28 KOREAN INDUSTRIAL HEALTH ASSOCIATION Deep Information CARBON DISULFIDE 연세대학교보건대학원교수 / 김치년 CAS 번호 : 75-15-0 동의어 : Carbon disulphide, Carbon bisulfide, Carbon bisulphide, Carbon sulfide, Sulphocarbonic anhydride, Carbon bisulfur, Dithiocarbonic anhydride, Weeviltox 분자식 : CS 2 BEI 권고 분석대상물질 채취시간 BEI Notation 2-Thioxothiazolidine-4-carboxylic acid(ttca) in urine End of shift 0.5 mg/g creatinine Ns, B 생물학적노출지수 (Biological Exposure Index) 의근거 이황화탄소농도 1 ppm(3.13 mg / m3 ) 에직업적으로노출된근로자에서발생하는건강상악영향에는운동 및감각신경세포의전도속도감소등이있다. 권고된 BEI 0.5 mg TTCA/g creatinine 은이황화탄소 TLV 1 ppm 을근거로하였다. TLV 노출기준은이황화탄소노출에따라발생되는건강상악영향으로부터 근로자를보호하기위해설정되었다. TLV 는주로신경학적영향유발종말점에근거하지만, 이황화탄소 노출로인한심혈관계, 생식, 눈, 신장등전신의악영향으로부터보호하기위하여권고하였다. Dithiocarbamates 는이황화탄소와아미노산과반응하여형성된대사산물이며신경독성영향에일정 부분기여한다. 공기중이황화탄소노출과작업종료후소변중 2-thioxothiazolidine-4-carboxylic acid(ttca) 사이에상관관계가확인되었다. 공기중이황화탄소평균농도 3 ppm 으로노출된경우소변 중 TTCA 의배설반감기가약 6 시간과 68 시간인두개의양상이관찰되었고, 일반적인축적은작업시간 종료후반복노출로인해발생할수있다.
비직업적노출군인평균배경농도수준은 0.09 mg TTCA/g creatinine 이며, 이수준은 BEI인 0.5 mg TTCA/g creatinine 의약 20% 로관찰되었다. 따라서비직업적노출요인 ( 음식물섭취등 ) 이소변중 TTCA 배설에영향을미칠수있어 BEI notation 에배경농도참조에해당하는 B 가표기되었다. TTCA는이황화탄소노출이외의살충제노출에서도배설될수있어비특이적의미인 Ns notation 을권고하였다. 농도단위변환 소변중이황화탄소 1 mg/l = 0.013 mmol/l; 1 mmol/l = 76.1 mg/l 소변중 2-Thioxothiazolidine-4-carboxylic acid (TTCA) 1 mg/g creatinine = 0.70 mmol/mol creatinine 1 mmol/mol creatinine = 1.4 mg/g creatinine 1 mg/l = 6 μmol/l 1 mmol/l = 163 mg/l 용도와물리화학적특성 이황화탄소는실온에서투명하며, 노란색의액체이다. 이황화탄소는클로로폼과같은달콤한냄새를유발하며, 공업용으로사용되는이황화탄소의경우강하고, 불쾌한황화수소냄새를유발한다 (ATSDR, 1996). 포화증기압력은 20 C 에서 297 torr(39.6 kpa) 이다 (ATSDR, 1996). 이황화탄소는혈액과지방, 물에는잘용해된다 (22 C 일때 2.3 g/l). 