◎⑥BBP報告書_委員会当日_
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- まな しもとり
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2 1. (BBP) ( ) 1) BBP 2) 3) 4) 3),4) 5),6) 7),8) + 7) BBP mg/kg/day 24 Crj:CD(SD) IGS 2 F0 200 mg/kg F1 100 mg/kg F0 F1 BBP 400 mg/kg F0 F1 F0 F1 BBP F1 400 mg/kg F1 F0 BBP 200 mg/kg 400 mg/kg BBP F0 200 mg/kg 400 mg/kg F1 200 mg/kg 400 mg/kg BBP F0 400 mg/kg F1 100 mg/kg 400 mg/kg 100 mg/kg 400 mg/kg - 2 -
3 F1 F2 BBP F1 100 mg/kg F2 F1 BBP F1 100 mg/kg F2 100 mg/kg F1 F2 400 mg/kg 9) 10) 11),12) 13) 14) 15) BBP FSH 16) BBP F0 F1 BBP 100 mg/kg 400 mg/kg F1 F2 100 mg/kg BBP 2 BBP 100 mg/kg (NOEL) (NOAEL) 100 mg/kg/day 400 mg/kg 200 mg/kg/day - 3 -
4 100 mg/kg 100 mg/kg/day - 4 -
5 2. (BBP) 98.0 ( Lot No. GI01) (NEDO) 2 5. Crj:CD(SD)IGS ( ) 1 24 F0 5 F F0 F ( ) 7. ( 016OAA) ( ) ( ) 1 5mL/kg mg/kg/day ( 8/3mm 8-12cm) 10 ( 10/3mm 13-15cm) 4 BBP 8. BBP 2 ( ) BBP ,000 mg/kg/day 1 8 Crj:CD(SD)IGS 4 1,000 mg/kg 500 mg/kg 250 mg/kg - 5 -
6 400 mg/kg/day mg/kg/day (NIH-07M 30kGy ) ( ) / 12 (7-19 ) (280 W 440 D 150 H mm ) 17 ( ) (265 W 426 D 200 H mm ) - 6 -
7 F1 ( 21 ) ( 0 ) ( 0 ) F F F1 5 F0 1 2 F ( ) - 7 -
8 ( )( ) ( ) F1 10 (IVOS F1 (F1 ( 21 ) 6 LH FSH EIA RIA LH Rat LH EIA system Amersham pharmacia biotech FSH Rat FSH EIA system Amersham pharmacia biotech Testosterone EIA Kit Cayman Chemical Company DPC Diagnostic Products Corporation ( 4 4 ) 10% ( ) ( 0 ) ( ) ( 4 0 )
9 21 ( ) ( 21 4 ) F0 F1 ( ) ( ) ( ) ( 21 ) F1 F2 ( ) 10% F1 ( 21 ) F0 F1 ( ) ( ) F0 F1 ( ) - 9 -
10 F2 F1 F2 Bartlett 5% Dunnett Kruskal-Wallis Dunnett F0 F1 F1 F2 ( ) F0 F1 ( 10 Fisher ) F0 F1 (motility ) F1 F2 4 Kruskal-Wallis Dunnett F1 F % 5%. F : ( ) ( )
11 F ( 4 4 ( ) 21 ( % ) F0/F1 ( ) 21 ( 25 ) ( 1 ) ( ) 6 ( FSH LH )
12 F : ( ) ( ) ( 4 4 ( ) 21 ) ( ) 10%
13 F1/F2 ( ) 21 ( 25 ) ( 21 ) ( ) 6 ( FSH LH )
14 tk tk tk tk tk tk
15 (1) F0 1) mg/kg mg/kg BBP ( ) 200 mg/kg 1 2) mg/kg mg/kg mg/kg mg/kg mg/kg mg/kg (2) F1 1) mg/kg mg/kg BBP ( ) 0 mg/kg mg/kg 1 2) mg/kg mg/kg mg/kg mg/kg mg/kg 200 mg/kg 1 BBP BBP 17,18 ( 1 )
16 F0 F1 19),20) ( 1 2) Tables 1 and 16 (1) F0 1) mg/kg 0 mg/kg 2) 200 mg/kg F1 (2) F1 1) mg/kg 0 mg/kg 2) 400 mg/kg BBP 400 mg/kg F0 F Tables and 18 (1) F0 1) 200 mg/kg mg/kg 2 3 F1 2) 400 mg/kg mg/kg F1 (2) F1 1) 400 mg/kg ) 400 mg/kg
17 100 mg/kg mg/kg mg/kg 10 F1 400 mg/kg BBP 200 mg/kg F0 F1 400 mg/kg F0 F Tables and 29 F0 F1 ( ) BBP 21) F0 F1 F
18 ( ) 100 mg/kg mg/kg ( ) mg/kg
19 ( 2 ) BBP BBP 400 mg/kg 3 BBP 22) BBP 200 mg/kg BBP BBP (F1 ) 24/
20 BBP (1) 2. Table 14 F1 400 mg/kg BBP 23) F0 F1 F0 F1 F0 5 F1 F1 F0 F2 F1 F0 F0 Crj:CD(SD)IGS 2 1 ( 2) F1 400 mg/kg 200 mg/kg BBP 200 mg/kg BBP BBP 200 mg/kg
21 mg/kg Tables and 24 (1) F0 200 mg/kg 400 mg/kg 200 mg/kg F1 BBP (2) F1 200 mg/kg 400 mg/kg BBP 16),23) BBP 22),24) 750 mg/kg 400 F0 200 mg/kg ) PPAR(Peroxisome proliferator-activated receptor) 29 31) BBP 200 mg/kg F0 400 mg/kg F1 200 mg/kg 400 mg/kg Tables 7 and 22 (1) F0 FSH LH (2) F1-21 -
