DCHP

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2 1. 1) 2) 2 Crj:CD(SD)IGS SPF ppm 2 F0 10 F0 10 F1 21 F F F ppm 1 F mg/kg/day F mg/kg/day F mg/kg/dya F mg/kg/day F0 F ppm 6000 ppm F ppm F ppm F1 F1 F ppm 6000 ppm F ppm F

3 NOEL NOAEL 240 ppm F mg/kg/day F mg/kg/day F mg/kg/day F mg/kg/day NOEL NOAEL 240 ppm 1200 ppm F mg/kg/day F mg/kg/day NOEL NOAEL 240 ppm 1200 ppm - 3 -

4 2. (DCHP) 99.9 (MERCK-Schuchardt Lot No. S26063) NEDO 2 5. Crj:CD(SD)IGS ( ) 1 24 F F F1 21 F F2 21 F0 F ppm NIH-07M ppm ppm ppm 600 ppm ppm 6000 ppm 6000 ppm ppm 240 ppm - 4 -

5 (NIH-07M ) m / 12 (7-19 ) (265W 426D 200H mm ) F F F F1-5 -

6 35 27 F0 13 F F0 F1 10 HTM-IVOS Ver ppm 10 HTM-IVOS Ver.10.8F ppm ppm 2000 ppm F0 F RIA FSH LH FSH LH - 6 -

7 10.8, % F1 14 * F2 12 * * F1 F2 F ppm F1 14 F F0 F1-7 -

8 1 F1 F F0 F ppm ppm F0 F1 F1 F Bartlett Kruskal-Wallis Dunnett Dunnett Kruskal-Wallis Dunnett Fisher 5 Kruskal-Wallis Dunnett - 8 -

9 Fisher / - 9 -

10 1. F : %

11 F0/F F : FSH LH FSH LH

12 F % F1/F FSH LH FSH LH

13 tk tk tk tk tk # tk #

14 Tables A4 to A7 and B6 to B9 F0 F1 F0 F1 240 ppm ppm ppm ppm ppm ppm ppm ppm ppm F0 F Tables A8 to A15, B11 to B14, and B16 to B ppm F F , , 0-21, F , 28-91, ,F1 21, , ppm F0 7 F F F

15 240 ppm F0 0 F0 F ppm F0 F Tables A16 to A18 and B20 to B ppm F F F0 F ppm F F0 14 F ppm F0 F1 240 ppm F0 F1 F ppm F ppm Tables A19 to A21 and B23 to B ppm F0 7 F1 28 F1 7 F0 35 F ppm F0 7 F ,F1 7 F0 35 F ppm F1 7 F0 F ppm F0 F1-15 -

16 Tables A22 and B ppm F0 F ppm F0 F1 F ppm F ppm F Tables A22, A24, B30, and B32 F0 F ppm F ppm F0 F Table A23 B31 F ppm 6000 ppm F1 1 F ppm 1200 ppm F Tables A25, A26, B34, and B ppm F0 F0 F1-16 -

17 F0 F1 F0 F ppm F0 F ppm F0 F0 F1 F ppm F0 F1 F1 240 ppm F1 F ppm F0 F1 F0 F Table A27, A28, B38, and B ppm F0 F ppm F ppm F1 F0 F1 F ppm F ppm F ppm F ppm F ppm F ppm F0 F1 F0 F1 240 ppm

18 6000 ppm F ppm ppm ppm ppm 3 F ppm 1 F0 F ppm F ppm F ppm F ppm F0 F ppm F0 F ppm F Table A29 B ppm F0 240 ppm F 1 FSH 6000 ppm 6000 ppm FSH LH Tables B5, and C2 F1 F ppm F1 F Tables B10, B15, C3, and C ppm F F

19 ppm F1 F ppm F1 F2, Tables B4, B26, B29, B41, C1, C5, C8, and C ppm F1 F ppm F2 240 ppm F1 F ppm F ppm F Tables B27, B28, C6, and C7 F1 F2 F1 F ppm F ppm F1 F Table2 B33, B35, C9, and C ppm F1 F1 F2 F1 F2 F1 F1 F2-19 -