피 / 가스분배계수는 2.4이며 (Ghittori 등, 1998) 옥탄올 / 물분배계수 (log Pow) 는대략 2(range 1.84 ~ 2.16) 정도이다 (ATSDR, 1996). 이황화탄소의전세계의생산량은 100 만톤으로추정된다 (Newhook, Meek, 2002). 이황화탄소의 주요산업용도는비스코스레이온제조, 셀로판필름, 사염화탄소, 크잔토젠, 아황산나트륨, 메르캅탄, 티오우레아, 미네랄부유제, 고무화학제, 염료, 농약, 왁스및가용성오일, 고무, 인, 브롬및요오드, 셀레늄, 일염화황등이있다 (ATSDR, 1996; Newhook and Meek, 2002). 이황화탄소는신선한과일 보관, 식품포장시접착제조성물, 성장억제제용매추출시, 곤충및선충의토양훈증제로서미국 근로자들에게노출된다 (ATSDR, 1996; NSC, 2007). 29 산업보건
30 KOREAN INDUSTRIAL HEALTH ASSOCIATION Deep Information NIOSH 는미국내대략 46,000 명의근로자가이황화탄소에노출되었다고추정하고있다 (NIOSH, 2007). 그러나, 실제노출근로자수는훨씬높을수있으며, 노출인구조사시이황화탄소를포함하는화학물질사용근로자는포함시키지않았다. 비직업적으로가능한노출 일반인구집단은주로외부공기중함유되어있는이황화탄소에노출된다. 이황화탄소는공기, 물, 퇴적물, 토양같은천연자원 ( 토양내침전미생물, 화산, 식물, 숲, 잔디등에서화재 ) 에서발생될수있다 (Newhook & Meek, 2002). 이황화탄소는또한식물과토양내 dithiocarbamates 와같은일부살충제의대사중에생성된다. 담배연기로도환경에배출된다 (Horton & Guerin, 1974). 2002 년과 2004년사이, 미국에서는제조및가공시설내에서점오염원의대기배출로인해연간평균 2천 7백만파운드의이황화탄소가대기중에배출되고있다고발표했다 (U.S. EPA, 2006). 산업단지근처에서환경측정시가장높은공기중농도는 156 μg / m3이었으며, 특히천연가스처리시설및황이함유된천연가스배출굴뚝에서측정시높게나타났다 (Legge 등, 1990 년 ). 옥외환경측정시미국과유럽에서이황화탄소가각각 1.1 μg / m3, 1.2 μg / m3으로검출되었다 (ATSDR, 1996; Maroulis & Bandy, 1980; Phillips, 1992; Sandalls & Penkett, 1977). 공기중이황화탄소의반감기는 1주에서 2주정도되며, 이는주로수산기와반응하여공기중에서제거된다 (Wine 등, 1981). 빠른속도로생물에의해대사되어생물내농축되거나농축물로존재하지않는다 (Beauchamp 등, 1983). 제초제인 Captan(Krieger & Thongsinthusak, 1993; van Welie 등, 1991) 의노출, 안티- 알코올약물 disulfiram(antabuse) 의노출, 일부고무가소제및 dithiocarbamates( 예, Thiram[tetramethylthiuram disulfide]) 의노출은이황화탄소로대사되고체내에서이황화탄소및그대사산물을배설한다 (van Doorn 등, 1982). Simon 등은비직업적으로노출된개인에서의평균배경농도가 0.09 mg TTCA/g creatinine 이라고보고하였다 (Simon 등, 1994). 이수준은 BEI인 0.5 mg TTCA/g creatinein 의약 20% 정도수준이라고제안하였다. 따라서직업적으로이황화탄소에노출된근로자의소변중 TTCA 를측정하여결과해석을할때에는기타외부적인요인에의한영향을고려해야한다.
