08-07-장상환

Transcription

1 대한산업의학회지제 20 권제 3 호 (2008 년 9 월 ) Korean J Occup Environ Med, 2008;20(3): 제조업근로자들의혈청 Perfluorooctanoic Acid (PFOA) 농도와생활습관및직업적관련요인 인제대학교부산백병원산업의학과, 환경 산업의학연구소, 인제대학교약물유전체연구센터 1) Abstract 장상환 이채관 김대환 김권복 1) 안진홍 김휘동 이창희 김정호 이종태 Lifestyle and Work related Factors Associated with Serum PFOA among Workers at Manufacturing Companies Sang Hwan Jang, Chae Kwan Lee, Dae Hwan Kim, Kwon-Bok Kim 1), Jin Hong Ahn, Hwi Dong Kim, Chang Hee Lee, Jeong Ho Kim, Jong Tae Lee Department of Occupational and Environmental Medicine & Institute of Environmental and Occupational Medicine, BusanPaik Hospital, Inje University, Department of Pharmacology and PharmacoGenomics Research Center, Inje University 1) Objectives: The objective of this study was to determine serum perfluorooctanoic acid (PFOA) concentrations and to investigate the relationship of lifestyle, health status and work-related factors among workers at manufacturing companies with possible occupational exposure to PFOA. Methods: The study subjects were 315 workers (male 203, female 112) of manufacturing companies with possible exposure to PFOA from August to December, A questionnaire was administered to investigate lifestyle and work-related factors. Serum PFOA concentrations were analyzed by LC- MS/MS, and liver function and total cholesterol were also tested. Results: Serum PFOA concentrations ranged from 1.0 to 40.9 ng/ml (mean 8.0 ng/ml). Serum PFOA concentrations increased with age. Male workers had higher PFOA concentration than female workers (male 9.0 ng/ml; female 6.3 ng/ml). According to stepwise multiple regression analysis, factors significantly associated with PFOA concentration were male, being older, higher total cholesterol, and lower body mass index. Adjusted for age and gender by logistic regression, dyeing and finishing textiles had significantly higher odds ratio (OR) of 6.16, and moulding patterns, moulds and industrial patterns (OR=4.84), sections for ships (OR=3.87), and plastics synthetic leather (OR=10.05) had marginally significantly high odds ratios. Conclusions: This study demonstrated the factors affecting serum PFOA concentration of workers at manufacturing companies. Further study is needed to ensure the effect of occupational exposure on serum PFOA concentration. Key Words: PFOA, Related factors, Workers, Manufacturing companies < 접수일 : 2008년 7월 24일, 채택일 : 2008년 8월 7일 > 교신저자 : 이채관 (Tel: ) lck3303@hanmail.net 이논문은 2007년도정부재원 ( 교육인적자원부학술연구조성사업비 ) 으로한국학술진흥재단의지원을받아연구되었음 (KRF D00221). 233

2 대한산업의학회지제 20 권제 3 호 2008 년 서 론 의관련성등을조사하고자하였다. 과불화화합물 (perfluorochemicals; PFCs) 은인공화합물이며우리주변에서프라이팬의코팅제인테플론의원료, 카펫이나의류의방수마감재등으로광범위하게사용된다. 그리고각종포장지와건축자재의표면마감재, 냉장고의냉매, 화장품, 샴푸, 주방재료, 반도체등에도사용되며, 자동차, 기계, 화학, 전자, 의약등거의모든산업분야에사용되고있으며추정되는노출빈도또한높은편이다. Perfluorooctanoic acid (PFOA) 는대표적인과불화화합물중하나로써화학적으로안정성이높고생체내에서대사율이낮아쉽게축적될수있다. 동물실험에서는간과췌장및고환등에서선종이발생하였고, 발암성및생식발생독성등도보고되었다 1). PFOA는경구및호흡기를통해주로흡수되며, 피부흡수는적게일어난다. 생체내에흡수된후에는간과혈장에주로분포하며, 일부는신장과폐에분포한다. 인체의약물역동학적기전은아직까지자세히밝혀져있지않으나인체내에서 90% 이상의 PFOA가혈청알부민과결합된상태로존재하며 2) 혈장내반감기는약 3.8 년으로알려져있다 3). 인체의 PFOA의주요한노출경로는식음용수를통한노출, PFOA를함유한생활용품을통한노출, 그리고직업적노출등이다. 여러국가들에서일반인들보다직업적노출근로자들에서더높은농도의혈청 PFOA가검출되었고 4-7), 노출양및기간과관련이있었다 8). 