0774 CAS No. 111-15-9 2014 3 25

0774

1 3 1 3 11 3 12 3 13 3 2 3 3 4 31 4 32 4 4 4 5 1 5 11 5 12 5 13 5 14 5 15 5 16 6 17 6 2 7 21 7 22 7 23 7 1 7 2 8 3 8

3 8 31 8 32 9 33 9 34 9 35 9 36 9 37 10 1 10 2 10 3 10 4 10 41 10 42 11 12 1 12 2 12 3 12 4 13 5 13 6 13 7 13 8 14 81 14 82 14 83 14 84 15 16 1 16 2 16 3 17 4 17

19 20 22

F344/DuCrlCrlj 2 104 3 1 4 50 400 1 6 1 5 104 01250 200 ppm 200 ppm 200 ppm 200 ppm 200 ppm F344/DuCrlCrlj 2 104-1-

(ppm) 0 12 50 200 50 50 50 50 4 4 4 3 6 2 4 1 6 7 3 3 8 9 12 6 C 9 15 8 9 4 3 8 6 43 46 40 44 3 4 2 4 1 0 3 0 Peto Cochran- Armitage (ppm) 0 12 50 200 Peto Cochran- Armitage 50 50 50 50 12 12 12 9 C 2 7 2 6 4 7 3 7 10 6 6 2 * 9 7 5 2 * C 1 1 4 1 0 3 0 1 3 0 2 2 5% * : p0.05 ** : p0.01 Fisher : p0.05 : p0.01 Peto, Cochran-Armitage : p0.05 : p0.01 Cochran-Armitage -2-

1 11 Ethylene glycol monoethyl ether acetate IUPAC 2-2-Ethoxyethyl acetate CAS No. 111-15-9 12 1 CH3-COO-CH2CH2-O-CH2CH3 132.16 13 1 0.97520 156.4 1.2 torr20 23g/100g20 2 EPF1259 2011.2.12011.8.8 DCM1007 2011.8.92012.5.14 TLN6888 2012.5.152013.1.28 () 99.699.7%() -3-

3 31 () M-80B() FTIR-8200PC 2 3 APPENDIX 1-1 32 5890A APPENDIX 1-2 4 () 795 F344/DuCrlCrlj SPF 220 4 1 200 107130g89102g F344/DuCrlCrlj SPF -4-

1 11 12 13 1 6 1 5 104 490 14 1250 200 ppm v/v 3 4 15 4 OECD 451 52 104 13 0743 613 02550100200 400 ppm 2 400 ppm 87% 83%400 ppm 200 ppm -5-

90% 92% 90% 200 ppm 13 100 ppm 13 25 ppm 200 ppm 5012 ppm 4 16 () 17 () GC-14B 15 TABLE A 100100 1.0% -6-

2 21 3 1 4 50 50 10011050 50 20012050 12 ppm 50 11011150 50 21012150 50 ppm 50 12011250 50 22012250 200 ppm 50 13011350 50 23012350 22 1 7 512 23 1 517518 512 APPENDIX 2 232 517 22.50.1518 23.10.1 222 512 22.30.3 232 5515% 517 5510%518 509% 5020% -7-

1 12 (8:0020:00)12 (20:008:00) 1517 79 121 01510Pa 5 340(W)294(D)176(H) mm/5 6 125(W)216(D)176(H) mm/ 5 150(W)216(D)176(H) mm/ 2 () 8-2 CRF-1 30kGy- () 3 () 729-5 3 31 1 1-8-

32 14 1 4 1 104 33 14 1 4 1 104 1 1 34 EDTA-2 APPENDIX 3 (MCV) (MCH)(MCHC) 35 APPENDIX 3 A/G ASTALTLDHALP-GTPCK 36 104 ph -9-

37 1 2 3 10% 1 2 3 3 8 4 41 ppm 3 2 1 g 1 g 1 1 2 1 g 3 4 3-10-

APPENDIX 3 42 Bartlett Dunnett Kruskal-Wallis Dunnett 0 14 2 2 Peto 9Cochran-Armitage Fisher Peto () 34 012 04 5%Peto Fisher 5% 1% Peto 0 1 2 1 3 4 4-11-

1 TABLE B 1, 2 FIGURE 1, 2 104 45 90%12 ppm 40 80%50 ppm 43 86% 200 ppm 47 94% 104 42 84%12 ppm 40 80%50 ppm 40 80% 200 ppm 42 84% 2 TABLE C 1, 2 3 TABLE D 14 FIGURE 3, 4 200 ppm 104 12 ppm 98%50 ppm 97% 200 ppm 94% 200 ppm 104 12 ppm 97%50 ppm 96% 200 ppm 93% -12-

4 TABLE E 14 FIGURE 5, 6 200 ppm 200 ppm 5 TABLE F 1, 2 MCV MCH 200 ppm 200 ppm 200 ppm other 200 ppm 6 TABLE G 1, 2 -GTP 200 ppm 50 ppm 200 ppm LDH 200 ppm 50 ppm 200 ppm 7 TABLE H 1, 2 ph 200 ppm -13-

