Estimation of benchmark doses as threshold levels of urinary cadmium, based on excretion of beta2-microglobulin in cadmium-polluted and non-polluted regions in Japan.

The threshold level of urinary cadmium (Cd) for beta2-microglobulin (MG)-uria was calculated using a benchmark dose (BMD) approach. Total number of subjects was 3103 for Cd-polluted areas and 2929 for non-polluted areas. Multiple logistic regression analysis was employed to fit the dose-response model taking into consideration an age effect. Cut-off values for urinary beta2-MG were defined as those corresponding to the 84th and 97.5th percentile of beta2-MG levels in the controls, and 1000 microg/g creatinine (cr). The BMD low (BMDL) was calculated using the profile likelihood method. When the benchmark response was 5%, the BMD/BMDL of Cd for the 84th percentile of beta2-MG for mean age, 55, 65, and 75 years was 3.0/2.7, 4.6/4.2, 2.8/2.6, and 1.8/1.6 microg/g cr in men and 3.4/3.2, 5.8/5.5, 3.2/3.1, and 1.8/1.7 microg/g cr in women, respectively. The value for the 97.5th percentile for each age was 4.9/4.5, 7.6/7.0, 4.6/4.3, and 2.6/2.4 microg/g cr in men and 5.9/5.6, 9.7/9.2, 5.6/5.3, and 2.8/2.6 microg/g cr in women. Namely it became clear that the margin between the threshold level and average excretion level of urinary Cd was small in the older population in Japan. To prevent the adverse health effects caused by exposure to Cd, it is important to establish the threshold level of Cd exposure at each age.