미국과유럽및아시아의수개국을비교한 Kannan 등 5) 의연구에서는한국인여성의혈청 PFOA 농도가상대적으로높게검출된바있다. 대표적인 PFOA 함유제품인테플론의제조회사중하나였던 3M사의조사에의하면 PFOA 제조부서에서 10 년이상종사한근로자들에서 PFOA 관련이없는부서의근로자들보다전립선암의발생빈도가증가하였고, 남성에서생식호르몬의작용을교란시킬가능성이있는것으로추정하였다 9). 직업적노출자들의간및혈청지질에관한 Olsen 등 10) 과 Emmett 등 11) 의단면적연구에서는 PFOA 노출과간독성사이에유의한차이가없다고보고한바있다. 그러나최근 Sakr 등 7) 의연구에서는 PFOA 노출과혈청콜레스테롤및간효소사이에양의상관성이있는것으로조사되어상반된결과를제시하였다. 지금까지국내에서 PFOA 노출과인체영향에관한연구는부족한실정이며, 특히직업적노출근로자들을대상으로한연구는거의이루어진바가없다. 따라서본연구에서는 PFOA에노출이가능한제조업사업장의근로자들을대상으로혈청 PFOA의농도와생활습관및직업적노출관련요인, 간기능검사및지질검사결과와 대상및방법 1. 연구대상본연구는 2007년 8월부터 12 월까지부산지역 1개대학병원산업의학과에서근로자건강진단을받은제조업사업장근로자남자 203명, 여자 112명의총 315명을대상으로하였다. 대상사업장은문헌고찰 12,13) 을통하여 PFOA에노출될가능성이있는업종중에서선정하였다. 업종분류는한국표준산업분류 ( 통계청 ) 에따랐으며, 금속원료재생업 (recovery of metal waste and scrap), 기타방적업 (spinning of other textile fibers), 기타전자부품제조업 (other electronic components), 도장및기타피막처리업 (plastic laminating, coating and other surface processing products), 동물용사료및조제식품제조업 (livestock feeds and prepared animal feeds), 방송및무선통신장비제조업 (broadcasting and wireless telecommunication apparatuses), 분사기및소화기제조업 (spraying, projecting and dispersing machines), 선박구성부분품제조업 (sections for ships), 섬유제품염색, 정리및마무리가공업 (dyeing and finishing textiles), 신발부분품제조업 (parts of footwear), 인쇄업 (printing), 자동차부품제조업 (parts and accessories for motor vehicles and engines), 전자부품제조업 (electronic components), 주형및금형제조업 (moulding patterns, moulds and industrial patterns), 플라스틱적층, 도포및기타표면처리제품제조업 (coating and similar treatment of metals), 플라스틱합성피혁제조업 (plastics synthetic leather), 합성고무및플라스틱물질제조업 (synthetic rubber and of plastics in primary forms), 합성수지및기타플라스틱물질제조업 (synthetic resin and other plastic materials) 등의 18개업종의 26개사업장이었다 14). 2. 연구방법 1) 설문조사설문지는사회인구학적특성, 직업적노출요인및비직업적노출요인등으로구성하였는데, 사회인구학적요인에는성별, 연령, 흡연및음주여부등의변수를, 직업적노출요인으로는업종, 취급물품, 근무부서및근무기간등의변수를, 그리고비직업적노출요인으로생활습관및 234

3 장상환등 제조업근로자들의혈청 Perfluorooctanoic Acid (PFOA) 농도와생활습관및직업적관련요인 생활용품사용에서 PFOA 노출과관련이있는인스턴트식품섭취빈도, 종이컵, 컵라면등의 1회용음식용기사용빈도및모발용샴푸사용빈도등을포함하였다. 설문조사는사전에훈련된설문조사자가연구취지를설명하고근로자의동의를받은후개별적으로직접설문조사하였다. 2) 혈청간기능및지질검사혈청 PFOA 농도와간기능및지질에대한인체영향과의관련성을조사하기위하여 aspartate aminotransferase (AST, IU/L), alanine aminotransferase (ALT, IU/L), gamma glutamyl transferase (γ-gtp, IU/L) 및 total cholesterol (mg/dl) 등을검사하였다. 3) 체질량지수 (body mass index: BMI) 체질량지수는 2002년세계보건기구 (WHO) 의 IOTF (International Obesity Task Force) 에의해작성된아시아태평양기준 15) 에따라정상 (BMI<23), 과체중 (23 BMI<25) 및비만 (BMI 25) 으로범주화하여분석하였다. 4) 혈청 PFOA 농도의분석 PFOA의분석은 Fromme 등 (2007) 과 Midasch 등 (2006) 의방법에따라시행하였다 4,16). 250 μl의적출한혈청에 700 μl의아세토니트릴 (acetonitrile) 용액과내부표준용액을가하고혼탁한후원심분리 (1,500 g, 15 min) 한후 30 μl의상층액을 LC-MS/MS (API Qtrap 4000) 에주입하였다. LC-MS/MS 운영조건은 Table 1과같다. 그외검량선작성과정도관리를위해 PFOA 농도 0.5 ng/ml 이하인소태아혈청 (fetal bovine serum) 을사용하였으며, 검량선범위는 ng/ml, r> 이었다. 3. 자료분석 연구대상자의사회인구학적요인, 생활습관요인, 그리고업종별로혈청 PFOA의농도를비교하였다. 혈액검사결과혈청지질및간기능검사와혈청 PFOA 농도와의관계를파악하기위하여 PFOA 농도를사분위수로범주화하여경향성이있는지에관해 ANOVA를시행하였다. 그리고혈청 PFOA 농도에영향을주는요인들을조사하기위하여각특성별로통계적인유의성이있는요인들을선별하였고, 이요인들을포함하는모델을구축하여다중회귀분석을시행하였다. 업종별노출수준의차이를조사하기위하여혈청 PFOA 농도의중앙값을기준으로이분화하여종속변수로설정하고, 업종을독립변수로하여로지스틱회귀분석을실시하였다. 통계분석은 SPSS 14K 프로그램을이용하였으며, 통계적유의수준은 0.05로하였다. 결 1. 혈청 PFOA 농도와사회인구학적요인및생활습관과의관련성 조사대상의혈청 PFOA 농도의산술평균은전체가 8.0 ng/ml( 범위 : 1.0~40.9 ng/ml) 이었으며, 남자가 9.0 ng/ml( 범위 : 1.0~40.9 ng/ml), 여자가 6.3 ng/ml( 범위 : 2.4~15.0 ng/ml) 로남자가여자보다통계적으로유의하게높았다 (p<0.001)(fig. 1). 