Confusion about Cadmium Risks: The Unrecognized Limitations of an Extrapolated Paradigm

BACKGROUND Cadmium (Cd) risk assessment presently relies on tubular proteinuria as a critical effect and urinary Cd (U-Cd) as an index of the Cd body burden. Based on this paradigm, regulatory bodies have reached contradictory conclusions regarding the safety of Cd in food. Adding to the confusion, epidemiological studies implicate environmental Cd as a risk factor for bone, cardiovascular, and other degenerative diseases at exposure levels that are much lower than points of departure used for setting food standards. OBJECTIVE The objective was to examine whether the present confusion over Cd risks is not related to conceptual or methodological problems. DISCUSSION The cornerstone of Cd risk assessment is the assumption that U-Cd reflects the lifetime accumulation of the metal in the body. The validity of this assumption as applied to the general population has been questioned by recent studies revealing that low-level U-Cd varies widely within and between individuals depending on urinary flow, urine collection protocol, and recent exposure. There is also evidence that low-level U-Cd increases with proteinuria and essential element deficiencies, two potential confounders that might explain the multiple associations of U-Cd with common degenerative diseases. In essence, the present Cd confusion might arise from the fact that this heavy metal follows the same transport pathways as plasma proteins for its urinary excretion and the same transport pathways as essential elements for its intestinal absorption. CONCLUSIONS The Cd risk assessment paradigm needs to be rethought taking into consideration that low-level U-Cd is strongly influenced by renal physiology, recent exposure, and factors linked to studied outcomes. CITATION Bernard A. 2016. Confusion about cadmium risks: the unrecognized limitations of an extrapolated paradigm. Environ Health Perspect 124:1-5; http://dx.doi.org/10.1289/ehp.1509691.