1 3 3 4 5. 6 1. 6 2. 6 3. 6 4. 6 5. 6 6. 6 7. 6. 7 1. 7 2. 8 (1) 8 (2) 9 (3) 9 (4) 10 (5) 10 3. 11 (1) 11 (2) 11 (3) 11 (4) 12 4. 12 (1) 12 (2) 12 (3) 13 5. 13 6. 13 7. 14 8. 15 9. 16 10. 16 (1) 90 16-1 -
(2) 90 17 (3) 6 18 (4) 90 18 11. 19 (1) 1 19 (2) 2 / 19 (3) 18 22 12. 22 (1) 2 22 (2) 24 (3) 24 13. 24 14. 25 (1) in vivo 25 (2) 26 (3) 26. 29 1 32 33-2 -
1981 2 27 2003 12 19 2003 12 25 1225009 150 2003 12 26 2004 01 08 26 51 2004 02 25 7 52 2005 04 12 53 2005 08 31 35 54 2005 11 29 55 2006 7 18 0718001 56 2006 7 20 153 57 2006 9 29 58 2007 2 19 8 59 2007 3 28 14 60 2007 5 24 191 2007 5 24 6 22 2007 7 18 2007 7 19 199 2006 6 30 2006 12 20 2006 12 21 * ** *2007 2 1 **2007 4 1-3 -
2006 3 31 * *2005 10 1 2007 3 31 2007 4 1 * ** *2007 4 11 **2007 4 25-4 -
IUPAC2,4,6,8- -1,3,5,7-- / 2 2 / 2.2mg/kg / 100 0.022mg/kg /ADI 5
metaldehydeiso IUPAC 2,4,6,8--1,3,5,7-- 2,4,6,8-tetramethyl-1,3,5,7-tetraoxacyclo-octane CAS (No.108-62-3) 2,4,6,8--1,3,5,7-2,4,6,8-tetramethyl-1,3,5,7-tetraoxacyclooctane C8H16O4 176.2 1495358 6
.14 14 C 14 C- 1 SD 5 14 C- 10 mg/kg 100 mg/kg 14 15 48 TAR 71.792.9 168 2.6 5.1% 2.52.8% 7898%TAR 9495% 7.310.7%TAR Cmax 14 5.8 6.4 µg/ml T1/2 3.48.8 1 168 168 (24.5), (9.32), (8.36), (7.59), (7.13), (6.86), (2.04),(1.69),(1.69), (1.18),(0.95),(0.89),(0.88), (6.79), (6.34), (5.63), (5.33), (5.06), (4.67), (0.83),(0.82),(0.76),(0.75), (0.67),(0.66),(0.55), (4.64),(4.46) (0.54),(0.50),(0.46) (31.0),(8.29), (7.93), (2.13), (2.03), (1.87), (7.83),(7.75), (7.60), (7.07), (6.72), (6.17), (6.09) (1.79), (1.54), (1.34), (1.29),(1.00),(0.91),(0.81), (0.72),(0.64),(0.57),(0.51), (0.43) (38.9), (28.9), (22.3) (21.5), (12.2), (11.3),(11.3),(11.0),(10.9), (8.96),(7.97),(7.93),(6.96), (6.95),(6.00),(5.88),(5.25) 7
2 3 (24.9), (24.1), (15.7), (14.5), (12.5),(12.5), (10.9),(10.9),(10.7),(7.23), (6.76),(6.39),(6.28),(6.20), (5.81),(5.64),(5.09) (2.07), (1.89), (1.76), (1.48), (1.47), (1.34), (1.23),(1.18),(1.18),(1.01), (0.89),(0.72),(0.71),(0.65), (0.63),(0.58) (2.42), (1.83), (1.76), (1.52),(1.23),(1.19),(1.02), (1.01), (0.96), (0.94), (0.75),(0.66),(0.63),(0.56), (0.52), (0.50), (0.45), (0.39) Cmax 4.907.37 µg/ml 0.621.14 µg /ml T1/2 1.422.42 µg /ml 0.801.37 µg /ml 25356 14 C- 4 % 1.5 kg ai/ha 1 9 22.9 cm171428 42567084 98 56 0.015 mg/kg 0.018 mg/kg 1 8
