TDI 노출 작업자에서 직업성천식 및 항체반응

김덕인 ( Deok In Kim ),김형렬 ( Hyoung Ryoul Kim ),박해심 ( Hae Sim Park ),박신구 ( Sin Gu Park ),임종한 ( Jong Han Leem ),노재훈 ( Jae Hoon Roh ),김정구 ( Jeong Goo Kim ),윤병갑 ( Byeong Kab Yoon ),김철우 ( Cheol Woo Kim ) 대한천식알레르기학회 2005 천식 및 알레르기 Vol.25 No.4

Background: Toluene diisocyanate (TDI) is known to be the most common cause of occupational asthma (OA) in Korea. Although TDI can elicit humoral immune responses including specific-IgE (sIgE) and specific-IgG (sIgG) responses, the exact role of these immune responses has not been clearly clarified yet. Objective: This study was carried out to estimate the prevalence of TDI-induced OA, and to evaluate the clinical significance of TDI-related humoral immune responses in currently TDI-exposed workers. Method: Questionnaire interview for respiratory symptoms was conducted to 170 workers with direct exposure to TDI (exposed group). After screening survey, workers with suspected occupational asthma were selected for methacholine and TDI bronchial provocation tests (BPTs). Serum sIgG and sIgE antibodies to TDI-HSA conjugate, and sIgG to cytokeratin (CK) 8, 18, and 19 were detected by enzyme-linked immunosorbent assay in 170 exposed workers, and compared with 61 unexposed workers in the same workplace (unexposed group) and 75 unexposed healthy controls(healthy control group). Result: Eleven (6.9%) among 170 workers complained symptoms of OA, and 7 of 11 symptomatic workers showed positive airway hyperresponsiveness to methacholine (4.1%). One worker with spray-painting job was confirmed as having TDI-induced asthma by showing positive responses to both methacholine and TDI BPTs. The prevalence of sIgG to TDI-HSA conjugate was significantly higher in TDI-exposed workers (10.1%) than in unexposed workers (0%) and healthy control (2.7%). However, no significant difference was noted between symptomatic (18.2%) and asymptomatic workers (9.5%) among the exposed group. The prevalences of sIgE to TDI-HSA conjugate and sIgG to CK 8, 18, 19 were not significantly different between the three groups. Conclusion: The prevalence of TDI-induced OA was noted to 0.58% in the current working environments. The clinical significance of TDI-induced humoral immune responses may be clarified by further prospective studies. (Korean J Asthma Allergy Clin Immunol 2005;25:276-283)

