A systematic review of adverse health effects associated with oral cadmium exposure

Scientific data characterizing the adverse health effects associated with dietary cadmium (Cd) exposure were identified in order to make informed decisions about the most appropriate toxicological reference value (TRV) for use in assessing dietary Cd exposure. Several TRVs are available for Cd and regulatory organizations have used epidemiologic studies to derive these reference values; however, risk of bias (RoB) evaluations were not included in the assessments. We performed a systematic review by conducting a thorough literature search (through January 4, 2020). There were 1714 references identified by the search strings and 328 studies identified in regulatory assessments. After applying the specific inclusion and exclusion criteria, 208 studies (Human: 105, Animal: 103) were considered eligible for further review and data extraction. For the epidemiologic and animal studies, the critical effects identified for oral Cd exposure from the eligible studies were a decrease in bone mineral density (BMD) and renal tubular degeneration. A RoB analysis was completed for 49 studies (30 epidemiological and 19 animal) investigating these endpoints. The studies identified through the SR that were considered high quality and low RoB (2 human and 5 animal) can be used to characterize dose-response relationships and inform the derivation of a Cd TRV.