持久性有机氯污染物的人群暴露及其健康风险评估
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摘要
以农药滴滴涕(dichloro-diphenyl-trichloroethane, DDT)、六六六(hexachlorocyclohexane, HCH),工业用品PCB (polychlorinated biphenyl, PCB)为代表的持久性有机氯污染物(persistent organochlorines, POCs)是一类在环境中能长期滞留,具有生物放大效应,可蓄积在脂肪组织中的内分泌干扰物。研究表明POCs类污染物会对生物的呼吸系统、神经内分泌系统、生殖系统等多个系统产生毒性效应。评估POCs在环境中及人体中的暴露水平从而进一步得到POCs对健康影响的危险度对人类采取相应的防治措施具有重大意义。本研究主要内容及成果如下：
(1)本研究共采集并检测了几乎覆盖中国各省(除香港、澳门)的132个农田土壤样本；构建了在四个不同膳食结构区域、由六类食物摄入而富集的DDTs的剂量模型；最后用人群归因分值(population attributable factor, PAF)来表征DDT暴露的乳腺癌发病风险。结果发现中国主要农业区域土壤中DDT残留浓度较高,DDT总量的浓度中位数为2.61ng/g,范围为0.37-547.03ng/g,超标(100ng/g)的土壤威胁4230万中国人口的健康。考虑到不同地区人群的膳食结构不同,通过模型计算得的日均膳食摄入DDT剂量估计为0.34μg/(kg体重)p,p'-DDE (DDT的生物活性组分)。而PAF中位数为0.60%(IQR，0.23%-2.11%),这个结果表明p,p'-DDE贡献的中国女性年乳腺癌发病率为十万分之0.06。尽管DDT暴露是乳腺癌发病风险之一,但较低的贡献率说明其他影响因素,如基因易感性、生活习惯等才是乳腺癌发病的主要因素。
(2)许多研究发现POCs会通过胎盘屏障从而影响下一代的健康。本研究以中国浙江舟山嵊泗县的母婴人群为研究对象进行流行病学调查研究。嵊泗群岛位于长江出海口以东,长江流域的农业面源污染会威胁岛上居民健康。通过调查母亲的一般人口学状况、饮食特点、生育经历,新生儿的生长发育指标,以及对脐血血浆中HCHs浓度的实验室检测来评估HCHs对新生儿生长发育的影响。结果发现嵊泗新生儿体重、身长普遍高于全国其他地区水平；与国外其他研究相比,HCHs脐血残留处于较高水平；通过t检验并未发现HCHs暴露与新生儿生长发育指标有相关性。
(3) POCs暴露可能是二型糖尿病(type2diabetes mellitus, T2DM)发病的风险因素之一,本研究用meta分析的方法合并了不同研究的结果并且定量评估了两者的关系。通过对Medline和Web of science数据库的检索,我们最终纳入了23篇研究论文进行统计分析,合并了所有研究中的比值比(odds ratio, OR)或相对风险度(relative risk, RR)。每一篇研究都进行了详细的质量评估,在存在异质性的情况下进行了亚组分析来探究异质源。最终估计值的合并结果中PCB-153的相对风险度为1.52(CI,1.19-1.94),PCBs为2.14(CI,1.53-2.99),p,p'-DDE为1.33(CI,1.15-1.54)。结果表明暴露于POCs污染物是T2DM发病的风险因素。
Persistent organochlorines (POCs), represented by hexachlorocyclohexane (HCH), polychlorinated biphenyl (PCB), and dichlorodiphenyltrichloroethane (DDT), are endocrine disrupters which have persistency, biomagnification effect, and can accumulate in human adipose tissues. Some studies give evidences that POCs may have toxicity to respiratory system, neuroendocrine system, and reproductive system. Assessing the exposure level of POCs in human and the risk ratios to human health is very important to take appropriate preventive measures in future. The main study contents and results are as follows:
(1) DDT levels in132agricultural soil samples covering the entire region of China (except for Hongkong and Macau) were determined. Dietary intake of DDT for six food types and four dietary regions was modeled. Population attributable fraction (PAF) was used to assess the DDT exposure risk to breast cancer. Higher DDT concentrations were found in the main agricultural regions, the median value of total DDT components was2.60ng/g with range from0.37to547.03ng/g, and DDT exceeding the regulatory limit of100ng/g was found to impact42.3million Chinese population. Considering the geographical differences with diverse DDT contributions and different diet products and habits, the average daily dietary intake (DDI) was estimated to be0·34μg/kg/day p,p'-DDE (the main bioactive constituent in DDT). Based on the estimated PAF with a median value of0·60%(IQR0·23%-2·11%), the excess annual breast cancer incidence rate attributable to p,p'-DDE exposure averaged006×10-5in Chinese females. Exposure to DDT is a contributor to breast cancer, but the overall limited PAF imply confounding factors for breast cancer in Chinese females such as gene susceptibility and lifestyle.
