ニトロトルエン

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1 4-115

2 116

3

4 4- g/kg/day mg/kg/day ( ) ( ) ( ) ( ) F

5 ER M 1% M ER 10-4 M 3% M E-screen M AR ( ) M AR ( ) M AR IC50= M M TR <10-4 M TR <10-4 M 119

6 120

7 2. F0 (mg/kg/day) /13 0/14 0/14 0/14 1/14 0/12 0/13 0/14 0/14 0/14 0/14 0/12 (g) ± ± ± ± ± ± ± ± (g) ± ± ± ± ± ± (g) ± ± ± ± ± ± (%) (%) ± ± ± (%) ± (p0.05) 121

8 2. F0 (mg/kg/day) /mm ± g/dl ± (%) ± µ ± pg ± (%) ± /mm ± /mm ± (%) ± ± ± ± ± ± ± ( ) ± g ( ) ± mg ± mg ± mg ± mg ± mg ± mg ± mg ± mg ± (p0.05) ( p0.05 p0.01) 122

9 2. F0 (mg/kg/day) (,%) ± ± ± ± ± ± ± ± ± /13 0/14 0/14 0/14 1/14 0/12 0/13 1/14 1/14 0/14 0/14 0/12 3/13 0/14 2/14 5/14 0/14 1/12 # / /14-0/13 0/14 0/14 1/14 0/14 0/12 1/13 0/14 0/14 1/14 0/14 0/12 2/13 1/14 1/14 1/14 1/14 2/12 2/13 2/14 1/14 4/14 3/14 3/12 13/13 14/14 12/14 12/14 14/14 12/12 0/13 1/14 0/14 0/14 0/14 0/12 1/13 1/14 1/14 2/14 1/14 1/12 0/13 1/14 1/14 0/14 0/14 0/12 1/13 0/14 0/14 1/14 1/14 2/12 1/13 0/14 0/14 1/14 0/14 0/12 0/13 0/14 0/14 1/14 1/14 0/12 1/13 0/14 0/14 1/14 2/14 0/12 0/13 0/14 1/14 0/14 0/14 0/12 (p0.05) # 123

10 2. 3 F0 F1 0 (mg/kg/day) F / ± * 0/12 0/14 1/14 0/14 0/14 0/12 0/63 0/83 1/74 0/95 0/81 0/58 0/13 0/14 1/14 0/14 0/14 0/12 0/81 0/79 2/85 0/67 0/80 0/75 (%) ± ± ± ± (g) ± ± ± ± ± ± ± ± ± ± ± ± ± ± ( p0.05 p0.01) * 124

11 2. 4 F0 F1 0 (mg/kg/day) (mm) ± ± (/BW 1/3 ) ± ± () ± () ± () ± ( 11-13,%) ± () ± () ± () ± ( 11-13,%) ± (p0.01) 125

12 2. 5 F0 F13 (mg/kg/day) (10 4 /mm 3 ) ± (g/dl) ± (%) ± (µ 3 ) ± pg ± (%) ± (10 2 /mm 3 ) ± (10 4 /mm 3 ) ± (%) ± ± ± ± ± ± ± ( ) ± (p0.05) 126

13 2. 6 F0 F13 (mg/kg/day) (10 4 /mm 3 ) ± (g/dl) ± (%) ± (µ3) ± pg ± (%) ± (10 2 /mm 3 ) ± (10 4 /mm 3 ) ± (%) ± ± ± ± ± ± ± ( ) ± (p0.05) ( p0.05 p0.01) 127

14 2. 7 F0 F13 (mg/kg/day) g ( ) ± mg ± mg ± mg ± mg ± mg ± mg ± (mg) ± mg ± g ± mg ± mg ± mg ± mg ± mg ± mg ±

15 2. 8 F0 F13 (mg/kg/day) F (,%) ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± * 1/12 0/14 0/14 0/14 0/14 0/12 1/23 0/28 0/28 0/28 0/28 0/23 0/12 1/14 0/14 0/14 2/14 1/12 0/23 1/28 0/28 0/28 2/28 1/23 0/12 0/14 0/14 1/14 0/14 0/12 0/23 0/28 0/28 1/28 0/28 0/23 0/12 0/14 0/14 1/14 0/14 0/12 0/23 0/28 0/28 1/28 0/28 0/23 2/13 3/14 1/14 2/14 0/14 1/12 2/26 3/28 1/27 2/28 0/28 2/24 (p0.05) * 129