인천지역 TDI 노출 작업자에서 직업성천식 유병율

김형렬,김철우,홍윤철,전형준,김치년,김현수,이지나,신주연,고동희,노재훈 大韓産業醫學會 2004 대한직업환경의학회지 Vol.16 No.2

목적 : TDI는 직업성천식을 일으키는 대표적인 물질로 알려져 있다. 과거 TDI에 노출된 작업자들의 천식 발생률을 5~6%가량 보고하였고, 국내에서도 2-20%에 이르는 유병율을 보고한바 있다. 작업환경이 많이 개선되고, 노출량이 감소된 최근에도 TDI에 의한 직업성천식에 대한 보고가 많이 이루어지고 있어, 이에 대한 적극적인 조사와 진단과정을 통해 유병율을 구하고 질병발생의 변화양상을 파악해 보고자 하였다. 방법 : 인천지역에서 특수건강진단을 수행하는 2개 기관의 TDI 노출 근로자 400여명 중, 사업장의 규모가 50인 이상이며 사업주가 연구진행을 허락한 사업장에서 근무하는 근로자 중 직접적으로 TDI에 노출되는 작업에 종사하는 근로자 170명을 연구대상으로 하였다. 이들에 대해 설문지와 산업의학의사의 면담을 통한 작업관련성 평가를 근거로 정밀대상자를 선정하고 이들에 대해 메타콜린 유발시험, TDI 유발시험 등을 수행하여 직업성천식을 확인하였다. 결과 : 설문조사 결과 11명이 직업과 관련하여 천식증상을 보이는 것으로 나타났고(6.9%), 이중 7명에서 메타콜린 유발검사 양성소견을 보였다. TDI에 의한 특이유발시험 결과 1명에서 양성반응이 나타나, 이 집단에서 TDI에 의한 직업성천식의 유병율은 0.58%였다. 결론 : 과거 국내연구에서 TDI에 의한 직업성천식의 유병율이 2~20%에 이르렀던 데 비해, 본 연구에서는 0.58%로 나타났다. 이는 국외 논문에서도 나타나는 경향으로 작업장 노출량 감소로 점차 발생률이 감소하는 양상을 보이고 있다. 그러나 이미 증상이 나타난 근로자들이 부서를 옮기거나, 직장을 그만둠으로 인해 그 유병율이 과소평가되었을 가능성도 있다고 판단된다. Objecdives: This study was carried out to estimate the prevalence of isocyanate-induced occupational asthma in toluene diisocyanate (TDI) exposed workers. Methods: We examined 170 workers who had been directly exposed to TDI through a medical questionnaire, physical examination, and pulmonary function test. Based on screening examination, workers with suspected occupational asthma were selected for further evaluation such as methacholine and TDI challenge tests. Results: Eleven (6.9%) among 170 workers complained of symptoms of occupational asthma. and 7 among these 11 symptomatic workers showed positive responses to the methacholine challenge test (4.1 %). One spray painter was confirmed as having the TDI induced occupational asthma following a positive response to TDI challenge test. Conclusions: The prevalence of TDI-induced asthma was at 0.58% was lower than that for former studies (2-20%). Improved workplace environment, lower level of TDI exposure compared to the past, and the healthy workers effect may have contributed to this low rate of asthma prevalence in workers with TDI exposure.

보문: 공업화학(전기화학, 분석화학 포함)·촉매/반응공학·약물전달기술·기능성 코팅기술 ; Toluene diisocyanate(TDI) 합성을 위한 Pd/SiO2 촉매상 직접 카보닐화반응에서의 피리딘 첨가효과

서명기 ( Myung Gi Seo ),김성민 ( Seong Min Kim ),이대원 ( Dae Won Lee ),이관영 ( Kwan Young Lee ) 한국화학공학회 2012 Korean Chemical Engineering Research(HWAHAK KONGHA Vol.50 No.3

본 연구는 Pd/SiO2 촉매를 이용하여 2,4-dinitrotoluene(2,4-DNT)을 2,4-toluene diisocyanate(2,4-TDI)로 환원시키는 반응에 관한 연구이다. 반응 조건은 200 oC에서, 일산화탄소를 주입하여 100 bar에서 실험을 진행하였으며, 피리딘이 TDI의 수율에 미치는 영향에 대해 연구 하였다. 반응 실험 결과 피리딘을 넣지 않은 경우 TDI는 생성되지 않았고, 피 리딘을 첨가하면 TDI가 생성되었다. 직접 카보닐화를 이용한 균질계상에서의 TDI 합성 연구 결과에 의하면 팔라듐과 피리딘의 착이온이 형성되어 촉매작용을 하는 것으로 알려져 있다. 피리딘을 첨가하였을 경우 TDI가 합성되는 것이 팔 라듐 용출에 의한 것인지 확인하기 위해 ICP-AES 분석을 시행하였다. 20 vol% 피리딘을 첨가한 반응에서 반응 후 촉 매의 팔라듐 함량이 반응 전에 비해 52% 감소하였다. 이러한 결과는 피리딘을 첨가한 반응실험에서 용출된 팔라듐이 피리딘과 착이온을 형성하는 과정을 거쳐 TDI가 생성되는 것으로 설명될 수 있다. This study is about reduction reaction making 2, 4-dinitrotoluene (2, 4-DNT) to 2, 4-toluene diisocyanate (2,4-TDI) with Pd/SiO2. Catalytic systems based on Pd/SiO2 at about 200˚C and under 100 bars of carbon monoxide. We studied the effect of pyridine on the yield of the TDI. TDI was not created without pyridine, but created with pyridine, at the reaction result. According to research, homogeneous synthesis of TDI with direct carbonylation, palladium and pyridine complexion is known to catalyze. When adding pyridine the reason of TDI synthesis is palladium leaching, ICP-AES was performed to confirm it. As a result, the proportion of Pd loaded in SiO2 was decreased 52% than before, after the reaction by adding 20 vol% pyridine. Generating TDI by adding pyridine might be the effect of the complex ion, which is composed of leached palladium and pyridine.

