title: 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.
authors.affiliation: Department of Occupational and Environmental Medicine, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuoku, Chiba 260-8670, Japan. suwa@faculty.chiba-u.jp
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Suwazono
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Nogawa
authors.forename: Mirei
authors.initials: M
authors.lastname: Uetani
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Miura
authors.forename: Kiyomi
authors.initials: K
authors.lastname: Sakata
authors.forename: Akira
authors.initials: A
authors.lastname: Okayama
authors.forename: Hirotsugu
authors.initials: H
authors.lastname: Ueshima
authors.forename: Jeremiah
authors.initials: J
authors.lastname: Stamler
authors.forename: Hideaki
authors.initials: H
authors.lastname: Nakagawa
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000652:urine; D002104:Cadmium / Q000009:adverse effects* / Q000652:urine*; D003404:Creatinine / Q000652:urine; D004781:Environmental Exposure / Q000009:adverse effects*; D004785:Environmental Pollutants / Q000633:toxicity*; D005260:Female; D006801:Humans; D007564:Japan / Q000453:epidemiology; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D011507:Proteinuria / Q000652:urine; D012015:Reference Standards; D051437:Renal Insufficiency / Q000139:chemically induced*; D001613:beta 2-Microglobulin / Q000652:urine
chemical_list: D015415:Biomarkers; D004785:Environmental Pollutants; D001613:beta 2-Microglobulin; D002104:Cadmium; D003404:Creatinine