INSERM, INRAE, Institut NUMECAN (Nutrition, Metabolisms and Cancer) UMR_A 1341, UMR_S 1241, Univ Rennes, F-35000, Rennes, France.
Pharmacy, Rennes University Hospital, F-35033, Rennes, France.
Int J Legal Med. 2022 Nov;136(6):1585-1596. doi: 10.1007/s00414-022-02885-z. Epub 2022 Sep 2.
Carbofuran is a pesticide widely used in agricultural context to kill insects, mites, and flies by ingestion or contact. Along with literature review, we aimed to (i) present the clinical, autopsy, and toxicological findings of carbofuran self-poisonings in two 69-year-old twins, resulting in the death of one of them and (ii) assess carbofuran metabolite distribution using molecular networking. Quantitative analysis of carbofuran and its main metabolites (3-hydroxycarbofuran and 3-ketocarbofuran) was carried out using an original liquid chromatography-tandem mass spectrometry method on biological samples (cardiac or peripheral blood, urine, bile, and gastric contents). Toxicological analysis of post-mortem samples (twin 1) highlighted high concentrations of carbofuran and its metabolites in cardiac blood, bile, and gastric contents. These compounds were also quantified in blood and/or urine samples of the living brother (twin 2), confirming poisoning. Using molecular networking approach to facilitate visualization of mass spectrometry datasets and sample-to-sample comparisons, we detected two more metabolites (7-phenol-carbofuran and 3-hydroxycarbofuran glucuronide) in bile (twin 1) and urine (twin 2). These results highlight the value of (i) these compounds as carbofuran consumption markers and (ii) bile samples in post-mortem analysis to confirm poisoning. From an analytical point of view, molecular networking allowed the detection and interpretation of carbofuran metabolite ammonium adducts which helped to confirm their identification annotations, as well as their structural data. From a clinical point of view, the different outcomes between the two brothers are discussed. Overall, these cases provide novel information regarding the distribution of carbofuran and its metabolites in poisoning context.
呋喃丹是一种在农业中广泛使用的杀虫剂，通过摄入或接触来杀死昆虫、螨虫和苍蝇。我们通过文献回顾，旨在：(i) 介绍两例 69 岁双胞胎因呋喃丹自服中毒导致其中一人死亡的临床、尸检和毒理学发现；(ii) 使用分子网络评估呋喃丹代谢物的分布。采用原创的液相色谱-串联质谱法对生物样本（心或外周血、尿液、胆汁和胃内容物）中的呋喃丹及其主要代谢物（3-羟基呋喃丹和 3-酮基呋喃丹）进行定量分析。对死后样本（双胞胎 1）的毒理学分析显示，心血液、胆汁和胃内容物中呋喃丹及其代谢物浓度较高。在存活兄弟（双胞胎 2）的血液和/或尿液样本中也检测到这些化合物，证实了中毒。使用分子网络方法促进了质谱数据集的可视化和样品间的比较，我们在胆汁（双胞胎 1）和尿液（双胞胎 2）中检测到另外两种代谢物（7-苯酚呋喃丹和 3-羟基呋喃丹葡萄糖醛酸苷）。这些结果突出了这些化合物作为呋喃丹消耗标志物的价值和在死后分析中胆汁样本对确认中毒的价值。从分析的角度来看，分子网络允许检测和解释呋喃丹代谢物的铵加合物，这有助于确认它们的鉴定注释和结构数据。从临床的角度来看，讨论了两兄弟之间的不同结果。总的来说，这些案例提供了有关中毒情况下呋喃丹及其代谢物分布的新信息。