6 15.2 cm) 0.65 mg/kg 0.001 mg/kg 70 47.3% 75.1TAR 70 47.3%TAR 353 14 C- 4 % 15 kg ai/ha remolacha 9 22.9 cm 48 0.612.92.1 1100 mg/kg 404864 99% 13% 453 14 C- 1000mg/kg 5 kg ai/ha 1 114 TRR 0.590.550.65 0.88 mg/kg TRR 0.0960.17 mg/kg 92%TRR - 43% 26% 14 C 83%TRR 19%TRR 17%TRR 10%TRR 9
5 14 C- 15kg ai/ha 0.46%TAR 80 % 6.61 mg/kg (25.4%TRR) 133 mg/kg (67.8%TRR) 0.06%TAR 1.48 mg/kg (61.4%TRR) 1.0 mg/kg (14.0%TRR) 4.92 mg/kg(21.9%trr) 0.622 mg/kg (2.8%TRR) 0.040 mg/kg (1.7%TRR) 0.194 mg/kg (2.6%TRR) 71.215.812.0% 0.764 mg/kg (41.8%TRR) 0.008 mg/kg 0.048 mg/kg 14 C- 8.3% 0.038 mg/kg 1 6 14 C- 4 15 kg ai/ha lechuga 9 22.9 cm28 2.42.43.9 1530 mg/kg 90% 22% 10
262167 2080% ( 7 14 C- 10.5 µg/g 25 365 365 74% KOH 87% 64%TARKOH 5.3%TAR 365 11.0%TAR 55.471.9% 365 4.0% 59 6 1618 67.2 8 14 C- 4.8 µg/g 20 200 200 1.31.6TAR 5.33 43.1 9.89 50 70 9.62 9 14 C- 10.2 µg/g 25 30 90 11
30 87.8 %TAR KOH 8.31%TAR 2.06%TAR 10.4TAR 6673TAR KOH 90 9.48TAR 68 7.0%TAR45 0.87%TAR 166 222 10 [ Koc 31.2 90% 11 ph 4 ph7 ph9 5 µg/ml 25 40 60 ph 425 40 15 37 ph 7 9 ( 12) 14 C- ph5 ph7 Tris ph7 HEPES ph9 23 µg/ml(ph5)25 µg/ml(ph7,tris)23.1 µg/ml(ph7, HEPES)25.5 µg/ml(ph9)25 32 30 13 12
14 C- ph7.0 HEPES 32 µg/ml 28 µg/ml25 626 269 W/m 2 300750 nm 526 1110 2220 1380 14 2 6125 1 8 140200 1 1516 125 25 mg /kg 105 D 6 1.0 mg ai/kg 8 140 6.0 mg/kg 200 SC 4 2.1kg ai/ha 3 G 1 2.7 kg ai/ha 8 G 1 6 kg ai/ha 1 DSCG 3 1719 13
kg ai/ha () (mg/kg) PHI () 1997 1997 2 6.0 2 2 6.0 2 76 80 76 80 <0.05 <0.05 <0.05 <0.05 aiphi 4 20 / mg/kg 3 0,10,30, 100 8 10 6 6 0,10,30, 100 0,3,10,30, 100 0,30,100 300 0,10,30, 100,300 mg/kg mg/kg 10 30 100-3 10 100 300 10 30 30mg/kg 100 mg/kg 10mg/kg 30mg/kg 12 30mg/kg 300mg/kg 6 0, 30,100, 300 100 300 46 14
0,10,30, 8 100 0,10,30, 8 100 100-0, 30, 6 300 PTAPTT 100,300 - SD BKW SD 5 212753 LD50mg/kg SD 283 283 SD 750 383 BKW 411 443 SD 422
SD 5000 5000 LC50mg/L SD 15 15 NZW 2830 Hartley Buehler 31 SD 10 0250750 2500 ppm 6 90 250 ppm 750 ppm 2500 ppm 18.9 59.8 198 mg/kg / 22.5 68.9 231 7 750 ppm 250 ppm18.9 mg/kg /22.5 mg/kg / 32 2500 ppm 2 1 2 16
750 ppm 250 ppm ICR 15 010030010003000 10000 ppm 8 90 100 ppm 300 ppm 1000 ppm 3000 ppm 10000 ppm 19.0 53.7 178 560 1920 mg/kg / 23.7 69.5 235 742 2300 9 300ppm 100ppm19.0 mg/kg /23.7 mg/kg / 3353 10000 ppm 5 / 3000 ppm 3000ppm 10000ppm 1000 ppm 300ppm 100ppm 17