과 Table 1. Analytical condition of PFCs Column Eclipse Zorbax XDB-C8 analytical column (Agilent Technology Palo Alto, CA USA, mm 2 ) Retention time Mobile phase Flow rate Gradient Detection -2 min 75% acetonitrile, 24% water, 1% acetic acid, v/v in water 0.3 ml/min 2-7 min 1% acetic acid, 75% acetonitrile, 24% water 0.3 ml/min 99% acetonitrile, 1% acetic acid 7-11 min 99% acetonitrile, 1% acetic acid 1.0 ml/min min 75% acetonitrile, 24% water, 1% acetic acid 1.0 ml/min min 75% acetonitrile, 24% water, 1% acetic acid 0.3 ml/min Negative ionization MS/MS mode, multiple reaction monitoring (MRM). PFOA: m/z (C 3F 7- ) PFOS: m/s 499 0(SO 3- ) 1, 2-13 C 2-PFOA, m/z (C 6F CF 2- ). 235

4 대한산업의학회지제 20 권제 3 호 2008 년 Fig. 1. Distribution of serum PFOA concentration PFOA 농도가높게나타났으나 (p=0.001), 남녀를층화한후에는통계적유의성이없었다. 체질량지수가높을경우혈청 PFOA의농도가통계적으로유의하게낮았다 (p=0.049). 남녀를층화한후남자에서통계적유의성이있었으며 (p=0.042), 여자의경우유의성이없었다. 2. 혈청 PFOA 농도와간기능및혈청지질농도와의관련성 Fig. 2. Distribution of serum PFOA concentration by age and gender 연령별및근무기간별혈청 PFOA의농도분포결과는 Table 2와같았으며, 성과연령별 PFOA 농도분포는 Fig. 2와같았다. 연령이증가함에따라혈청 PFOA 농도가증가하는경향을보였으며 (p=0.002). 남녀를층화하여분석하였을경우도유사한결과를나타내었다 ( 남자, p=0.003 여자, p=0.001). 근무기간이증가함에따라혈청 PFOA 농도가증가하였으며 (p<0.001), 남녀를층화하여분석하였을때에도유사한결과를나타내었다 ( 남자, p<0.001; 여자, p=0.017). 사회인구학적요인, PFOA 노출과관련이있는생활용품사용빈도, 그리고 BMI 와혈청 PFOA농도와의관련성분석결과는 Table 3과같았다. 전체조사대상자에서현재흡연자의혈청 PFOA 농도가비흡연자보다높았으나 (p=0.002), 남녀를층화하여분석할경우통계적인유의성이없었다. 알코올섭취의경우에도유사한결과를나타내었다. 인스턴트식품섭취빈도의경우유의한차이가없었다. 1회용포장용기사용의경우도사용빈도에따른혈청 PFOA 농도의차이를발견할수없었다. 모발용샴푸사용의경우, 사용빈도가낮은군에서혈청 혈청 PFOA 농도와혈청지질및간기능검사결과와의관련성을조사하기위하여혈청 PFOA 농도를분포에따라사분위수로나누어분석한결과는 Table 4와같았다. 혈청 PFOA 농도가증가함에따라 γ-gtp만이유의한차이가있었으며 (p<0.001), 총콜레스테롤, AST 및 ALT 는유의한차이가없었다. 성별로나누어층화분석한결과여자의경우혈청 PFOA농도가증가함에따라총콜레스테롤 (p=0.004) 과 γ-gtp (p=0.002) 가통계적으로유의하게증가하였으나, 남자에서는유의한차이가없었다. 위결과를근거로혈청 PFOA의농도에영향을주는요인들을파악하기위해다중회귀분석을수행한결과는 Table 5와같았다. 독립변수로는연령, 성별, 흡연여부, 음주여부, 근무기간, 모발용샴푸의사용빈도, 체질량지수, 지질검사 ( 총콜레스테롤 ) 및간기능검사 (AST, ALT, γ-gtp) 등을포함하여모델선정방법을입력 (enter) 방법으로분석하였다. 그결과혈청 PFOA의농도에영향을주는요인들은연령, 성, 체질량지수등이통계적인유의성이있었으며, 총콜레스테롤은경계역의통계적유의성을나타내었고, 모델의설명력은 18.4% 이었다. 모델선정방법을단계선택으로하여다중회귀분석을시행한결과는최종적으로성, 연령, 체질량지수, 총콜레스테롤등이선정되었으며, 이들의설명력은 20% 이 236

5 장상환등 제조업근로자들의혈청 Perfluorooctanoic Acid (PFOA) 농도와생활습관및직업적관련요인 Table 2. Serum PFOA concentration by gender according to age and work duration Unit: ng/ml Male Female Total N Mean (SD) Median Range p-value N Mean (SD) Median Range p-value N Mean (SD) Median Range p-value Age (years) < (2.8) (1.2) (2.8) (3.3) (2.1) (3.3) (4.8) (2.7) (4.4) (3.1) (2.3) (2.9) Work duration (years) <0.001< < (2.6) (2.2) (2.4) (3.3) (3.4) (3.4) (4.2) (2.3) (4.0) Total (3.9) (2.5) (3.7) <0.001 p-value by ANOVA(test for trend) and t-test 었다. 즉, 성별로는여성보다남성에서, 연령이많을수록, 총콜레스테롤이높을수록, 체질량지수가낮을수록혈청 PFOA의농도가통계적으로유의하게높았다. 3. 업종별혈청 PFOA 농도비교 PFOA 노출가능성이있는 18 개업종에대하여업종별로혈청PFOA 농도의평균과표준편차를구하였다 (Table 6). 평균혈청 PFOA 농도가높았던업종들은섬유제품염색, 정리및마무리가공업 ( 평균 10.5 ng/ ml), 분사기및소화기제조업 ( 평균 10.2 ng/ml), 선박구성부분품제조업 ( 평균 10.1 ng/ml) 등이었으며, 낮았던업종들은기타전자부품제조업 ( 평균 5.3 ng/ml), 동물용사료및조제식품제조업 ( 평균 5.6 ng/ml), 합성수지및기타플라스틱물질제조업 ( 평균 6.0 ng/ml) 등이었다. 업종별노출농도의차이를조사하기위하여혈청 PFOA 농도의중앙값 (7.7 ng/ml) 을기준으로이분화하여종속변수로설정하고, 업종을독립변수로하여로지스틱회귀분석을실시하여성과연령을보정한교차비를산출하였다 (Table 7). 