흡수 (Absorption) 이황화탄소는광범위하게흡입, 피부, 구강경로를통해흡수된다. 이황화탄소흡수는특히간, 뇌등의 친유성조직과기관에의해서몸전체에분배된다. 이황화탄소는지질에용해되기도하며, 아미노산과 단백질에대해친화력을가지고있다. 따라서체내에축적될수있는성질을가지고있다. 페 (Pulmonary) 공기중이황화탄소를흡입한사람에서신속하고광범위한흡수가관찰되었다. 노출시작시폐잔류율은약 80% 이며, 1 시간이내에농도는약 45% 로지속적으로감소하였다 (Beauchamp 등, 1983; Harashima & Masuda, 1962; Petrovic & Duric, 1966; WHO, 1979). 경피 (Dermal) 이황화탄소는사람의피부를통해쉽게흡수된다. 이황화탄소농도가 0.33 g/l ~ 67 g/l 함유되어있는수용액에한시간동안지원자의손을담그는피부침투율을측정한결과 0.23 mg / cm2 /h에서 0.79 mg / cm2 /h이었다(dutkiewicz & Baranowska, 1967). 더높은피부흡수는이전의연구에서실시되었다 (Baranowska, 1965). 물리화학적특성또한상당한경피흡수율 ( 흡수율 : 0.89 mg / cm2 /h) 을예측할수있다. 이황화탄소증기및액체의광범위한경피흡수실험은동물실험연구에서확인되었다 (Cohen 등, 1958; Izmerov, 1983). 경피흡수가흡입노출에의해발생된악영향을증가시킨다고유용한증거자료에의해제안되었다 (Grandjean, 1990). 위장 (Gastrointestinal) 인간을대상으로실시한이황화탄소경구노출연구는찾을수없었다. 그러나흰쥐를대상으로 10 mg/kg 14C- 이황화탄소를위내투여하였을때, 빠르게흡수되는결과를관찰할수있었다 (De Matteis & Seawright, 1973). 참고문헌 1. ATSDR (Agency for Toxic Substances and Disease Registry): Toxicological profile for carbon disulfide (update), p. 219. US Department of Health and Human Services, Public Health Service. ATSDR, Atlanta, GA (1996). 2. Baranowska B: [Appraisal of the skin as a route of resorption of carbon disulfide] German. Int Arch Arbeitsmed 21:362 368 (1965). 3. Beauchamp RO Jr; Bus JS; Popp JA; et al.: A critical review of the literature on carbon disulfide toxicity. Crit Rev Toxicol 11:169 278 (1983). 4. Cohen AE; Paulus HJ; Keenan RG; et al.: Skin absorption of carbon disulfide vapor in rabbits. I. Associated changes in blood protein and zinc. AMA Arch Ind Health 17:164 169 (1958). 31 산업보건
32 KOREAN INDUSTRIAL HEALTH ASSOCIATION Deep Information 5. De Matteis F; Seawright AA: Oxidative metabolism of carbon disulphide by the rat. Effect of treatments which modify the liver toxicity of carbon disulphide. Chem Biol Interact 7:375 388 (1973). 6. Dutkiewicz T; Baranowska B: The Significance of Absorption of Carbon Disulfide through the Skin in the Evaluation of Exposure. In: Toxicology of Carbon Disulfide, pp 50 51, H Brieger, J Teisinger (Eds). Excerpta Medica Foundation, Amsterdam (1967). 7. Ghittori S; Maestri L; Contardi I; et al.: Biological monitoring of workers exposed to carbon disulfide (CS2) in a viscose rayon fibers factory. Am J Ind Med 33:478 484 (1998). 8. Grandjean P: Skin Penetration: Hazardous Chemicals at Work, 187 pp. Taylor & Francis Ltd, London (1990). 9. Harashima S; Masuda Y: Quantitative determination of absorption and elimination of carbon disulfide through different channels in human body. Int Arch Gewerbepathol Gewerbehyg 19:263 269 (1962). 10. Horton AD; Guerin MR: Quantitative determination of sulfur compounds in the gas phase of cigarette smoke. J Chromatogr 90:63 70 (1974). 11. Krieger RI; Thongsinthusak T: Captan metabolism in humans yields two biomarkers, tetrahydrophthalimide (THPI) and thiazolidine-2- thione-4-carboxylic acid (TTCA) in urine. Drug Chem Toxicol 16:207 225 (1993). 12. Legge AH; Nosal M; Peake E; et al.: Air quality of an area proximal to anthropogenic emissions. In: Acidic deposition: Sulphur and nitrogen oxides the Alberta Government/Industry Acid Deposition Research Program (ADRP), pp 249 345, AH Legge, SV Krupka (Eds). Lewis Publishers, Chelsea, MI (1990a). 