22 FSH LH 400 mg/kg BBP FSH 14) 500 mg/kg 400 BBP 400 mg/kg F0 F Tables 10, 11, and 30 (1) F0 400 mg/kg F1 BBP (2 ) F1 400 mg/kg mg/kg 400 mg/kg 100 mg/kg 400 mg/kg BBP 16),32),33) F1 F0 400 mg/kg F1 (TCDD) 34),35) TCDD 36) 400 mg/kg F1 BBP 100 mg/kg F1-22 -
23 Tables 12 and 27 (1) F mg/kg BBP (2) F mg/kg BBP BBP 400 mg/kg F1 F Tables 16 and 31 (1) F1 100 mg/kg 0 (2) F2 100 mg/kg mg/kg 0 BBP BBP 100 mg/kg F Tables and 29 F1 F2 (1) F1 100 mg/kg (mm/ 3 ) F2 BBP 16) BBP (2) F2 100 mg/kg (mm/ 3 ) mg/kg (mm)
24 BBP 16),23) BBP 100 mg/kg F1 F Tables 14 and 29 F1 F2 BBP 400 mg/kg F1 F Tables 15 and 30 F1 F2 BBP 400 mg/kg F1 F Tables 25 and 34 F1 F2 F1 F2 BBP BBP 400 mg/kg F1 F Tables and 33 (1) F1 400 mg/kg (2) F2 400 mg/kg BBP 400 mg/kg F1 F2 F1-24 -
25 11.3 NOEL NOAEL F0 F1 BBP 100 mg/kg 400 mg/kg F1 F2 100 mg/kg BBP 2 BBP 100 mg/kg (NOEL) (NOAEL) 100 mg/kg/day 400 mg/kg 200 mg/kg/day 100 mg/kg 100 mg/kg/day
26 12. 1) ( ) (1997) 2) Hashimoto, Y., Moriguchi, Y., Oshima, H., Nishikawa, J., Nishihara, T., and Nalamura, M. (2000) Estrogenic activity of chemicals for dental and similar use in vitro. J. Materials Sci., 11, ) CREI( ) (2001) 12. 4) Zacharewski, T.R., Meek, M.D., Clemons, J.H., Fielden, M.R., and Matthews, J.B. (1998) Examination of the in vitro and in vivo estrogenic activities of eight commercial phthalate esters. Toxicol. Sci., 46, ) Komer, W., Hanf, V., Schuller, W., Bartsch, H., Zwirmer, M., and Hagenmaier, H. (1998) Validation and application of a rapid in vitro assay for assessing the estrogenic potency of halogenated phenolic chemicals. Chemosphere, 37, ) Jones, P.A., Baker, V.A., Irwin, A.J.E., and Earl, L.K. (1998) Interpretation of the in vitro proliferation response of MCF-7 cells to potential oestrogens and nonoestrogenic substances. Toxicol. in Vitro, 12, ) CREI( ) (2001) 11. 8) Coldham, N.G., Dave, M., Sivapathasundaram, S., McDonnel, D.P., Connor, C., and Sauer, M.J. (1997) Evaluation of a recombinant yeast cell estrogen screening assay. Environ. Health. Perspect., 105, ) Gray, L.E., Kelce, W.R., Wiese, T., Tyl, R., Gaido, K., Cook, J., Klinefelter, G., Desaulniers, D., Wilson, E., Zacharewski, T., Wallter, C., Foster, P., Laskey, J., Reel, J., Giesy, J., Laws, S., McLachlan, J., Breslin, W., Cooper, R., Di Giulio, R., Johnson, R., Purdy, R., Mihaich, E., Safe, S., Sonnenschein, C., Welshons, W., Miller, R., McMaster, S., and Colborn, T. (1997) Endocrine screening methods workshop report: detection of estrogenic and androgenic hormonal and antihormonal activity for chemicals that act via receptor or steroidogenic enzyme mechanisms. Reprod. Toxicol., 11, ) Lucier, G.W., Lee, I.P., and Dixon, R.L.(1970) Effect of environmental agents on male reproduction. In: Johnson, A.D., and Gomes, W.R., editors. The Testis, Vol., NY: Academic Press, p ) O Connor, J.C., Cook, J.C., Slone, T.W., Makovec, G.T, Frame, S.R., and Davis, L,G. (1998) An ongoing validation of a Tier screening battery for detecting endocrineactive compounds (EACs). Toxicol. Sci., Nov; 46(1),
