@article{01JP7RXQK1RRD65720R82V9AZ0,
  abstract     = {{BACKGROUND: Tenuazonic acid (TeA), a mycotoxin produced by Alternaria alternata, contaminates various food commodities and is known to cause acute and chronic health effects. However, the lack of human toxicokinetic (TK) data and the reliance on external exposure estimates have stalled a comprehensive risk assessment for TeA. OBJECTIVE: To bridge this gap, a human TK trial and population-based TK (PopTK) modeling were applied to determine human TK parameters of TeA, and the results were applied for risk screening using population biomonitoring data and threshold of toxicological concern (TTC)-based approaches. METHODS: Ten healthy volunteers participated in the TK trial during which the volunteers ingested a bolus dose of TeA at the (external) TTC (1500 ng/kg bw). Blood, urine, and fecal samples were collected over 48 h and analyzed using UPLC-MS/MS. Concentration-time profiles were fi t with a multi-compartmental PopTK model using a hierarchical Bayesian population structure. Utilizing a probabilistic framework, fi tted TK parameters were used to derive internal TTC (iTTC) values for comparison to blood and urine biomonitoring data. Risk screening with data from fi ve diverse biomonitoring cohorts was performed using Hazard Quotient (HQ) and probabilistic individual margin of exposure (IMOE) approaches. RESULTS: TeA was estimated to have a population median half-life of 1.9 [90% CI: 1.4-2.7] hours and volume of distribution of 4.4 [3.1-6.1] L/kg, with inter-individual variability geometric standard deviations of 2.4- and 1.7-fold, respectively. Probabilistic lower confidence bound iTTCs were derived of 0.5 nmol/L in blood and 2.53 nmol/kg-d urinary excretion. Risk screening HQs were mostly >1 for the three blood biomonitoring cohorts and < 1 for the two urinary biomonitoring cohorts; results from probabilistic IMOE calculations were qualitatively consistent. SIGNIFICANCE: A comprehensive human TK study was performed for TeA for the fi rst time, demonstrating the importance of integrating TK and population variability for a more comprehensive risk evaluation, particularly for interpreting biomonitoring data. The results for TeA point to the critical need for toxicity data to move beyond TTC-based risk screening.}},
  author       = {{Visintin, Lia and Lu, En-Hsuan and Lin, Hsing-Chieh and Bader, Yasmine and Nguyen, Truong Nhat and Mouchtaris Michailidis, Thanos and De Saeger, Sarah and Chiu, Weihsueh A. and De Boevre, Marthe}},
  issn         = {{1559-0631}},
  journal      = {{JOURNAL OF EXPOSURE SCIENCE AND ENVIRONMENTAL EPIDEMIOLOGY}},
  keywords     = {{Tenuazonic acid,risk screening,toxicokinetic,iTTC}},
  language     = {{eng}},
  number       = {{4}},
  pages        = {{632--643}},
  title        = {{Derivation of human toxicokinetic parameters and internal threshold of toxicological concern for tenuazonic acid through a human intervention trial and hierarchical Bayesian population modeling}},
  url          = {{http://doi.org/10.1038/s41370-025-00746-6}},
  volume       = {{35}},
  year         = {{2025}},
}

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