Variation in benchmark dose (BMD) and the 95% lower confidence limit of benchmark dose (BMDL) among general Japanese populations with no anthropogenic exposure to cadmium

Sakuragi, Sonoko; Takahashi, Ken; Hoshuyama, Tsutomu; Moriguchi, Jiro; Ohashi, Fumiko; Fukui, Yoshinari; Ikeda, Masayuki

doi:10.1007/s00420-012-0734-z

Cited by 17 publications

(19 citation statements)

References 38 publications

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“…In these Japanese studies, the estimated BMDLs of urinary Cd for renal tubular markers ranged from 0.6 - 4.1 μg/g Creat and 0.6 - 3.7 μg/g Creat in men and women, respectively after adjusting for age and smoking status [15-17]. In another study conducted in 17,375 adult women living in 16 Cd non-polluted areas in Japan, significant relationships were observed between urinary Cd and β2-MG in 15 areas, with the estimated BMDLs of urinary Cd for β2-MG ranging from 0.9 - 3.8 μg/g Creat with a median of 1.4 μg/g Creat [18]. However, in the present study, the calculated BMDLs were greater than those in the Japanese studies.…”

Section: Discussionmentioning

confidence: 99%

“…Accordingly, the statistical validity and efficiency of the BMD and BMDL values were greater using the hybrid approach compared with methods involving categorization of continuous exposure and effect markers. By using this hybrid approach, the BMDL of urinary Cd for renal effect markers in the Japanese [15-18] and Swedish population have been estimated [19]. However, the relationship between urinary Cd and renal dysfunction has not been evaluated in the Thai population.…”

Section: Introductionmentioning

confidence: 99%

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Risk assessment for Thai population: benchmark dose of urinary and blood cadmium levels for renal effects by hybrid approach of inhabitants living in polluted and non-polluted areas in Thailand

et al. 2014

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BackgroundThe aim of the present study was to estimate the benchmark doses (BMD) for renal effects for health risk assessment of residents living in Cd-polluted and non-polluted areas in a Thai population.MethodsThe study participants consisted of inhabitants aged 40 years or older who lived in a non-polluted area (40 men and 41 women) and in the environmentally polluted Mae Sot District (230 men and 370 women) located in northwestern Thailand. We measured urinary and blood cadmium (Cd) as markers of long-term exposure and urinary β2-microglobulin (β2-MG) and N-acetyl-β-D-glucosaminidase (NAG) as renal tubular effect markers. An updated hybrid approach was applied to estimate the benchmark doses (BMD) and their 95% lower confidence limits (BMDL) of urinary and blood Cd for Cd-induced renal effects in these subjects. BMD and BMDL corresponding to an additional risk (BMR) of 5% were calculated with the background risk at zero exposure set to 5% after adjusting for age and smoking status.ResultsThe estimated BMDLs of urinary Cd for renal effect markers were 6.9 for urinary β2-MG and 4.4 for NAG in men and 8.1 for β2-MG and 6.1 for NAG μg/g creatinine (Creat) in women. These BMDLs of urinary Cd (μg/g Creat) for NAG were less than the geometric mean urinary Cd in the polluted area (6.5 in men and 7.1 in women). The estimated BMDLs of blood Cd (μg/L) were 6.2 for urinary β2-MG and 5.0 for NAG in men and 5.9 for β2-MG and 5.8 for NAG in women. The calculated BMDLs were similar or less compared with the geometric mean blood Cd (μg/L) in the polluted Thai area (6.9 in men and 5.2 in women).ConclusionThe BMDLs of urinary and blood Cd for renal effects were estimated to be 4.4 - 8.1 μg/g Creat and 4.4 - 6.2 μg/L in the Thai population aged ≥ 40 years old, suggesting that more than 40% of the residents were at risk of adverse renal effects induced by Cd exposure in Thailand.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Risk assessment for Thai population: benchmark dose of urinary and blood cadmium levels for renal effects by hybrid approach of inhabitants living in polluted and non-polluted areas in Thailand

et al. 2014

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“…20 µg Cd-D/day; see Section 5), Cd-D did not induce meaningful increase in β 2 -MG in urine 58) . It should also be noted that BMD shows substantial variations subject to variations in ages and Cd exposure intensities among the populations studied 48) .…”

Section: Discussionmentioning

confidence: 90%

“…It is apparently too optimistic to expect that the BMD approach will give a single reliable value across populations even in a country predominantly of a single race such as Japan. Further analysis disclosed that the BMD value is affected by Cd exposure levels and ages 48) (Table 11). …”