혈청 PFOA의평균농도가가장낮게조사되었던기타전자부품제조업을기준으로하였을때, 섬유제품염색, 정리및마무리가공업의교차비가 6.16 (95% CI: ) 으로유의하게높았다. 주형및금형제조업 (OR 4.84, 95% CI: ) 과선박구성부분품제조업 (OR: 3.87, 95% CI: ), 플라스틱합성피혁제조업 (OR 10.05, 95% CI: ) 의경우는교차비가상대적으로높았으나통계적인유의성은없었다. 고찰 PFOA는과불화화합물의하나로동물실험등을통해발암성등생체에서의유해성이알려지면서미국과유럽등에서는과불화화합물제조업체근로자등대표적인직업적노출자들에대한조사가수행되어왔다. 우리나라에서도과불화화합물은산업장에서광범위하게사용되고있으나아직까지 PFOA의노출실태와인체영향에관한연구는부족한실정이다. 본연구에서는우리나라에서직업적으로 PFOA 노출가능성이있는업종의근로자들을대상으로생활습관및직업적특성이혈청 PFOA의농도에미치는영향을파악하기위하여혈청 PFOA, 간기능, 혈청지질을분석하고, 사회인구학적인특성과직업적특성및비직업적과불화화합물노출인자들에관하여설문조사를실시하여비교분석하였다. 성별로는여성보다남성에서, 연령이많 237

6 대한산업의학회지제 20 권제 3 호 2008 년 Table 3. Serum PFOA concentration by life style and BMI Unit: ng/ml Variables Male Female Total N Mean (SD) Range p-value N Mean (SD) Range p-value N Mean (SD) Range p-value Smoking Non- and ex-smoker (4.7) (2.5) (3.8) Current smoker (3.3) (1.7) (3.3) Alcohol drinking None (4.5) (2.6) (3.9) /week (2.4) (2.0) (2.6) >1/week (3.4) (2.0) (3.5) Instant food intake <1/week (2.7) (2.6) (2.8) /week (4.2) (2.4) (4.0) Disposables use None (5.0) (2.5) (4.1) <1/day (3.7) (2.7) (3.7) /day (3.3) (2.6) (3.5) /day (2.9) (1.5) (2.8) Hair shampoo use None (5.2) (5.2) per week (3.2) (3.0) (3.3) per week (3.1) (2.2) (2.9) BMI(kg/m 2 ) Normal (BMI<23) (4.4) (2.5) (4.1) Overweight (23 BMI<25) (3.0) (2.6) (3.0) Obesity (BMI 25) (2.8) (2.1) (2.8) p-value by ANOVA(test for trend) and t-test 238

7 장상환등 제조업근로자들의혈청 Perfluorooctanoic Acid (PFOA) 농도와생활습관및직업적관련요인 Table 4. Quartile distribution of serum cholesterol, AST, ALT and γ-gtp by gender Q1 Q2 Q3 Q4 N Mean (SD) N Mean (SD) N Mean (SD) N Mean (SD) p-value Male Total Cholesterol (mg/dl) (34.0) (39.0) (31.7) (35.6) AST (IU/L) (11.9) (14.6) (14.7) (08.4) ALT (IU/L) (33.8) (23.2) (13.7) (18.5) γ-gtp (IU/L) (37.7) (45.9) (53.7) (60.3) Female Total Cholesterol (mg/dl) (23.7) (35.4) (21.9) (32.0) AST (IU/L) (13.4) (04.4) (04.8) (07.1) ALT (IU/L) (13.9) (05.8) (08.6) (10.9) γ-gtp (IU/L) (10.0) (08.1) (05.6) (17.7) Total Total Cholesterol (mg/dl) (31.5) (35.8) (32.0) (35.9) AST (IU/L) (12.7) (10.0) (13.8) (09.3) ALT (IU/L) (29.4) (16.1) (17.2) (16.5) γ-gtp (IU/L) (23.2) (40.9) (42.6) (55.2) < p-value by ANOVA (test for trend) 을수록, 총콜레스테롤이높을수록, 체질량지수가낮을수록혈청 PFOA의농도가통계적으로유의하게높았다. 업종별로는섬유제품염색, 정리및마무리가공업이다른업종에비하여유의하게혈청 PFOA 농도가높았고, 선박구성부분품제조업, 주형및금형제조업과플라스틱합성피혁제조업등에서상대적으로높았다. 직업적노출자들에관한연구는근로자들의혈청 PFOA 농도와건강검진자료와의관련성에관한역학연구위주로수행되었다 6,7,11,17,18). PFOA 제조업체근로자들에서혈청 PFOA 농도는노출수준및노출기간과연관이있었다 8). 혈청 PFOA 농도는노출수준에따라차이가있었는데, Olsen 등 6,17) 이 PFOA 제조공정근로자들을대상으로수행한연구들에서평균이 1,780 및 2,210 ng/ml이었고, Emmett 등 11) 이수행한연구에서는 PFOA 생산부서근로자 18 명의평균은 824 ng/ml, 잠재적노출이있는근로자 48 명의평균은 406 ng/ml 이었다. 본연구에서의혈청 PFOA 농도의평균은 8.0 ng/ml ( 범위 1.0~40.9 ng/ml) 으로 PFOA 생산부서근로자들을대상으로한위의연구들에비하면상대적으로매우낮게검출되었다. 국내의한연구에서산업체근로자평균이 2.19 ng/ml, 일반인구의평균이 1.55 ng/ml로보고한결과보다는높게검출되었다 19). Olsen 등 6,17) 과 Emmett 등 11) 의연구에서는 PFOA를직접제조하는사업장의근로자들과오염원주변지역의거주자들을대상으로하여 PFOA에고농도로노출될수있는반면에, 본연구는국내에서 PFOA의화학적중간생성물 (chemical intermediate) 로취급함으로써상대적으로저농도에노출되는근로자들을대상으로하여그노출정도의차이가클것이므로이러한결과를직접비교하기는어렵다고생각된다. Emmett 등 11) 이 PFOA 제조공장주변의지역주민들을대상으로혈청 PFOA의농도를조사한결과 20 세이상에서연령이증가함에따라평균혈청 PFOA 농도가증가하였고, 특히 60 세이상에서혈청 PFOA의농도가높았다. 본연구결과에서도연령이증가함에따라평균혈청 PFOA 농도가통계적으로유의하게증가하여 Emmett 등의연구와유사한결과를나타내었다. 남녀를층화하여분석한결과남자의경우 40~49 세에서가장높았고, 여자의경우연령이증가함에따라혈청 PFOA의농도도증가하여 50 세이상에서가장높았다. 반면 Olsen 등 20) 이미국의적십자헌혈자 645 명 ( 연령 20~69) 을대상으로실시한연구에서혈청 PFOA 농도와연령은유의한관계가없다고보고하였으며, Midasch 등 16) 도독일의남부에거주하는직업력을알지못하는 105 명의비흡연자들 ( 남자 51 명, 여자 54 명연령 5~84 세 ) 을대상으로실시한연구에서연령에따른혈청 239