2-Chlorobenzyl alcohol을 이용한 TDI의 가스 크로마토그래피 분석

윤주송,박준호,이규원,엄민용,이은정,유철,최홍순,서동섭,최병길,유호영,임정연,이강명,서종철,노재훈,조영봉 한국EHS평가학회 2004 한국EHS평가학회지 Vol.2 No.2

Isocyanates는 OECD의 high production volume (HPV) chemical list에 등록되어 있다.Isocyanates에 노출시 피부,눈 및 호흡기계의 염증,천식,기관지염,그리고 폐 부종 등을 발생시킨다.TDI의 발암성에 대해서 IARC는 Griop 2B로,그리고 NTP는 Group B로 지정되어있다.1984년 12월 3일 인도 보팔에서 발생한 누출 사고로 인해서 2,800명이 사망하고 200,000명 이상이 부상당했다.TDI에 대한 ACGIH의 TWA는 0.005ppm (0.04 mg/m3)이고,STEL는 0.02 ppm (0.14 mg/m3)이다.NIOSH와 OSHA의 TDI에 대한 HPLC 분석법은 임핀저나 glass fiber filter로 포집하는데 이 방법은 다른 물질의 간섭과 재현성이 좋지 않다.따라서 본 연구는 2-CBA를 이용하여 TDI를 유도체화 및 가수분해하여 GC/ FID 및 GC/ ECD 분석법을 설정하고자 한다.2,4-TDI는 2-CBA와 반응하여 urethane을 합성하였고 수율은 71.74%이었으며,합성된 urethane은 TLC로 확인하였다.2-CBA로 코팅된 glass fiber filter를 87˚C, 20mmHg로 lhr 이상 건조처리 하였을 때 모두 증발하였지만 urethane 코팅된 glass fiber filter를 같은 조건에서 처리하였을 경우 3hr까지 증발하지 않았다.Urethane의 가수분해 수율은 1, 3, 5N HCI 및 l, 3, 5N H2SO4에서 약 100% 이었다.가수분해물인 2-CBA는 GC/FID와 GC/ PD-ECD에서 정량적으로 분석되 었고 LOD는 각각 0.02199 mg/m3 및 0.02503mg/m3이었다.또한 2-CBA 및 urethane의 가수분해물 내의 2-CBA는 GC/MSD에서 정상적으로 확인되었다.그렇지만 GC/FID로 분석한 2-CBA의 최저 농도인 2.5ppm을 적용하였을 때 (1.5 l/min, 6hr 포집)대기 중의 분석 가능한 최저 TDI 농도는 0.00567mg/m3(ACGIH TWA : 0.04 mg/m3) 이었다.만약 좀더 감도가 좋은 알콜류를 사용한다면 GC/PD-ECD로 더 낮은 농도까지 분석 가능할 것이다.따라서 2,4- 및 2,6-TDI의 동시 분석 및 total isocyanate 분석이 GC/FID 및 GC/PD- ECD로 가능할 것이다. Isocyanate is on OECD high production volume(HPV) chemical list. Hazard of TDI are Inflammation of skin, eye and respiratory system, asthma, bronchitis and lung edema etc. Carcinogenicity of TDI are IARC - Group 2B, NTP - Group B. Isocyanate leakage accident in 1984. 12. 03(bopal, India), Union Carbide killed 2,800 man and, injured more than 200,000. TDI's ACGIH TWA is 0.005ppm(0.04 mg/m3) and STEL is 0.02 ppm(0.14 mg/m3). NIOSH and OSHA method of 2,4-TDI is HPLC method collected by impinger or glass fiber filter. These methods have a interference and bad reproducibility. So, this study find new method of GC/FID or GC/ECD by derivation of TDI and hydrolysis using 2-CBA. 2,4-TDI and 2-CBA makes urethane and yield is 71.74% and urethane is verificated by TLC. Glass fiber filter coating 2-CBA is treated in 87˚C and 20mmHg decompression evaporation more than 1 hr and evaporate entirely but, glass fiber filter coating urethane is treated in same condition have no evaporation to 3 hr. Urethane hydrolysis yield in 1, 3, 5N HC1 and H2S04 are about 100%. Hydrolysate the 2-CBA is analyzed by GC/FID and GC/PD-ECD, and LOD is 0.02199 mg/m3 and 0.02503mg/m3 respectively. 2-CBA and 2-CBA in hydrolysate of urethane are identified by GC/MSD. But, Lowest concentration of 2-CBA solution analyzed by GC/FID is 2.5ppm(l.5 l/min, 6hr collect). According to lowest analytical concentration, usual analytical limit of TDI in air is 0.00567mg/m3 (ACGIH TWA : 0.04 mg/m3). If use more sensitive alcohols, a very small amount can be analyzed by GC/PD-ECD. So, simultaneous analysis of 2,4- and 2,6-TDI and total isocyanate analysis can be available by GC/FID and GC/PD-ECD.

