Benchmark Dose for Urinary Cadmium based on a Marker of Renal Dysfunction: A Meta-Analysis
Background: Low dose of cadmium could cause adverse health effects. Benchmark dose (BMD) to derive reference point for urinary cadmium exposure has been estimated in several previous studies, but the methods to derive BMD and the estimated BMDs differed. Objectives: We aimed to find the associated factors that affect BMD calculation in the general population, and to estimate the BMD and the one-sided 95% lower confidence limit of benchmark dose (BMDL) for urinary cadmium using reported BMDs. Methods: A meta-regression was performed and the pooled BMD/BMDL was estimated using studies reporting a BMD and its corresponding standard error that were calculated from individual data based on markers of renal dysfunction. Results: BMDs were highly heterogeneous across studies. Meta-regression analysis showed that significant predictor of BMD was cut-off point which denotes an abnormal level. BMDL estimates for 5% benchmark responses (BMR) of β2-microglobulinuria (β2-MG) ranged from 1.3 to 4.7 μg/g creatinine, and BMDLs for 5% BMR of N-acetyl-β-d-glucosaminidase (NAG) ranged from 1.7 to 3.1 μg/g creatinine. Conclusion: The urinary cadmium BMDL for 5% BMR of β2-MG was 1.3 µg/g creatinine in the lowest cut-off point group. However, the BMD/BMDL was derived differently based on the calculation method used, especially by cut-off point for prevalence of abnormal level.