡢቑຍࢆక࠺෌⏕ࡀㄆࡵࡽ

ࢀࡓࠋ⣽⬊㉁㓝⣲࡛࠶ࡿ࢔ࣛࢽࣥ࢔࣑ࣀ࣌ࣉࢳࢲ࣮ࢮࡢ⭈άᛶࡣࠊ2ࠊ5ࠊ6ཬࡧ7᪥┠࡟

㸫33㸫 ቑຍࡋࡓ (Fukuoka et al. 1988a)ࠋ

࣭ࣁ࣒ࢫࢱ࣮ࠊࣔࣝࣔࢵࢺࠊ࣐࢘ࢫࡢ࠸ࡎࢀࡶTDBPPࢆ500㹼1,000 mg/kgయ㔜ࡢ⏝㔞

࡛ᛴᛶ⭈㞀ᐖࢆⓎ⑕ࡋ࡞࠿ࡗࡓࡇ࡜࠿ࡽࠊTDBPPࡢ⭈ẘᛶ࡟ࡣ኱ࡁ࡞✀ᕪࡀ࠶ࡿ

(Søderlund et al. 1982a)ࠋ

࣭௦ㅰ≀࡛࠶ࡿBDBPPࡣWistar⣔ཬࡧSprague-Dawleyࣛࢵࢺ࡛᫂ࡽ࠿࡟TDBPPࡼ

ࡾࡶ⭈ẘᛶࡀᙉ࠿ࡗࡓࡀࠊࣔࣀ (2,3-ࢪࣈࣟࣔࣉࣟࣆࣝ) ࣜࣥ㓟ࡢ⭈ẘᛶࡣᙅ࠿ࡗࡓ (Elliott et al. 1982ࠊSøderlund et al. 1982b㸧ࠋ୍᪉ࠊTDBPPࡢⓎࡀࢇᛶࡀ㞤ື≀࡟࠾

