The association between dietary cadmium exposure and renal dysfunction – the benchmark dose estimation of reference levels: the ChinaCad study

The tolerable dietary intake of cadmium was recommended at provisional tolerable monthly intake of 25 μg kg-1 body weight. However, several studies indicated that this tolerable level should be re-evaluated for sufficient health protection. In this study, we show the reference levels of dietary cadmium intake for renal dysfunction by using a benchmark dose (BMD) approach. A total of 790 subjects (302 men and 488 women) living in control and cadmium-polluted areas were included. The dietary cadmium intake was estimated by a food survey. Blood cadmium, urinary cadmium and renal function markers (microalbuminuria, N-acetyl-β-d-glucosaminidase [NAG] and its isoform B [NAGB], β2 -microglobulin and retinol binding protein) in urine were measured. We calculated the 95% lower confidence bounds of BMD (BMDLs) of cumulative cadmium intake. In control and two polluted areas, the median cumulative cadmium intake was 0.5, 2.1 and 11.1 g. The odds ratio of the intermediate (1.0-3.0 g), second highest (3.0-11.0 g) and the highest cumulative cadmium intake (>11.0 g) compared with the lowest cumulative cadmium intake (<1.0 g) were 2.8 (95% CI: 1.4-5.8), 8.1 (95% CI: 3.8-17.2) and 11.4 (95% CI: 6.5-26.4) for urinary NAG and 6.6 (95% CI: 3.2-13.8), 14.8 (95% CI: 6.8-32.2) and 22.5 (95% CI: 10.7-47.5) for urinary NAGB. The BMDLs of cumulative cadmium intake were 1.1-1.2 g (benchmark response [BMR] = 5%) for urinary NAG, and were 0.7-0.9 g (BMR = 5%) for urinary NAGB, and were 1.3-1.4 g (BMR = 5%) for urinary β2 -microglobulin. The BMDLs of cumulative cadmium intake in a Chinese population were lower than the critical standard previously reported. Further evaluations are needed for sufficient health protection.