In France, part of the population is overexposed to cadmium by the diet. In our work, we first revised the tolerable daily intake (TDI) of 0.36 μg Cd.kg bw.d.-1 proposed by the European Food Safety Authority (EFSA), derived from effects on kidneys and based on the critical urinary Cd concentration of 1.0 μg Cd.g-1 creatinine for humans. After reviewing the epidemiological data on Cd toxicity published after 2011, bone effects were selected as the critical effects. Body burden data of 0.5 µg.g-1 creatinine was chosen for the critical threshold for human urinary cadmium concentrations. To be used for the derivation of the new oral toxicological reference value, we used a modified physiologically based pharmacokinetic model (PBPK). The reverse calculation on the PBPK model gave a TDI of 0.35 µg Cd.kg bw-1.day-1. This TDI is compatible with a urinary Cd concentrations not exceeding 0.5 µg Cd.g-1 creatinine, in a 60 year-old adult, assuming that ingestion is the only source of exposure to Cd at 60 years. After implementing the PBPK model with French physiological data, Cd biological reference values as a function of age were modelled so as to remain below the revised health-based guidance values.

中文翻译：

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基于建模的法国人群镉健康指导值的细化

在法国，部分人口因饮食而过度接触镉。在我们的工作中，我们首先修订了欧洲食品安全局 (EFSA) 提出的 0.36 μg Cd.kg bw.d.-1 的每日耐受摄入量 (TDI)，该摄入量源自对肾脏的影响并基于临界尿镉浓度1.0 μg Cd.g-1 肌酐对人类。在回顾了 2011 年之后发表的有关 Cd 毒性的流行病学数据后，选择骨骼效应作为关键效应。选择 0.5 µg.g-1 肌酐的身体负荷数据作为人体尿镉浓度的临界阈值。为了用于推导新的口服毒理学参考值，我们使用了改进的基于生理学的药代动力学模型 (PBPK)。PBPK 模型的反向计算得出的 TDI 为 0.35 µg Cd.kg bw-1.day-1。该 TDI 与 60 岁成人的尿镉浓度不超过 0.5 µg Cd.g-1 肌酐相容，假设摄入是 60 岁时接触镉的唯一来源。在使用法国生理数据实施 PBPK 模型后，对作为年龄函数的 Cd 生物学参考值进行建模，以保持低于修订后的基于健康的指导值。