8 대한산업의학회지제 20 권제 3 호 2008 년 Table 5. Multiple regression analysis of factors associated with serum PFOA concentration Method Variables Beta Std. Error p-value R-square Enter BMI (kg/m 2 ) Total Cholesterol (mg/dl) AST (IU/L) ALT (IU/L) γ-gtp (IU/L) Age (year) Gender (male/female) Shampoo use (frequency) Smoking (smoker/nonsmoker) Alcohol (drinking/non-drinking) Work duration (year) Stepwise Gender (male/female) <0.001< Age (year) <0.001< BMI (kg/m 2 ) Total Cholesterol (mg/dl) Table 7. Adjusted Odds Ratios by type of manufacturing companies Type of manufacturing companies OR* p-value 95% CI. Other electronic components Dyeing and finishing textiles Moulding patterns, moulds and industrial patterns Sections for ships Plastics synthetic leather Livestock feeds and prepared animal feeds Parts and accessories for motor vehicles and engines Broadcasting and wireless telecommunication apparatuses Plastic laminating, coating and other surface processing Recovery of metal waste and scrap Synthetic resin and other plastic materials Printing Coating and similar treatment of metals Spinning of other textile fibers Electronic components Synthetic rubber and of plastics in primary forms Spraying, projecting and dispersing Machines Parts of footwear *: adjusted for gender and age by logistic regression analysis PFOA의농도가유의한차이가없다고보고한바있다. 지금까지의연구결과에서는직업적노출군과잠재적노출군을대상으로한연구에서는혈청 PFOA의농도와연령과의관련이있었으나, 비직업적노출군에서는관련성을확인할수없었다. 본연구는연령과혈청 PFOA 농도가관련이있는것으로조사되었다. 앞서언급된 Olsen 등 20) 의연구에서성별 PFOA 농도를비교한결과혈청 PFOA 농도가남자 (n=332) 에서여자 (n=313) 보다높았으며, Harada 등 21) 의연구에서도일 본의긴키지역거주자 34 명의자료에서남자 (n=14) 가여자 (n=20) 보다혈청 PFOA 농도가높았다. Jin 등 22) 과 Midasch 등 16) 이각각중국과독일의일반인을대상으로수행한연구에서도남자가여자보다혈청 PFOA 농도가높게나타났다. 본연구에서도남자가여자에비하여혈청 PFOA 농도가유의하게높았다. PFOA의가능한노출원은음식물, 식수섭취및오염된분진의흡입등으로알려져있으며 23-25), Midasch 등 16) 은일반인에서 PFOA 농도의성별에따른차이는아직그명확한원인을알수 240

9 장상환등 제조업근로자들의혈청 Perfluorooctanoic Acid (PFOA) 농도와생활습관및직업적관련요인 Table 6. Serum PFOA concentration by type of manufacturing companies Unit: ng/ml Male Female Total Type of manufacturing companies N Mean (SD) Range N Mean (SD) Range N Mean (SD) Range Other electronic components (2.4) (1.7) (1.9) Livestock feeds and prepared animal feeds (1.9) (-) (2.0) Synthetic resin and other plastic materials (4.3) (2.0) (2.4) Coating and similar treatment of metals (1.4) (2.7) (2.6) Broadcasting and wireless telecommunication apparatuses (1.1) (1.1) Parts of footwear (2.3) (2.5) (2.5) Electronic components (3.3) (1.6) (2.6) Spinning of other textile fibers (1.7) (1.9) (2.2) Printing (2.7) (1.1) (3.0) Synthetic rubber and of plastics in primary forms (3.2) (2.2) (3.0) Plastic laminating, coating and other surface processing (0.8) (0.0) (0.8) Parts and accessories for motor vehicles and engines (3.5) (4.0) (3.6) Recovery of metal waste and scrap (2.8) (2.8) Plastics synthetic leather (5.3) (0.9) (3.8) Moulding patterns, moulds and industrial patterns (2.4) (2.4) Sections for ships (6.9) (0.8) (6.3) Spraying, projecting and dispersing Machines (3.8) (3.8) Dyeing and finishing textiles (2.7) (4.1) (2.8) Total (3.9) (2.5) (3.7)

