國家衛生研究院 NHRI:Item 3990099045/16073
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    題名: Benchmark dose of melamine exposure for a renal injury marker mediated by oxidative stress: Examples in patients with urolithiasis and occupational workers
    作者: Chen, CC;Liu, CC;Wang, YH;Wu, CF;Tsai, YC;Li, SS;Hsieh, TJ;Wu, MT
    貢獻者: Institute of Population Health Sciences
    摘要: Establishing a safe exposure level from epidemiological studies while providing direct hazard characterization in humans often faces uncertainty in causality, especially cross-sectional data. With advances in molecular epidemiology, it is reasonable to integrate identified intermediate biomarkers into health risk assessment. In this study, by considering the mediation of the oxidative stress marker malondialdehyde (MDA), we explored the exposure threshold of melamine on the early renal injury marker N-acetyl-β-D glucosaminidase (NAG). The benchmark dose (BMD) was derived from model averaging of the composite direct effect of melamine exposure and the indirect effect through the mediation of MDA on NAG levels. As illustrative examples, we analyzed 309 adult patients with calcium urolithiasis and 80 occupational workers for the corresponding exposure thresholds. The derived threshold was subpopulation-dependent, with the one-sided lower bound BMDL(10) for the patients with urolithiasis with (without) the mediator MDA for the patients with kidney stones and the occupational workers being 0.88 (0.96) μg/kg_bw/day and 22.82 (18.09) μg/kg_bw/day, respectively. The derived threshold levels, considering the oxidative stress marker MDA, were consistent with those without adjusting for the mediation effect. However, the study outcomes were further supported by the suggested mechanism pathway. The threshold for the patients with urolithiasis was up to two orders lower than the current tolerable daily intake level of 200 μg/kg_bw/day recommended by the WHO (EFSA).
    日期: 2024-08-11
    關聯: Toxics. 2024 Aug 11;12(8):Article number 584.
    Link to: http://dx.doi.org/10.3390/toxics12080584
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=2305-6304&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:001304869200001
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85202491478
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