Section: Estimation Of Cd-u Level To Induce Adverse Health Effects Inmentioning

confidence: 99%

Cadmium Exposure in General Populations in Japan: a Review

et al. 2015

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Cadmium (Cd) intake via diet (Cd-D) has been a long-standing focus of administrative as well as public concern in Japan after the endemic of Itai-itai disease (chronic cadmium poisoning). The aim of this report was to review cadmium exposure in Japan by introducing publications from our study group and related articles. Literature survey disclosed that Cd-D was high (up to 100 µg/day) in 1960s even in non-polluted areas. Such high Cd-D levels were followed by gradual decreases in 1970s-1980s to current level of well below 20 µg/day. Once, a very high Cd-D (600 µg/day) was reported for a Cd-polluted area. Replacement of Cd-polluted rice paddy soil with clean soil resulted in substantial reduction in riceassociated Cd-D. In large-scale surveys in 10 prefectures all over Japan conducted early in 2000s, the geometric mean (GM) of Cd-U cr (Cd in urine as corrected for creatinine concentration) was 1.26 µg/g cr, but was higher in one north-west sea coast prefecture in Honshu Island (>3 µg/g cr). Supplemental survey in 6 neighboring prefectures on the sea coast disclosed that Cd-U cr in some prefectures were higher as compared with the national average. It was reported that Cd in brown rice was also high. However no clear-cut indication was detected to suggest renal tubular dysfunctions. Surveys in major cities in East and South-East Asia in 1980s-1990s made it clear that Cd-D was substantially lower there than in Japanese cities; Cd exposure of general populations was almost exclusively from foods. Statistical analysis revealed that tubular dysfunction markers increased sharply when Cd-U cr exceeded 10-12 µg/g cr. The Cd-U cr level of 11 µg/g cr corresponded to Cd-D level of 59 µg/day. This level was in agreement with the tolerable weekly intake of 7 µg/kg body weight/week, the value recommended by the Food Safety Commission of Japan.

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“…Thus, these results in previous studies were generally closely consistent with the present results, supporting the reliability of the respective results. However, recently obtained BMDL of urinary Cd for β2-MG in a non-polluted area using the hybrid approach (Sakuragi et al, 2012;Suwazono et al, 2006Suwazono et al, , 2011aSuwazono et al, ,2011b ranged from 0.7 to 2.6 μg g -1 cre, being very close to the representative level of urinary Cd in older Japanese whose geometric mean of urinary Cd was reported to be 1.8 in men and 2.4 μg g -1 cre in Cd nonpolluted areas (Suwazono et al, 2000). Therefore, the standard abnormality rates in previous studies have uncertainty due to the low-level Cd exposure in the control non-polluted area.…”

Section: Discussionmentioning

confidence: 99%

Benchmark dose of cadmium concentration in rice for renal effects in a cadmium‐polluted area in Japan

Nogawa

Kido

Nishijo

et al. 2014

J of Applied Toxicology

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The aim of this study was to estimate the reference level of cadmium in rice as the benchmark doses (BMD) and their 95% lower confidence limits (BMDL) for various renal effects by applying an updated hybrid approach. The participants were 1120 men and 1274 women aged 50 years or older who lived in the environmentally exposed Kakehashi river basin for at least 30 years. As indicators of renal dysfunction, glucose, protein, aminonitrogen, metallothionein and β(2) -microgrobulin in urine were measured. Cadmium concentration was determined for rice samples stored in warehouses of the farmers in all of the polluted hamlets. The BMD and BMDL that corresponded to an additional risk of 5% were calculated with background risk at a zero exposure set at 5%. The obtained BMDLs were 0.39 (aminonitrogen), 0.26 (metallothionein), 0.25 (β(2) -microgrobulin) mg kg(-1) in men and 0.44 (glucose), 0.32 (protein), 0.33 (aminonitrogen), 0.28 (metallothionein) and 0.24 (β(2) -microgrobulin) mg kg(-1) in women. The lowest BMDL was 0.25 and 0.24 mg kg(-1) (β(2) -microgrobulin) in men and women respectively. These values were lower than the maximum level (0.4 mg kg(-1)) determined by the Codex Alimentarius Commission, indicating that these BMDLs may contribute to further discussion on the health risk assessment of cadmium exposure.

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Variation in benchmark dose (BMD) and the 95% lower confidence limit of benchmark dose (BMDL) among general Japanese populations with no anthropogenic exposure to cadmium

Cited by 17 publications

References 38 publications

Risk assessment for Thai population: benchmark dose of urinary and blood cadmium levels for renal effects by hybrid approach of inhabitants living in polluted and non-polluted areas in Thailand

Risk assessment for Thai population: benchmark dose of urinary and blood cadmium levels for renal effects by hybrid approach of inhabitants living in polluted and non-polluted areas in Thailand

Cadmium Exposure in General Populations in Japan: a Review

Benchmark dose of cadmium concentration in rice for renal effects in a cadmium‐polluted area in Japan

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