27 12) Perez-Martinez, C., Garcia-Iglesias, M.J., Ferreras-Estrada, M.C., Bravo-Moral, A.M., Espinosa-Alvarez, J., and Escudero-Diez, A. (1996) Effects of in-utero exposure to zernol or diethylstilbestrol on morphological development of the fetal testis in mice. J. Comp. Pathol., 114 (4), ) Heinrichs, W.L. (1985) Current laboratory approaches for assessing female reproductive toxicity. In Dixon, R.L., editor. Reproductive Toxicology. New York: Raven Press, pp ) Clemens, L.G., Gladue, B.A., and Caniglio, L.P. (1978) Prenatal endogenous androgenic influences on masculine sexual behavior and genital morphology in male and female rats. Horm. Behav., 129, ) Levy, J.R., Faber, K.A., Ayyash, L., and Hughes Jr, C.L. (1995) The effect of prenatal exposure to the phytoestrogen genistein on sexual differentiation in rats. Proc. Soc, Exp. Biol. Med., 208, ) Nagao, T., Ota, R., Marumo, H., Shindo, T., Yoshimura, S., and Ono, H. (2000) Effect of butyl benzyl phthalate in Sprague-Dawley rats after gavage administration: a two-generation reproductive study. Reprod. Toxicol., 14, ) Hammond, B.G., Levinskas, G.J., Robinson, E.C., and Johannsen, F.R.(1987) A review of the subchronic toxicity of butyl benzyl phthalate. Toxicol. Ind. Health, 3(2), ) Mallette, F., von Haam, E. (1952) Studies on the toxicity and skin effects of compounds used in the rubber and plastic industries: Plasticizers. Arch. Ind. Hyg. Occup. Med., 6(3), ) (1996),,, 3, ) (1994),,, 1, ) NTP (1997) Toxicology and carcinogenesis studies of butyl benzyl phthalate (CAS no ). In F344/N rats (feed studies). Rep nr. NTP TR 458, NIH publication No : U.S. Department of Health and Human Services, Public Health Service, National Institute of Health. 22) Piersma, A.H., Verhoef, A., and Dortant, P.M. (1995) Evaluation of the OECD 421 reproductive toxicity screening test protocol using butyl benzyl phthalate. Toxicology, 99, ) Ashby, J., Tinwell, H., Lefevre, P.A., Odum, J., Paton, D., Millward, S.W., Tittensor, S., and Brooks, A.N. (1997) Normal sexual development of rats exposed to butyl benzyl phthalate from conception to weaning. Regul. Toxicol. Pharmacol., 56, ) Gray, L.E., Ostby, J., Furr, J., Price, M., Rao Veeramachaneni, D.N., and Parks, L