6 02060 90 mg/kg / 10 6 20 mg/kg / 60 mg/kg / 90 mg/kg / 20.2 61.5 91.8 mg/kg / 19.7 62.2 86.7 60 mg/kg / 60 mg/kg / 20.2 mg/kg / 86.7 mg/kg / 3453 SD 10 0100500 2500 ppm 11 90 100 ppm 500 ppm 2500 ppm 7 36 178 mg/kg / 8 41 192 12 2500 ppm 1 68 500 ppm 100 ppm7 mg/kg /8 mg/kg / 35 2500 ppm 1 18
500 ppm 100 ppm 4 01030 90 mg/kg / 1 13 30 mg/kg / 10 mg/kg / 3653 90mg/kg / HbMCVMCHAPTT ALPGGT HbHtMCH ALPGGT 30mg/kg / 10mg/kg / SD 60 2 60 0501000 5000 ppm 14 2 / 50 ppm 1000 ppm 5000 ppm 2.2 44.0 224 mg/kg / 3.0 60.4 314 15 1000ppm 19
50 ppm2.2 mg/kg /3.0 mg/kg / 3753 5000 ppm MCVMCH TPGlob A/G 1000 ppm T.Chol 50 ppm 16 17 18 50 ppm 1 2 50 ppm ppm 0 1 50 1000 5000 0 [708-0 0 722] 0 0 2 1 50 1000 5000 0 2 16 [295-728] 8 [393-710] 13 [557-713] 11 [283-718] 6 3 4 3 [666- [575- [609- [565-728] 728] 722] 728] 1 4 [477-722] 7 [456-729] 11 [421-704] 11 [323-729] 9 [421-728] 13 [462-729] 2 1 4 [407-0 0 [428- [274-0 722] 429] 686] 1 1 0 0 0 [484- [708] 485] 0 4 3 2 8 4 6 9 8 11 5 20
3 2 1 [477- [435- [468] 666] 624] 8 3 5 [349- [548- [468-715] 609] 723] 10 4 8 [505- [421- [435-729] 708] 729] [516-591] [554-702] [568-660] [489-715] [407-722] [464-666] 3 2 4 2 1 1 [646- [635- [564- [358- [714] [587] 691] 646] 663] 582] 0 0 0 1 [630] 0 0 0 2 [421-593] 3 [481-582] 6 [400-729] [ ] [422-729] 3 [574-680] 1 [715-728] 1 [652-708] 5 [446-652] 11 [547-725] 11 [441-729] [344-725] [435-728] [530-729] 3 1 [609- [565] 678] 0 0 0 0 1 2 0 [603- [463-666] 576] ppm 0 1 50 1000 5000 0 0 2 1 50 1000 5000 60 60 60 60 60 60 60 60 60 60 1 0 0 0 0 1 1 0 6* 0 2 4 4 2 0 1 1 0 1 0 3 4 4 2 0 2 2 0 7* 0 Fisher 2 p<0.05 0 2 ppm 0 1 50 1000 5000 0 0 2 1 50 1000 5000 60 60 60 60 60 60 60 60 60 58 0 2 21
0 6 a 20 bd 38 bd 2 5 0 c 11 36 bd 5 Fisher a 1 p<0.05b: 1 p<0.01 c: 2 p<0.05d 2 p<0.01 ICR 60 2 60 025100 300 ppm 19 18 25 ppm 100 ppm 300 ppm 4 16 49 mg/kg / 5 20 60 300 ppm 300 ppm 10% 3 20 ppm 0 1 25 100 300 0 2 60 60 60 60 60 0 2 1 6* 3 % 0.0 3.3 1.7 10.0* 5.0 Fisher * 1 p<0.05 300 ppm 100 ppm16 mg/kg /20 mg/kg / 3853 SD 28 0501000 2000 ppm 3 ICRCD-1 26 1 47 60 1102 81 116 / 7.2%1.726.0%/ 22