톨루엔 디이소시아네이트 폭로 근로자들의 작업방법에 따른 대사물질의 비교 및 면역능에 관한 연구

이수일,조병만,황인경,이철호,박정래 大韓産業醫學會 1998 대한직업환경의학회지 Vol.10 No.3

Following recent advanced industrialization, the amount of polyurethane to use as thermal insulating materials, upholstery, mattresses and packing materials in automotive and furniture industry is increasing world-widely, and the number of polyurethane-producing worker will be increased. Because the numerous organic solvents are used in polyurethane-producing factory, the workers in this work site is exposed to many organic solvents. Of the organic solvents, Toluene Diisocyanate(TDI) has many hazardous effects to human. The effects of TDI on human are the irritation to respiratory mucosa and gastrointestinal symptoms. Conjunctival irritation, dermal inflammation (redness, pain, vesicular formation) and gastrointestinal symptom(nausea, vomiting. abdominal pain) are reported just after short-term exposure of TDI. TDI is known to give rise to bronchial asthma, as the immune disorder. And because of strongly volatile characteristics of TDI, it is suggested as a more injurious material to human health, especially human immune system, than other organic solvents. Bronchial asthma inducing mechanism of TDI is not clearly known, but on the analogy of TDI induced symptoms and recent studies, early-onset asthma is type I hypersensitivity reaction mediated by immunoglobulin E(IgE), and late-onset asthma is maybe type III hypersensitivity reaction by circulating IgG. And we know that the complicated human immune function is likely to move in such that mechanisms, there are not studies on immune indices evaluating the bronchial asthma-related immune function. The evaluation of change patterns of humoral immunity including IgE and IgG and cellular immunity including T-helper cell. T-suppressor cell and T-cytotoxic cell will be helpful to evaluate exposure degrees and prognosis in TDI exposed workers. Because TDA(toluene diamine) as a biological exposure index of TDI becomes the focus of interest, we know that a study on the correlation between urinary TDA and air TDI and immunological indices will make a contribution to biological effect monitoring indicies. We examined human immunity indicators such as WBC, %Lymph (percentile of Lymphocyte in WBC), %T-cell(percentile of T-lymphocyte in total lymphocyte). CD4, CD8, C3, C4, IgA, IgG, IgM, IgE in peripheral blood to evaluate the health hazard of the TDI-exposed workers. And we examined TDA to evaluate correlation between exposure and effect. Total 90 subjects was selected, 45 workers who worked in the polyurethane-producing factories as an exposed group, and 45 cases who were office workers(10 cases), other blue collors(27 cases), and medical college students(8 cases) as a control group. And the results were as follows; 1. The logarithm of IgE-Log10(IgE)±SD-in peripheral blood of a exposed group was significantly higher than a control group, 2.22 ±0.62 in case group compared with 1.98±0.53 in control group. (p<0.05) 2. IgA and IgM in the polyurethane-producing workers were 261.02±83.12㎎/㎗, 151.97 ±59.64 ㎎/㎗, respectively, and 292.77±100.45, 179.17±100.78 in control group. IgA and IgM was slightly lower in polyurethane-producing group than control.(p>0.05) 3. WBC, %Lymph. %T-cell, C3, C4, CD4, CD8, CD4/CD8 ratio and IgG in case group were 6.391.1 ea/㎖, 37.53 %, 59.54 %, 76.68 ㎎/㎗, 0.76×10(9) ea/L, 0.63×10(9) ea/L, 1.39, and 1606.29 ㎎/㎗, respectively, and 6,974.7 ea/㎖, 35.12 %, 59.64 %, 71.95 ㎎/㎗, 33.94 ㎎/㎗, 0.80×10(9) ea/L, 0.61×10(9) ea/L, 1.39, and 1581.51 ㎎/㎗ in control group. There was no statistical significance between two groups.(p>0.05) 4. In the comparison of each other companies, average of individual urinary TDA in polyurethane paint manufacturing companies is higher than that of polyurethane sponge foaming companies. And, the concentration of 2.6-TDA which is a metabolite of well-vaporized 2.6-TDI is higher than that of 2.4-TDA in the polyurethane sponge foaming companies. But, the concentration of 2.4-TDA which is a metabolite of illvaporized but well skin-absorbed 2.4-TDI is higher in polyurethane paint manufactures. 5. There were no statistical significance in the correlations between individual urinary TDA and immunologic indices.