16 2. 9 F0 F13 (mg/kg/day) F * 12/12 14/14 14/14 14/14 14/14 12/12 23/23 28/28 28/28 28/28 28/28 23/23 1/12 0/14 0/14 0/14 0/14 0/12 1/23 0/28 0/28 0/28 0/28 0/23 0/12 1/14 0/14 0/14 0/14 0/12 0/23 1/28 0/28 0/28 0/28 0/23 0/12 1/14 0/14 0/14 0/14 0/12 0/23 1/28 0/28 0/28 0/28 0/23 1/12 1/14 0/14 0/14 0/14 1/12 1/23 1/28 0/28 0/28 0/28 1/23 0/12 2/14 1/14 0/14 0/14 1/12 0/23 2/28 1/28 0/28 0/28 1/23 0/12 0/14 0/14 0/14 0/14 1/12 0/23 0/28 0/28 0/28 0/28 1/23 0/12 0/14 0/14 0/14 1/14 1/12 0/23 0/28 0/28 0/28 1/28 1/23 0/12 1/14 0/14 0/14 2/14 1/12 0/23 1/28 0/28 0/28 2/28 1/23 0/12 0/14 0/14 0/14 1/14 1/12 0/23 0/28 0/28 0/28 1/28 1/23 0/12 1/14 0/14 0/14 0/14 0/12 0/23 1/28 0/28 0/28 0/28 0/23 0/12 0/14 0/14 1/14 0/14 0/12 0/23 0/28 0/28 1/28 0/28 0/23 1/12 1/14 1/14 1/14 0/14 0/12 1/23 1/28 1/28 1/28 0/28 0/23 0/12 0/14 1/14 2/14 3/14 0/12 0/23 0/28 2/28 2/28 4/28 0/23 0/12 1/14 3/14 1/14 3/14 2/12 0/23 1/28 3/28 1/28 3/28 2/23 1/12 1/14 0/14 0/14 1/14 0/12 1/23 1/28 0/28 0/28 1/28 0/23 * 130

17 2. 10 F0 F13 (mg/kg/day) F * 13/13 14/14 14/14 14/14 14/14 12/12 26/26 28/28 27/27 28/28 28/28 24/24 1/13 0/14 0/14 1/14 1/14 0/12 1/26 0/28 0/27 1/28 1/28 0/24 0/13 0/14 1/14 1/14 1/14 0/12 0/26 0/28 1/27 1/28 1/28 0/24 0/13 0/14 0/14 3/14 0/14 0/12 0/26 0/28 0/27 3/28 0/28 0/24 1/13 0/14 0/14 0/14 0/14 0/12 1/26 0/28 0/27 0/28 0/28 0/24 1/13 1/14 0/14 0/14 0/14 0/12 1/26 1/28 0/27 0/28 0/28 0/24 2/13 4/14 2/14 2/14 0/14 1/12 2/26 5/28 2/27 2/28 0/28 2/24 0/13 0/14 1/14 0/14 0/14 0/12 0/26 0/28 1/27 0/28 0/28 0/24 1/13 0/14 0/14 0/14 0/14 0/12 1/26 0/28 0/27 0/28 0/28 0/24 1/13 0/14 0/14 0/14 0/14 0/12 1/26 0/28 0/27 0/28 0/28 0/24 0/13 0/14 0/14 0/14 1/14 0/12 0/26 0/28 0/27 0/28 1/28 0/24 1/13 0/14 0/14 0/14 1/14 0/12 1/26 0/28 0/27 0/28 1/28 0/24 0/13 0/14 1/14 2/14 3/14 0/12 0/26 0/28 1/27 3/28 3/28 0/24 1/13 3/14 1/14 4/14 2/14 2/12 1/26 4/28 1/27 4/28 3/28 2/24 0/13 1/14 0/14 0/14 1/14 0/12 0/26 1/28 0/27 0/28 1/28 0/24 0/13 0/14 1/14 0/14 0/14 1/12 0/26 0/28 1/27 0/28 0/28 1/24 * 131

