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Benchmark Dose of Melamine Exposure for a Renal Injury Marker Mediated by Oxidative Stress: Examples in Patients with Urolithiasis and Occupational Workers.

ABSTRACT: 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 BMDL₁₀ 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).

SUBMITTER: Chen CC

PROVIDER: S-EPMC11359403 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature

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Benchmark Dose of Melamine Exposure for a Renal Injury Marker Mediated by Oxidative Stress: Examples in Patients with Urolithiasis and Occupational Workers.

Chen Chu-Chih CC Liu Chia-Chu CC Wang Yin-Han YH Wu Chia-Fang CF Tsai Yi-Chun YC Li Sih-Syuan SS Hsieh Tusty-Jiuan TJ Wu Ming-Tsang MT

Toxics 20240811 8

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 ma ...[more]

PMID: 39195686

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Project description:BackgroundBenchmark dose (BMD) modeling is an important step in human health risk assessment and is used as the default approach to identify the point of departure for risk assessment. A probabilistic framework for dose-response assessment has been proposed and advocated by various institutions and organizations; therefore, a reliable tool is needed to provide distributional estimates for BMD and other important quantities in dose-response assessment.ObjectivesWe developed an online system for Bayesian BMD (BBMD) estimation and compared results from this software with U.S. Environmental Protection Agency's (EPA's) Benchmark Dose Software (BMDS).MethodsThe system is built on a Bayesian framework featuring the application of Markov chain Monte Carlo (MCMC) sampling for model parameter estimation and BMD calculation, which makes the BBMD system fundamentally different from the currently prevailing BMD software packages. In addition to estimating the traditional BMDs for dichotomous and continuous data, the developed system is also capable of computing model-averaged BMD estimates.ResultsA total of 518 dichotomous and 108 continuous data sets extracted from the U.S. EPA's Integrated Risk Information System (IRIS) database (and similar databases) were used as testing data to compare the estimates from the BBMD and BMDS programs. The results suggest that the BBMD system may outperform the BMDS program in a number of aspects, including fewer failed BMD and BMDL calculations and estimates.ConclusionsThe BBMD system is a useful alternative tool for estimating BMD with additional functionalities for BMD analysis based on most recent research. Most importantly, the BBMD has the potential to incorporate prior information to make dose-response modeling more reliable and can provide distributional estimates for important quantities in dose-response assessment, which greatly facilitates the current trend for probabilistic risk assessment. https://doi.org/10.1289/EHP1289.

Dataset Information

Benchmark Dose of Melamine Exposure for a Renal Injury Marker Mediated by Oxidative Stress: Examples in Patients with Urolithiasis and Occupational Workers.

Publications

Benchmark Dose of Melamine Exposure for a Renal Injury Marker Mediated by Oxidative Stress: Examples in Patients with Urolithiasis and Occupational Workers.

Similar Datasets

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