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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

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Abstract

Background

The use of benchmark dose (BMD) and the 95% lower confidence limit of benchmark dose (BMDL) have been gaining popularity not only in experimental studies but also in epidemiological studies including those on toxicology of cadmium (Cd), a ubiquitous hazardous element in the environment. However, the reproducibility of BMD and BMDL values has seldom been examined.

Objectives

This study was initiated to determine whether consistent BMD and BMDL values are obtained for similar non-exposed populations, i.e., the populations with no anthropogenic exposure to Cd in a single nation of Japan.

Methods

Cd (an exposure marker), α1-microglobulin (α1-MG), β2-microglobulin (β2-MG) and N-acetyl-β-D-glucosaminidase (NAG) (three effect markers of tubular dysfunction) levels in the urine of adult Japanese women from five previous publications of this study group were examined. Overall, data were available for 17,375 cases (in 16 prefectures) regarding Cd, α1-MG and β2-MG, and 6,409 cases (in ten prefectures) regarding NAG. The data were used to calculate BMD and BMDL values taking advantage of the hybrid approach (Budtz-Jǿrgensen et al. in Biometrics 57:698–706, 2001). It was possible to calculate BMD and BMDL values for α1-MG and β2-MG for all of the 16 prefectures with 17,375 cases, whereas the values for NAG were successfully calculated for nine prefectures with 5,843 cases.

Results

The application gave BMD values of 1.92, 2.46 and 2.32 μg Cd/g cr for α1-MG, β2-MG and NAG, respectively, and BMDL values of 1.83, 2.32 and 2.09 μg Cd/g cr. Large inter-prefectural variations were observed in the BMD and BMDL; there was about fourfold difference both in BMD and in BMDL calculated for α1-MG and β2-MG in 16 prefectures, and the variation was greater (i.e., by about sevenfold) in BMD and BMDL for NAG in nine prefectures. A survey of relevant literature revealed variation in BMD and BMDL values of similar folds as observed in the present analyses in five studies of Japanese populations. Multiple regression analyses taking BMD or BMDL as a dependent variable and age, CR concentration and Cd concentration as independent variables showed both BMD and BMDL were significantly influenced by Cd concentration in cases of α1-MG and β2-MG, whereas BMD and BMDL for NAG was by CR.

Conclusions

Even when the analysis was conducted in a single nation, both BMD and BMDL for the Cd effect markers varied by ca. fourfold when examining α1-MG or β2-MG and the values varied by ca. sevenfold for NAG among Cd-non-exposed populations. The most influential factors in the study population may include urine density and Cd levels in the urine.

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Acknowledgments

The authors are grateful to the administration and staff of the Kyoto Industrial Health Association, Kyoto, Japan, for their interest in and support for this study.

Conflicts of interest

The authors declare that they have no conflicts of interest.

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Authors and Affiliations

  1. Kyoto Industrial Health Association (Mibu Office), 4-1 Mibu-Shujaku-cho, Nakagyo-ku, Kyoto, 604-8871, Japan

    Sonoko Sakuragi & Jiro Moriguchi

  2. Kyoto Industrial Health Association (Main Office), 67 Nishinokyo-Kitatsuboicho, Nakagyo-ku, Kyoto, 604-8472, Japan

    Fumiko Ohashi, Yoshinari Fukui & Masayuki Ikeda

  3. Department of Environmental Epidemiology, Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, 807-8555, Japan

    Ken Takahashi & Tsutomu Hoshuyama

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  1. Sonoko Sakuragi
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Correspondence to Sonoko Sakuragi.

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Sakuragi, S., Takahashi, K., Hoshuyama, T. et al. 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. Int Arch Occup Environ Health 85, 941–950 (2012). https://doi.org/10.1007/s00420-012-0734-z

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