Tetrachlorodibenzo-p-dioxin (TCDD) is a ubiquitous, toxic, persistent and bioaccumulative organic pollutant. TCDD can potentially enter the food chain through contaminated food of animal origin as a consequence of feed contamination. Prediction of the TCDD transfer from feed into animal products is thus important for human health risk assessment. Here, we develop several physiologically based toxicokinetic (PBTK) models of TCDD transfer from contaminated feed into growing pigs (Sus scrofa) exposed to doses ranging from 24.52 to 3269.25 ng of TCDD. We test the consequences of explicit dose-dependent absorption (DDA) versus the indirect effects of a self-induced liver metabolism (SIM). The DDA and SIM models showed similar fit to experimental data, although currently it is not possible to unequivocally make statement on a mechanistic preference. The performance of both toxicokinetic models was successfully evaluated using the 1999 Belgian case of contaminated fats for feeding. In combination with toxicokinetic models of other dioxin congeners, they can be used to formulate maximum allowance levels of dioxins in feedstuffs for pigs. Additionally, the implementation of in silico-predicted partition coefficients was explored as a useful alternative to predict TCDD tissue distribution in low-dose scenarios without recurring to animal experiments.

中文翻译：

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基于生理学的毒物动力学模型和计算机模拟预测的分配系数，以估算四氯二苯并-对-二恶英从饲料转移到生长中的猪中。

四氯二苯并-对-二恶英（TCDD）是一种普遍存在，有毒，持久和具有生物蓄积性的有机污染物。由于饲料污染，TCDD可能通过受污染的动物源性食品进入食物链。因此，从饲料到动物产品的TCDD转移的预测对于人类健康风险评估很重要。在这里，我们开发了几种基于TCDD的生理学毒代动力学（PBTK）模型，将TCDD从受污染的饲料转移到暴露于TCDD剂量为24.52至3269.25 ng的成年猪（Sus scrofa）中。我们测试了显着的剂量依赖性吸收（DDA）与自我诱导的肝代谢（SIM）的间接影响的后果。DDA和SIM模型显示出与实验数据相似的拟合度，尽管目前尚无法明确地就机械性偏好做出陈述。两种毒物动力学模型的性能已通过1999年比利时一例受污染的脂肪喂养案例成功进行了评估。结合其他二恶英同类物的毒物动力学模型，它们可用于制定猪饲料中二恶英的最大限量。另外，探索了计算机预测的分配系数的实现方法，作为预测低剂量场景中TCDD组织分布的有用替代方法，而无需进行动物实验。