21 2 50 ppm 1000 ppm 2000 ppm 3.4 69 138 P 4.2 81 160 (mg/kg /) F1 3.2 65 134 4.0 81 164 22 2000 ppm F1 3 1 2 1000 ppm F1 1 50 ppm P 1 P 2 1 1 F1 2 1 1 2000ppm F1 1000 ppmp 69 mg/kg /P 81 mg/kg /F1 65 mg/kg /F1 81 mg/kg / 2000 ppm 2000 ppm 1000 ppmf1 138mg/kg /F1 81mg/kg /F2 134mg/kg /F2 81mg/kg / 395358 PF1 F1F2 2000 ppm / // 1000 ppm 2000 ppm 1000 ppm 23
SD 25 615 0255075 150 mg/kg / 150 mg/kg /6 ) 150 mg/kg / 75 mg/kg / 150 mg/kg / 4053 NZW 16 618 01040 80 mg/kg / 80 mg/kg / 41 DNA CHO 23 4247 in vitro DNA E.coli WP2, WP67 uvra, pola, CM871(uvrA, reca, lexa) 10010000 µg/ +/S9 S. typhimurium 0.26160 TA98, TA100, TA1535, µg/ TA1537, TA1538 +/S9 432 µg/ +/S9 24
S. typhimurium 505000 TA98, TA100, µg/ TA1535,TA1537 +/S9 E.coli WP2uvrA 20200 µg/mls9 L5178Y 20167 µg/mls9 20200 µg/mls9 (+/S9) CHO 20167 µg/mls9 in vivo BKW 2550100 mg/kg 1 5 +/S9 in vivo Fischer 15 9 N- DEN(200 mg/kg 2 02001000 5000 ppm 24 PB 5000 ppm DEN 05000 ppm 6 200 ppm 1000 ppm 5000 ppm mg/kg / 15 73 355 1 1000 ppm DEN PB 5000 ppm 3 3 4 5 mm -S-GST-P) GST-P DEN DEN DEN 25
5000ppm GST-P 1000ppm DEN PB 5000 ppm355 mg/kg / 1000 ppm73 mg/kg / 4853 02001000 5000 ppm GLP 2 /5000 ppm 1000 200 ppm 25 200 ppm (ppm) 5000 19/28 641/641 625/676 659/665 559/629 1000 657/665 652/713 200 569/574 3 5000 ppm PF1 F 13 15 10/20 1000 ppm F1 F2 1 3/20 200 pm 1000 ppm 49 GLP 26 27 58 26
(mg/kg /) (mg/kg /) 100 200 100 200 400 526 304 400 90 18.9 22.5 90 19.0 23.7 90 20.2 86.7 90 7 36 8 41 1 10 90 10 90 2 / 2.2 224 3.0 314 18 16 20 2 P 69 P 81 160 F1 65 F1 81 75 80 27
mg/kg mg/kg 10 30 100 2 3 10 100 300 10 30 100 300 30 100 100 PTAPTT 300 28
1 4 3.48.8 168 5.3367.2 222 ph 4 25 40 15 37 ph 7 9 6125 181402001 LD50 283750 mg/kg 411 443 mg/kg LD50 422mg/kg LD50 5000 mg/kg LC50 15 mg/l 7 mg/kg / 19.0 mg/kg / 20.2 mg/kg / 2.2 mg/kg / 16 mg/kg / 10 mg/kg / 355 mg/kg / 65 mg/kg / 81mg/kg / / 2000 ppm/ 29
3 49 5000 ppm MAO GABA NA5HT GABA 75 mg/kg / 150 mg/kg / 80 mg/kg / DNA CHO ( 28 4 mg/kg / mg/kg / 90 18.9 59.8 22.5 68.9 90 7 36 8 41 2 2.2 44.0 / 3.0 60.4 4 30
2 P 69 P 138 P 81 P 160 F1 65 F1 134 F1 81 F1 164 F1 138 F1 F1 81 F1 160 F2 134 F2 F2 81 F2 164 75 150 90 19.0 23.7 18 16 20 80 80 6 20.2 86.7 1 10 10 150 53.7 69.5 49 60 61.5 30 30 2 / 2.2 mg/kg / 100 0.022 mg/kg /ADI ADI 0.022 mg/kg / ADI / 2 2.2 mg/kg / 100 31
32 1 5HT 5- ai A/G / ALP APTT Cmax DEN GABA γ- GGT γ- =γ γ-gtp Glob GST-P -S- Hb Ht MCHC MCH MCV MAO NA PB PHI PT T1/2 TAR T.Chol TP TRR