13. Legge AH; Peake E; Strosher M; et al.: Characteristics of the background air quality. In: Acidic deposition: Sulphur and nitrogen oxides the Alberta Government/Industry Acid Deposition Research Program (ADRP), pp 129 240, AH Legge, SV Krupka (Eds). Lewis Publishers, Chelsea, MI (1990b). 14. Newhook R; Meek ME: Concise International Chemical Assessment Document 46: Carbon Disulfide, p 49. World Health Organization, Geneva (2002). 15. NIOSH (National Institute for Occupational Safety and Health): National Occupational Exposure Survey (1981-1983). NIOSH, Cincinnati, OH (2007). 16. NSC (National Safety Council): Carbon Disulfide Chemical Backgrounder. National Safety Council (2007). 17. Petrovic D; Duric D: [Carbon disulfide in the air exhaled by exposed workers] Serbian. Arh Hig Rada Toksikol 17:159 163 (1966). 18. Phillips M: Detection of carbon disulfide in breath and air: a possible new risk factor for coronary artery disease. Int Arch Occup Environ Health 64:119 123 (1992). 19. Sandalls FJ; Penkett SA: Measurements of carbonyl sulphide and carbon disulphide in the atmosphere. Atmospheric Environment 11:197 199 (1977). 20. Simon P; Nicot T; Dieudonne M: Dietary habits, a non negligible source of 2-thiothiazolidine-4-carboxylic acid and possible overestimation of carbon disulfide 21. exposure. Int Arch Occup Environ Health 66:85 90 (1994). 22. US EPA (US Environmental Protection Agency): Toxics Release Inventory (TRI) Program: Carbon Disulfide. US EPA, Washington, DC (2006). 23. van Doorn R; Delbressine LP; Leijdekkers CM; et al.: Identification and determination of 2-thiothiazolidine-4-carboxylic acid in urine of workers exposed to carbon disulfide. Arch Toxicol 47:51 58 (1981a). 24. van Doorn R; Leijdekkers CM; Henderson PT; et al.: Determination of thio compounds in urine of workers exposed to carbon disulfide. Arch Environ Health 36:289 297 (1981b). 25. van Doorn R; Leijdekkers CM; Nossent SM; et al.: Excretion of TTCA in human urine after administration of disulfiram. Toxicol Lett 12:59 64 (1982). 26. van Welie RT; van Duyn P; Lamme EK; et al.: Determination of tetrahydrophtalimide and 2-thiothiazolidine-4-carboxylic acid, urinary metabolites of the fungicide captan, in rats and humans. Int Arch Occup Environ Health 63:181 186 (1991). 27. WHO (World Health Organization): Environmental Health Criteria 10: Carbon Disulfide. WHO, Geneva (1979). 28. WHO (World Health Organization): Recommended healthbased limits in occupational exposure to selected organic solvents. WHO Tech Rep Ser 664:1 81 (1981). 29. Wine PH; Chameides WL; Ravishankara AR: Potential role of CS photooxidation in tropospheric sulfur chemistry. Geophysical Res Lett 8:543 546 (1981). 30. WHO (World Health Organization): Environmental Health Criteria 10: Carbon Disulfide. WHO, Geneva (1979). 31. WHO (World Health Organization): Recommended healthbased limits in occupational exposure to selected organic solvents. WHO Tech Rep Ser 664:1 81 (1981). 32. Wine PH; Chameides WL; Ravishankara AR: Potential role of CS photooxidation in tropospheric sulfur chemistry. Geophysical Res Lett 8:543 546 (1981).