Refinement of health-based guidance values for cadmium in the French population based on modelling

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.