10 대한산업의학회지제 20 권제 3 호 2008 년 는없으나, 남녀간의식이및생활습관의차이때문으로추정하였으며, 음주와흡연의경우에는혈청 PFOA 농도와관련성이없는것으로보고하였고, 본연구에서도음주및흡연이 PFOA 농도와관련성이없었다. PFOA의독성에관한동물실험에서간암및간손상등이보고됨에따라인체에서도간이표적장기일가능성이제시되었으며 26-28), 이에따라직업적노출자들을대상으로인체에서의 PFOA의간기능에대한연구들이우선적으로수행되었다. Ubel 등 8) 은 1976년부터 3년간 PFOA 제조공장의근로자들을대상으로 PFOA의건강영향에관하여조사한결과혈청 PFOA농도가높은군에서γ-GTP가증가함을보고하면서혈청 γ-gtp는알코올섭취에민감도가높았기때문에혈청 PFOA 농도와관련이있다고결론내리기는어렵다고하였다. Gilliland 등 29) 의연구에서는비만근로자들에서 PFOA 농도가증가함에따라 AST와 ALT의농도가증가하였다. 반면 Emmett 등 30) 이 PFOA 제조공장부근의주민들을대상으로수행한연구에서는 AST, ALT 및 γ-gtp 등의간효소수치는혈청 PFOA 농도와상관관계가없다고보고하였다. 본연구에서는혈청 AST 와 ALT 는혈청 PFOA 농도와통계적으로유의한관련이없었으며 γ- GTP 또한연령및성별과 BMI 등의관련교란요인들을보정하였을때 Emmett 등의연구와유사하게 PFOA 농도와관련이없었다. 중성지방과혈청 PFOA 농도사이의관련성에관한 Olsen 등 6) 의연구에서양의상관관계가있었으며, Sakr 등 7) 이 PFOA 제조공장근로자들을대상으로수행한단면연구에의하면총콜레스테롤도 PFOA와상관관계가있었다. 또한 Sakr 등 18) 이같은회사의근로자들을대상으로수행한코호트연구에의하면연령, 성별, BMI, 알코올섭취등의교란요인들을보정하였을때혈청 PFOA가 1 ppm 증가하면총콜레스테롤이 1.06 mg/ dl 증가하였으나혈청 PFOA 농도와중성지방과저밀도지단백및고밀도지단백의농도와는상관성이없었다. 본연구에서는총콜레스테롤농도에대하여연령과성, BMI 등의교란요인들을보정한결과혈청 PFOA 농도가증가함에따라총콜레스테롤이증가하였다. 본연구에서혈청 PFOA의농도에영향을줄수있는교란요인들을보정한결과인스턴트식품의섭취, 1회용음식용기및모발용샴푸의사용은혈청 PFOA 농도와상관성이없었다. 이는실제조리상황의프라이팬및조리기구에서 PFOA가검출되지않았다는기존연구들과부합하는소견이었다 31-33). Emmett 등 11) 이직업적노출과관련하여 PFOA 제조공장주변의거주자들을대상으로직업적노출이없는군, 잠재적인노출군 ( 소방수, 불화중합체제조공장의비 생산직근로자, 카펫청소부, 카펫재처리기사, 전문적인카펫설치기사 ) 과제조공장근로자의 3군으로분류하여혈청 PFOA의농도를조사한연구에서혈청 PFOA 농도는직업적노출이없는군에서가장낮았고, 잠재적노출군, 제조공장근로자순으로높게나타나직업적노출과혈청 PFOA와의상관성을보고한바있다. 본연구에서는 PFOA에대한노출가능성이있는 18 개업종의생산직근로자들을대상으로연령과성별을보정하여업종별혈청 PFOA 농도를비교하기위하여혈청 PFOA 농도가가장낮게조사되었던기타전자부품제조업을기준으로교차비를산출한결과섬유제품염색, 정리및마무리가공업이 6.16배로유의하게높았으며, 주형및금형제조업이 4.84배, 선박구성부분품제조업이 3.87배, 플라스틱합성피혁제조업이 10.05배로나타났으나통계적인유의성은없었다. 본연구의제한점은설문지를이용하여훈련된면접자가직접면담을통하여정보를수집하였으나그과정에서응답자의회상편견 (recall bias) 이작용할수있으며, 현재직업에종사하고있는사람들만을대상으로하였으므로건강근로자효과의가능성이있다는점이다. 또한혈청 PFOA 농도에대해주요한환경인자로음용수와식이및다양한생활습관등이영향을미칠수있으므로향후에는이러한점들을보완한조사가필요할것이다. 지금까지국내에서직업적 PFOA 노출실태에대한조사가제대로이루어지지않았다. 이에본연구는 PFOA에노출이가능한제조업근로자들을대상으로혈청 PFOA의농도와생활습관, 직업적관련요인, 간기능검사및지질검사와관련성등을조사하였고, 업종별로혈청 PFOA농도의차이를제시함으로써향후 PFOA의인체위해성을평가하는기초자료로활용가치가있을것으로기대된다. 요약목적 : PFOA에노출이가능한제조업근로자들을대상으로혈청 PFOA 농도를조사하고생활습관, 직업적요인, 간기능및혈청지질과의관련성을연구하고자하였다. 방법 : 2007년 8월부터 12 월까지부산지역 1개대학병원산업의학과에서건강진단을받은 PFOA노출가능성이있는제조업사업장근로자남자 203 명과여자112 명의총315 명을대상으로하였다. 생활습관및직업적요인을설문조사하였고, 혈청 PFOA 농도를 LC-MS/MS로분석하였으며, 간기능및혈청지질검사를실시하였다. 결과 : 혈청 PFOA 농도의평균은전체가 8.0 ng/ml 이었으며, 남자가 9.0 ng/ml, 여자가 6.3 ng/ml 로 242

11 장상환등 제조업근로자들의혈청 Perfluorooctanoic Acid (PFOA) 농도와생활습관및직업적관련요인 남자가여자보다통계적으로유의하게높았다 (p<0.001). 다중회귀분석을시행한결과성, 연령, 체질량지수, 총콜레스테롤등이유의하게나타났으며, 성별로는남성에서, 연령이많을수록, 총콜레스테롤이높을수록, 체질량지수가낮을수록혈청 PFOA의농도가통계적으로유의하게높았다. 로지스틱회귀분석을실시하여성과연령을보정한교차비를산출한결과, 섬유제품염색, 정리및마무리가공업 (OR 6.16) 이통계적으로유의하게높았고, 주형및금형제조업 (OR 4.84), 선박구성부분품제조업 (OR 3.87), 플라스틱합성피혁제조업 (OR 10.05) 등이상대적으로높았다. 결론 : 제조업근로자들의혈청 PFOA 농도는성, 연령및총콜레스테롤등과관련성이있었고, 업종별로는섬유제품염색, 정리및마무리가공업에서높은것으로조사되었다. 이러한결과는 PFOA의인체위해성을조사하기위한기초자료로활용가치가있을것이다. 