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
US Food and Drug Administration, Center for Food Safety and Applied Nutrition, College Park, MD, USA.
US Food and Drug Administration, Center for Food Safety and Applied Nutrition, College Park, MD, USA.
Regul Toxicol Pharmacol. 2023 Oct;144:105487. doi: 10.1016/j.yrtph.2023.105487. Epub 2023 Aug 26.
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.
美国食品药品监督管理局（FDA）制定了一项口服毒理学参考值（TRV），用于描述因饮食接触镉（Cd）而可能产生的健康问题。TRV的制定利用了FDA先前发表的研究成果，包括（1）对与口服镉暴露相关的不良健康影响进行的系统综述，以及（2）根据Kjellstrom和Nordberg（1978年）改编的基于人体生理学的药代动力学（PBPK）模型，用于应用于美国人群的反向剂量测定。根据现有流行病学数据，镉对骨骼和肾脏的不良影响与50-60岁女性约0.50μg镉/克肌酐的相似起始点（POD）相关。我们还将50岁美国人群中出现的肾皮质浓度上限估计值（50μg/克镉）用作POD。根据我们的反向剂量测定PBPK模型的输出结果，确定TRV的范围为0.21-0.36μg/千克体重/天。用于推导动物TRV的动物数据（0.63-1.8μg/千克体重/天）证实了骨骼和肾脏终点的生物学合理性。
