Benchmark Dose Estimation for Cadmium-Induced Renal Tubular Damage among Environmental Cadmium-Exposed Women Aged 35-54 Years in Two Counties of China

Background: A number of factors, including gender, age, smoking habits, and occupational exposure, affect the levels of urinary cadmium. Few studies have considered these influences when calculating the benchmark dose (BMD) of cadmium. In the present study, we aimed to calculate BMDs and their 95% lower confidence bounds (BMDLs) for cadmium-induced renal tubular effects in an age-specific population in south-central China. Methods: In this study, urinary cadmium, beta 2-microglobulin, and N-acetyl-beta-D-glucosaminidase levels were measured in morning urine samples from 490 randomly selected non-smoking women aged 35-54 years. Participants were selected using stratified cluster sampling in two counties (counties A and B) in China. Multiple regression and logistic regression analyses were used to investigate the dose-response relationship between urinary cadmium levels and tubular effects. BMDs/BMDLs corresponding to an additional risk (benchmark response) of 5% and 10% were calculated with assumed cut-off values of the 84th and 90th percentile of urinary beta 2-microglobulin and N-acetyl-beta-D-glucosaminidase levels of the controls. Results: Urinary levels of beta 2-microglobulin and N-acetyl-beta-D-glucosaminidase increased significantly with increasing levels of urinary cadmium. Age was not associated with urinary cadmium levels, possibly because of the narrow age range included in this study. Based on urinary beta 2-microglobulin and N-acetyl-beta-D-glucosaminidase, BMDs and BMDLs of urinary cadmium ranged from 2.08 to 3.80 (1.41-2.18) mu g/g cr for subjects in county A and from 0.99 to 3.34 (0.74-1.91) mu g/g cr for those in county B. The predetermined benchmark response of 0.05 and the 90th percentiles of urinary beta 2-microglobulin and N-acetyl-beta-D-glucosaminidase levels of the subjects not exposed to cadmium (i.e., the control group) served as cut-off values. Conclusions: The obtained BMDs of urinary cadmium were similar to the reference point of 1 mu g/g cr, as suggested by the European Food Safety Authority, indicating that cadmium exposure must be reduced to protect human health.