참고문헌 01) Hundley SG, Sarrif AM, Kennedy GL. Absorption, distribution, and excretion of ammonium perfluorooctanoate (APFO) after oral administration to various species. Drug Chem Toxicol 2006;29(2): ) Han X, Snow TA, Kemper RA, Jepson GW. Binding of perfluorooctanoic acid to rat and human plasma proteins. Chem Res Toxicol 2003;16(6): ) Olsen GW, Burris JM, Ehresman DJ, Froehlich JW, Seacat AM, Butenhoff JL, Zobel LR. Half-life of serum elimination of perfluorooctanesulfonate,perfluorohexanesulfonate, and perfluorooctanoate in retired fluorochemical production workers. Environ Health Perspect 2007; 115(9): ) Fromme H, Midasch O, Twardella D, Angerer J, Boehmer S, Liebl B. Occurrence of perfluorinated substances in an adult German population in southern Bavaria. Int Arch Occup Environ Health 2007;80(4): ) Kannan K, Corsolini S, Falandysz J, Fillmann G, Kumar KS, Loganathan BG, Mohd MA, Olivero J, Van Wouwe N, Yang JH, Aldoust KM. Perfluorooctanesulfonate and related fluorochemicals in human blood from several countries. Environ Sci Technol 2004;38(17): ) Olsen GW, Burris JM, Burlew MM, Mandel JH. Epidemiologic assessment of worker serum perfluorooctanesulfonate (PFOS) and perfluorooctanoate (PFOA) concentrations and medical surveillance examinations. J Occup Environ Med 2003;45(3): ) Sakr CJ, Kreckmann KH, Green JW, Gillies PJ, Reynolds JL, Leonard RC. Cross-sectional study of lipids and liver enzymes related to a serum biomarker of exposure (ammonium perfluorooctanoate or APFO) as part of a general health survey in a cohort of occupationally exposed workers. J Occup Environ Med 2007;49(10): ) Ubel FA, Sorenson SD, Roach DE. Health status of plant workers exposed to fluorochemicals--a preliminary report. Am Ind Hyg Assoc J 1980;41(8): ) Gilliland FD, Mandel JS. Mortality among employees of a perfluorooctanoic acid production plant. J Occup Med 1993;35(9): ) Olsen GW, Burris JM, Burlew MM, Mandel JH. Plasma cholecystokinin and hepatic enzymes, cholesterol and lipoproteins in ammonium perfluorooctanoate production workers. Drug Chem Toxicol 2000;23(4): ) Emmett EA, Shofer FS, Zhang H, Freeman D, Desai C, Shaw LM. Community exposure to perfluorooctanoate: relationships between serum concentrations and exposure sources. J Occup Environ Med 2006;48(8): ) Olsen GW, Logan PW, Hansen KJ, Simpson CA, Burris JM, Burlew MM, Vorarath PP, Venkateswarlu P, Schumpert JC, Mandel JH. An occupational exposure assessment of a perfluorooctanesulfonyl fluoride production site: biomonitoring. AIHA J (Fairfax, Va) 2003;64(5): ) Kennedy GL, Jr., Butenhoff JL, Olsen GW, O'Connor JC, Seacat AM, Perkins RG, Biegel LB, Murphy SR, Farrar DG. The toxicology of perfluorooctanoate. Crit Rev Toxicol 2004;34(4): ) Lee CH. Manufacturing. In: Korean Standard Industrial Classification (2008). National Statistical Office, Daejeon pp , (Korean) 15) Weisell RC. Body mass index as an indicator of obesity. Asia Pac J Clin Nutr 2002;11 Suppl 8:S ) Midasch O, Schettgen T, Angerer J. Pilot study on the perfluorooctanesulfonate and perfluorooctanoate exposure of the German general population. Int J Hyg Environ Health 2006;209(6): ) Olsen GW, Zobel LR. Assessment of lipid, hepatic, and thyroid parameters with serum perfluorooctanoate (PFOA) concentrations in fluorochemical production workers. Int Arch Occup Environ Health 2007;81(2): ) Sakr CJ, Leonard RC, Kreckmann KH, Slade MD, Cullen MR. Longitudinal study of serum lipids and liver enzymesin workers with occupational exposure to ammonium perfluorooctanoate. J Occup Environ Med 2007; 49(8): ) Kim YJ. The survey of exposure level for PFOS and PFOA in human. KFDA, Seoul pp (Korean) 20) Olsen GW, Church TR, Miller JP, Burris JM, Hansen KJ, Lundberg JK, Armitage JB, Herron RM, Medhdizadehkashi Z, Nobiletti JB, O'Neill EM, Mandel JH, Zobel LR. Perfluorooctanesulfonate and other fluorochemicals in the 243

