Health effects of cadmium exposure in the general environment in Japan with special reference to the lower limit of the benchmark dose as the threshold level of urinary cadmium

Objectives This study investigates renal dysfunction in areas without known environmental cadmium pollution and calculates the threshold level of urinary cadmium. Methods Urinary total protein, beta(2)-microglobulin (beta(2)-MG), and N-acetyl-beta-D-glucosaminidase (NAG), used as indicators of renal dysfunction, and urinary cadmium concentration, used as an indicator of cadmium exposure, were measured in two sets of 24-hour urine samples from each of 828 participants (410 men, 418 women), aged 40-59 years and living in three areas without any known environmental cadmium pollution. In multiple regression and logistic regression analyses the association between indicators of cadmium exposure and indicators of renal dysfunction were studied. The lower 95% confidence limit of the dose (benchmark dose) corresponding to a 5% (BMDL5) or 10% (BMDL10) level of each indicator of renal dysfunction above the background level) was calculated as the threshold level of urinary cadmium. Results With all the expressed units [g creatinine(-1) and day(-1)] in the multiple regression analysis, the partial regression coefficients showed a significant association between urinary cadmium concentration and total protein, beta(2)-MG, and NAG for both genders, except for total protein for women (g creatinine(-1) and day(-1)). The same results were obtained for both genders in the logistic regression analysis. The BMDL10 was 0.6-1.2 mu g/g creatinine and 0.8-1.6 mu g/day for the men and 1.2-3.6 mu g/g creatinine, and 0.5-4.7 mu g/day for the women. Conclusions Cadmium exposure and the levels of the indicators of renal dysfunction were associated among the men and women aged 40-59 years in areas without any known environmental cadmium pollution. The threshold level of urinary cadmium in Japan seems to be almost the same as in Belgium and Sweden.