Université de Lorraine, INRAE, USC 340, UR AFPA, 2 Avenue de la Forêt de Haye, TSA 40602, 54518, Vandœuvre-lès-Nancy, France.
INTHERES, Université de Toulouse, INRAE, ENVT, 31000, Toulouse, France.
Chemosphere. 2020 Jul;250:126151. doi: 10.1016/j.chemosphere.2020.126151. Epub 2020 Feb 11.
The use of chlordecone (CLD), a chlorinated polycyclic pesticide used in the French West Indies banana fields between 1972 and 1993, resulted in a long-term pollution of agricultural areas. It has been observed that this persistent organic pollutant (POP) can transfer from contaminated soils to food chain. Indeed, CLD is considered almost fully absorbed after involuntary ingestion of contaminated soil by outdoor reared animals. The aim of this study was to model toxicokinetics (TKs) of CLD in growing pigs using both non-compartmental and nonlinear mixed-effects approaches (NLME). In this study, CLD dissolved in cremophor was intravenously administrated to 7 Creole growing pigs and 7 Large White growing pigs (1 mg kg body weight). Blood samples were collected from time t = 0 to time t = 84 days. CLD concentrations in serum were measured by GCMS/MS. Data obtained were modeled using Monolix (2019R). Results demonstrated that a bicompartmental model best described CLD kinetics in serum. The influence of covariates (breed, initial weight and average daily gain) was simultaneously evaluated and showed that average daily gain is the main covariate explaining inter-individual TKs parameters variability. Body clearance was of 76.7 mL kg d and steady-state volume of distribution was of 6 L kg. This modeling approach constitutes the first application of NLME to study CLD TKs in farm animals and will be further used for rearing management practices in contaminated areas.
多氯环戊二烯（CLD）的使用，一种在 1972 年至 1993 年期间在法属西印度群岛香蕉田中使用的氯化多环农药，导致了农业区的长期污染。已经观察到这种持久性有机污染物（POP）可以从受污染的土壤转移到食物链。事实上，在户外饲养的动物因摄入受污染的土壤而无意识地摄入后，CLD 被认为几乎完全被吸收。本研究旨在使用非房室和非线性混合效应方法（NLME）对生长猪的 CLD 毒代动力学（TKs）进行建模。在这项研究中，将溶解在 Cremophor 中的 CLD 静脉注射到 7 头克里奥尔生长猪和 7 头大白生长猪（1mg/kg 体重）中。从时间 t=0 到时间 t=84 天采集血样。通过 GCMS/MS 测量血清中 CLD 的浓度。使用 Monolix（2019R）对获得的数据进行建模。结果表明，双室模型最能描述血清中 CLD 的动力学。同时评估了协变量（品种、初始体重和平均日增重）的影响，结果表明，平均日增重是解释个体间 TKs 参数变异性的主要协变量。清除率为 76.7 mL/kg/d，稳态分布容积为 6 L/kg。这种建模方法是 NLME 在研究农场动物 CLD TKs 中的首次应用，将进一步用于污染地区的养殖管理实践。