28 (2000) Perinatal exposure to the phthalate DEHP, BBP, and DINP, but not DEP, DMP, or DOTP, alter sexal differentiation of the male rat. Toxicol. Sci., 58, ) Oihsi, S., and Hiraga, K.(1980) Testicular atrophy induced by phthalic acid esters: Effect on testosteron and zinc concentrations. Toxicol.. Appl. Pharmacol., 1980, 53, ) Lake, B.G., Foster, J.R., Collins, M.A., Stubberfield. C.R., Gangolli, S.D., and Srivastava, S.P. (1982) Studies on the effects of orally administered dicyclohexyl phthalate in the rat. Act. Pharmacol Et Toxicol., 51 (3), ) NTP (1993) NTP Technical Report. Toxicology and carcinogenesis studies of diethylphthalate in F344/Nrats and B6C3F 1 mice (dermal studies) with dermal intiation/promotion study of diethlphthalate and dimethlphthalate in male Swiss (CD-1) mice. NTR TR 429. US Department of Health and Human Services. 28) Wine R.N., Li, L.H., Barnes, L.H., Gulai, D.K., and Chapin. R.E. (1997) Reproductive toxicity di-n-butyl phthalate in acontinuous breeding protocol in Sprague-Dawley rats. Environ. Hialth Persp., 105, ) Bojes, H.K., and Thurman, R.G. (1996) Potent peroxisome proliferators inhibit betaoxidation in the isolated perfused rat liver. Toxicol. Appl. Pharmacol. 140(2), ) Ward J.M., Peters, J.M., Perella C.M. and Gonzalez, F.J. (1998) Receptor and nonreceptor-mediated organ-specific toxicity of di(2-ethylhexyl)phthalate (DEHP) in peroxisome proliferator-activated receptor alpha-null mice. Toxicol Pathol. 26(2), ) Willhite C.C. (2001) Weight-of-evidence versus strength-of-evidence in toxicologic hazard identification.: Di(2-ethylhexyl)pthalate (DEHP). Toxicology, Mar7; 160(1-3), ) Agrawal, D.K., Marpnpor, R.R., Lamb, J.I.V., and Kluwe, W.M. (1985) Adverse effects of butyl benzyl phthalate on the reproductive and hematopoietic systems of male rats. Toxicology. 35, ) Piersma, A.H., Verhoef, A., and Dortant, P.M. (1995) Evaluation of the OECD 421 reproductive toxicity screening test protocol using butyl benzyl phthalate. Toxicology, 99, carbinol or 2,3,7,8-tetraaacahlorodibenzo-p-dioxin or reproductive potential of male rat offspring. Toxico. Appl. Pharmacol., 141(1), ). 2,3,7,8- -p- 34) Wilker, C., Johnson, L., and Safe. S. (1996) Effects of developmental exposure to indole- ( ) ) Musto, N.A., Santen R.J., Huckins C., and Bardin C.W. (1978) The H re Rats: A model for late-onset seminiferous tubule failure in man In Animal Models for Research on Contraception and Fertility. Edited by. Alexander, N.J., Harper &Row, Publisher, pp
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31 2 Crj:CD(SD)IGS 2 / 100 1) 1. 2 F0 22/25 (88.0%) F1 17/22 (77.3%) 2) 2. 2 F0 22/25 (88.0%) F1 18/22 (81.8%) 3) 3. 2 F0 24/25 (96.0%) F1 23/25 (92.0%) 4) 4. 1 F1 Mating index(number of animals with evidence of copulation/number of animals cohabitated 100)=80.0% F1 Fecundity index(number of animals bearing litters/number of animals copulating 100)=87.5% =70% 5. ( 7 21 ) 5) F1 16/21(76.2%) 1) Nagao, T., Ohta, R., Marumo, H., Shindo, T., Yoshimura, S., and Ono, H. (2000) Effect of butyl benzyl phthalate in Sprague-Dawley rats after gavage administration: a two-generation study. Reprod. Toxicicol., 14,
