Application of hybrid approach for estimating the benchmark dose of urinary cadmium for adverse renal effects in the general population of Japan

Abstract

We used an updated hybrid approach to estimate the benchmark doses and their 95% lower confidence limits (BMDL) for cadmium-induced renal effects in humans. Participants were 828 inhabitants (410 men, 418 women), aged 40-59 years who lived in three areas without any known environmental cadmium pollution. We measured urinary cadmium (U-Cd) as a marker of exposure, and urinary protein, β2-microglobulin (β2-MG) and N-acetyl-β-D-glucosaminidase (NAG) as markers of renal effects. For urinary protein, the BMDL ranged from 0.9 to 1.1 µg g⁻¹ creatinine (cre) and approximately 1.6 µg per 24 h in men, and from 1.9 to 3.4 µg g⁻¹ cre and 2.0 µg per 24 h in women. For the renal tubular markers β2-MG and NAG, the BMDL for U-Cd ranged from 0.6 to 1.2 µg g⁻¹ cre and from 0.8 to 1.7 µg per 24 h in men, and from 0.6 to 2.3 µg g⁻¹ cre and from 0.6 to 2.1 µg per 24 h in women. The lowest BMDL for urinary cadmium (0.6 µg g⁻¹ cre) was somewhat lower than average urinary cadmium in Japanese older population. These results suggest the importance of measures to decrease cadmium exposure in the general population of Japan.