࠸࡚ప࠸ࡇ࡜࡜ఝ࡚ࠊSprague-Dawleyࣛࢵࢺࡢ㞤࡛ࡣBDBPPࡢ⭈ẘᛶ࡟⪏ᛶࡀ࠶ࡗࡓ (Elliott et al. 1982㸧ࠋ

࣭TDBPPࡢ⭈ẘᛶࡀ➼ࣔࣝ⏝㔞ࡢBDBPPࡢ⭈ẘᛶ࡜ẚ㍑ࡉࢀ࡚࠸ࡿࠋ୧໬ྜ≀ࡣࠊᒀ

⣽⟶ቯṚࢆక࠺ྍ㏫ⓗ࡞ᛴᛶ⭈୙඲ࢆᘬࡁ㉳ࡇࡋࠊከᒀࠊ㧗ᒀ୰ࢢࣝࢥ࣮ࢫࠊங㓟ཬࡧ㓝

⣲ࣞ࣋ࣝཬࡧ⾑Ύࢡࣞ࢔ࢳࢽࣥࡢୖ᪼ࡀほᐹࡉࢀࡓࠋࡑࢀ࡟ࡼࡾBDBPPཪࡣBDBPPࡢ

௦ㅰ≀ࡀTDBPP࡟ࡼࡿ⭈ẘᛶ࡟㛵୚ࡋ࡚࠸ࡿࡇ࡜ࡀ♧၀ࡉࢀࡓ (Takada et al. 1991㸧ࠋ

࣭BDBPPࡀTDBPPࡢ୺せ࡞ᒀ୰௦ㅰ≀࡛࠶ࡾࠊࡇࡢ໬ྜ≀ࡀᑡ࡞ࡃ࡜ࡶTDBPP࡜ྠ

⛬ᗘ࡟⭈ẘᛶ≀㉁࡛࠶ࡿ࡜࠸࠺▱ぢࡣࠊTDBPPࡢ┤᥋ⓗ࡞⭈ẘᛶ௦ㅰ≀࡛࠶ࡿࡇ࡜ࢆ♧

ࡋ࡚࠸ࡿ (Lynn et al. 1980ࠊSøderlund et al. 1982b㸧ࠋ

3.1.4 ࣄࢺ࡛ࡢ▱ぢ 3.1.4.1 ␿Ꮫㄪᰝཬࡧ஦౛

࣭TDBPPฎ⌮ࡋࡓ⧊≀ࡣ㛗᫬㛫⓶⭵࡜᥋ゐࡍࡿࡇ࡜ࡀண᝿ࡉࢀࡿࡢ࡛ࠊ஦๓࡟TDBPP࡛

ฎ⌮ࡋࡓ࣮ࣞࣚࣥ࡜࢔ࢭࢸ࣮ࢺࡢ୧᪉ࡢᕸᆅࢆࣄࢺ࡟᥋ゐࡉࡏࡓࡀࠊ⓶⭵཯ᛂࡣㄏⓎࡉࢀ

࡞࠿ࡗࡓ (Brieger et al. 1968)ࠋ

࣭࣎ࣛࣥࢸ࢕࢔52ேࢆᑐ㇟࡟TDBPP (1.1 g) ࢆ24᪥㛫࡟ࢃࡓࡗ࡚10ᅇ㐺⏝ࡋࠊࡑࡢᚋ14

ࠥ21᪥ᚋ࡟1ᅇࡢࣃࢵࢳ㐺⏝࡛ច㉳ࢆᐇ᪋ࡋࡓ⤖ᯝࠊ50ேࡀ㝜ᛶ࡛࠶ࡗࡓࠋ2ேࡀ6ᅇ┠࠶

ࡿ࠸ࡣ7ᅇ┠ࡢ㐺⏝ᚋ࡟⑛ࡳࠊࡌࢇࡲ⑈ࢆ♧ࡋࡓࡓࡵࠊࡇࡢ2ே࡟ࡘ࠸࡚ࡣ㐺⏝ࢆ1ࣧ᭶㛫 ఇṆࡋࠊ1ࣧ᭶ᚋ࡟㐺⏝ࢆ෌㛤ࡋࡓ࡜ࡇࢁࠊ2ே࡜ࡶᙳ㡪ࡣぢࡽࢀ࡞࠿ࡗࡓࠋⴭ⪅ࡣࠊ TDBPPࡀ୍ḟ⓶⭵่⃭ࠊ⓶⭵⑂ປࠊཪࡣ⓶⭵ឤసᛶࢆᘬࡁ㉳ࡇࡉ࡞࠿ࡗࡓ࡜⤖ㄽࡋࡓ (Kerst 1974ࠊUS EPA 1976)ࠋ