32 2/2 2) Nagao, T., Wada, K., Marumo, H., Yoshimura, S., and Ono, H. (2001) Reproductive effects of nonylphenol in rats after gavage administration: a two-generation study. Reprod. Toxicol., 15, ) Ema, M., Fujii, S., Furukawa, M., Kiguchi, M. Ikka, T., and Harazono, A. (2001) Rat twogeneration reproductive toxicity study of bisphenol A. Reprod. Tocicol., 15, ) Malley, L.A., Everds, N.E., Makovec, G.T., and Kennedy, Jr., G.L. (2002) Reproductive and repeated dose toxicity of cyclododecatriene(cddt) in rats following oral(gavage) treatment. Drug Chem. Toxicol. 25(2), ) Sato, T. and Nonaka, N. Accumulation of background data in Crj:CD(SD)IGS rats on reproductive and developmental toxicity study. In biological reference data on CD(SD)IGS rats CD(SD)IGS study group, Yokohama,
33 2. F0 F1 F1 F2 mg/kg/day /24 0/24 1/24 0/24 2/24 1/24 0/24 0/24 0/24 0/24 0/24 0/24 0/24 0/24 1/24 0/24 14/24 19/24 20/24 24/24 5/24 15/24 22/24 24/24 4/24 3/24 18/24 24/24 1/24 2/24 7/24 24/24 1/24 0/22 11/22 22/23 0/21 0/22 4/20 17/20 0/20 0/19 2/20 19/21 0/15 0/20 2/16 11/13 (g) ) ) ) (g) ) ) ) ) ) ( ) ) ) ) ) ) ) ) ( 43 ) 23/24 17/24 22/24 14/24 [Mean S.D.] 24/24 22/24 22/23 23/24 21/23 22/24 20/24 20/24 ( ) 20/24 19/22 20/22 21/23 16/21 21/22 17/20 13/ a) (x10 6 /g) (%) a) (%) a) p 0.05 p 0.01 a
34 2. 2 [Mean S.D.] [Mean S.D.] F0 F1 F1 F2 mg/kg/day ( 36 ) 24/24 24/24 22/24 22/24 24/24 24/24 21/23 22/24 21/23 17/24 23/24 24/24 24/24 22/24 22/23 23/24 21/23 22/24 20/24 20/24 20/24 19/22 20/22 21/23 16/21 21/22 17/20 13/20 20/20 19/19 20/20 21/21 15/16 20/21 16/17 13/ ( ) ( )(%) (g) ( )(g) ( )(g) ( )(g) ( )(g) ( )(g) ( )(g) (g) (g) (g) (g) (mg) (mg) ( )(mg) ( )(mg) (g) (wt/100g) ( )(g) ( )(g) ( )(g) ( )(g) ( )(g) ( )(g) (g) (g) (g) (g) (mg) (mg) ( )(mg) ( )(mg) p 0.05 p 0.01
35 2. 3 [Mean S.D.] F0 F1 F1 F2 mg/kg/day (g) ( )(g) ( )(g) ( )(mg) ( )(mg) (g) (g) (g) (mg) (mg) ( )(mg) ( )(mg) (g) (wt/100g) ( )(g) ( )(g) ( )(mg) ( )(mg) (g) (g) (g) (mg) (mg) ( )(mg) ( )(mg) /24 0/24 0/24 0/24 0/24 0/24 0/24 6/24 0/24 0/24 0/24 0/24 0/24 1/24 2/24 4/24 0/24 0/24 0/24 0/24 0/24 0/24 0/24 1/24 0/24 0/24 0/24 0/24 0/24 0/24 0/24 3/24 0/24 0/24 0/24 0/24 0/24 0/24 0/24 4/24 24/24 24/24 24/24 24/24 24/24 24/24 24/24 24/24 0/4 0/5 0/3 0/3 0/7 0/3 0/7 1/11(3/13) b) 0/4 0/5 0/3 0/3 0/7 0/3 0/7 2/11(0/13) b) 0/4 0/5 0/3 0/3 0/7 0/3 0/7 1/11(0/13) b) 0/4 0/5 0/3 0/3 0/7 0/3 0/7 3/11(0/13) b) 0/4 0/5 0/3 0/3 0/7 0/3 0/7 1/11(0/13) b) 0/4 0/5 0/3 0/3 0/7 0/3 0/7 2/11(0/13) b) 0/4 0/5 0/3 0/3 0/7 0/3 0/7 2/11(0/13) b) p 0.05 p 0.01 b
