The threshold cadmium level that causes a substantial increase in beta2-microglobulin in urine of general populations

Cadmium (Cd) is a toxic element ubiquitous in the environment, and general populations have been exposed to this element primarily via foods. Thus, the critical level of non-occupational Cd exposure to cause any health effects among general populations is of public health as well as toxicological concern. The objectives of the present study were to examine the quantitative relationship between cadmium (Cd-U) and beta2-microglobulin in urine (beta2-MG-U) as a marker of exposure to Cd and as a marker of renal tubular dysfunction, respectively, and to identify a threshold Cd-U, if present, in causing a substantial increase in beta2-MG-U. Thus, paired data on geometric mean (GM) Cd-Ucr (i.e., Cd-U as corrected for creatinine [cr] concentration) and GM beta2-MG-Ucr (beta2-MG-U as corrected for cr) of residents in polluted as well as nonpolluted areas in Japan were retrieved in international and domestic sources. In practice, 245 cases of the data pairs were obtained in 51 articles published since 1975. Statistical analysis on ordinary scales disclosed that beta2-MG-Ucr increased markedly when Cd-Ucr exceeded a certain level. The relation between the two parameters after double-logarithmic conversion was in a shape of the letter J or a stick for ice hockey. Analysis for Cd-Ucr at the flexion point gave Cd-Ucr of 4 (on double logarithmic scales) or 7 microg/g cr (on ordinary scales). Cd-Ucr levels that correspond to a beta2-MG-Ucr of 1,000 microg/g cr were estimated to be 8-9 microg/g cr, by ordinary and logarithmic assumption as well as by the 3rd degree regression analysis. Thus, it is concluded that there is a threshold Cd-Ucr level that leads to a substantial increase in beta2-MG-Ucr, and that the threshold level is greater than 4 microg/g cr.