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[Octachlorostyrene, CAS No. 29082-74-4] ( ) OCS C 8 C l8 379.71 0.0018 Pa (25 ) Log Pow = 6.29 ( ) 2) 0.00174 mg/l (25 ) HSDB, 2001; 2 PHYSPROP, 2000. 1

1. 1) (OCS) 9 OCS OCS 75 4 Selden et al., 1997 2 OCS (Selden et al., 1998) Selden et al., 1999 16 OCS 6 8 2 0.20 ppb 0.24 ppb 1.24 ppb OCS Lunde et al., 1977 1969 1985 108 PCBs DDT OCS 1 ng/g (Mes et al., 1990) 25 OCS (< 0.06 ng/g ) 0.5 ng/g Mes, 1992 1986 412 OCS (< 0.102 ng/g ) Mes et al., 1993 1992 497 OCS 497 7% 0.05 ng/g 2.16ng/g Newsome et al., 1995 OCS 136 OCS 1.5 ng/ml < 0.5-9.2 ng/ml Lommel et al., 1985, 1992 2) (1) in vitro -1 OCS 10-4 M 2

CERI, 2001 10-11 -10-5 M ERE CERI, 2001; Yamasaki et al., 2001 (2) -2 OECD SD 20 3 OCS 0 2 20 200 mg/kg/day Yamasaki et al., 2001 OCS SD OCS 0 1,300 1,690 2,190 2,850 3,710 mg/kg 1,300 mg/kg Chu et al., 1982a SD OCS 3 (1) 0 0.5 5 50 500 ppm ( : 0 0.034 0.37 3.5 35 mg/kg/day. : 0 0.043 0.41 4.2 42 mg/kg/day ) 28 Chu et al., 1982a (2) 0 0.05 0.5 5 50 500 ppm ( : 0 0.0036-41 mg/kg/day. : 0 0.0043-47 mg/kg/day ) 90 (Chu et al., 1984) (3) 0 0.005 0.05 0.5 5 50 ppm ( : 0 0.0003 0.003 0.031 0.31 3.1 mg/kg/day. : 0 0.0004 0.004 0.042 0.4 4.4 mg/kg/day ) 12 (Chu et al., 1986) 12 0.05 ppm 0.5 ppm 5 ppm 3) (1) -1 SD 0 1,300 1,690 2,190 2,850 3,710 mg/kg 1,300 mg/kg 2,850 mg/kg 3,710 mg/kg (Chu et al., 1982a) 3

-1 LD 50 > 3,710 mg/kg LC 50 LD 50 LD 50 (2) -3 SD OCS 2)-(2) Chu 1 0 0.5 5 50 500 ppm ( : 0 0.034 0.37 3.5 35 mg/kg/day. : 0 0.043 0.41 4.2 42 mg/kg/day ) 28 (Chu et al., 1982a) 2 0 0.05 0.5 5 50 500 ppm ( : 0 0.0036-41 mg/kg/day. : 0 0.0043-47 mg/kg/day ) 90 (Chu et al., 1984) 3 0 0.005 0.05 0.5 5 50 ppm ( : 0 0.0003 0.003 0.031 0.31 3.1 mg/kg/day. : 0 0.0004 0.004 0.042 0.4 4.4 mg/kg/day ) 12 (Chu et al., 1986) OCS 12 50 ppm 5.0 ppm 0.005-0.5 ppm 5 ppm 0.005-0.5 ppm 5 ppm 50 ppm 5 ppm 50 ppm 90 50 ppm 500 ppm 0.05 ppm 50 ppm / (M/E) 4 (1) -2 OCS (Tarkpea et al., 1985) 4

in vitro -2 * TA98 TA100 S9(-/+) 2-4,000 µg/plate * Tarkpea et al., 1985 (2) -3 SD 12 OCS (Chu et al., 1986) -3 EPA IRIS, 2002 EU ECB, 2000 NTP NTP, 2000 IARC IARC, 2001 ACGIH ACGIH 2001, 2001 5 6 SD (300-350 g) [8-14 C] ( 14 C-OCS) 20 mg/kg OCS 14 C-OCS 40 mg/kg 1 8% 90% 10% Chu et al., 1982b) OCS C57BL/6J (B6) OCS 0 10 50 100 200 mg/kg 5 P450 b5 NADPH-P450 -N- 4- -O- -4-5

