多氯聯苯及多氯呋喃中毒者及其子代之長期健康效應研究

Long-Term Health Outcome after Exposure/Prenatal Exposure to Polychlorinated Biphenyls and Dibenzofurans

李銘杰(Ming-Chieh Li)

指導教授 ： 郭育良

共同指導教授 ： 陳保中

國立臺灣大學/公共衛生學院/職業醫學與工業衛生研究所/博士(2015年)

https://doi.org/10.6342/NTU.2015.02587

摘要

1979年，約兩千人誤食遭到多氯聯苯與多氯呋喃污染的米糠油，稱做臺灣油症事件。此重大公衛議題，與1968年在日本發生的食用油中毒事件，無論是在毒性物質和意外發生的方式皆相當類似，又稱日本油症事件。兩起事件，官方統計受害的人數大約都快2000人，但真正的人數並不清楚。
我們長期追蹤這群中毒者，比較油症受害者和其性別、年齡與社經地位配對之鄰居對照組在各種死因死亡率是否有差異，以觀察油症受害者之長期健康效應；由於臺灣油症患者和日本油症患者毒物的暴露濃度類似、暴露毒物組成類似，且同為亞洲人，我們將兩個族群合併並進行統合分析，以重新評估各種死因別死亡率；多氯聯苯與多氯呋喃在人體中難以代謝，受害者體內長時間帶有高濃度的毒物，女性生產時也不例外。正因如此，油症女性受害者懷孕時，體內高濃度的多氯聯苯與多氯呋喃是否會對其子代造成影響，也是我們關注的重要議題。過去的研究認為產前暴露多氯聯苯會引發神經毒性，並傷害聽覺系統。有鑑於此，我們另外檢驗油症女性所生下的油症兒，其聽力是否受到影響。
此系列研究的重要發現如下: 1) 30年的追蹤研究發現，油症受害者比起其鄰居對照組，其整體死亡率、肝病、循環系統疾病以及肌肉骨骼系統及結締組織疾病死亡率皆顯著增加；男性油症受害者在胃癌以及淋巴及造血組織癌症之死亡率顯著上升。2) 臺灣與日本油症的統合分析結果發現，全體油症受害者的整體死亡率明顯上升；全體男性油症受害者在總癌症死亡率、肺癌、心臟疾病以及肝疾病的死亡率明顯上升；此外，全體女性油症受害者其肝癌死亡率亦顯著上升，這是第一次發現女性油症受害者之肝癌死亡率也有上升。3) 油症兒在產前暴露多氯聯苯與多氯呋喃，成年後會有聽力損失問題。且聽力損失的程度，與油症兒出生時，其母親體內推估的多氯呋喃濃度呈現正相關。
根據上述的研究結果，本文建議實施油症患者健康照護政策時，應盡可能增加各種癌症疾病的篩檢項目，特別是肝癌、肺癌、胃癌以及淋巴及造血組織癌症等，但不應僅限於上述列舉的癌症項目。此外，油症兒亦有許多健康上的損害，除了本文所發現的聽力損失問題，過去亦曾發現許多疾病與產前暴露多氯聯苯/多氯呋喃有關，其健康損害的程度並不亞於第一代油症患者。目前油症兒的健康問題，受到關注的程度仍比不上第一代，建議未來油症兒的照護政策，應盡可能比照第一代。

關鍵字

多氯聯苯 ； 多氯呋喃 ； 油症 ； 死因 ； 聽力損失 ； 產前暴露

並列摘要

In 1979, there was an outbreak of severe acne, skin pigmentation, and conjunctivitis in central Taiwan. Most of the cases had consumed the same brand of cooking oil, bought at the same stores. The illness, and its relation to cooking oil consumption, resembled a form of polychlorinated biphenyls (PCBs) and dibenzofurans (PCDFs) poisoning (called “Yusho,” oil disease in Japanese) that had occurred in western Japan in 1968, and oil and blood samples sent to Tokyo for analysis had high concentrations of PCBs and PCDFs. Yucheng (“oil disease” in Chinese) thus became the second recorded disease outbreak due to rice bran cooking oil contaminated by PCBs/PCDFs during manufacture. Although about 2000 persons registered with health agencies as being exposed after each episode, the exact number of victims is unknown.
We followed the exposed persons and compared their cause-specific mortality with that of neighborhood referents 30 years after the accident. Furthermore, we conducted a meta-analysis of Yucheng and Yusho cohorts to reevaluate the effects of PCBs and PCDFs on major causes of mortalities. PCBs have been suggested as neurotoxicants especially when exposed during prenatal and early postnatal periods, and known to cause neurological effects including auditory impairments. Thus we conducted a follow-up study to examine the association between gestational PCBs/PCDFs exposure and auditory function in Yucheng children’s early adulthood.
The main findings of current studies were as follows: 1) 30 year follow-up of mortality in the Yucheng cohort as compared to a neighborhood reference group found increased deaths from liver diseases, cardiovascular diseases, systemic lupus erythematosus, and neoplasms including stomach cancer and lymphatic and hematopoietic tissue cancer. 2) A meta-analysis of Yucheng and Yusho cohorts showed similar elevation from all cancer, lung cancer, heart disease, and hepatic disease mortalities in exposed men. Furthermore, a new finding of elevated liver cancer mortality in exposed women was identified. 3) Gestational exposure to PCDFs caused adverse asymmetrical hearing effects detectable even in early adulthood.
Our studies suggest that the health care policy for Yucheng victims should include, but not limited to, stomach, liver, lung, and lymphatic and hematopoietic tissue cancer screening as part of the regular health examination. Besides, we suggest that Yucheng children should receive as much health care as first-generation Yucheng victims.

並列關鍵字

Polychlorinated Biphenyls ； Polychlorinated Dibenzofurans ； Yucheng ； Mortality ； Hearing Loss ； Prenatal ； Gestational

參考文獻

Adcock IM, Brown CR, Kwon O, et al. Oxidative stress Induces NFκB DNA binding and inducible NOS mRNA in human epithelial cells. Biochemical and Biophysical Research Communications 1994;199:1518-24.

Sergeev AV and Carpenter DO. Hospitalization rates for coronary heart disease in relation to residence near areas contaminated with persistent organic pollutants and other pollutants. Environ Health Perspect 2005;113:756-61.

Anderson HA. General population exposure to environmental concentration of halogenated biphenyls. In: Kimbrough RD, Hansen AA, editors. Halogenated Biphenyls, Terphenyls, Naphthalenes, Dibenzodioxinx and Related Products. Amsterdam: Elsevier; 1989:325-44.

Bastomsky CH. Enhanced thyroxine metabolism and high uptake goiters in rats after a single dose of 2,3,7,8-tetrachlorodibenzo-p-dioxin. Endocrinology 1977;101:292-6.

Bertazzi PA, Riboldi L, Pesatori A, et al. Cancer mortality of capacitor manufacturing workers. Am J Ind Med 1987;11:165-76.