12 대한산업의학회지제 20 권제 3 호 2008 년 serum of American Red Cross adult blood donors. Environ Health Perspect 2003;111(16): ) Harada K, Saito N, Inoue K, Yoshinaga T, Watanabe T, Sasaki S, Kamiyama S, Koizumi A. The influence of time, sex and geographic factors on levels of perfluorooctane sulfonate and perfluorooctanoate in human serum over the last 25 years. J Occup Health 2004;46(2): ) Jin YH, Dong GH, Shu WQ, Ding M, Zhai C, Wang L, Liu X, Saitou N, Sasaki K. Comparison of perfluorooctane sulfonate and perfluorooctane acid in serum of non-occupational human from Shenyang and Chongqing areas. Wei Sheng Yan Jiu 2006;35(5): ) Kubwabo C, Stewart B, Zhu J, Marro L. Occurrence of perfluorosulfonates and other perfluorochemicals in dust from selected homes in the city of Ottawa, Canada. J Environ Monit 2005;7(11): ) Moriwaki H, Takatah Y, Arakawa R. Concentrations of perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) in vacuum cleaner dust collected in Japanese homes. J Environ Monit 2003;5(5): ) Saito N, Harada K, Inoue K, Sasaki K, Yoshinaga T, Koizumi A. Perfluorooctanoate and perfluorooctane sulfonate concentrations in surface water in Japan. J Occup Health 2004;46(1): ) Abdellatif AG, Preat V, Vamecq J, Nilsson R, Roberfroid M. Peroxisome proliferation and modulation of rat liver carcinogenesis by 2,4-dichlorophenoxyacetic acid, 2,4,5- trichlorophenoxyacetic acid, perfluorooctanoic acid and nafenopin. Carcinogenesis 1990;11(11): ) Cook JC, Murray SM, Frame SR, Hurtt ME. Induction of Leydig cell adenomas by ammonium perfluorooctanoate: a possible endocrine-related mechanism. Toxicol Appl Pharmacol 1992;113(2): ) Biegel LB, Hurtt ME, Frame SR, O'Connor JC, Cook JC. Mechanisms of extrahepatic tumor induction by peroxisome proliferators in male CD rats. Toxicol Sci 2001;60(1): ) Gilliland FD, Mandel JS. Serum perfluorooctanoic acid and hepatic enzymes, lipoproteins, and cholesterol: a study of occupationally exposed men. Am J Ind Med 1996; 29(5): ) Emmett EA, Zhang H, Shofer FS, Freeman D, Rodway NV, Desai C, Shaw LM. Community exposure to perfluorooctanoate: relationships between serum levels and certain health parameters. J Occup Environ Med 2006;48(8): ) Powley CR, Michalczyk MJ, Kaiser MA, Buxton LW. Determination of perfluorooctanoic acid (PFOA) extractable from the surface of commercial cookware under simulated cooking conditions by LC/MS/MS. Analyst 2005;130(9): ) Sinclair E, Kim SK, Akinleye HB, Kannan K. Quantitation of gas-phase perfluoroalkyl surfactants and fluorotelomer alcohols released from nonstick cookware and microwave popcorn bags. Environ Sci Technol 2007;41(4): ) Begley TH, White K, Honigfort P, Twaroski ML, Neches R, Walker RA. Perfluorochemicals: potential sources of and migration from food packaging. Food Addit Contam 2005;22(10):