࣭TDBPPࡢ100%⁐ᾮ࡛࣐࢟ࢩ࣐࢖ࢮ࣮ࢩࣙࣥἲࢆᐇ᪋ࡋࡓ24ே୰8ேࡢ࣎ࣛࣥࢸ࢕࢔࡛

ឤస཯ᛂࡀほࡽࢀࠊ20%⁐ᾮ࡛ࡣ25ே୰2ேࡀឤసࡉࢀࡓࠋTDBPPࡣࣄࢺ࡟ᑐࡋ㍍ᗘࡢ⓶

⭵ឤసᛶࢆ᭷ࡍࡿ࡜⪃࠼ࡽࢀࡓࠋࡲࡓࠊ20%⁐ᾮ࡟ឤస཯ᛂࢆ♧ࡋࡓ࣎ࣛࣥࢸ࢕࢔࡛ࡣ

TDBPP࡛ฎ⌮ࡋࡓ⏕ᆅ࡟ᑐࡍࡿ཯ᛂࡶぢࡽࢀࡓࡀࠊࡑࡢ཯ᛂࡣ⏕ᆅ (ᇶ㉁) ࡢ✀㢮࡛␗࡞

ࡗࡓࠋឤసࡢ⛬ᗘࡣ⧄⥔⾲㠃ࡢ⸆๣ࡢ྾཰⋡࡟౫Ꮡࡍࡿࡼ࠺࡟ᛮࢃࢀࠊ⏕ᆅࡢ✀㢮ࡸ㞴⇞

ฎ⌮᪉ἲ࡛␗࡞ࡾࠊὙ℆ࡣ⏕ᆅ⾲㠃ࡢ⃰ᗘࢆῶᑡࡉࡏࡓ (Morrow et al. 1976)ࠋ

࣭Ḣᕞ7ࣧᅜࡢ1,103ேࡢ࣎ࣛࣥࢸ࢕࢔ࢆᑐ㇟࡜ࡋࡓࣃࢵࢳࢸࢫࢺ (TDBPP5%⁐ᾮ) ࡛ ࡣࠊ㝧ᛶ཯ᛂࡣ2ேࡔࡅ࡛࠶ࡗࡓ (Andersen 1977)ࠋ

㸫34㸫

࣭1935ᖺ࠿ࡽ1976ᖺࡢ㛫࡟TDBPPࡸ1,2-ࢪࣈࣟࣔ-3-ࢡࣟࣟࣉࣟࣃࣥ (DBCP)ࠊ࣏ࣜ⮯໬

ࣅࣇ࢙ࢽࣝ (PBB) ࢆྵࡴ⮯⣲໬ྜ≀ཬࡧDDT࡟₯ᅾⓗ࡟᭚㟢ࡉࢀࡓ3,579ேࡢⓑே⏨ᛶ

ࢆᑐ㇟࡟⾜ࢃࢀࡓ␿Ꮫㄪᰝ࡛ࡣࠊDBCP࡟᭚㟢ࡉࢀࡓປാ⪅࡛ᚠ⎔ჾ⣔⑌ᝈ࡟ࡼࡿṚஸ⋡

ࡀ᭷ព࡟ቑຍࡋࡓࠋࡲࡓࠊࡑࡢ௚ࡢ᭷ᶵ⮯⣲໬ྜ≀࡟᭚㟢ࡉࢀࡓປാ⪅࡛⢭ᕢࡀࢇ࡟ࡼࡿ

Ṛஸ⋡ࡢ᭷ព࡞ቑຍࢆㄆࡵࠊ⢭ᕢࡀࢇ࡛Ṛஸࡋࡓປാ⪅࡟ඹ㏻ࡋࡓ᭚㟢≀㉁ࡣ⮯໬࣓ࢳࣝ

࡛࠶ࡗࡓࠋࡋ࠿ࡋࠊTDBPP࠶ࡿ࠸ࡣDDT࡟᭚㟢ࡉࢀࡓປാ⪅࡛ࡣࠊ඲Ṛஸ࠶ࡿ࠸ࡣṚᅉ

ูࡢṚஸ࡟᭷ព࡞㐣๫Ṛஸࡣぢࡽࢀ࡞࠿ࡗࡓ (Wong et al. 1984) ࠋ

3.1.4.2 Ⓨࡀࢇᛶホ౯

⾲3-7 Ⓨࡀࢇᛶศ㢮

ホ౯ᶵ㛵 ศ㢮⤖ᯝ タᐃᖺ ฟ඾

IARC 2A ࣄࢺ࡟ᑐࡍࡿⓎࡀࢇᛶࡀ࠾ࡑࡽ

ࡃ࠶ࡿ 1999 IARC 2018

NTP ࣄࢺ࡟ᑐࡋ࡚Ⓨࡀࢇᛶࡢ࠶ࡿࡇ࡜ࡀ

ྜ⌮ⓗ࡟ண᝿ࡉࢀࡿࠋ 2000 NTP 2016

᪥ᮏ⏘ᴗ⾨⏕Ꮫ఍ 2A ␿Ꮫ◊✲࠿ࡽࡢドᣐࡀ㝈ᐃⓗ࡛

࠶ࡿࡀࠊື≀ᐇ㦂࠿ࡽࡢドᣐࡀ༑ศ

࠶ࡿࠋ

1991 ⏘⾨ㄅ 2018

ECHA ࣁ࣮ࣔࢼ࢖ࢬࡉࢀࡓ⤖ᯝࡣ࡞࠸ ECHA 2018

࣭EPAࠊACGIHཬࡧDFG࡛ࡣⓎࡀࢇᛶホ౯ࡣ࡞ࡉࢀ࡚࠸࡞࠿ࡗࡓࠋ

ࣘࢽࢵࢺࣜࢫࢡ➼ࡢ᝟ሗ

࣭⡿ᅜ࢝ࣜࣇ࢛ࣝࢽ࢔ᕞEPAࡣࠊ⤒ཱྀᢞ୚࡟ࡼࡿ㞝ࣛࢵࢺࡢ⭈⭘⒆Ⓨ⏕ࡢ⤖ᯝ࠿ࡽCancer Potencyࢆ2.3 (mg/kg/᪥)^-1࡜ሗ࿌ࡋ࡚࠸ࡿ (Cal EPA 1992)ࠋ

