Benchmark Dose for Urinary Cadmium based on a Marker of Renal Dysfunction: A Meta-Analysis.
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BACKGROUND: Low doses of cadmium can cause adverse health effects. Benchmark dose (BMD) and the one-sided 95% lower confidence limit of BMD (BMDL) to derive points of departure for urinary cadmium exposure have been estimated in several previous studies, but the methods to derive BMD and the estimated BMDs differ. OBJECTIVES: We aimed to find the associated factors that affect BMD calculation in the general population, and to estimate the summary BMD 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 BMDL, weighted by sample size, that were calculated from individual data based on markers of renal dysfunction. RESULTS: BMDs were highly heterogeneous across studies. Meta-regression analysis showed that a significant predictor of BMD was the cut-off point which denotes an abnormal level. Using the 95th percentile as a cut off, BMD5/BMDL5 estimates for 5% benchmark responses (BMR) of 2-microglobulinuria (2-MG) estimated was 6.18/4.88 g/g creatinine in conventional quantal analysis and 3.56/3.13 g/g creatinine in the hybrid approach, and BMD5/BMDL5 estimates for 5% BMR of N-acetyl--d-glucosaminidase (NAG) was 10.31/7.61 g/g creatinine in quantal analysis and 3.21/2.24 g/g creatinine in the hybrid approach. However, the meta-regression showed that BMD and BMDL were significantly associated with the cut-off point, but BMD calculation method did not significantly affect the results. The urinary cadmium BMDL5 of 2-MG was 1.9 g/g creatinine in the lowest cut-off point group. CONCLUSION: The BMD was significantly associated with the cut-off point defining the abnormal level of renal dysfunction markers.