Estimation of the benchmark dose of urinary cadmium as the reference level for renal dysfunction: a large sample study in five cadmium polluted areas in China

Abstract

BackgroundItai-itai disease primarily results from cadmium (Cd) exposure and is known as one of the four major pollution diseases in Japan. Cd pollution is more serious in several areas of China than in Japan. However, there is still a lack of information regarding the threshold level of Cd exposure for the adverse health effects in the general Chinese population. This study aims to evaluate the reference value of urinary Cd (UCd) for renal dysfunction in a Chinese population as the benchmark dose lower confidence limit (BMDL) based on a large sample survey.MethodsA total of 6103 participants who lived in five Cd polluted areas of China participated in this study. We analyzed UCd levels as a biomarker of exposure and urinary β2-microglobulin (Uβ2-MG) levels as a renal tubular effect biomarker. The BMD studies were performed using BMD software. The benchmark response (BMR) was defined as a 10 % additional risk above the background.ResultsThere was a positive correlation between the UCd levels and the prevalence of Uβ2-MG. The BMD of UCd for Uβ2-MG was estimated for each province. The findings showed that the BMD levels were related to the participants’ geographic region, which may be partially due to the large differences in Cd exposure level, ethnic group, lifestyle and diet of the sample population in these study areas. The reference level of UCd for the renal effects was further evaluated by combining the five sets of data from all 6103 subjects. The overall BMDLs of UCd for Uβ2-MG with an excess risk of 10 % were 2.00 μg/g creatinine (μg/g cr) in males and 1.69 μg/g cr in females, which were significantly lower than the World Health Organization (WHO) threshold level of 5 μg/g cr for Cd-related renal effects.ConclusionsThe selection of the sample population and geographic region affected the BMDL evaluation. Based on the findings of this survey of a large sample population, the UCd BMDLs for Uβ2-MG in males with BMRs at 10 % were 2.00 μg/g cr. The BMD was slightly lower in females, which indicated that females may be relatively more sensitive to Cd exposure than males.

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

“…However, only few studies, conducted in cadmium‐polluted Jinzu and Kakehashi river basin in Japan, have shown the allowable values of cumulative cadmium intake for cadmium‐induced health effects (Kobayashi et al, ; Kobayashi, Suwazono, Dochi, Honda, & Kido, ; Nogawa et al, ). Several studies in China have shown the reference level of UCd or BCd for cadmium‐induced renal dysfunction (Jin et al, ; Ke et al, ; Wang et al, ) or osteoporosis (Chen, Gan, Zhu, & Jin, ). However, no study has shown the reference level of dietary cadmium intake in the Chinese population.…”

Benchmark dose estimation of urinary and blood cadmium as biomarkers of renal dysfunction among 40‐75‐year‐old non‐smoking women in rural areas of southwest China

“…This value is higher than that in studies involving other areas of China. One large sample study conducted in five Cd‐polluted provinces in China found that the BMD 10 /BMDL 10 of U‐Cd for women in the different areas varied from 1.16/1.00 to 3.20/1.94 μg/g Cr (1.87/1.69 μg/g Cr, if the data in the five provinces were combined) for β 2 ‐MG and from 3.14/2.18 to 6.10/4.05 μg/g Cr for NAG (95% cut‐off value) (Ke, Cheng, Zhang, et al, ; Ke, Ke, Jia, et al, ). Another study conducted in two Cd‐polluted areas in south and central China showed that the BMD/BMDL values of U‐Cd for 35‐55‐year‐old women were 1.07/0.44 and 2.12/0.53 μg/g Cr based on β 2 ‐MG and NAG, respectively, at a 90% cut‐off value and 5% BMR (Qi et al, ).…”

“…Model selection was performed using Akaike's information criterion, in which the model with the lowest Akaike's information criterion value was preferred. The subjects were divided into five subgroups (i.e., U‐Cd: 0‐2, 2‐4, 4‐6, 6‐8 and >8 μg/g Cr; B‐Cd: 0‐1, 1‐2, 2‐4, 4‐6 and >6 μg/L), which were selected based on previous studies (Ke, Cheng, Li, et al, ; Ke, Cheng, Zhang, et al, ) and the range and distribution of Cd exposure in the present study. BMD/BMDLs corresponding to an additional risk (BMR) of 5% and 10% were calculated.…”

“…Residents in these Cd‐polluted areas are at risk of renal effects due to long‐term exposure to Cd. However, only a few studies (Hong, Jin, & Zhang, ; Hu et al, ; Jin et al, ; Ke et al, ; Ke et al, ; Qi et al, ) have investigated the body burden of Cd and renal dysfunction effects and utilized BMD to estimate the threshold levels of U‐Cd or B‐Cd for residents in these polluted areas in China until now.…”

Recommended Rice Intake Levels Based on Average Daily Dose and Urinary Excretion of Cadmium in a Cadmium-Contaminated Area of Northwestern Thailand

“…However, safe levels of U-Cd have been determined differently in different studies, because even the 0.5 μg Cd/g creatinine level commonly found in the non-smoking population and in people living in areas without cadmium contamination has been found to have adverse effects on health ( 3 , 4 ). However, the WHO has established that U-Cd levels not exceeding 2 μg/g creatinine are safe for the general population ( 5 , 6 ). Thus, the safety margin between the cadmium level found in the general population and that causing cadmium toxicity is unclear.…”