Systematic review of cardiotoxicity associated with oral cadmium exposure

The Food and Drug Administration (FDA) developed an oral cadmium (Cd) toxicological reference value (TRV) range of 0.21-0.36 μg/kg bw/day, based on similar points of departure (POD) for the bone and kidney (urinary Cd 0.5 μg/g creatinine) and 50 μg/g in the kidney cortex. Increasing evidence suggests that Cd exposure also affects the cardiovascular system. We conducted a systematic review through mid-September 2025 to determine if the current TRV is protective of cardiovascular events. We screened the title and abstract of 1354 references and conducted a full text review for 123 manuscripts. Fifty-three studies were excluded based on inclusion and exclusion criteria and 12 additional studies were included from the 2022 FDA systematic review for a total of 82 references. Animal studies indicated that Cd concentrations of 1-5 mg/L in drinking water resulted in elevated blood pressure in rats. For the epidemiological data, moderate evidence supports that atherosclerosis, myocardial infarction, cardiovascular mortality and blood pressure are presumed hazards to human health. Blood and urinary Cd levels for these effects are reported at ≥0.5 μg/g creatinine, respectively, the same POD used for the current TRV. Therefore, the current TRV of 0.21-0.36 μg/kg bw/day is protective of cardiovascular effects.