Use of Urinary β₂-Microglobulin in the Assessment of the Health Risk from Environmental Cadmium Exposure

Cadmium (Cd) is a ubiquitous environmental pollutant with no nutritional value or physiological role in the body. It readily accumulates in various tissues as it is easily absorbed from the diet but only poorly excreted. Due to the widespread contamination of staple foods, exposure to this toxic metal is inevitable for most people. The health risk due to dietary Cd exposure has long been underappreciated. This is primarily due to the use of urinary excretion of β2-microglobulin (β2M) as an indicator of an adverse health effect. Herein, advanced benchmark dose (BMD) modelling is employed to identify the critical Cd exposure levels, based on two toxic endpoints; changes in β2M excretion and the reduction of the estimated glomerular filtration rate (eGFR). Data on Cd excretion, β2M excretion and eGFR were from a Thai cohort of 799 persons without diabetes, aged 18-87 years. The BMD limit (BMDL) value for Cd excretion was 0.17 μg/g creatinine, when eGFR was used as an endpoint. In contrast, the BMDL for Cd excretion could not reliably be estimated, when β2M was used as an endpoint. Given that a reduced eGFR more reliably indicates the development of chronic kidney disease, we recommend the use of the eGFR to derive a meaningful health protective BMDL. This study reveals that the current Cd excretion threshold of 5.24 µg/g creatinine is vastly inadequate to protect human health. We strongly advocate a Cd excretion rate of below 0.20 µg/g creatinine is used to inform future Cd exposure guidelines.