How Adequate Are the Guidelines for Dietary and Workplace Exposure to Cadmium?

Cadmium (Cd) is a heavy metal pollutant to which most people are exposed daily through their diet because of its presence in nearly all food types, including potatoes, vegetables, cereals, grains, legumes, shellfish, and organ meat. Cd has no physiological role or nutritional value in the body and causes toxicity to multiple tissues and organs via oxidative stress and chronic inflammation; as such, at high prevalence, it is frequently associated with diseases, notably cancer, heart disease, diabetes, osteoporosis, and chronic kidney disease. Using kidneys and bones as critical toxicity targets, current dietary Cd exposure guidelines vary from 0.21 to 0.83 μg/kg b.w./d. There is a widespread concern about these guidelines because they were based on the excretion of β2-microglobulin (β2M) at a rate of 300 µg/g of creatinine as an endpoint. Concerningly, rice is a staple food for over 50% of the world's population; however, the permissible Cd level in this commodity has not been adequately addressed. This narrative review focuses on critiquing existing food standards and exposure guidelines for Cd. It discusses the threshold-based risk assessment that was used to define the no-observed-adverse-effect level (NOAEL) for Cd, when β2M excretion was used with Cd excretion at a rate of 5.24 µg/g of creatinine being a threshold. The estimated glomerular filtration rate (eGFR) is recommended as an appropriate kidney disease endpoint. The current view around how Cd uses various transport proteins to enter and induce toxicity to its target cells are summarized. The strategies to minimize Cd accumulation and mitigate its nephrotoxicity are highlighted.