The Validity of Benchmark Dose Limit Analysis for Estimating Permissible Accumulation of Cadmium

Soisungwan Satarug (), David A. Vesey, Glenda C. Gobe and Aleksandra Buha Đorđević
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Soisungwan Satarug: Kidney Disease Research Collaborative, Translational Research Institute, Brisbane 4102, Australia
David A. Vesey: Kidney Disease Research Collaborative, Translational Research Institute, Brisbane 4102, Australia
Glenda C. Gobe: Kidney Disease Research Collaborative, Translational Research Institute, Brisbane 4102, Australia
Aleksandra Buha Đorđević: Department of Toxicology “Akademik Danilo Soldatović”, Faculty of Pharmacy, University of Belgrade, 11000 Belgrade, Serbia

IJERPH, 2022, vol. 19, issue 23, 1-15

Abstract: Cadmium (Cd) is a toxic metal pollutant that accumulates, especially in the proximal tubular epithelial cells of kidneys, where it causes tubular cell injury, cell death and a reduction in glomerular filtration rate (GFR). Diet is the main Cd exposure source in non-occupationally exposed and non-smoking populations. The present study aimed to evaluate the reliability of a tolerable Cd intake of 0.83 μg/kg body weight/day, and its corresponding toxicity threshold level of 5.24 μg/g creatinine. The PROAST software was used to calculate the lower 95% confidence bound of the benchmark dose (BMDL) values of Cd excretion (E Cd ) associated with injury to kidney tubular cells, a defective tubular reabsorption of filtered proteins, and a reduction in the estimated GFR (eGFR). Data were from 289 males and 445 females, mean age of 48.1 years of which 42.8% were smokers, while 31.7% had hypertension, and 9% had chronic kidney disease (CKD). The BMDL value of E Cd associated with kidney tubular cell injury was 0.67 ng/L of filtrate in both men and women. Therefore, an environmental Cd exposure producing E Cd of 0.67 ng/L filtrate could be considered as Cd accumulation levels below which renal effects are likely to be negligible. A reduction in eGFR and CKD may follow when E Cd rises from 0.67 to 1 ng/L of filtrate. These adverse health effects occur at the body burdens lower than those associated with E Cd of 5.24 µg/g creatinine, thereby arguing that current health-guiding values do not provide a sufficient health protection.

Keywords: benchmark dose; BMD lower confidence limit; BMDL; BMD upper confidence limit; BMDU; cadmium; ? 2 -microglobulin; eGFR; N-acetyl-?-D-glucosaminidase; NOAEL (search for similar items in EconPapers)
JEL-codes: I I1 I3 Q Q5 (search for similar items in EconPapers)
Date: 2022
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