University of South Australia Clinical and Health Sciences, University of South Australia, Adelaide, Australia.
Therapeutics Research Centre, Basil Hetzel Institute for Translational Health Research, The Queen Elizabeth Hospital, Adelaide, Australia.
Clin Toxicol (Phila). 2024 Aug;62(8):483-496. doi: 10.1080/15563650.2024.2375584. Epub 2024 Jul 29.
Common major co-formulants in glyphosate-based herbicides, polyethoxylated tallow amine surfactants, are suspected of being more toxic than glyphosate, contributing to the toxicity in humans. However, limited information exists on using polyethoxylated tallow amine concentrations to predict clinical outcomes. We investigated if plasma concentrations of glyphosate, its metabolite and polyethoxylated tallow amines can predict acute kidney injury and case fatality in glyphosate poisoning.
We enrolled 151 patients with acute glyphosate poisoning between 2010 and 2013. Plasma concentrations of glyphosate, its metabolite, aminomethylphosphonic acid, and polyethoxylated tallow amines were determined in 2020 using liquid chromatography-tandem mass spectrometry. Associations between exposure and poisoning severity were assessed.
Plasma concentrations of glyphosate and aminomethylphosphonic acid demonstrated good and moderate performances in predicting acute kidney injury (≥2), with an area under the receiver operating characteristic curve of 0.83 (95% CI 0.69-0.97) and 0.76 (95% CI 0.59-0.94), respectively. Polyethoxylated tallow amines were detected in one-fifth of symptomatic patients, including one of four fatalities and those with unsaturated tallow moieties being good indicators of acute kidney injury (area under the receiver operating characteristic curve ≥0.7). As the number of repeating ethoxylate units in tallow moieties decreased, the odds of acute kidney injury increased. Glyphosate and aminomethylphosphonic acid concentrations were excellent predictors of case fatality (area under the receiver operating characteristic curve >0.9).
The 2.7% case fatality rate with 49% acute, albeit mild, acute kidney injury following glyphosate poisoning is consistent with previously published data. A population approach using model-based metrics might better explore the relationship of exposure to severity of poisoning.
Plasma concentrations of glyphosate and its metabolite predicted the severity of clinical toxicity in glyphosate poisoning. The co-formulated polyethoxylated tallow amine surfactants were even more strongly predictive of acute kidney injury but were only detected in a minority of patients.
草甘膦类除草剂中的常见主要共溶剂聚氧乙基化牛脂胺表面活性剂，被怀疑比草甘膦毒性更大，导致人类中毒。然而，目前关于使用聚氧乙基化牛脂胺浓度来预测临床结果的信息有限。我们研究了草甘膦中毒患者的血浆草甘膦、其代谢物和聚氧乙基化牛脂胺浓度是否可以预测急性肾损伤和病死率。
我们招募了 2010 年至 2013 年期间 151 名急性草甘膦中毒患者。2020 年使用液相色谱-串联质谱法测定了血浆草甘膦、其代谢物氨甲基膦酸和聚氧乙基化牛脂胺的浓度。评估了暴露与中毒严重程度之间的关系。
血浆草甘膦和氨甲基膦酸浓度在预测急性肾损伤（≥2）方面表现出良好和中度的性能，受试者工作特征曲线下面积分别为 0.83（95%置信区间 0.69-0.97）和 0.76（95%置信区间 0.59-0.94）。在有症状的患者中，有五分之一检测到聚氧乙基化牛脂胺，包括四名死亡患者中的一名，并且具有不饱和牛脂部分的患者是急性肾损伤的良好指标（受试者工作特征曲线下面积≥0.7）。随着牛脂部分中重复乙氧基单元的数量减少，急性肾损伤的几率增加。草甘膦和氨甲基膦酸浓度是病死率的优秀预测因子（受试者工作特征曲线下面积>0.9）。
草甘膦中毒后 2.7%的病死率和 49%的急性、尽管是轻度的急性肾损伤与先前发表的数据一致。使用基于模型的指标的人群方法可能更好地探索暴露与中毒严重程度的关系。
血浆草甘膦及其代谢物浓度预测了草甘膦中毒的临床毒性严重程度。共配制的聚氧乙基化牛脂胺表面活性剂对急性肾损伤的预测作用更强，但仅在少数患者中检测到。