8 81 TABLE I 16 82 TABLE J 1, 2 TABLE K 1, 2 200 ppm 200 ppm 200 ppm 50 ppm 200 ppm 12 ppm 83 TABLE L 16 TABLE M 1, 2 TABLE N 1, 2 Peto Cochran-Armitage Fisher TABLE O 1, 2 TABLE P 1, 2 12 1 2 200 ppm 200 ppm -14-

200 ppm 2 12 ppm C 200ppm 1 Cochran-Armitage Fisher 200 ppm Cochran-Armitage Fisher 200 ppm Fisher 200 ppm 2 200 ppm 200 ppm 200 ppm 84 TABLE Q 1, 2-15-

2 01250 200 ppm 1 200 ppm 12 ppm 98%50 ppm 97% 200 ppm 94% 12 ppm 97%50 ppm 96% 200 ppm 93% 200 ppm 200 ppm 2 IARC 10 10% NCI 11 10% Maximum Tolerated Dose (MTD) 200 ppm 94% 93% 200 ppm MTD -16-

3 -GTP 200 ppm 50 ppm 200 ppm LDH 200 ppm 50 ppm 200 ppm ph 200 ppm 200 ppm 50 ppm 200 ppm 200 ppm 200 ppm 200 ppm 200 ppm 104 12200 ppm 13141516 13 6 200 ppm 400 ppm 100 ppm 200 ppm 50 ppm 13 2 4-17-

IARC ( 17)Slesinski 18 TA98TA100 TA102TA104TA1535TA1537 WP2uvrAWP2uvrA/pKM101 1.225000 g/plate S9 Slesinski Ames CHO HGPRT CHO SCESwiss-Webster CHO S9 CHO in vitro in vivo in vitro -18-

F344/DuCrlCrlj 2 104-19-

1. ACGIH. 2001. 2-Ethoxyethyl Acetate. Documentation of the Threshold Limit Values and Biological Exposure Indices. Cincinnati, OH: American Conference of Governmental Industrial Hygienists. [CD-ROM 2007]. 2. McLafferty FW, ed. 1994. Wiley Registry of Mass Spectral Data. 6th ed. New York, NYJohn Wiley and Sons. 3. (). 2009.,. 4.. 1997.. 144 9 3 11. 5. OECD. 2009. OECD Guideline for Testing of Chemicals 451 "Carcinogenicity Studies". Paris: Organisation for Economic Co-operation and Development. 6.. 2011. 13. :. 7.. 1986.. 14: 7285-7302. 8. Nagano K, Katagiri T, Aiso S, Senoh H, Sakura Y, Takeuchi T. 1997. Spontaneous lesions of nasal cavity in aging F344 rats and BDF1 mice. Exp Toxic Pathol. 49: 97-104. 9. Peto R, Pike MC, Day NE, Gray RG, Lee PN, Parish S, et al. 1980. Guidelines for simple, sensitive significance tests for carcinogenic effects in long-term animal experiments. In: Long-Term and Short-Term Screening Assays for Carcinogens: A Critical Appraisal. Lyon: IARC. IARC Monographs Suppl 2: 311-426. 10. Bannasch P, Griesemer RA, Anders F, Becker R, Cabral JR, Della Porta G, et al. 1986. Long-term assays for carcinogenicity in animals. In: Long-Term and Short-Term -20-

Assays for Carcinogens: A Critical Appraisal. (Montesano R, Bartsch H, Vainio H, Wilbourn J, Yamasaki H. eds.). Lyon: IARC. IARC Scientific Publications No. 83: 13-83. 11. Sontag JM, Page NP, Saffiotti U. 1976. Guidelines for carcinogene bioassay in small rodents. NCI-CG-TR-1. DHEW Publication No.(NIH)76-801. Bethesda,MD: National Cancer Institute. 13-15. 12. Nagano K, Katagiri T, Aiso S, Senoh H, Sakura Y, Takeuchi T. 1997. Spontaneous lesions of nasal cavity in aging F344 rats and BDF1 mice. Exp Toxic Pathol. 49: 97-104. 13. Buckley LA, Morgan KT, Swenberg JA, James RA, Hamm TE Jr, Barrow CS. 1985. The toxicity of dimethylamine in F-344 rats and B6C3F1 mice following a 1-year inhalation exposure. Fundam Appl Toxicol. 5: 341-352. 14. Monticello TM, Morgan KT, Uraih L. 1990. Nonneoplastic nasal lesions in rats and mice. Environ Health Perspect. 85: 249-255. 15. Renne R, Brix A, Harkema J, Herbert R, Kittel B, Lewis D, March T, Nagano K, Pino M, Rittinghausen S, Rosenbruch M, Tellier P, Wohrmann T. 2009. Proliferative and nonproliferative lesions of the rat and mouse, respiratory tract. Toxicol Pathol 37: 5S-73S. 16. Wolf DC, Morgan KT, Gross EA, Barrow C, Moss OR, James RA, et al. 1995. Two-year inhalation exposure of female and male B6C3F1 mice and F344 rats to chlorine gas induces lesions confined to the nose. Fundam Appl Toxicol. 24: 111-131. 17.. 2000. 2.. 63-65. 18. Slesinski RS, Guzzie PJ, Tyler TR. 1988. Cytotoxicity and genotoxic potential of ethylene glycol monoethyl ether acetate (EGEEAc) in a battery of short term test systems. Environ Mol Mutagen, 11 Suppl 11: 97-21-

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