繁殖性に及ぼす影響
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- みいか よどぎみ
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1 5. 2
2 1. (DEP) 1) DEP 2) 3) 4) DEP ppm( mg/kg/day mg/kg/day ) 24 Crj:CD(SD) IGS 2 DEP ppm F F1 F0 F1 DEP F1 F ppm ppm F0 F1 F0 F0 P-450 (CYP1A1/2 CYP2B1 CYP3A2 CYP4A1)15000 ppm CYP4A1 CYP3A2 CYP3A 6 5) F ppm DEP - 2 -
3 F1 F2 DEP ppm F F1 F2 21 F1 F2 DEP ppm F1 F2 4 F1 F2 DEP 3000 ppm F1 F ppm F1 F2 F1 F2 F2 F1 F2 F1 F1 F2 F0 F ppm ppm F0 P-450 CYP3A ppm F0 F0 F ppm F1 F ppm ppm 2 (NOEL) 3000 ppm(210 mg/kg/day 261 mg/kg/day )(NOAEL) ppm(1083mg/kg/day 1336 mg/kg/day ) 600 ppm(43 mg/kg/day 54 mg/kg/day ) 3000 ppm(210 mg/kg/day 261 mg/kg/day ) 3000 ppm - 3 -
4 600 ppm(43 mg/kg/day 54 mg/kg/day ) ppm(1083mg/kg/day 1336 mg/kg/day ) - 4 -
5 2 (DEP) 99.8 ( Lot No. SEM5441) 3 4 (NEDO) 2 5 Crj:CD(SD) IGS () 1 24 F0 5 6 F0 F ( ) 7 0, 600, ppm (NIH-07M) 8 2 ( ) 0 () ppm 1 8 Crj:CD(SD)IGS 4 F ppm ppm ppm ppm ppm ppm F ppm ppm ppm ppm
6 9 9.1 NIH-07M(H7010 H ±3 50± :00 20: W 410D 200H mm,
7 F0 15 F F1 F1 24 F F1 F F () ( ) () ( ) ()
8 10.6 ( ) ( ) (HTM-IVOS Hamilton Thorne research ) ( 200 ) 10.7 P F0 P-450 (CYP1A1/2 CYP2B1 CYP3A2 CYP4A1) P-450 F0 DPC DPC RIA ( ) ( 0 ) ( ) ( 4 0 ) ( ) ( 21 4 )
9 F0 F1 ( ) 1 F1 F2 ( ) F1 F1 F F0 F1 F1 6 F1 F2 6 F Bartlett - 9 -
10 Dunnett Kruskal-Wallis Mann-Whitney U 1 1 Wilcoxon Fisher
11 . F : ( ) ( ) ( 4 4 ) ( ) ( ) ( ) ( )
12 F0/F1 F F1 ( 1 2 F1 F1 26 ) F0 6 P ( ) 6 F :1 0 F1 2 3 ( ) ( )
13 F ( 4 4 ) ( ) ( ) ( ) ( ) F1/F2 F2 26 ( ) 1 ( )
14 - 14 -
15 Tables 1 and 2 F0F1 DEP DEP( )3000 ppmf0 1 ( ) F0 2 (1 1 ) DEP ppmf0f Tables 3 to 6 F0F ppm3000ppm F0 600 ppm ppmf0 F10-1 F00-21 F121 F1 DEP ppmf0 F Tables 7 and 8 F0F13000 ppm F ppm ppmf0f1 1 DEP DEP ppmf0f1-15 -
16 Tables 13, 14, and 16 F0F1 DEP F1 1)2. Table 13 F ppm (22 23 ) 2) 2. Table 15 F ppm F ppm Tailless DEP 3)2. Table 16 F ppm ppmf1 DEP ppm F0F Tables 21 and 22 F0F ppm3000 ppm ppmf0f1 F0 DEP ()F1 F1 DEP
17 DEP ppm F0F1 F0 DEP P Table 17 F0 P-450 (CYP1A1/2 CYP2B1 CYP3A2 CYP4A1) 3000 ppm15000 ppm CYP4A1CYP3A2 DEP P-450 CYP4A1P-450 6) 7) DEP CYP3A6 5) F0 DEP ppm P-450(CYP4A1 CYP3A2) P Table 18 F0RIA ppmcyp3a ppm ppm 8) DEP 3000 ppm CYP3A
18 2. Tables 19, 20, 23, and 24 F0F1 DEP15000 ppm DEP ppmf0 F Tables 25 and 26 F1F2DEP DEP ppmf1f Table ppmf1f2 F F1 F221 DEP ppmf1f Tables 13, 28, and 32 to 34 F1F DEP DEP ppmf1f Tables 29 to 31 F1F ppm
19 DEP ppm Tables 35 and 36 F1 F24F1 F2 F1F1 F2 DEP DEP ppm F1F Tables and 39 F1F2600 ppm F ppmf1f ppm ppmf1f2 F1F2 F1 F2 F1F2 F2 F1F2 F1 F1F2 DEP in vitro 2) in vivo 3) F1F1 F2 F1 F1 F2 DEP 3000 ppmf1f ppm F1F2 F1F2 F2 F1F2 F1 F1F2-19 -