36 2. 4 F0 F1 F1 F2 mg/kg/day /24 0/5 0/3 0/24 1/24 1/24 3/24 9/24 0/24 0/5 0/3 1/24 0/24 1/24 0/24 5/24 0/24 0/5 0/3 0/24 0/24 0/24 0/24 1/24 0/24 0/5 0/3 0/24 0/24 0/24 0/24 2/24 0/24 0/5 0/3 0/24 0/24 0/24 0/24 3/24 0/24 0/5 0/3 0/24 0/24 1/24 2/24 3/24 0/24 0/5 0/3 1/24 0/24 1/24 3/24 1/24 24/24 24/24 24/24 24/24 24/24 24/24 24/24 24/24 0/4 0/5 0/3 0/3 1/7(0/14) b) 0/3 0/7 2/11(4/13) b) ( 0/4 0/5 0/3 0/3 0/7 0/3 0/7 3/11(0/13) b) ) 0/4 0/5 0/3 0/3 0/7 0/3 0/7 3/11(0/13) b) 0/4 0/5 0/3 0/3 0/7 0/3 0/7 1/11(0/13) b) 0/4 0/5 0/3 0/3 0/7 0/3 0/7 2/11(0/13) b) 0/4 0/5 0/3 0/3 0/7 0/3 0/7 3/11(0/13) b) 0/24 2/24 1/23 1/24 2/23 2/24 4/24 4/24 4/24 3/22 2/22 2/23 5/21 1/22 3/20 7/20 ( ) 0/4 0/5 0/3 0/3 1/7 1/3 0/7 0/ (pg/ml) FSH(ng/ml) LH(ng/ml) (pg/ml) (pg/ml) FSH(ng/ml) LH(ng/ml) (pg/ml) p 0.05 p 0.01 b
37 2. 5 F0 F1 F1 F2 mg/kg/day / / / /136 95/89 134/140 73/75 82/69 (%) / / / /132 95/95 134/134 73/73 82/82 142/ / / /136 89/89 140/140 75/75 69/ /113-72/72 109/109-68/68 140/140-78/78 132/132/-75/75 95/95-58/58 134/134-72/72 73/73-43/43 82/82-49/ /142-83/83 121/121-76/76 122/122/-73/73 136/136-81/81 89/89/-57/57 140/140-79/79 75/75-60/60 69/69-47/47 (g) [Mean S.D.] (mm) (mm/ 3 BW) / / / /124 95/95 128/128 70/70 78/ /72 57/68 74/78 71/75 54/58 63/72 39/43 46/ /72 65/68 74/78 74/75 56/58 72/72 42/43 49/ / / / /129 88/88 129/129 70/70 69/ /83 75/76 71/73 80/82 52/57 68/79 57/60 43/ /83 76/76 69/73 80/81 57/57 76/ /47 p 0.05 p 0.01
38 2. 6 F0 F1 F1 F2 mg/kg/day /72 68/68 78/78 76/76 58/58 72/72 43/43 49/ /72 68/68 78/78 75/76 58/58 72/72 43/43 49/ /72 68/68 78/78 75/75 58/58 72/72 43/43 49/49 (1,000Hz) 16 72/72 68/68 78/78 75/75 58/58 72/72 43/43 49/49 (20,000Hz) 16 72/72 68/68 78/78 75/75 58/58 72/72 43/43 49/ /83 76/76 73/73 82/82 57/57 79/79 60/60 47/ /83 76/76 73/73 82/82 57/57 79/79 60/60 47/ /83 76/76 73/73 81/81 57/57 79/79 60/60 47/47 (1,000Hz) 16 83/83 76/76 73/73 81/81 57/57 79/79 60/60 47/47 (20,000Hz) 16 83/83 76/76 73/73 81/81 57/57 79/79 60/60 47/ ( 21 ) (mg) [Mean S.D.] (mg) (mg) (mg) (wt/100g) (mg) (mg) (mg) (mg) (mg) (mg) (wt/100g) (mg) (mg) /48 44/44 54/54 51/51 58/58 72/72 43/43 49/49 ( 21 ) 59/59 52/52 49/49 57/57 57/57 79/79 60/60 47/47 p 0.05 p 0.01
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
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
CAS NC(CH 2 ) 4 CN 1,4- C 6 H 8 N c.c d = Pa
1 200117 21512 CAS 111693 110 NC(CH 2 ) 4 CN 1,4- C 6 H 8 N 2 108.14 1 99 2-1. 2 1 295 159 c.c. 550 3 1.7-4.9 20 d 0.965 4 3.73 = 1 0.3 Pa 0.002 mmhg20 2 log Pow-0.32 m/z 41, 1.0 68 0.54 54 0.43 4 Koc9-16
t 492 t mg/l 30 mg/l BOD 95 OH = cm 3 / sec 25 8 OH /cm 3 12 = ph ph
2-1 200169 2740 CAS 110-49-6 1103 2- O H 3 C C O CH 2 CH 2 O CH 3 C 5 H 10 O 3 118.13 200168 2-1 99 2-1. 2 2, 3-65 2, 3 144145 45 o.c. 3 392 3 1.512.3 d19 1.009 2 4.07 = 1 30 Pa 0.23 mmhg20 2 4 log Pow0.10
CHEMOTHERAPY APR. 1984
VOL.32 S-3 CHEMOTHERAPY dihydro-4-oxo-7-(1-piperazinyl)-1, 8-naphthyridine- CHEMOTHERAPY APR. 1984 VOL.32 S-3 CHEMOTHERAPY Table 1 Implantation rates and post- implantation survival rates in females mated
