Reassessment of the cadmium toxicological reference value for use in human health assessments of foods

• Published in: Regulatory toxicology and pharmacology 2023-10, Vol.144, p.105487-105487, Article 105487
• Main Authors: Schaefer, Heather R., Flannery, Brenna M., Crosby, Lynn M., Pouillot, Régis, Farakos, Sofia M Santillana, Van Doren, Jane M., Dennis, Sherri, Fitzpatrick, Suzanne, Middleton, Karlyn
• Format: Article
• Language: English
• Subjects: Dietary; Food; TRV
• ISSN: 0273-2300; 1096-0295
• DOI: 10.1016/j.yrtph.2023.105487

The U.S. Food and Drug Administration (FDA) developed an oral toxicological reference value (TRV) for characterizing potential health concerns from dietary exposure to cadmium (Cd). The development of the TRV leveraged the FDA's previously published research including (1) a systematic review for adverse health effects associated with oral Cd exposure and (2) a human physiological based pharmacokinetic (PBPK) model adapted from Kjellstrom and Nordberg (1978) for use in reverse dosimetry applied to the U.S. population. Adverse effects of Cd on the bone and kidney are associated with similar points of departure (PODs) of approximately 0.50 μg Cd/g creatinine for females aged 50–60 based on available epidemiologic data. We also used the upper bound estimate of the renal cortical concentration (50 μg/g Cd) occurring in the U.S. population at 50 years of age as a POD. Based on the output from our reverse dosimetry PBPK Model, a range of 0.21–0.36 μg/kg bw/day was developed for the TRV. The animal data used for the animal TRV derivation (0.63–1.8 μg/kg bw/day) confirms biological plausibility for both the bone and kidney endpoints. [Display omitted] •Development of an oral toxicological reference value (TRV) for dietary exposure to cadmium.•Used an adapted human physiological based pharmacokinetic model to develop a cadmium TRV range.•Cadmium TRV range is supported by the animal data for the bone and kidney endpoints.