18 2. 11 F0 F13-12 (mg/kg/day) F /40 0/55 0/46 0/67 0/53 0/35 0/55 0/51 0/57 0/39 0/52 0/51 * 1/11 0/13 0/14 0/14 0/13 0/10 1/40 0/55 0/46 0/67 0/53 0/35 0/11 1/13 0/14 0/14 0/13 0/10 0/40 1/55 0/46 0/67 0/53 0/35 0/11 1/13 1/14 0/14 0/13 0/10 0/40 1/55 1/46 0/67 0/53 0/35 0/11 0/13 1/14 0/14 0/13 0/10 0/40 0/55 1/46 0/67 0/53 0/35 0/11 0/13 0/14 0/14 1/13 0/10 0/40 0/55 0/46 0/67 1/53 0/35 0/11 0/13 0/14 0/14 1/13 0/10 0/40 0/55 0/46 0/67 1/53 0/35 0/12 1/14 0/12 0/14 0/13 0/12 0/55 1/51 0/57 0/39 0/52 0/51 0/12 1/14 0/12 0/14 0/13 0/12 0/55 1/51 0/57 0/39 0/52 0/51 0/12 1/14 0/12 0/14 0/13 0/12 0/55 2/51 0/57 0/39 0/52 0/51 0/12 0/14 0/12 1/14 0/13 0/12 0/55 0/51 0/57 1/39 0/52 0/51 0/12 0/14 1/12 0/14 0/13 0/12 0/55 0/51 2/57 0/39 0/52 0/51 * 132

19 2. 12 F0 F13-12 (mg/kg/day) (g) ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± (p0.05) 133

20 2. 13 F0 F13-12 (mg/kg/day) (g) ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± (g) ± ± (kg) ± ± (p0.05) 134

21 2. 14 F0 F112 (mg/kg/day) (10 4 /mm 3 ) ± (g/dl) ± (%) ± (µ 3 ) ± pg ± (%) ± (10 2 /mm 3 ) ± (10 4 /mm 3 ) ± (%) ± ± ± ± ± ± ± ( ) ±

22 2. 15 F0 F112 (mg/kg/day) (10 4 /mm 3 ) ± (g/dl) ± (%) ± (µ 3 ) ± pg ± (%) ± (10 2 /mm 3 ) ± (10 4 /mm 3 ) ± (%) ± ± ± ± ± ± ± ( ) ±

23 2. 16 F0 F112 (mg/kg/day) g ( ) ± mg ± mg ± mg ± mg ± mg ± mg ± mg ± mg ± (mg) ± mg ± g ± mg ± mg ± mg ± mg ± mg ± mg ± mg ± mg ± (p0.05) 137

24 2. 17 F0 F112 (mg/kg/day) F (,) ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± (p0.05) 138

25 2. 18 F0 F112 (mg/kg/day) F * 0/11 0/13 1/14 0/14 0/13 0/10 0/21 0/25 1/23 0/28 0/26 0/19 0/11 0/13 0/14 1/14 0/13 0/10 0/21 0/25 0/23 1/28 0/26 0/19 0/11 1/13 0/14 0/14 0/13 0/10 0/21 1/25 0/23 0/28 0/26 0/19 1/11 2/13 3/14 2/14 0/13 0/10 1/21 2/25 3/23 2/28 0/26 0/19 0/11 0/13 1/14 0/14 0/13 0/10 0/21 0/25 1/23 0/28 0/26 0/19 0/11 0/13 0/14 0/14 1/13 0/10 0/21 0/25 0/23 0/28 2/26 0/19 0/11 1/13 1/14 0/14 0/13 0/10 0/21 1/25 1/23 0/28 0/26 0/19 0/12 0/14 0/12 0/14 0/13 1/12 0/23 0/27 0/23 0/27 0/26 1/23 0/12 0/14 0/12 0/14 0/13 1/12 0/23 0/27 0/23 0/27 0/26 1/23 1/12 2/14 1/12 1/14 0/13 1/12 1/23 3/27 1/23 1/27 0/26 2/23 0/12 0/14 0/12 1/14 0/13 0/12 0/23 0/27 0/23 1/27 0/26 0/23 /12 0/14 0/12 0/14 0/13 0/12 /23 0/27 0/23 0/27 0/26 0/23 /12 0/14 0/12 0/14 0/13 0/12 /23 0/27 0/23 0/27 0/26 0/23 /12 0/14 0/12 0/14 0/13 0/12 /23 0/27 0/23 0/27 0/26 0/23 0/12 0/14 0/12 1/14 0/13 0/12 0/23 0/27 0/23 1/27 0/26 0/23 * 139