TDI가 포함된 페인트 경화제에 의한 직업성 천식 1례

이정호,양창헌,김종목,임현술,이동철,이영현 東國大學校醫學硏究所 1994 東國醫學 Vol.2 No.-

TDI(Toluene diisocyanate)는 도료, 단열제, 도장제, 광택제 등에 널리 사용하는 화학물질로, TDI에 폭로된 근로자의 약 5-10%에서 기관지 천식이 발생하는 것으로 보고되어 있으며, 발생기전은 면역학적 기전, 약리학적 기전, 독성 반응 및 다른 비면역학적 기전으로 할려져 있다. 본 증례는 TDI에 폭로된 후에 약 5년의 잠복기를 거친 후 기관지 천식이 발생한 39세 여자 환자로 호산구 수와 총 Ig E 치는 정상이고, 내원시 폐기능 검사는 정상치를 보였으나, methacholine 기관지 유발검사에서 6.25㎍/ml에서 PD20의 양성반응을 보이고, TDI 포함된 페인트 경화제에 의한 기간지 유발검사상 양성반응이 나타나 TDI에 의한 기관지 천식으로 확진된 환자로, 확진을 위하여 실시한 TDI 기관지 유발 검사는 이중반응형을 보였다. 그러므로 본 증례는 TDI가 포함된 페인트 경화제에 의한 직업성 천식으로 확진할 수 있었다. Isocyanates can induce occupational asthma in exposured workers. Isocyanates are most significant cause of occupational asthma in our country. Studies on the pathogenesis of isocyanate induced asthma have yielded conflicting result. Immunologic reaction were suggested by several authors. Isocyanates are used in the manufacture of numourous products including insulation, foam filling for furniture and polyurethane paints. We experienced one case of occupational asthma due to TDI in polyurethane paints manufacturing process. Therefore we report with brief reviews of literature. The patient was 39 years old woman. She developed cough, dyspnea, wheezing from 5 years after exposure. Eosinophil count, total Ig E level. and pulmonary function test at admission was within normal limit. On methacholing challange test, PD20 was 6.25 ㎍/ml and 1,600 ㎍/ml before and after TDI provocation test. Bronchial provocation test with paint working. TDI was positive and dual reaction was observed.

