Medical University of Vienna, Institute of Medical Genetics, Vienna, Austria.
Medical University of Vienna, Institute of Medical Genetics, Vienna, Austria; Medical University of Vienna, Department of Environmental Health, Center for Public Health, Vienna, Austria.
Int J Hyg Environ Health. 2021 Sep;238:113855. doi: 10.1016/j.ijheh.2021.113855. Epub 2021 Oct 13.
Lead (Pb) is a ubiquitous environmental pollutant and a potent toxic compound. Humans are exposed to Pb through inhalation, ingestion, and skin contact via food, water, tobacco smoke, air, dust, and soil. Pb accumulates in bones, brain, liver and kidney. Fetal exposure occurs via transplacental transmission. The most critical health effects are developmental neurotoxicity in infants and cardiovascular effects and nephrotoxicity in adults. Pb exposure has been steadily decreasing over the past decades, but there are few recent exposure data from the general European population; moreover, no safe Pb limit has been set. Sensitive biomarkers of exposure, effect and susceptibility, that reliably and timely indicate Pb-associated toxicity are required to assess human exposure-health relationships in a situation of low to moderate exposure. Therefore, a systematic literature review based on PubMed entries published before July 2019 that addressed Pb exposure and biomarkers of effect and susceptibility, neurodevelopmental toxicity, epigenetic modifications, and transcriptomics was conducted. Finally included were 58 original papers on Pb exposure and 17 studies on biomarkers. The biomarkers that are linked to Pb exposure and neurodevelopment were grouped into effect biomarkers (serum brain-derived neurotrophic factor (BDNF) and serum/saliva cortisol), susceptibility markers (epigenetic markers and gene sequence variants) and other biomarkers (serum high-density lipoprotein (HDL), maternal iron (Fe) and calcium (Ca) status). Serum BDNF and plasma HDL are potential candidates to be further validated as effect markers for routine use in HBM studies of Pb, complemented by markers of Fe and Ca status to also address nutritional interactions related to neurodevelopmental disorders. For several markers, a causal relationship with Pb-induced neurodevelopmental toxicity is likely. Results on BDNF are discussed in relation to Adverse Outcome Pathway (AOP) 13 ("Chronic binding of antagonist to N-methyl-D-aspartate receptors (NMDARs) during brain development induces impairment of learning and memory abilities") of the AOP-Wiki. Further studies are needed to validate sensitive, reliable, and timely effect biomarkers, especially for low to moderate Pb exposure scenarios.
铅（Pb）是一种普遍存在的环境污染物，也是一种有毒化合物。人类通过吸入、摄入和皮肤接触，经由食物、水、烟草烟雾、空气、灰尘和土壤接触到铅。铅在骨骼、大脑、肝脏和肾脏中积累。胎儿通过胎盘传播接触到铅。最关键的健康影响是婴儿的发育神经毒性和成年人的心血管影响和肾毒性。在过去几十年中，铅暴露一直在稳步下降，但来自欧洲普通人群的最新暴露数据很少；此外，还没有设定安全的铅限值。需要敏感的暴露、效应和易感性生物标志物，以可靠和及时地指示与铅相关的毒性，以评估低至中度暴露情况下的人类暴露-健康关系。因此，进行了一项基于 2019 年 7 月之前发表的 PubMed 条目的系统文献综述，该综述涉及铅暴露以及效应和易感性生物标志物、神经发育毒性、表观遗传修饰和转录组学。最终包括 58 篇关于铅暴露的原始论文和 17 项关于生物标志物的研究。与铅暴露和神经发育相关的生物标志物分为效应生物标志物（血清脑源性神经营养因子（BDNF）和血清/唾液皮质醇）、易感性标志物（表观遗传标记和基因序列变体）和其他生物标志物（血清高密度脂蛋白（HDL）、母体铁（Fe）和钙（Ca）状况）。血清 BDNF 和血浆 HDL 是作为常规使用的 HBM 研究中铅的效应标志物进一步验证的潜在候选物，辅以 Fe 和 Ca 状态的标志物，以解决与神经发育障碍相关的营养相互作用。对于几种生物标志物，铅诱导的神经发育毒性的因果关系很可能存在。BDNF 的结果与 AOP-Wiki 中的 AOP13（“大脑发育过程中 N-甲基-D-天冬氨酸受体（NMDAR）的慢性拮抗剂结合导致学习和记忆能力受损”）有关。需要进一步研究以验证敏感、可靠和及时的效应生物标志物，特别是对于低至中度铅暴露情况。