26 2. 19 F0 F112 (mg/kg/day) F * 2/11 2/13 0/14 0/14 0/13 0/10 2/21 2/25 0/23 0/28 0/26 0/19 0/11 0/13 0/14 1/14 0/13 0/10 0/21 0/25 0/23 1/28 0/26 0/19 0/11 1/13 0/14 0/14 0/13 0/10 0/21 1/25 0/23 0/28 0/26 0/19 0/11 0/13 0/14 1/14 0/13 0/10 0/21 0/25 0/23 1/28 0/26 0/19 0/11 1/13 0/14 0/14 0/13 0/10 0/21 1/25 0/23 0/28 0/26 0/19 0/11 1/13 0/14 0/14 0/13 0/10 0/21 1/25 0/23 0/28 0/26 0/19 0/11 1/13 0/14 0/14 0/13 0/10 0/21 1/25 0/23 0/28 0/26 0/19 0/11 0/13 0/14 1/14 0/13 0/10 0/21 0/25 0/23 1/28 0/26 0/19 4/11 1/13 1/14 4/14 3/13 1/10 4/21 1/25 1/23 4/28 3/26 1/19 0/11 0/13 1/14 0/14 0/13 0/10 0/21 0/25 1/23 0/28 0/26 0/19 2/11 1/13 0/14 0/14 0/13 2/10 2/21 2/25 0/23 0/28 0/26 2/19 0/11 0/13 0/14 2/14 0/13 0/10 0/21 0/25 0/23 3/28 0/26 0/19 1/11 2/13 3/14 2/14 0/13 0/10 1/21 2/25 3/23 2/28 0/26 0/19 0/11 1/13 1/14 0/14 0/13 0/10 0/21 1/25 1/23 0/28 0/26 0/19 0/11 0/13 0/14 0/14 1/13 0/10 0/21 0/25 0/23 0/28 1/26 0/19 0/11 0/13 1/14 0/14 1/13 0/10 0/21 0/25 1/23 0/28 2/26 0/19 6/11 5/13 10/14 7/14 7/13 5/10 6/21 5/25 10/23 9/28 9/26 6/19 # - 1/1 1/ /1 1/ /11 0/13 1/14 1/14 0/13 0/10 2/21 0/25 1/23 1/28 0/26 0/19 0/11 0/13 1/14 1/14 2/13 0/10 0/21 0/25 1/23 2/28 2/26 0/19 0/11 2/13 1/14 1/14 1/13 2/10 0/21 2/25 1/23 1/28 1/26 2/19 1/11 0/13 0/14 0/14 2/13 0/10 1/21 0/25 0/23 0/28 2/26 0/19 0/11 0/13 1/14 0/14 0/13 0/10 0/21 0/25 1/23 0/28 0/26 0/19 0/11 1/13 0/14 0/14 0/13 0/10 0/21 1/25 0/23 0/28 0/26 0/19 # 140

27 2. 20 F0 F112 (mg/kg/day) F * 4/12 2/14 1/12 0/14 1/13 1/12 5/23 2/27 1/23 0/27 1/26 1/23 4/12 4/14 1/12 3/14 2/13 1/12 4/24 5/27 1/23 3/27 2/26 1/23 0/12 0/14 0/12 1/14 0/13 0/12 0/23 1/27 0/23 1/27 0/26 0/23 3/12 1/14 1/12 4/14 4/13 2/12 3/23 1/27 1/23 4/27 5/26 2/23 9/12 11/14 9/12 10/14 13/13 9/12 14/23 16/27 12/23 16/27 20/26 14/23 0/12 0/14 0/12 1/14 1/13 0/12 0/23 0/27 0/23 1/27 1/26 0/23 2/12 0/14 1/12 1/14 0/13 0/12 2/23 0/27 1/23 1/27 0/26 0/23 1/12 4/14 1/12 1/14 0/13 2/12 1/23 6/27 1/23 1/27 0/26 3/23 0/12 0/14 0/12 0/14 0/13 1/12 0/23 0/27 0/23 0/27 0/26 1/23 0/12 0/14 0/12 1/14 0/13 0/12 0/23 0/27 0/23 1/27 0/26 0/23 2/12 0/14 1/12 1/14 0/13 0/12 2/23 0/27 1/23 1/27 0/26 0/23 # 1/ / / / / / / / / / /12 0/14 0/12 1/14 1/13 0/12 0/23 0/27 0/23 1/27 1/26 0/23 # / / / / /12 0/14 2/12 2/14 1/13 1/12 0/23 0/27 2/23 2/27 1/26 1/23 0/12 0/14 0/12 2/14 4/13 0/12 0/23 0/27 0/23 3/27 5/26 0/23 3/12 2/14 2/12 2/14 2/13 1/12 3/23 3/27 2/23 2/27 2/26 2/23 1/12 1/14 0/12 2/14 0/13 2/12 1/23 1/27 0/23 2/27 0/26 2/23 (p0.05) # 141