20 1200 ppm 6000 ppm F1 F Tables B37 and C11 F1 240 ppm 6000 ppm 2, 240 ppm 1200 ppm 1, F2 1, 1-2,, F2 1, ppm F1 F NOELNOAEL F0 F ppm 6000 ppm F1 3,4) 7 P ) 6) F0 F ppm 2U

21 7) 2U 8) 2U F ppm ,10) 2500 mg/kg ) 11) F0 F ppm F ppm F1 12 F0 F1 11) F ppm 1200 ppm F1 F ppm 6000 ppm F ppm F2,

22 13) n- 14) 6000 ppm F ppm F2 2 NOEL NOAEL 240 ppm F mg/kg/day F mg/kg/day F mg/kg/day F mg/kg/day NOELNOAEL 240 ppm 1200 ppm F mg/kg/day F mg/kg/day NOELNOAEL 240 ppm 1200 ppm 12. 1) HSDB 2001 Hazardous Substance Data Bank, National Library of Medicine. 2) CERI 2001a 12 3) Gopinath C, Prentice, DE, Lewis DJ. (1987): The liver. Morphological lesions in the liver. Hypertrophy. In: Gopinath C, Prentice, DE, Lewis DJ, editors. Atlas of experimental toxicological pathology. Lancaster: MTP Press Limited; p.53. 4) Greaves P. Digestive system 2. (1990): Liver. Hepatocellular hypertrophy and hyperplasia. In: Greaves P, editor. Histopathology of preclinical toxicity studies. Amsterdam: Elsevier; p ) Lake BG, Foster JR, Collins MA, Stubberfield CR, Gangolli SD, Srivastava SP. (1982): Studies on the effects of orally administered dicyclohexyl phthalate in the rat. Acta Pharmacol Toxicol (Copenh) ) Gopinath C, Prentice DE, Lewis DJ. (1987): The endocrine glands. Thyroid. In: Gopinath C, Prentice DE, Lewis DJ, editors. Atlas of experimental toxicological pathology. Lancaster: MTP Press Limited; p ) Greaves P. Urinary tract. Kidney. Hyaline droplets. (1990): Greaves P, editor. Histopathology of preclinical toxicity studies. Amsterdam: Elsevier; p ),...,.. : ; p

23 9) Gopinath C, Prentice DE, Lewis DJ. The reproductive system. Male reproductive system. Testis and epididymis. In: Gopinath C, Prentice DE, Lewis DJ, editors. Atlas of experimental toxicological pathology. Lancaster: MTP Press Limited; p ),....,.. : ; p ) CERI 2001b 11 12) Chapin, R.E., Gulati,D.K., Barnes,L.H., and Teague, J.L. (1993): The Effects of Feed Reproductive Function in Sprague-Dawley Rats. Fundam. Appl. Toxicol. 20, ) Gray, L.E., et al. (2001): Effects of environmental antiandorigens on reproductive development in experimental animals. Human Reproduction Update, 7, ) Shultz, V.D., et al (2001): Altered Gene Profiles in Fetal Rat Testes after in Utero Exposure to Di(n-butyl) Phthalate. Toxicol. Sci.64,

24 2. F0 F1 F1 F2 ppm mg/kg/day /24 0/24 0/24 0/24 0/20 0/23 0/20 0/22 0/24 0/24 0/24 0/24 0/20 1/23 1) 0/20 1/22 2) 0/24 0/24 0/24 1/24 0/20 0/23 0/20 0/22 0/24 0/24 0/24 1/24 0/20 0/23 0/20 0/22 0/24 1/24 0/24 1/24 0/20 0/23 1/20 0/22 0/24 0/24 1/24 0/24 0/24 1/24 0/24 0/24 0/20 0/20 0/23 0/23 1/20 0/20 0/22 0/22 1/24 1/24 2/24 0/24 3/24 0/24 5/24 0/24 4/20 0/20 2/23 0/23 0/20 0/20 1/22 0/22 1/24 0/24 0/24 0/24 0/20 0/23 0/20 0/ ) ) ) ) (g) ) ) [MeanS.D.] ) ) ) ) ) ) ) ) (g) ) ) ) ) ) ) ) (%) ) ) ) ) ) ) ) )

