Univerity of North Carolina Neuroscience Center, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Department of Cell Biology and Physiology, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Environ Health Perspect. 2022 Feb;130(2):27013. doi: 10.1289/EHP9808. Epub 2022 Feb 24.
Azoxystrobin (AZ) is a broad-spectrum strobilurin fungicide that is used in agriculture and was recently added to mold- and mildew-resistant wallboards. AZ was found to have toxic effects in animals at embryonic stages and was listed as a frontline target for biomonitoring in children.
This study investigated exposure to AZ in pregnant women and young children, whether AZ could be transferred from an exposed mother to offspring, and whether AZ or one of its primary metabolites, AZ-acid, was neurotoxic .
We quantified AZ-acid, a sensitive indicator of AZ exposure, in urine samples collected from 8 pregnant women (12 urine samples) and 67 children (40-84 months old; 96 urine samples) with high-resolution mass spectrometry. Gestational and lactational transfer was assessed in C57Bl/6 mice. Neurotoxicity of AZ and AZ-acid was investigated with mouse cortical neuron cultures.
AZ-acid was present above the limit of quantification () in 100% of the urine samples from pregnant women and in 70% of the urine samples from children, with median concentration of 0.10 and , and maximal concentration of 2.70 and , respectively. Studies in mice revealed that AZ transferred from the mother to offspring during gestation by crossing the placenta and entered the developing brain. AZ was also transferred to offspring via lactation. High levels of cytotoxicity were observed in embryonic mouse cortical neurons at concentrations that modeled environmentally relevant exposures.
Our study suggested that pregnant women and children were exposed to AZ, and at least 10% of the children (2 out of 20 that were evaluated at two ages) showed evidence of chronic exposure. Future studies are warranted to evaluate whether chronic AZ exposure affects human health and development. https://doi.org/10.1289/EHP9808.
唑醚菌酯(AZ)是一种广谱的 strobilurin 类杀菌剂,用于农业,并于近期被添加到防霉防潮墙板中。AZ 已被发现对胚胎期动物具有毒性作用,并被列为儿童生物监测的一线目标。
本研究调查了孕妇和幼儿接触 AZ 的情况,母体暴露的 AZ 是否能转移到后代身上,以及 AZ 或其主要代谢物 AZ-酸是否具有神经毒性。
我们采用高分辨质谱法,对 8 名孕妇(12 份尿液样本)和 67 名儿童(40-84 个月大;96 份尿液样本)的尿液样本中 AZ 的敏感指示物 AZ-酸进行了定量检测。我们在 C57Bl/6 小鼠中评估了妊娠和哺乳期的转移情况。我们还利用小鼠皮质神经元培养物研究了 AZ 和 AZ-酸的神经毒性。
孕妇尿液样本中 100%(12 份尿液样本)和儿童尿液样本中 70%(96 份尿液样本)存在可定量的 AZ-酸,中位数浓度分别为 0.10 和 ,最高浓度分别为 2.70 和 。在小鼠研究中,AZ 通过胎盘穿过胎盘转移到胎儿,并进入发育中的大脑,从而从母体转移到后代。AZ 还通过哺乳传递给后代。在模拟环境相关暴露浓度的情况下,胚胎期小鼠皮质神经元中观察到高水平的细胞毒性。
本研究表明孕妇和儿童接触到 AZ,至少有 10%的儿童(20 名接受了两次年龄评估的儿童中的 2 名)表现出慢性暴露的证据。需要进一步研究来评估慢性 AZ 暴露是否会影响人类健康和发育。