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Advancing probabilistic risk assessment by integrating human biomonitoring, new approach methods, and Bayesian modeling : a case study with the mycotoxin deoxynivalenol

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Deoxynivalenol (DON) is a mycotoxin frequently observed in cereals and cereal-based foods, with reported toxicological effects including reduced body weight, immunotoxicity and reproductive defects. The European Food Safety Authority used traditional risk assessment approaches to derive a deterministic Tolerable Daily Intake (TDI) of 1 mu g/kg-day, however data from human biomarkers studies indicate widespread and variable exposure worldwide, necessitating more sophisticated and advanced methods to quantify population risk. The World Health Organization/International Programme on Chemical Safety (WHO/IPCS) has previously used DON as a case example in replacing the TDI with a probabilistic toxicity value, using default uncertainty and variability distributions to derive the Human Dose corresponding to an effect size M in the Ith percentile of the population (HDMI) for M = 5 % decrease in body weight and I = 1 %. In this study, we extend this case study by incorporating (1) Bayesian modeling approaches, (2) using both in vivo data and in vitro population new approach methods to replace default distributions for interspecies toxicokinetic (TK) differences and intraspecies TK and toxicodynamic (TD) variability, and (3) integrating biomonitoring data and probabilistic dose-response functions to characterize population risk distributions. We first derive an HDMI of 5.5 [1.4-24] mu g/kg-day, also using TK modeling to converted the HDMI to Biomonitoring Equivalents, BEMI for comparison with biomonitoring data, with a blood BEMI of 0.53 [0.17-1.6] mu g/L and a urinary excretion BEMI of 3.9 [1.0-16] mu g/kg-day. We then illustrate how this integrative approach can advance quantitative risk characterization using two human bio-monitoring datasets, estimating both the fraction of population with an effect size M >= 5 % as well as the distribution of effect sizes. Overall, we demonstrate that integration of Bayesian modeling, human biomonitoring data, and in vitro population-based TD data within the WHO/IPCS probabilistic framework yields more accurate, precise, and comprehensive risk characterization.
Tijdschrift: ENVIRONMENT INTERNATIONAL
ISSN: 1873-6750
Volume: 182
Jaar van publicatie:2023
Toegankelijkheid:Open