(2) The POCs may pass through the placental barrier and affect the development of the next generation. We conduct an epidemiological survey on the pregnant women and their infant who are fish consumers living on the island facing the Yangtze River estuary. Most agricultural non-point source pollution discharge into sea through the Yangtze River estuary and these pollutions may threaten the health of the islanders. Questionnaires including the mother's sociodemographic characteristics, dietary structure, reproductive history, the growth and development of infants were collected. Combined with the detection of HCHs concentration in umbilical cord blood, we assessed the effect of infant development from exposure to HCHs. The result showed that the weight and and longth of the infant were in a higher level compared with infants in other regions; HCHs concentrations in umbilical cord blood were high compared with the results is other studies; and we found no association between HCHs residue and T2DM by t test.
(3) Exposure to organochlorine pollutants is considered the risk factor of type2diabetes. To quantitatively evaluate the association and pool the inconsistent evidence, we performed a meta-analysis. Publications in English were searched in medline and web of science databases and finally23studies were extracted. All the estimate values including odds ratio (OR) and relative risk (RR) were pooled. Rigorous quality assessment was performed, and considering the heterogeneity sources, subgroup analyses were conducted. The pooled OR of PCB-153, PCBs, and p,p'-DDE was1.52(confidence interval, CI,1.19-1.94),2.14(CI,1.53-2.99),1.33(CI,1.15-1.54), respectively. The results indicates that exposure to POCs is associated with an increased risk of T2DM.
(1)本研究共采集并检测了几乎覆盖中国各省(除香港、澳门)的132个农田土壤样本；构建了在四个不同膳食结构区域、由六类食物摄入而富集的DDTs的剂量模型；最后用人群归因分值(population attributable factor, PAF)来表征DDT暴露的乳腺癌发病风险。结果发现中国主要农业区域土壤中DDT残留浓度较高,DDT总量的浓度中位数为2.61ng/g,范围为0.37-547.03ng/g,超标(100ng/g)的土壤威胁4230万中国人口的健康。考虑到不同地区人群的膳食结构不同,通过模型计算得的日均膳食摄入DDT剂量估计为0.34μg/(kg体重)p,p'-DDE (DDT的生物活性组分)。而PAF中位数为0.60%(IQR，0.23%-2.11%),这个结果表明p,p'-DDE贡献的中国女性年乳腺癌发病率为十万分之0.06。尽管DDT暴露是乳腺癌发病风险之一,但较低的贡献率说明其他影响因素,如基因易感性、生活习惯等才是乳腺癌发病的主要因素。
(2)许多研究发现POCs会通过胎盘屏障从而影响下一代的健康。本研究以中国浙江舟山嵊泗县的母婴人群为研究对象进行流行病学调查研究。嵊泗群岛位于长江出海口以东,长江流域的农业面源污染会威胁岛上居民健康。通过调查母亲的一般人口学状况、饮食特点、生育经历,新生儿的生长发育指标,以及对脐血血浆中HCHs浓度的实验室检测来评估HCHs对新生儿生长发育的影响。结果发现嵊泗新生儿体重、身长普遍高于全国其他地区水平；与国外其他研究相比,HCHs脐血残留处于较高水平；通过t检验并未发现HCHs暴露与新生儿生长发育指标有相关性。
(3) POCs暴露可能是二型糖尿病(type2diabetes mellitus, T2DM)发病的风险因素之一,本研究用meta分析的方法合并了不同研究的结果并且定量评估了两者的关系。通过对Medline和Web of science数据库的检索,我们最终纳入了23篇研究论文进行统计分析,合并了所有研究中的比值比(odds ratio, OR)或相对风险度(relative risk, RR)。每一篇研究都进行了详细的质量评估,在存在异质性的情况下进行了亚组分析来探究异质源。最终估计值的合并结果中PCB-153的相对风险度为1.52(CI,1.19-1.94),PCBs为2.14(CI,1.53-2.99),p,p'-DDE为1.33(CI,1.15-1.54)。结果表明暴露于POCs污染物是T2DM发病的风险因素。
Persistent organochlorines (POCs), represented by hexachlorocyclohexane (HCH), polychlorinated biphenyl (PCB), and dichlorodiphenyltrichloroethane (DDT), are endocrine disrupters which have persistency, biomagnification effect, and can accumulate in human adipose tissues. Some studies give evidences that POCs may have toxicity to respiratory system, neuroendocrine system, and reproductive system. Assessing the exposure level of POCs in human and the risk ratios to human health is very important to take appropriate preventive measures in future. The main study contents and results are as follows:
(1) DDT levels in132agricultural soil samples covering the entire region of China (except for Hongkong and Macau) were determined. Dietary intake of DDT for six food types and four dietary regions was modeled. Population attributable fraction (PAF) was used to assess the DDT exposure risk to breast cancer. Higher DDT concentrations were found in the main agricultural regions, the median value of total DDT components was2.60ng/g with range from0.37to547.03ng/g, and DDT exceeding the regulatory limit of100ng/g was found to impact42.3million Chinese population. Considering the geographical differences with diverse DDT contributions and different diet products and habits, the average daily dietary intake (DDI) was estimated to be0·34μg/kg/day p,p'-DDE (the main bioactive constituent in DDT). Based on the estimated PAF with a median value of0·60%(IQR0·23%-2·11%), the excess annual breast cancer incidence rate attributable to p,p'-DDE exposure averaged006×10-5in Chinese females. Exposure to DDT is a contributor to breast cancer, but the overall limited PAF imply confounding factors for breast cancer in Chinese females such as gene susceptibility and lifestyle.
(2) The POCs may pass through the placental barrier and affect the development of the next generation. We conduct an epidemiological survey on the pregnant women and their infant who are fish consumers living on the island facing the Yangtze River estuary. Most agricultural non-point source pollution discharge into sea through the Yangtze River estuary and these pollutions may threaten the health of the islanders. Questionnaires including the mother's sociodemographic characteristics, dietary structure, reproductive history, the growth and development of infants were collected. Combined with the detection of HCHs concentration in umbilical cord blood, we assessed the effect of infant development from exposure to HCHs. The result showed that the weight and and longth of the infant were in a higher level compared with infants in other regions; HCHs concentrations in umbilical cord blood were high compared with the results is other studies; and we found no association between HCHs residue and T2DM by t test.
(3) Exposure to organochlorine pollutants is considered the risk factor of type2diabetes. To quantitatively evaluate the association and pool the inconsistent evidence, we performed a meta-analysis. Publications in English were searched in medline and web of science databases and finally23studies were extracted. All the estimate values including odds ratio (OR) and relative risk (RR) were pooled. Rigorous quality assessment was performed, and considering the heterogeneity sources, subgroup analyses were conducted. The pooled OR of PCB-153, PCBs, and p,p'-DDE was1.52(confidence interval, CI,1.19-1.94),2.14(CI,1.53-2.99),1.33(CI,1.15-1.54), respectively. The results indicates that exposure to POCs is associated with an increased risk of T2DM.
引文
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