3.1.4.3 チᐜ⃰ᗘ࡟㛵ࡍࡿ᝟ሗ ㄪᰝࡋࡓ⠊ᅖ࡛ࡣ᝟ሗࡣ࡞࠿ࡗࡓࠋ

3.2 ࣅࢫ (2,3-ࢪࣈ࣒ࣟࣉࣟࣆࣝ) ࣍ࢫࣇ࢙࢖ࢺ [BDBPP] ໬ྜ≀

ࣅࢫ (2,3-ࢪࣈ࣒ࣟࣉࣟࣆࣝ) ࣍ࢫࣇ࢙࢖ࢺ (௨ୗࠊBDBPP) ࡢẘᛶ᝟ሗࢆ௨ୗ࡟♧

ࡍࠋẘᛶ᝟ሗࡣྛᅜつไᙜᒁཪࡣᅜ㝿ᶵ㛵 (IPCSࠊIARC࡞࡝) ࡢホ౯ᩥ᭩ࢆ฼⏝ࡋࠊ≀

⌮໬Ꮫⓗ᝟ሗࠊయෆືែࠊࣄࢺཬࡧᐇ㦂ື≀࡟࠾ࡅࡿẘᛶ᝟ሗࢆ཰㞟ࡋࡓࠋホ౯᭩࡜ࡋ࡚

1995ᖺࡢIPCS࡟ࡼࡿホ౯᭩ (IPCS 1995) ࡀ࠶ࡾࠊࡑࢀ௨㝆ࡢ᪂ࡋ࠸ホ౯᭩ࡣㄪᰝࡋࡓ

⠊ᅖ࡛ࡣぢࡘ࠿ࡽ࡞࠿ࡗࡓࡢ࡛ࠊIPCS (1995) ࡟ࡲ࡜ࡵࡽࢀ࡚࠸ࡿ᝟ሗࢆ୰ᚰ࡟ᩚ⌮ࡋ ࡓࠋ

㸫35㸫 3.2.1 ≀⌮໬Ꮫⓗᛶ≧

ICSCࡢࢹ࣮ࢱ࣮࣋ࢫࢆྵࡵࠊㄪᰝࡋࡓ⠊ᅖ࡛ࡣ᝟ሗࡣ࡞࠿ࡗࡓࠋ

3.2.2 యෆືែ

ㄪᰝࡋࡓ⠊ᅖ࡛ࡣBDBPPࡢ྾཰࡟㛵ࡍࡿ᝟ሗࡣ࡞࠿ࡗࡓࠋ

࣭BDBPPࡣTDBPPࡢ௦ㅰ≀࡛࠶ࡾࠊࡑࡢ⤌⧊ศᕸཬࡧ᤼ἥࡣTDBPP࡜㢮ఝࡋ࡚࠸ࡿ

(NICNAS 2001㸧ࠋ

࣭㞝Sprague-Dawleyࣛࢵࢺ࡟¹⁴C-TDBPPࢆ㟼⬦ෆᢞ୚ࡋࡓᚋࠊ⣙༙ศࡀᒀ୰࡟120᫬ 㛫௨ෆ࡟᤼ἥࡉࢀࠊᅇ཰ࡉࢀࡓᒀ୰ᨺᑕ⬟ࡢ7.8%ࡀBDBPP࡛࠶ࡗࡓࠋᢞ୚ᚋ24᫬㛫࡛

33.9%ࡀ⫹Ồ࡟᤼ἥࡉࢀࠊ⫹Ồ୰ᨺᑕ⬟ࡢ21.5%ࡀBDBPP࡛࠶ࡗࡓࠋTDBPPᢞ୚ᚋࡢ

BDBPPࡢ⤌⧊ศᕸࢆ⤒᫬ⓗ࡟ (5ศࠊ30ศࠊ8᫬㛫ࠊ24᫬㛫ࠊ120᫬㛫ࠊ5᪥) ㄪ࡭ࡓ

࡜ࡇࢁࠊBDBPPࡣᢞ୚5ศ௨ෆ࡟࡯ࡰࡍ࡭࡚ࡢ⮚ჾ᳨࡛ฟࡉࢀࡓࠋᢞ୚5ཪࡣ30ศᚋ

࡟኱⭠ཬࡧ࣮࢝࢝ࢫࢆ㝖ࡃࡍ࡭࡚ࡢ㒊఩࡛ࠊ⤌⧊୰ᨺᑕ⬟ࡀపୗࡋࡓࠋᢞ୚5ศᚋࡢ⾑₢

୰ᨺᑕ⬟ࡢ75%ࡀBDBPP࡛࠶ࡗࡓࠋBDBPPࡢ⾑₢୰⃰ᗘࡣࠊᢞ୚0㹼1᫬㛫࡛ቑຍ ࡋࠊࡑࡢᚋ஧┦ᛶ࡟పୗࡋࠊ๓༙⾑₢༙ῶᮇࡣ6᫬㛫࡛ࠊᚋ༙ࡣ⣙36᫬㛫࡛࠶ࡗࡓ (Lynn et al. 1980ࠊ1982㸧ࠋ

࣭BDBPPࡣ⫢⮚࡟࠾࠸࡚ࠊTDBPPࡢ2఩ཪࡣ3఩ࡢⅣ⣲ࡀP450ࡢ㓟໬స⏝࡟ࡼࡾ㓟

໬ࡉࢀࡿࡇ࡜࡛⏕ᡂࡍࡿࠋࡑࡢᚋࠊBDBPPࡣ⭈⮚࡟㐠ࡤࢀࠊ཯ᛂᛶࡢ୰㛫య࡟௦ㅰࡉࢀ

࡚DNAࢆᦆയࡋࠊP450㠀౫Ꮡᛶ࡟ࢢࣝࢱࢳ࢜ࣥᢪྜ࡟ࡼࡿάᛶ໬ࡀ㛵୚ࡋ࡚⭈ࢱࣥࣃࢡ

㉁࡜⤖ྜࡍࡿ (Pearson et al. 1993)ࠋ

3.2.3 ᐇ㦂ື≀࡛ࡢ▱ぢ

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