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

Author

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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
    Department of Nephrology, Princess Alexandra Hospital, Brisbane 4102, Australia)

  • Glenda C. Gobe

    (Kidney Disease Research Collaborative, Translational Research Institute, Brisbane 4102, Australia
    School of Biomedical Sciences, The University of Queensland, Brisbane 4072, Australia
    NHMRC Centre of Research Excellence for CKD QLD, UQ Health Sciences, Royal Brisbane and Women’s Hospital, Brisbane 4029, Australia)

  • Aleksandra Buha Đorđević

    (Department of Toxicology “Akademik Danilo Soldatović”, Faculty of Pharmacy, University of Belgrade, 11000 Belgrade, Serbia)

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.

Suggested Citation

  • Soisungwan Satarug & David A. Vesey & Glenda C. Gobe & Aleksandra Buha Đorđević, 2022. "The Validity of Benchmark Dose Limit Analysis for Estimating Permissible Accumulation of Cadmium," IJERPH, MDPI, vol. 19(23), pages 1-15, November.
    • Handle: RePEc:gam:jijerp:v:19:y:2022:i:23:p:15697-:d:984205
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    References listed on IDEAS

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    1. Yiliang Zhu & Tao Wang & Jenny Z.H. Jelsovsky, 2007. "Bootstrap Estimation of Benchmark Doses and Confidence Limits with Clustered Quantal Data," Risk Analysis, John Wiley & Sons, vol. 27(2), pages 447-465, April.
    2. Soisungwan Satarug & David A. Vesey & Glenda C. Gobe, 2022. "Dose–Response Analysis of the Tubular and Glomerular Effects of Chronic Exposure to Environmental Cadmium," IJERPH, MDPI, vol. 19(17), pages 1-14, August.
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