낙동강 상류 수계에서 부착돌말류를 이용한 생물학적 수질 평가

최재신,채현식,김한순 한국환경영향평가학회 2019 환경영향평가 Vol.28 No.2

This study assessed biological water quality using epilithic diatoms in the Yeong river, Naeseong stream and Wi stream in the upper region of the Nakdong river from May to October 2016. Epilithic diatoms were not mobile, so they could reflect long-term water quality. The sampled epilithic diatoms were identified a total 158 taxa which were composed to 2 orders, 3 suborders, 8 families, 34 genera, 143 species and 15 varieties. Dominant species were Achnanthes convergens and Achnanthes minutissima at Yeong river, Nitzschia inconspicua at Naeseong stream, and Achnanthes minutissima, Cocconeis placentula var. lineata and Navicula minima at Wi stream. As a result of the CCA, Electrical conductivity, total nitrogen and total phosphorus were important factors determining the diatom species composition in the upper region of the Nakdong river. The correlation between diatom indices (DAIpo & TDI) measured to be high in the correlation coefficient (0.87) from the result of correlation analysis. In the result of the assessment of biological water quality using DAIpo and TDI, Yeong river was rated as class A at most sites. Naeseong stream was rated as class C to D at all sites except for N1 which was rated as Class A. Wi stream was rated as class B to C for DAIpo of W1, and TDI was rated as class D. The assessment of biological water quality at this site showed inferior TDI result compared to that of DAIpo. DAIpo and TDI of W2 were rated as class A to D, and the water quality has changed a lot. W3 and W4 were mostly rated as class B and C respectively. 낙동강 상류 수계에 위치한 영강, 내성천과 위천을 대상으로 2016년 5월부터 10월까지 부착돌말류를 이용한 생물학적 수질 평가를 하였다. 부착돌말류는 이동성이 없어 장기적인 수질상태를 반영할 수 있다. 채집된 부착돌말류는 총 158 분류군으로 2목 3아목 8과 34속 143종 15변종으로 구성되어 있다. 영강은 Achnanthes convergens 와 Achnanthes minutissima, 내성천은 Nitzschia inconspicua, 위천은 Achnanthes minutissima, Cocconeis placentula var. lineata와 Navicula minima가 우점하였다. CCA 분석 결과, 낙동강 상류 수계에서는 전기전도도, 총인과 총질소가 부착돌말류의 종조성에 중요한 요인들로 나타났다. 상관분석 결과, 부착돌말지수들(DAIpo 와 TDI)은 서로 높은 상관성(0.87)을 보였다. 부착돌말지수(DAIpo와 TDI)를 이용한 생물학적 수질평가 결과, 영강은 대부분의 지점에서 A등급으로 평가되었다. 내성천은 A등급으로 평가된 N1을 제외한 모든 지점에서 C~D등급으로 평가되었다. 위천은 W1의 DAIpo가 B~C등급이나 TDI는 D등급으로 평가되어, 이 지점의 생물학적 수질 평가는 DAIpo보다 TDI의 결과가 더 불량한 것으로 나타났다. W2의 DAIpo와 TDI는 A~D등급으로 수질의 변화가 심하였다. W3와 W4의 DAIpo와 TDI는 대부분 B와 C등급으로 각각 평가되었다.

Toluene diisocyanate 에 의한 직업성천식 환자의 객담내 호중구 활성화의 증거

김희연,남동호,박해심 ( Hee Yeon Kim,Dong Ho Nahm,Hae Sim Park ) 대한천식알레르기학회 1998 천식 및 알레르기 Vol.18 No.3

Background: Toluene diisocyanate (TDI) is the most prevalent agent to cause occupational asthma (OA) in Korea. The pathogenic mechanism of TDI-induced OA is still unclear. Involvement of both immunological and non-immunologicaI mechanisms have been suggested. Objeetive '. To evaluate a possible role of neutrophil in the development of TDI-asthma. Object and method: Myeloperoxidase (MPO) as a neutrophil activation marker in both serum and induced sputum, and IL-8 in induced sputum were measured. Induced sputa and sera were collected from 15 TDI-induced OA patients (classified to group I) during TDI- bronchoprovocation test and were compared with those from 11 asthmatic subjects with negative TDI-bronchoprovocation test (group II). MPO levels were measured by radioimmunoassay, IL-8 levels, by enzyme linked immunosorbent assay and albumin levels, by nephelometry. Sputum MPO and IL-8 levels were presented as a ratio to albumin. Result: Serum MPO level tended to decrease during the TDI-bronchoprovocation test in two groups, but no statistical significance was reached (p>0.05). However, the ratios of MPO (the ratio of MPO level measured at 30 min to MPO level at baseline, and the ratio MPO level measured at 360 min to MPO baseline) in group I were significantly lower than group II (p=0.004, p=0.03 respectively). The IL-8/albumin and MPO/albumin levels in induced sputum from group I were significantly increased after the TDI-bronchprovocation test in comparison to the baseline value which was obtained before the bronchoprovocation test (p=0.0l, p=0.02 respectively). There was a significant correlation between the percent increase of IL-8/albumin and the MPO/albumin in induced sputum (r=0.89, p<0.05). Conclarsiog '. These findings suggest a possible involvement of neutrophil in the development of bronchoconstiction after the TDI exposure, and IL-8 might contribute to neutrophil recruitment to airway mucosa. Further investigation will be needed to investigate mechanism of neutrophil activation in the pathogenesis af TDI-induced OA.