20 11.3 NOEL F0 F ppm ppm F0 P-450 CYP3A ppm F0 F0 F ppm F1 F ppm ppm 2 (NOEL) 3000 ppm(210 mg/kg/day 261 mg/kg/day )(NOAEL) ppm(1083mg/kg/day 1336 mg/kg/day ) 600 ppm(43 mg/kg/day 54 mg/kg/day ) 3000 ppm(210 mg/kg/day 261 mg/kg/day ) 3000 ppm 600 ppm(43 mg/kg/day 54 mg/kg/day ) ppm(1083mg/kg/day 1336 mg/kg/day )
21 12. 1) 13398,,, 1998, pp ) Blair, R.M., Hong, F., William, S.B., Bruce, S.H., Stacey, L.D., Carrie, L.M., Weida, T., Leming, S., Roger, P., and Daniel, M.S. The estrogen receptor relative binding affinities of 188 natural and xenochemicals: structural diversity of ligands. Toxicol. Sci., 2000; 54: ) ) Harris, C.A., Henttu, P., Parker, M.G., Sumpter, J.P. The estrogenic activity of phthalate esters in vitro. Environ. Health Perspect., 1997; 105: ) Niwa, T., Yabusaki, Y., Honma, K., Matsuo, N., Tatsuta, K., Ishibashi, F. and Katagiri, M.: Contribution of human hepatic cytochrome P450 isoforms to regioselective hydroxylation of steroid hormones. Xenobiotica, 28, , ) Bell, D.R. and Elcombe, C.R. Induction of acyl-coa oxidase and cytochrome P450 IV A1 RNA in rat primary hepatocyte culture by peroxisome proliferators. Biochemical Journal, 280, , ) Okita, R.T. and Okita, J.R. Effects of diethyl phthalate and other plasticizers on laurate hydroxylation in rat liver microsomes. Pharmaceutical Research 9, , ). Markert, C.L., 1979:
22 2. F0() F1 F1 F2 ppm mg/kg/day /24 0/24 1/24 0/24 0/24 0/24 0/24 0/24 2/24 0/24 0/24 0/24 0/24 0/24 0/24 0/24 (g) f) [MeanS.D.] a)b) c) (g) g) d) g) e) [MeanS.D.] (g) /24 23/24 24/24 24/24 24/24 24/24 21/24 23/24 22/23 22/23 24/24 23/24 23/24 23/24 20/21 22/23 (x10 6 ) (x10 6 ) (%) (%) (g) /24 23/24 22/24 24/24 23/24 24/24 20/24 21/24 ( )() /24 23/24 24/24 24/24 24/24 24/24 23/24 24/24 23/24 22/23 24/24 23/24 23/24 23/24 22/23 23/24 22/23 22/22 24/24 22/23 23/23 23/23 22/22 23/23 () (%) a) (p0.01)b) (p0.05)c) 0-21 (p0.01)d) 910 (p0.05) e) (p0.05)f) 0-1 (p0.01)g) 1 (p0.05) p0.05 p0.01
23 2. 1 F0() F1 F1 F2 ppm a) (g) [MeanS.D.] (mg) (mg) (g) (%) (x10-3 ) (x10-3 ) (g) (g) (%) b) P-450 CYP3A (p mol/mg protein) CYP4A b) (ng/ml) p0.05 p0.01
24 2. 2 F0() F1 F1 F2 ppm (%) (g) [MeanS.D.] (mm) [MeanS.D.] /3 40.5/ / / / / / / /94.2 (, %) 10 /11 4.9/ / / / / / / / / / / / / / / / / /14 8.2/ / / / / / / / /3 39.1/ / / / / / / / / / / / / / / / / / / / / / / / / / / / / / / / / / / ( ) [MeanS.D.] p0.05 p0.01
25 2. 3 F0() F1 F1 F2 ppm a) (g) [MeanS.D.] (g) (g) (g) (mg) (mg) (mg) (mg) (mg) (x10-3 ) (x10-3 ) (x10-3 ) (x10-3 ) (x10-3 ) (g) (g) (g) (mg) (mg) (mg) (mg) (%) (x10-3 ) (x10-3 ) (x10-3 ) (x10-3 ) p0.05 p0.01
DCHP
2. 2 1. 1) 2) 2 Crj:CD(SD)IGS SPF 0 240 1200 6000 ppm 2 F0 10 F0 10 F1 21 F1 3 10 F1 3 10 F2 21 0 240 1200 6000 ppm 1 F0 0 15.88 79.57 401.8 mg/kg/day F0 0 20.80 104.19 510.7 mg/kg/day F1 0 17.84 89.89
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