Human Health Effects Of Exposure To Organochlorine Compounds

有机氯，如滴滴涕、其代谢物滴滴涕和多氯联苯，是持久性有机污染物，通过食物链暴露在一般人群遇到的水平上可能是有毒的。在动物实验中，多氯联苯会干扰神经发育，但人类的结果好坏参半。每种有机氯都有一种或多种生物活性，以及相应的潜在作用机制。例如，关于DDE对健康影响的一个主要担忧是，它干扰了雄激素与其受体的结合。 我在这方面的大部分工作是基于对孕妇血清的分析，这些孕妇参加了一项名为协作性围产期项目(CPP)的队列研究。在这里，我描述了我在CPP研究中的一些结果。我就持久性有机污染物对健康的影响所做的其他研究的结果显示在出版物清单中。 自1959-1965年以来，CPP中50,000多名孕妇的血清一直被冷冻在零下20摄氏度，关于她们后代的健康数据构成了许多调查人员仍在积极利用的资源。我们选择了大约2800名出生于1959-1966年的儿童，并在1997-1999年间测定了相应存储的孕妇妊娠血清中的有机氯浓度。 在早期的CPP论文中，我们研究了DDE水平与先前妊娠的胎儿丢失以及在CPP妊娠、早产、小于胎龄、出生体重和随后的身高之间的关系；在所有情况下，我们都发现了暗示不良影响的关联。为了寻找雄激素阻断的证据，我们检查了怀孕期间母亲的DDE水平与她们男性后代中调整后的隐睾症和尿道下裂的几率的关系；对于这些结果，结果是模棱两可的。 此外，我们评估了产前接触多氯联苯与8个月大、7岁时的发育评估表现以及8岁时听力检查所反映的听力的关系。所有这些研究都没有显示出任何关联。 去年的进展 由于该项目目前处于数据分析和报告阶段，报告和出版物反映了进展情况。今年，我们发表了一篇关于孕妇血清有机氯水平与男性后代出生缺陷风险关系的论文。我们还发表了一篇论文，研究了特定的多氯联苯同系物的水平是否对人类特定的肝酶活性具有信息性。一篇关于滴滴涕和神经发育的手稿正在准备提交给一家期刊。

Organochlorines such as DDT, its metabolite DDE, and polychlorinated biphenyls (PCBs) are persistent organic pollutants that may be toxic at levels encountered by the general population, through exposure in the food chain. PCBs interfere with neurodevelopment in animal experiments but human results are mixed. Each organochlorine has one or more types of biologic activity, and corresponding potential mechanisms of action. For example, a main concern about health effects of DDE has been because it interferes with androgen binding to its receptor. Most of my work in this area is based on analysis of serum from pregnant women who were in a cohort study named the Collaborative Perinatal Project (CPP). Here I describe some of my results from the CPP study. Results from other studies I have done on the health effects of persistent organic pollutants are indicated in the list of publications. Sera from over 50,000 pregnant women in the CPP have been frozen at -20 degrees Centigrade since 1959-1965, and with the health data on their offspring constitute a resource that is still actively used by many investigators. We selected a subset of about 2,800 children born in 1959-1966 and determined organochlorine concentrations in the corresponding stored maternal pregnancy sera, in 1997-1999. In earlier CPP papers we examined DDE levels in relation to fetal loss in previous pregnancies, and, in the CPP pregnancy, preterm birth, small-for-gestational-age, birthweight, and subsequent height; in all cases we found associations suggestive of adverse effects. To look for evidence of androgen-blocking, we examined maternal DDE level during pregnancy in relation to adjusted odds of cryptorchidism and hypospadias among their male offspring; for these outcomes the results were equivocal. Furthermore, we evaluated prenatal PCB exposure in relation to developmental assessment performance at 8 months of age, 7 years of age, and hearing as reflected by audiometric examination at age 8 years. None of these studies showed any associations. Last year's progress Because this project is now in the data analysis and reporting phase, the progress is reflected by presentations and publications. This year we published a paper on maternal pregancy serum organochlorine levels in relation to risk of birth defects in male offspring. We also published a paper examining whether levels of specific PCB congeners are informative regarding the activity of specific liver enzymes in humans. A manuscript on DDT and neurodevelopment is being prepared to submit to a journal.