TDI폭로 목재가구 근로자의 호흡기증상과 페기능의 변화

이세훈,박주형,이원철,박정일,이강숙,김오식 가톨릭대학산업의학센타 산업의학연구소 1992 韓國의 産業醫學 Vol.31 No.3

Toluene diisocyanate(TDI) has been well known to be one of the occupational asthmogenic agent. Recently, TDI-induced occupational asthma draws attention in Korea in accordance with increased case reports. This study was designed to investigete the asthma-like respiratory symptoms prevalence in the past history as well as pulmonary function changes between the shift of the 129 workers, who did not have respiratory diseases including asthma, and were occupationally exposed to TDI working at 5 wood furniture industries. One hundred and thirty-one clerks of the same factories were participated as contol group. Questionnaires on the detailed occupational history and respiratory symptoms were administered by 3 doctors, and pulmonary function test was given by a trained technician. TDI concentration in the 8(26%) working sites showed to be exceeded 0.005 ppm among the 31 working sites(26/129(18%) workers) including polyurethane spray booths and flow coater painting rooms. Significantly increased respiratory symptom prevalences were found in the TDI exposed workers comparing to control group. No exposure-effect relationship was found regarding symptom prevalences. We did not find decreased lung functions among TDI exposed group in comparing with control group before the shift. Signigicant decrease of lung functions(FVC(forced vital capacity), FEV??(forced expiratory volume in one second), FEF??(maximal mid-expiratory folw), PEF(peak expiratory flow)) were found between before and after the shift in the TDI exposed group. Particularly, decrement of FEF?? in the high exposure(≥0.005 ppm) group was significantly larger than that in the low group exposure(≤0,005 ppm) group, and that of FEV?? was affected by working duration or smoking. There was no significant associations between respiratory symptoms and the decreased lung functions between the shift. This study indicated that occupational exposure to TDI can induce respiratory symptoms without overt bronchial asthma or impaired lung functions in the healthy workers, and TDI exposure during the shift may give rise to acute reversible decrease of pulmonary functions.

Toluene diisocyanate (TDI ) 에 의한 천식 환자에서 transforming growth factor β1 ( TGFβ1 ) 과 TGFβ receptor II ( R II ) 의 발현 정도와 지속적인 천식 증상과의 관계

이수걸(Soo Keol Lee),이선민(Sun Min Lee),함기백(Ki Baik Hahm),임현이(Hyun Ee Yim),김선신(Sun Sin Kim),남동호(Dong Ho Nahm),박해심(Hae Sim Park) 대한내과학회 2001 대한내과학회지 Vol.61 No.6

N/A Background: The underlying mechanism to explain the poor prognosis of TDI-induced asthma is unknown. We performed this study to evaluate the role of TGFβ1 and its receptor, TFGβ receptor II (RII) in TDI-induced asthma. Methods : We applied immunohistochemistry with monoclonal antibodies to TGFβ1 and RII in bronchial mucosa from 22 subjects with TDI-induced asthma (group I: 10 newly diagnosed, group II: 12 subjects with persistent asthma symptoms for more than 4 years after diagnosis) and 8 non-asthmatics undergoing pneumonectomy from lung tumor. The expression was analyzed in 4 areas of bronchial tissue-epithelium (EP), vascular endothelium (VE), smooth muscle (SM), mucous gland (MG). The grade of intensity was presented from 0 to 3. Subepithelial basement memberane (SBM) and submucosal extracellular matrix (SECM) thickness were measured using an image analyzer. Serum specific IgE and IgG antibody levels to TDI- human serum albumin (HSA) conjugate were detected by ELISA. Results : Grade of TGFβ1 expression was significantly higher in EP, VE and SM in group II than those of group I of TDI-induced asthma (p<0.05 respectively), with significant difference in SM only inRII expression. SBM and SECM thickness of TDI-induced asthma were significantly higher than those of non-asthmatics (p<0.05, respectively), while there was no significant difference between group I and II (p>0.05). Significant correlations were noted between asthma duration after diagonsis and intensity of TGFβ1 expression in EP, VE and SM (p<0.05, respectively), with no significant correlations with RII expression (p>0.05). TGF 1 expression was significantly higher in EP, VE and SM in subjects with specific IgG antibody to TDI-HSA than those without it (p<0.05). Conclusion : These findings suggest that TGFβ1 may contribute to develop persistent asthma symptoms in TDI-induced asthma.(Korean J Med 61:623-633, 2001)