Marfo Jemima Tiwaa, Fujioka Kazutoshi, Ikenaka Yoshinori, Nakayama Shouta M M, Mizukawa Hazuki, Aoyama Yoshiko, Ishizuka Mayumi, Taira Kumiko
Laboratory of Toxicology, Department of Environmental Veterinary Sciences, Faculty of Veterinary Medicine, Hokkaido University, Hokkaido, Japan.
Hawaii Institute of Molecular Education, Honolulu, Hawaii, United States.
PLoS One. 2015 Nov 4;10(11):e0142172. doi: 10.1371/journal.pone.0142172. eCollection 2015.
Neonicotinoid insecticides are nicotinic acetylcholine receptor agonists used worldwide. Their environmental health effects including neurotoxicity are of concern. We previously determined a metabolite of acetamiprid, N-desmethyl-acetamiprid in the urine of a patient, who exhibited some typical symptoms including neurological findings. We sought to investigate the association between urinary N-desmethyl-acetamiprid and the symptoms by a prevalence case-control study. Spot urine samples were collected from 35 symptomatic patients of unknown origin and 50 non-symptomatic volunteers (non-symptomatic group, NSG, 4-87 year-old). Patients with recent memory loss, finger tremor, and more than five of six symptoms (headache, general fatigue, palpitation/chest pain, abdominal pain, muscle pain/weakness/spasm, and cough) were in the typical symptomatic group (TSG, n = 19, 5-69 year-old); the rest were in the atypical symptomatic group (ASG, n = 16, 5-78 year-old). N-desmethyl-acetamiprid and six neonicotinoids in the urine were quantified by liquid chromatography-tandem mass spectrometry. The detection of N-desmethyl-acetamiprid was the most frequent and highest in TSG (47.4%, 6.0 ppb (frequency, maximum)), followed by in ASG (12.5%, 4.4 ppb) and in NSG (6.0%, 2.2 ppb), however acetamiprid was not detected. Thiamethoxam was detected in TSG (31.6%, 1.4 ppb), in ASG (6.3%, 1.9 ppb), but not in NSG. Nitenpyram was detected in TSG (10.5%, 1.2 ppb), in ASG (6.3%, not quantified) and in NSG (2.0%, not quantified). Clothianidin was only detected in ASG (6.3%, not quantified), and in NSG (2.0%, 1.6 ppb). Thiacloprid was detected in ASG (6.3%, 0.1 ppb). The cases in TSG with detection of N-desmethyl-acetamiprid and thiamethoxam were aged 5 to 62 years and 13 to 62 years, respectively. Detection of N-desmethyl-acetamiprid was associated with increased prevalence of the symptoms (odds ratio: 14, 95% confidence interval: 3.5-57). Urinary N-desmethyl-acetamiprid can be used as a biomarker for environmental exposure to acetamiprid. Further multi-centered clinical research in larger patients groups with more metabolites analysis is needed.
新烟碱类杀虫剂是全球广泛使用的烟碱型乙酰胆碱受体激动剂。它们对环境健康的影响，包括神经毒性，备受关注。我们之前在一名患者的尿液中检测到了啶虫脒的一种代谢物N-去甲基啶虫脒，该患者表现出一些典型症状，包括神经系统症状。我们试图通过一项现患病例对照研究来调查尿液中N-去甲基啶虫脒与这些症状之间的关联。采集了35名病因不明的有症状患者和50名无症状志愿者（无症状组，NSG，4至87岁）的即时尿样。近期有记忆力减退、手指震颤且出现六种症状（头痛、全身疲劳、心悸/胸痛、腹痛、肌肉疼痛/无力/痉挛和咳嗽）中五种及以上症状的患者属于典型症状组（TSG，n = 19，5至69岁）；其余患者属于非典型症状组（ASG，n = 16，5至78岁）。通过液相色谱-串联质谱法定量测定尿液中的N-去甲基啶虫脒和六种新烟碱类杀虫剂。N-去甲基啶虫脒的检出率在TSG中最高且最为常见（47.4%，6.0 ppb（检出率，最大值）），其次是ASG（12.5%，4.4 ppb）和NSG（6.0%，2.2 ppb），然而未检测到啶虫脒。噻虫嗪在TSG中被检测到（31.6%，1.4 ppb），在ASG中被检测到（6.3%，1.9 ppb），但在NSG中未被检测到。烯啶虫胺在TSG中被检测到（10.5%，1.2 ppb），在ASG中被检测到（6.3%，未定量），在NSG中被检测到（2.0%，未定量）。氯噻啉仅在ASG中被检测到（6.3%，未定量），在NSG中被检测到（2.0%，1.6 ppb）。噻虫啉在ASG中被检测到（6.3%，0.1 ppb）。TSG中检测到N-去甲基啶虫脒和噻虫嗪的病例年龄分别为5至62岁和13至62岁。N-去甲基啶虫脒的检测与症状患病率增加相关（比值比：14，95%置信区间：3.5至57）。尿液中的N-去甲基啶虫脒可作为啶虫脒环境暴露的生物标志物。需要在更大的患者群体中进行进一步的多中心临床研究，并进行更多代谢物分析。