Holme and Dybing, 1982a Wistar OCS 0 10 50 100 200 mg/kg 5 P450 NADPH- P450 -N- 4- - O- -4- [a] OCS 250 mg/kg 1 8 Holme and Dybing, 1982b Wistar OCS 200 mg/kg P450 -S- UDP- Holme and Dybing, 1983 12 in vitro OCS 6

ACGIH (2001) American Conference of Governmental Industrial Hygienists. Documentation of the threshold limit values and biological exposure indices. Seventh Edition, Cincinnati, Ohio, 200. Chu, I., Secours, V.E., Villeneuve, D.C., and Valli, V.E., (1982a) Acute and subacute toxicity of octachlorostyrene in the rat. J. Toxicol. Environ. Health, 10, 285-296. Chu, I., Villeneuve, D.C., Secours, V., Benoit, F.M., and Viau, A. (1982b) The tissue distribution, metabolism, and excretion of octachlorostyrene in the rat. Drug Metab. Dispos., 10, 632-635. Chu, I., Villeneuve, D.C., Secours, V.E., Yagminas, A., Reed, B., and Valli, V.E. (1984) Octachlorostyrene: a 90-day toxicity study in the rat. Fund. Appl. Toxicol., 4, 547-557. Chu, I,. Villeneuve, D.C., Secours, V.E., Valli, V.E., Leeson, S., and Shen, S.Y. (1986) Long-term toxicity of octachlorostyrene in the rat. Fund. Appl. Toxicol., 6, 69-77. ECB (2000) Council Directive 67/548/EEC on the approximation of the laws, regulations and administrative provisions relating to the classification, packaging and labeling of dangerous substances ANNEX I (http://ecb.jrc.it/). Holme, J.A. and Dybing, E. (1982a) Induction of liver microsomal cytochrome P 450 and associated monooxygenases by octachlorostyrene in inbred strains of mice. Lack of correlation with the murine Ah locus. Biochem. Pharmacol., 31, 2523-2529. Holme, J.A. and Dybing, E. (1982b) Induction of liver microsomal cytochrome P-450 and associated monooxygenases by octachlorostyrene in the rat. Acta Pharmacol. Toxicol., 50, 41-49. Holme, J.A. and Dybing, E.(1983) Increased cytochrome P 450 independent drug metabolism and mutagen activation in rat liver by octachlorostyrene. Acta Pharmacol. Toxicol., 53, 325-332. HSDB (2001) Hazardous Substances Data Bank, National Library of Medicine, (http://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?hsdb). IARC (2001) IARC Monograph on the Evaluation of Carcinogenic Risks to Humans. http://www.iarc.fr IRIS (2002) Integrated Risk Information System, National Library of Medicine, (http://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?iris). Lommel, A., Kruse, H., and Wassermann, O. (1985) Organochlorines and mercury in blood of a fish-eating population at the River Elbe in Schleswig-Holstein, FRG. Arch. Toxicol., Suppl. 8, 264-268. Lommel, A., Kruse, H., Muller, E., and Wassermann, O. (1992) Organochlorine pesticides, octachlorostyrene, and mercury in the blood of Elb River residents, Germany. Arch. 7

Environ. Contam. Toxicol., 22, 14-20. Lunde, G. and Bjorseth, A. (1977) Human blood samples as indicators of occupational exposure to persistent chlorinated hydrocarbons. Sci. Total Environ., 8, 241-246. Mes, J., Marchand, L., and Davies, D.J. (1990) Organochlorine residues in adipose tissue of Canadians. Bull. Environ. Contam. Toxicol., 45, 681-688. Mes, J. (1992) Organochlorine residues in human blood and biopsy fat and their relationship. Bull. Environ. Contam. Toxicol., 48, 815-820. Mes, J., Davies, D.J., Doucet, J., Weber, D., and McMullen, E. (1993) Levels of chlorinated hydrocarbon residues in Canadian human breast milk and their relationship to some characteristics of the donors. Food. Addit. Contam., 10, 429-441. Newsome, W.H., Davies, D., and Doucet, J. (1995) PCB and organochlorine pesticides in Canadian human milk-1992. Chemosphere, 30, 2143-2153. NTP (2000) U.S. Department of Health and Human Services, Public Health Service, National Toxicology Program, 9th Report on Carcinogens. PHYSPROP (2000) Syracuse Research Corporation Physical Properties Database, (http://esc.syrres.com/interkow/physprop.htm). Selden, A.I., Nygren, Y., Westberg, H.B., and Bodin, L.S. (1997) Hexachlorobenzene and octachlorostyrene in plasma of aluminium foundry workers using hexachloroethane for degassing. Occup. Environ. Med., 54, 613-618. Selden, A.I., Floderus, Y., Bodin, L.S., Westberg, H.B., and Thunell, S. (1998) Porphyrins in aluminium foundry workers exposed to hexachlorobenzene and octachlorostyrene. Organohalogen Compounds, 38, 263-265. Selden, A.I., Floderus, Y., Bodin, L.S., Westberg, H.B., and Thunell, S. (1999) Porphyrin status in aluminum foundry workers exposed to hexachlorobenzene and octachlorostyrene. Arch. Environ. Health, 54, 248-253. Tarkpea, M., Hagen, I., Carlberg, G.E., Kolsaker, P., and Storflor, H. (1985) Mutgenicity, acute toxicity, and bioaccumulation potential of six chlorinated styrenes. Bull. Environ. Contam. Toxicol., 35, 525-530. Yamasaki, K., Takeyoshi, M., Yakabe, Y., Sawaki, M., Imatanaka, M., and Takatsuki, M. (2001) Comparison of reporter gene assay and immature rat uterotrophic assay of twenty-three chemicals. Toxicology, 170, 21-30. CERI ( ) 2001 12,62-67. (2001),, 43, 95-119. 8

