Effects of exposure to cadmium (Cd) in the general environment on health have been studied in several Cd-polluted areas in Japan. In this paper, results of investigations in the Kakehashi River basin, Ishikawa, a Cd-polluted area, are mainly reviewed as follows.
1. In an epidemiological study, prevalences of β²-microglobulinuria (β²-MG-uria) were 14. 3 and 18.7% in Cd-exposed men and women over 50 years of age, respectively, when a cutoff level of β²-MG of 1000μg/g.cr. was used. These values are significantly high compared with those of nonexposed subjects.
2. Using several urinary indicators of renal function, such as α₁-microglobulin, N-acetyl-β-D-glucosaminidase, human intestinal alkaline phosphatase, mucoprotein and albumin, levels of all indicators were significantly higher in Cd-exposed subjects than in nonexposed subjects. Furthermore, in a 5-year follow-up study, irreversibility of Cd-induced renal damage was shown after the level of β₂-MG rose above 1000μg/g.cr.
3. Exposure to Cd caused marked osteopenia, in particular in women, as assessed by microdensitometry, and this osteopenia was significantly associated with Cd-induced renal dysfunction. Serum 1α, 25 dihydroxy-vitamin D levels were lower and serum parathyroid hormone (PTH) levels were higher in Cd-exposed subjects with renal damage than in nonexposed subjects. We assume that disturbances in vitamin D and PTH metabolism may be one of the causative factors for Cd-induced bone damage.
4. The dose-response relationships between Cd exposure and renal dysfunction were assessed using several statistical methods such as simple linear regression, probit linear regression, logistic regression analysis and general linear models. The prevalences of β₂-MG-uria or metallothioneinuria were employed as indices of health effects, while urinary Cd and total Cd intake was used as indicators of Cd exposure. As the biological threshold, urinary Cd concentrations were calculated to be 3.8-4.2μg/g.cr. in men and 3.8-4.8μg/g.cr. in women, and a maximum allowable intake of about 2g Cd is considered to be a reasonable estimate for preventing Cd-induced renal dysfunction.
5. A significant association was found between urinary β₂-MG and mortality in a 9-year follow-up study of 3178 Cd-exposed inhabitants, using Cox's proportional hazards model. Moreover, mortality rates increased in proportion to increases in the amount of urinary β₂-MG excreted. These results suggest that the prognosis for Cd-exposed subjects with renal tubular dysfunction is unfavorable.