Estimation of urinary cadmium benchmark dose thresholds for preschool children in a cadmium-polluted area based on...

Urinary cadmium (U-Cd) values are indicators for determining chronic cadmium toxicity, and previous studies have calculated U-Cd indicators using renal injury biomarkers. However, most of these studies have been conducted in adult populations, and there is a lack of research on U-Cd thresholds in preschool children. We aimed to apply benchmark dose (BMD) analysis to estimate the U-Cd threshold level associated with renal impairment in preschool children in the cadmium-polluted area. 518 preschool children aged 3-5 years were selected by systematic sampling (275 boys, 243 girls). Urinary cadmium and three biomarkers of early renal injury (urinary N-acetyl-β-D-glucosaminidase, UNAG; urinary β₂-microglobulin, Uβ₂-MG; urinary retinol-binding protein, URBP) were determined. Bayesian model averaging estimated the BMD and lower confidence interval limit (BMDL) of U-Cd. The medians U-Cd levels in both boys and girls exceeded the recommended national standard threshold (5 μg/g cr) and U-Cd levels were higher in girls than in boys. Urinary N-acetyl-β-D-glucosaminidase (UNAG) was the most sensitive biomarker of renal effects in preschool children. The overall BMDL₅ (BMDL at a benchmark response value of 5) was 2.76 μg/g cr. In the gender analysis, the BMDL₅ values were 1.92 μg/g cr for boys and 4.12 μg/g cr for girls. This study shows that the U-Cd threshold (BMDL₅) is lower than the national standard (5 μg/g cr) and boys' BMDL₅ was lower than the limit set by the European Parliament and Council in 2019 (2 μg/g cr), which provides a reference point for making U-Cd thresholds for preschool children.