28 2. 21 F1 (mg/kg/day) F /19 0/30 0/23 0/39 0/27 0/16 0/27 0/19 0/30 0/12 0/25 0/28 * 1/9 0/11 0/8 0/13 0/12 0/6 1/19 0/30 0/23 0/39 0/27 0/16 0/9 1/11 0/8 0/13 0/12 0/6 0/19 1/30 0/23 0/39 0/27 0/16 0/9 0/11 0/8 0/13 1/12 0/6 0/19 0/30 0/23 0/39 1/27 0/16 0/10 1/8 0/10 0/7 0/11 0/11 0/27 1/19 0/30 0/12 0/25 0/28 0/10 0/8 0/10 0/7 1/11 0/11 0/27 0/19 0/30 0/12 1/25 0/28 0/10 0/8 1/10 0/7 0/11 1/11 0/27 0/19 2/30 0/12 0/25 1/28 (g) ± ± ± (g) ± ± (x10e6) ± g (x10e6/g) ± (x10e6) ± g (x10e6/g) ± (%) ± (%) ± * 142

29 2. 22 * F1 (mg/kg/day) F F F * 11/11 9/10 10/10 7/7 12/12 11/11 (100.0%) (90.0%) (100.0%) (100.0%) (100.0%) (100.0%) % ± /32 23/24 34/34 12/12 26/26 28/28 (100.0%) (95.8%) (100.0%) (100.0%) (100.0%) (100.0%) * 10/11 8/9 10/10 7/7 11/12 11/11 (90.9%) (88.9%) (100.0%) (100.0%) (91.7%) (100.0%) % ± /32 19/23 30/34 12/12 25/26 28/28 (84.4%) (82.6%) (88.2%) (100.0%) (96.2%) (100.0%) (%) ± (%) ±

30 2. 23 F1 (mg/kg/day) F * 0/9 0/11 0/8 0/13 1/12 0/6 0/19 0/30 0/23 0/39 1/27 0/16 0/9 1/11 0/8 0/13 0/12 0/6 0/19 1/30 0/23 0/39 0/27 0/16 1/9 4/11 2/8 3/13 4/12 1/6 2/19 4/30 4/23 5/39 4/27 1/16 0/9 2/11 0/8 0/13 0/12 0/6 0/19 2/30 0/23 0/39 0/27 0/16 1/9 0/11 0/8 0/13 0/12 0/6 1/19 0/30 0/23 0/39 0/27 0/16 0/9 0/11 0/8 0/13 0/12 1/6 0/19 0/30 0/23 0/39 0/27 1/16 0/9 0/11 0/8 0/13 0/12 1/6 0/19 0/30 0/23 0/39 0/27 1/16 0/9 1/11 0/8 0/13 0/12 0/6 0/19 1/30 0/23 0/39 0/27 0/16 0/11 0/10 0/10 0/7 1/12 0/11 0/32 0/24 0/34 0/12 1/26 0/28 0/11 0/10 0/10 0/7 1/12 0/11 0/32 0/24 0/34 0/12 1/26 0/28 0/11 1/10 0/10 0/7 0/12 0/11 0/32 1/24 0/34 0/12 0/26 0/28 0/11 1/10 0/10 1/7 2/12 1/11 0/32 1/24 0/34 1/12 2/26 3/28 0/11 1/10 0/10 0/7 0/12 0/11 0/32 1/24 0/34 0/12 0/26 0/28 0/11 1/10 0/10 0/7 0/12 0/11 0/32 1/24 0/34 0/12 0/26 0/28 1/11 0/10 0/10 0/7 0/12 0/11 1/32 0/24 0/34 0/12 0/26 0/28 0/11 1/10 0/10 0/7 0/12 0/11 0/32 1/24 0/34 0/12 0/26 0/28 0/11 1/10 0/10 0/7 0/12 0/11 0/32 1/24 0/34 0/12 0/26 0/28 0/11 0/10 0/10 0/7 0/12 1/11 0/32 0/24 0/34 0/12 0/26 1/28 0/11 0/10 1/10 0/7 0/12 0/11 0/32 0/24 2/34 0/12 0/26 0/28 0/11 1/10 0/10 0/7 0/12 0/11 0/32 1/24 0/34 0/12 0/26 0/28 * 144

31 2. 24 F1 (mg/kg/day) * / /1 1/ / / / / / / / / / / / / / / / / / / / / / / / / / / / / / / / / / #

32 146

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