1 2003 URLhttp://www.fsc.go.jp/hyouka/iken.html#02 2 GLP Biological Test Center1992 3 GLP Biological Test Center1991 4 GLP PTRL East, Inc.1996 5 GLP 1999 6 GLP 1999 7 GLP PTRL East, Inc.1996 8 1GLP Analytical Biochemistry Laboratories 1990 9 2GLP Battelle Europe1991 10 GLP Analytical Biochemistry Laboratories 1990 11 1998 12 GLP 2001 13 Analytical Bio-chemistry Laboratories Inc. 1989 14 GLP Analytical Bio-chemistry Laboratories Inc.1989 15 19721998 16 1998 17 1998199 18 1998 19 1999 20 1999 21 GLP SafePharm Laboratories1987 22 1Institut fur Biologishe Forschung1973 23 2Institut fur Biologishe Forschung1973 24 GLP SafePharm Laboratories1990 25 Institut fur Biologishe Forschung1973 26 Huntingdon Research Centre1974 33
27 Huntingdon Research Centre1973 28 GLP SafePharm Laboratories1990 29 Institut fur Biologishe Forshung 1974 30 Hazleton Laboratories1983 31 GLP Consumer Product Testing1984 32 90 GLP SafePharm Laboratories 1998 33 GLP Bushy Run Research Center1990 34 26 Laboratorium fur Pharmakologi und Toxikologie19801991 35 90 GLP SafePharm Laboratories2003 36 1 GLP Laboratory of Pharmacology and Toxicology2003 37 2 /GLP Bushy Run Research Center1992 38 GLP Bushy Run Research Center1993 39 GLP Bushy Run Research Center1993 40 GLP Bushy Run Research Center1990 41 GLP Bushy Run Research Center1990 42 DNA GLP Life Science Research1992 43 1981 44 GLP SafePharm Laboratories1998 45 GLP NOTOX C.V.1986 46 CHO in vitro GLP NOTOX C.V.1986 47 GLP SafePharm Laboratories1990 34
48 in vivo GLP 2004 49 H.G.Verschuuren et al., LONG-TERM TOXICICITY AND REPRODUCTION STUDIES WITH METALDEHYDE IN RATS. Toxicology, 4(1975) 97-115 50 26 1-1 URL http://www.fsc.go.jp/iinkai/i-dai26/dai26kai-siryou1-1.pdf 51 22 26 1-3 (URLhttp://www.fsc.go.jp/iinkai/i-dai26/dai26kai-siryou1-3.pdf) 52 7 URL http://www.fsc.go.jp/senmon/ nouyaku/n-dai7/index.html 53 2005 54 35 URLhttp://www.fsc.go.jp/senmon/nouyaku/ n-dai35/index.html 55 34 370 17 11 29 17 499 56 153 1-1-b URL http://www.fsc.go.jp/iinkai/i-dai153/dai153kai-siryou1-1-b.pdf 57 24 2 153 1-4 URL http://www.fsc.go.jp/iinkai/i-dai153/dai153kai-siryou1-4.pdf 58 2006 59 8 URL http://www.fsc.go.jp/senmon/nouyaku/sougou2_dai8/index.html 60 14 URL http://www.fsc.go.jp/senmon/nouyaku/kanjikai_dai14.html 35