CAS H 3 C C CH 2 C 9 H tert d = hpa
1 200140 35 CAS 98839 1335-2- H 3 C C CH 2 C 9 H 10 118.18 1 99 4-tert- 1. 2-23.2 2 163164 2 54 574 3 0.96.6 20 d 4 0.9082 2 4.07 = 1 2.5 hpa 1.9 mmhg20 2 4 log Pow3.48 3.44 m/z 118, 1.0 103 0.58 91 0.21
フタル酸ジ－ｎ－ブチル（CAS No 84－74－2）
[Butyl benzyl phthalate, CAS No. 85-68-7] C 19 H 20 O 4 312.4 1,2- BBP O C-O-(CH 2 3 CH 3 C-O-CH 2 O 1-35 1 370 1 d 25 = 1.113-1.121 25 1 1.1510-3 Pa (20 1 Log Pow = 4.91 1 BOD=81, 14 0.71 mg/l 1 13 1001,000
橡フタル酸ブチルベンジル.PDF
1 97 7 3 1312 CAS 85 68 7 O BBP 1, 2- C 19 H 20 O 4 312.4 C C O O O (CH 2 ) 3 1 99.9 % 1. 2-35 3 2, 3 370 3, 4 199 d 25 4 1.117 2 10.8 = 1 5 1.15 10-3 Pa 8.6 10-6 mmhg 20 5 253 Pa 1.9 mmhg 200 5 log Pow
橡アジポニトリル.PDF
1 200117 21512( ) CAS 111693 110( ) 1,4- NC(CH 2 ) 4 CN C 6 H 8 N 2 108.14 1) 99 2-1. 2) 1 2) 295 2) 159(c.c.) 3) 550 3) 1.7-4.9 vol % ( ) 3) d 20 0.965 2) 3.73 ( = 1) 4 0.3 Pa (0.002 mmhg) (20) 2) log
98-02.PDF
1 982 2207 CAS 67630 2- H 3 C H 3 C CH OH C 3 H 8 O 60.10 1 99.9 % n- 1. 2-88.5 3 82.5 3 11.7c.c. 455 4 212 d 20 4 0.78505 3 2.1 = 1 4 4.4 kpa 33 mmhg20 4 log Pow0.05 0.07 5 m/z45, 1.0 43 0.19 27 0.17
CHEMOTHERAPY Fig. 1 Body weight changes of pregnant mice treated orally with AM- 715 Day of sestation
CHEMOTHERAPY CHEMOTHERAPY Fig. 1 Body weight changes of pregnant mice treated orally with AM- 715 Day of sestation CHEMOTHERAPY Table 1 Preliminaly test of AM- 715 1): Mean } SD *: Significant difference
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[Styrene dimer, CAS No. 25247-68-1; Styrene trimer, 28213-80-1] -1,2 C 16 H 16 C 24 H 24 208.2 312.3 4 7 2-1,2 CH 2 CH 2 2,4- -1-2,4,6- -1-1,2-1,3,5-760 21,430 g/g 9,590 g/g 2 3 HSDB, 2001 ; 2, 1998; 3
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1 9625 2219 CAS 75569 1, 2-1, 2- H 2 C CH CH 3 C 3 H 6 O 58.08 1 99 % 1. 2 2, 3-112.13 2, 3 34.23-37 449 2.8-37 % 2 d 0 4 0.859 4 d 20 0.8304 2 2, 4 2.00 = 1 53.33 kpa 400 mmhg18 59.33 kpa 445 mmhg20 5
CAS O C O * DOP* DEHP 2- C O O * n- C 24 H 38 O CH 2 CH 2 CH 2 CH 3 CH (CH 2 ) % 2- A BHT , 4
2-1 9628 31307 CAS 117817 2- O C O * DOP* DEHP 2- C O O * n- C 24 H 38 O 4 390.56 CH 2 CH 2 CH 2 CH 3 CH (CH 2 ) 3 1 99 % 2- ABHT 1. 2-55 3 3, 4 386 171 350 6 0.1 % d 20 4 0.9861 4 13.48 0.30410-4 Pa 2.2810-7
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3, 3-1 200019 4800 CAS 91941 1138 3, 3-4, 4 - -3, 3 - H 2 N Cl Cl NH 2 C 12 H 10 C l2 N 2 253.13 1 95 1. 2 3, 4 132-133 402 5 >200 5 700kg/m 3 5 8.73 = 1 5.610-8 kpa 4.210-7 mmhg20 4 6 log Pow3.51 3.57
1 2 D- D- 1206 D- D- -2003 120 /2004 D-FDA GRAS D D- 3 5 5 D- 75 10g/kg 14 40 20 D-101520 90 1520 20%101520 1520 D- 5(D- 2300-6700mg//) () 2024 615 D- 41220g/kg/ 1220g/kg/ 20g/kg/ 1220g/kg/ () 50 D- 10%
