Urinary Nickel Exposure and Growth in Prepubertal Chinese Children: Threshold Effects and Benchmark Dose Analysis

Introduction: Nickel is a ubiquitous environmental heavy metal, and children are particularly vulnerable to its toxicity. However, nationwide evidence on the association between nickel exposure and growth in prepubertal children remains limited, and benchmark dose (BMD)-based reference values are lacking.

Methods: Based on a nationwide cross-sectional study, 10,008 prepubertal Chinese children were included. Urinary nickel levels were measured and adjusted for creatinine. Height-for-age (HAZ), weight-for-age (WAZ), and BMI-for-age (BAZ) Z-scores were calculated. Multivariable regression, restricted cubic spline (RCS), piecewise regression, and Bayesian BMD modeling were applied to assess associations and estimate the benchmark dose lower confidence limit (BMDL₅).

Results: Urinary nickel concentrations showed a right-skewed distribution, with a geometric mean of 5.68μg/g creatinine. Significant negative associations were observed between urinary nickel and height, weight, HAZ, and WAZ (all P < 0.001), with clear dose-response trends. RCS analyses indicated nonlinear relationships with HAZ and WAZ. Piecewise regression identified thresholds of 3.98μg/g creatinine for HAZ and 3.80μg/g creatinine for WAZ and BAZ. Below these levels, growth indicators decreased significantly (all P < 0.01), while effects plateaued above them. Bayesian analysis estimated BMDL₅values of 2.56, 3.08, and 4.77μg/g creatinine for HAZ, WAZ, and BAZ, respectively.

Conclusions: Urinary nickel exposure was significantly associated with impaired growth in prepubertal children, showing nonlinear dose–response relationships and clear threshold effects. Consistent findings across multiple analytical approaches suggest that even relatively low exposure levels may adversely affect child growth. This study provides important epidemiological evidence for risk assessment of nickel exposure in children.