Refinement of health-based guidance values for cadmium in the French population based on modelling. (1st April 2021)

• Record Type: Journal Article
• Authors: Leconte, Stéphane; Rousselle, Christophe; Bodin, Laurent; Clinard, François; Carne, Géraldine
• Is Part Of: Toxicology letters. Volume 340(2021)
• Page Start: 43
• Page End: 51
• Publication Date: 2021-04-01
• Subjects: PB-PK Physiologically based pharmacokinetic -- TRV toxicological reference value -- EFSA European Food Safety Agency -- TDS2 Second French Total Diet Study -- iTDS French infant Total Diet Study -- TWI tolerable weekly intake -- TDI tolerable daily intake -- Creat creatinine; Cadmium -- PB-PK model -- TRV; Toxicology -- Periodicals; 363.179
• DOI: 10.1016/j.toxlet.2020.12.021
• Languages: English
• ISSNs: 0378-4274

Abstract

Highlights: Cadmium health reference value by ingestion was refined. Change in the total cadmium body burden over a lifetime in the French population was estimated. Bone effects were identified as critical effect for the Cd's risk assessment by ingestion. Abstract: 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.