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1 967 2482 CAS 50000 CH 2 O 30.03 2952% 12.5 % 1. 2) -92 2) -19.5 2) 5085 3) 424 3) 7.073.0% 4) 20 d 4 0.815 5) 1.03 ( = 1) 5) 1.33 kpa (10 mmhg) (-88.0) 2) log Pow0.35 ( ) 6) 0.35 ( ) 7) 1) m/z 29 ( 1.0
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1 9924 2260 CAS 107186 H 2 C CH CH 2 OH 2- -1- C 3 H 6 O 58.08 1 99 1. 2, 3 3, 4, 5-129 96-97 2 21c.c. 24o.c. 2 6, 7 378 6, 7 2.5-18 d 20 4 0.8540 2, 5 2.00 = 1 2.7 kpa 20 mmhg204.3 kpa 32 mmhg30 4 log
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Table 1 Survival rates of infected mice given antibiotic doses producing peak serum a) S. aurcus Smith Challenge dose :7 ~10 (5% mucin) CFU/mouse. LD50: 1 ~103 (5% mucin) CFU/mouse. Table 2 Survival rates
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1 20019 1527 CAS 1317368 1230 PbO 223.20 1 99 1. 2 888 2 9.53 0.017 g/l 20 3 3 2 2. 10 29,309 t 22,069 t 7,240 t 4 1 3. 1 2 3.5 6 1 µg/l 9.1-24 2 µg/l < 43 6 27,431-70,000 4.5-1,300 13.4-17 31.7 0.48-3,459
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Fig. 1 Mean body weight changes of male rats administered cefaclor orally on fertility study Table. 1 Serum biochemical analysis in male rats administered cefaclor orally on fertility study The values
20mg CTD 2.4 2.4 2.4... 5 2.4.1... 5 2.4.2... 7 2.4.3... 10 2.4.4... 13 2.4.5... 18 2.4.6... 20 3 2.4 2.4 2.4.1 JNS002 ( HSPC) N-(Carbonyl-methoxypolyethylene glycol 2000)-1,2- distearoyl-sn-glycero-3-phosphoethanolamine
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1 20017 1543 CAS 1309644 125 Sb 2 O 3 291.52 1 99 1. 2 655 1,425 2 2 2 3 5.2 5.67 2 2 2. 10 12,161 t 9,753 t 2,408 t 4 3. 1 2 3 4. LC 50 mg/ L EC 50 mg/l * 5 : Selenastrum 6772-h, Sb 2 O 3, : capricornutum
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1 961 31 CAS 71432 C 6 H 6 78.11 1) 99 % 1. 5.5 2) 80.1 2) -11 3) 293563 3) 1.48.0% 3) d 20 0.8786 4) 2.77 ( = 1) 4) 4 13.33 kpa (100 mmhg) (26.9) 2) log Pow2.13 ( ) 5) 2.14 ( ) 6) m/z78 ( 1.0 )77 ( 0.20
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1% 1 mg 1 mg 2 CTD 6 Section 2.6.1 Introduction 2.6.1 H 1 descarboethoxyloratadinesch 34117 7.9 SCH 34117 2.6.1-1 O OC 2 H 5 Cl N N JAN Loratadine (JANINN) ethyl 4-(8-chloro-5,6-dihydro-11H-benzo[5,6]
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(1) CAS 302-01-2 N 2 H 4 32.0 CAS 7803-57-8 2 1) 2.0 2,3) 113.5 2,4) 1.011 (15 ) 2,3) 1.0036 (25 ) 2,4) 2.1 kpa (16 mmhg) (20 ) 3) 1ppm=1.31 mg/m 3 at 25, n- / -1.37 ( ) 3) 5) K b1 8.510-7 K b2 8.910-16
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(1) 1,2- DMP CAS 131-11-3 C 10 H 10 O 4 194.2 2 1) 5.5 2,3) 283.7 2,3) 1.192 (20 ) 4) 133 Pa (1 mmhg) (20 ) 5) 1ppm=7.94 mg/m 3 at 25, n- / 1.56 ( ) 6) 4) ( )3.2 (30 ph 7)11.6 (30 ph 9)25 (18 ph 9) 5)
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