婴幼儿不同发育阶段邻苯二甲酸酯的暴露负荷及代谢特征研究

Because of the fast growth and organ development, infant is believed to be one of the most vulnerable cohorts to the risks of environmental pollutants. Calculated by body weight, infants may burden more pollutants than adults. It is because they have immature metabolic system, and they are exposed to more chemicals like phthalates through several different routes including digestion, inhalation and skin contact than adults. The developmental stage-specific physiological behaviors, metabolic mechanisms and capacities add more uncertainty to the infant exposure risk and health risk than to the adult. Our previous study indicated that infant may expose more some phthalates such as DBP than adult. Due to the potential health risk of phthalates, the proposal intends to investigate infants' developmental stage-specific exposure to these pollutants and the metabolic capacity in pollutant clearance. By using follow-up biomonitoring, we will investigate infants' phthalate body burden and their metabolite profiles at each of the developmental stages, including 0-1, 1-3, 3-6, 6-12 month old and 1-2 year old. Referencing to phthalates' metabolic capacity and its dynamic changes in liver microsomes from baby rats, infants' developmental stage-specific metabolism of phthalates will be characterized by combining with the biomonitoring data and exposure factor questionnaires. Finally the study would contribute to some basic knowledge of infant exposure risk to phthalates, and in further, could refine the infant cohort risk assessment.

处于快速发育阶段的婴幼儿是环境污染物暴露和健康危害的敏感人群。婴幼儿生理和行为具有明显的发育阶段性特征，假设他们的污染物暴露和代谢能力也具有明显的发育阶段性特征，以单位体重计量，通过消化系统、呼吸系统和皮肤接触，他们可能比成人更多地暴露于环境污染物。我们的前期研究发现，婴幼儿尿液中DBP的暴露标志物MBP的含量显著高于成人。鉴于邻苯二甲酸酯类污染物（PAEs）对儿童发育的潜在风险，本项目将研究婴幼儿发育阶段的PAEs暴露和代谢特征。首先，通过连续跟踪的生物监测和流行病问卷调查，研究婴幼儿不同发育阶段PAEs的暴露和负荷特征；其次，结合大鼠幼崽肝微粒体代谢模型，研究代谢系统（酶）成熟过程中不同结构PAEs代谢变化，分析代谢差异与关键酶表达的关系，为理解婴幼儿代谢PAEs的发育阶段性特征提供参考。项目将为合理评价PAEs的婴幼儿期暴露和生长发育风险提供基础数据。

国家基金委的资助下，本项目成功建立了0-12月婴幼儿出生队列，完成人群基本信息和生物样品的收集工作。采用连续的人群生物监测研究策略，开展了婴幼儿期（0-6月）不同发育阶段PAEs的负荷及代谢物特征研究。由于队列研究人群基本信息收集和样品前处理耗时长等特点，前期人群的征集，基本信息收集和样品前处理投入了大量的经费和时间，因此，本项目研究重点聚焦于婴幼儿期不同发育阶段PAEs的负荷，代谢物特征及健康效应等方面。本项目运用SPE固相萃取的前处理技术，通过优化色谱和质谱条件，建立测定成人尿液中10种邻苯二甲酸酯类化合物暴露评价的稳定、灵敏、准确的HPLC-ESI-MS/MS结合稳定性同位素稀释的分析方法，并应用于尿液中邻苯二甲酸酯代谢物检测。研究发现，PAEs代谢物的种类（单酯、自由态、糖苷结合态、氧化态）、含量和不同形态的比率在婴幼儿期（0-6月）不同发育阶段PAEs的负荷及代谢物特征存在显著差异。随着婴幼儿身体和生理的发育，污染物的暴露负荷增加，代谢PAEs污染物的能力逐渐增强。奶粉可能是PAEs暴露的重要途径之一。邻苯二甲酸酯暴露对婴幼儿不同发育期的激素具有内分泌干扰效应。以上结果不仅为合理评价PAEs的婴幼儿期暴露和生长发育风险提供基础数据，而且为研究污染物在人体内的代谢转化机制及合理制定风险评价和预防措施提供科学依据。项目执行期间已发表SCI研究论文6篇，申请2项国家实用新型专利，部分文章已在投稿或撰写中；项目组成员参加多次环境化学相关领域学术会议交流；协助培养研究生3名。