The Validity of Benchmark Dose Limit Analysis for Estimating Permissible Accumulation of Cadmium
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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 (ECd) 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 ECd associated with kidney tubular cell ...injury was 0.67 ng/L of filtrate in both men and women. Therefore, an environmental Cd exposure producing ECd 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 ECd rises from 0.67 to 1 ng/L of filtrate. These adverse health effects occur at the body burdens lower than those associated with ECd of 5.24 µg/g creatinine, thereby arguing that current health-guiding values do not provide a sufficient health protection.
Кључне речи:
cadmium / benchmark dose / BMDL / BMDU / eGFR / NOAEL / BMD lower confidence limit / BMD upper confidence limit / N-acetyl-β-D-glucosaminidase / β2-microglobulinИзвор:
International Journal of Environmental Research and Public Health, 2022, 19, 23Издавач:
- MDPI
Институција/група
PharmacyTY - JOUR AU - Satarug, Soisungwan AU - Vesey, David AU - Gobe, Glenda AU - Buha-Đorđević, Aleksandra PY - 2022 UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4339 AB - 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 (ECd) 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 ECd associated with kidney tubular cell injury was 0.67 ng/L of filtrate in both men and women. Therefore, an environmental Cd exposure producing ECd 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 ECd rises from 0.67 to 1 ng/L of filtrate. These adverse health effects occur at the body burdens lower than those associated with ECd of 5.24 µg/g creatinine, thereby arguing that current health-guiding values do not provide a sufficient health protection. PB - MDPI T2 - International Journal of Environmental Research and Public Health T1 - The Validity of Benchmark Dose Limit Analysis for Estimating Permissible Accumulation of Cadmium VL - 19 IS - 23 DO - 10.3390/ijerph192315697 ER -
@article{ author = "Satarug, Soisungwan and Vesey, David and Gobe, Glenda and Buha-Đorđević, Aleksandra", year = "2022", 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 (ECd) 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 ECd associated with kidney tubular cell injury was 0.67 ng/L of filtrate in both men and women. Therefore, an environmental Cd exposure producing ECd 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 ECd rises from 0.67 to 1 ng/L of filtrate. These adverse health effects occur at the body burdens lower than those associated with ECd of 5.24 µg/g creatinine, thereby arguing that current health-guiding values do not provide a sufficient health protection.", publisher = "MDPI", journal = "International Journal of Environmental Research and Public Health", title = "The Validity of Benchmark Dose Limit Analysis for Estimating Permissible Accumulation of Cadmium", volume = "19", number = "23", doi = "10.3390/ijerph192315697" }
Satarug, S., Vesey, D., Gobe, G.,& Buha-Đorđević, A.. (2022). The Validity of Benchmark Dose Limit Analysis for Estimating Permissible Accumulation of Cadmium. in International Journal of Environmental Research and Public Health MDPI., 19(23). https://doi.org/10.3390/ijerph192315697
Satarug S, Vesey D, Gobe G, Buha-Đorđević A. The Validity of Benchmark Dose Limit Analysis for Estimating Permissible Accumulation of Cadmium. in International Journal of Environmental Research and Public Health. 2022;19(23). doi:10.3390/ijerph192315697 .
Satarug, Soisungwan, Vesey, David, Gobe, Glenda, Buha-Đorđević, Aleksandra, "The Validity of Benchmark Dose Limit Analysis for Estimating Permissible Accumulation of Cadmium" in International Journal of Environmental Research and Public Health, 19, no. 23 (2022), https://doi.org/10.3390/ijerph192315697 . .