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

Cadmium (Cd) is a heavy metal pollutant to which most people are exposed daily through their diet. This is because it is ubiquitously present 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 inflammation; as such it is frequently asso-ciated with diseases with high prevalence, notably cancer, osteoporosis, diabetes type 2, and chronic kidney disease (CKD). The consensus on Cd levels, considered to be safe, are limited. The permissible Cd level in rice which is a staple food for over 50% of the world’s population has not been adequately addressed. Using kidneys and bones as critical toxicity targets, current dietary Cd exposure guidelines vary from 0.21 to 0.83 μg/kg bw/d. There is a widespread concern about these guidelines because they were based on excretion of β2-microglobulin (β2M) at a rate of 300 µg/g creatinine as an endpoint. The present review discusses the threshold-based risk assessment that was used to define the no-observed-adverse-effect level (NOAEL) for Cd, when β2M excre-tion was used as endpoint measure with Cd excretion rate of 5.24 µg/g creatinine being a threshold. Arguably, the estimated glomerular filtration rate (eGFR) should be used as a disease outcome of Cd nephrotoxicity. The current view around how Cd uses various transport and channel proteins to enter and induce toxicity to its target cells are dis-cussed, along with the strategies to mitigate Cd cytotoxicity.