-1 in vitro ER ER IC50 >10-4 M ER CERI, 2001 ( ER (E2 1.0 10-9 M) ) ER 10-11 - 10-5 M ER CERI, 2001 ER HeLa (E2 PC50: <10 11 M) 10-11 - 10-5 M ER 10-11 -10-5 M ER Yamasaki et ER al., 2001 HeLa 10-11 - 10-5 M (E2: PC50: <10 9 M) ER: ; E2: 17 - ; PC50: E2 50 ; IC50: E2 50 9

-2 20 0 2 20 200 Yamasaki et al., (SD ) ( 3 mg/kg/day 2001 ) 1 0 1,300 1,690 1,300 mg/kg Chu et al., 1982a (SD ( 2,190 2,850 200 g ) ) 3,710 mg/kg 28 0 0.5 5 50 5 ppm Chu et al., 1982a (SD,119-138g;,127-138g) ( 500 ppm ) ( : 0 0.034 0.37 3.5 35 mg/kg/day : 0 0.043 0.41 4.2 42 mg/kg/day ) 90 0 0.05 0.5 5 0.05 ppm Chu et al., 1984 (SD / ) ( 50 500 ppm ) ( : 0 0.0036-41 mg/kg/day : 0 0.0043-47 500 ppm mg/kg/day ) 0.05 ppm 500 ppm 12 0 0.005 0.05 0.005 ppm Chu et al., 1986 (SD,152-167g;,111-118g) ( 0.5 5 50 ppm ) ( : 0 0.0003 0.003 0.031 0.31 3.1 mg/kg/day : 0 0.0004 5 ppm 0.004 0.042 0.005 ppm 0.4 4.4 mg/kg/day ) 5 ppm 10

-3 ; 28 0 0.5 5 50 500 ppm ( 50 ppm Chu et al., (SD ( : 0 0.034 0.37 3.5 500 ppm) 1982a,119-138g; 35 mg/kg/day,127-138g) : 0 0.043 0.41 4.2 42 mg/kg/day ) ( 5 ppm 0.5 ppm) ( 5 ppm 50 ppm) ( 50 ppm) ( 5 ppm 50 ppm) ( 500 ppm) ( 500 ppm) ( 500 ppm) 90 0 0.05 0.5 5 50 ; Chu et al., (SD / ) 500 ppm ( : 0 0.0036-41 mg/kg/day : 0 0.0043-47 mg/kg/day ) ( 5 ppm) 1984 ( 50 ppm) (500 ppm) (500 ppm) ; ( 0.05 ppm) M/E ( 0.5 ppm) ( 5 ppm) ; M/E ( 50 ppm) P/M ( ) ( 50 ppm) ( 0.05 ppm) ( 500 ppm) ( 5 ppm 50 ppm) ( 500 ppm) ( 500 ppm) 11

12 0 0.005 0.05 0.5 5 ( 0.005 Chu et al., (SD,152-167g; 50 ppm ( : 0 0.0003 0.003 ppm) 1986 ( 50 ppm ),111-118g) 0.031 0.31 3.1 mg/kg/day ( 0.005 ppm) : 0 0.0004 0.004 0.042 0.4 4.4 mg/kg/day ) ( 0.005ppm) (0.005-0.5 ppm) ( 5 ppm) (0.005-0.5 ppm) ( 5 ppm) ( 5 ppm 50 ppm) 12