25 2. -1 F0 F1 F1 F2 ppm (g) /24 23/24 22/24 23/24 19/20 23/23 20/20 19/ [MeanS.D.] (x 10 6 ) ) ) ( )(%) ) (%) (g) /24 0/24 0/24 0/24 1/20 2/23 0/20 0/ ) [MeanS.D.] 22/24 23/24 22/24 23/24 19/20 23/23 20/20 19/21 20/22 23/23 20/22 22/23 19/19 22/23 19/20 17/19 20/20 23/23 20/20 22/22 19/19 22/22 19/19 17/17 (%) (g) (mg) ()(mg) ()(mg) , (g) [MeanS.D.] () (g) ()(mg) ()(g) ()(g) (g) (g) (g) / / p0.05 p0.01

26 2. -2 [MeanS.D.] F0 F1 F1 F2 ppm (x10-3 ) () (x10-3 ) () (x10-3 ) (%) () () (x10-3 ) () () (g) ()(mg) ()(mg) (g) ()(g) ()(g) ()(mg) ()(mg) () (x10-3 ) () (x10-3 ) (%) () () () (x10-3 ) () (x10-3 ) / / p0.05 p

27 2. -3 F0 F1 F1 F2 ppm ) /24 0/24 0/24 24/24 0/20 0/23 0/20 8/22 26) 0/24 0/24 0/24 0/24 0/20 0/23 0/20 3/22 0/24 0/24 0/24 0/24 0/20 0/23 0/20 2/22 0/24 0/24 0/24 7/24 0/20 0/22 1/20 4/21 + 0/24 0/24 4/24 16/24 0/20 0/23 0/20 14/22 + 0/24 0/24 3/24 7/24 0/20 0/23 0/20 7/ /24 22/24 23/24 9/24 19/20 22/23 20/20 14/ /24 1/24-15/24 27) 1/20 1/23-8/22 27) /20 0/23 0/20 3/22 + 1/24 1/24 1/20 0/23 2/20 6/22 + 0/24 0/24 3/24 12/24 0/20 0/22 0/20 9/21 + 0/24 0/24 0/24 6/24 0/20 0/22 0/20 6/ (ng/ml) FSH (ng/ml) LH (ng/ml) (pg/ml) FSH (ng/ml) LH (ng/ml) ) F ppm ppm 6000 ppm 26) / - / 27) (++) / / p0.05 p0.01

28 2. -4 F0 F1 F1 F2 ppm ) / 0-21 / /1 28) (g) [MeanS.D.] AGDmm AGD/BW AGD 4 AGDmm [MeanS.D.] AGD/BW (%) F1Day 14 F2Day / / p0.05 p0.0128) / -

29 2. -5 F0 F1 F1 F2 ppm % % % ) % % % % [Mean] % % % (g) (mg) (g) (%) (x10-3 ) [MeanS.D.] (g) (g) (%) /19 30) 2/20 2/22-2/ / / 1/20 1/23 1/ / / p0.05 p ) 5 1, /

繁殖性に及ぼす影響

繁殖性に及ぼす影響 5. 2 1. (DEP) 1) DEP 2) 3) 4) DEP 0 600 3000 15000 ppm(0 43 210 1083 mg/kg/day 0 54 261 1336 mg/kg/day ) 24 Crj:CD(SD) IGS 2 DEP 15000 ppm F0 0-21 F1 F0 F1 DEP F1 F1 15000 ppm 15000 ppm F0 F1 F0 F0 P-450

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