Abstract
BackgroundCadmium (Cd) is a common heavy metal that mainly causes renal damage. There is a lack of research on the large-scale and systematic evaluation of the association between urinary Cd (U-Cd) and various effect biomarkers among Chinese residents.MethodsBased on the establishment process of dietary Cd limit standards by European Food Safety Authority (EFSA), the dose–response relationships between U-Cd and four biomarkers, β2-microglobulin (β2-MG), N-acetyl-β-glucosidase (NAG), microalbumin (mALB), and retinol binding Protein (RBP) were explored, respectively. Toxicokinetic model was used to derive the dietary Cd exposure limit for Chinese residents after critical U-Cd concentration was calculated.ResultsAs the sensitive biomarkers of renal injury, β2-MG and NAG were selected to estimate the 95% confidence interval lower limit of the U-Cd benchmark dose (BMDL5) to be 3.07 and 2.98 μg/g Cr, respectively. Dietary Cd exposure limit was calculated to be 0.28 μg/kg bw/day (16.8 μg/day, based on the body weight of 60 kg), which was lower than the average Chinese Cd exposure (30.6 μg/day) by the China National Nutrient and Health Survey.ConclusionThis study established an overall association between U-Cd and renal injury biomarkers, and explored the Chinese dietary Cd exposure limits, which helps improve Chinese Cd exposure risk assessment and provides a reference basis for formulating reasonable exposure standards.
Highlights
Cadmium (Cd) is a toxic heavy metal commonly found in the environment, with an average concentration in the earth’s crust of about 0.2 mg/kg [1]
Of all the included studies, 332 matched pairs of urinary Cd (U-Cd) and β2-MG levels can be gathered from 85 studies, followed by NAG (N = 29 with 143 data), mALB (N = 23 with 87 data), and retinol binding Protein (RBP) (N = 21 with 74 data)
The dose–response relationships between U-Cd and four renal injury biomarkers were established using Hill or exponential model. β2MG and NAG were used as the sensitive biomarkers to determine the B MDL5 of U-Cd safe thresholds (β2-MG: 3.07 μg/g Cr; NAG: 2.98 μg/g Cr)
Summary
Cadmium (Cd) is a toxic heavy metal commonly found in the environment, with an average concentration in the earth’s crust of about 0.2 mg/kg [1]. The TK model is an in vitro mathematical model based on physiology, biochemistry, dissection and pharmacokinetics, which could simulate the internal exposure dose in specific organs based on the external exposure of pollutants, and provide reliable information for quantitative assessment of the metabolic concentrations of toxic chemicals [8]. At present, it has been widely used in the risk assessment of pollutants such as heavy metals, persistent organic pollutants, and organic pesticides [9,10,11]. There is a lack of research on the large-scale and systematic evaluation of the association between urinary Cd (U-Cd) and various effect biomarkers among Chinese residents
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