Integrating Time-Resolved nrf2 Gene-Expression Data into a Full GUTS Model as a Proxy for Toxicodynamic Damage in Zebrafish Embryo

Environmental Science & Technology, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 4, 2024

The immense production of the chemical industry requires an improved predictive risk assessment that can handle constantly evolving challenges while reducing dependency on animal testing. Integrating omics data into mechanistic models offers a promising solution by linking cellular processes triggered after exposure with observed effects in organism. With emerging availability time-resolved RNA data, goal integrating gene expression be approached. We propose biologically anchored TKTD model, which describes key link level stress regulator nrf2 to detoxification and lethality associating toxicodynamic damage expression. Fitting such model complex sets consisting multiple endpoints required combination methods from molecular biology, dynamic systems modeling, Bayesian inference. In this study, we successfully integrate thus provide method for assessing influence markers survival. This novel was used test whether applied predict zebrafish embryos. presented approach, outline approach based data.

Language: Английский

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Honey Bee Exposure to the Fungicide Propiconazole in Lowbush Blueberry Fields

Agronomy, Journal Year: 2022, Volume and Issue: 12(12), P. 3081 - 3081

Published: Dec. 5, 2022

The fungicide propiconazole is a commonly used in small fruit and tree production the U.S.A. In Maine wild blueberry production, it almost exclusively for mummy berry disease control. goal of this study to assess risk exposure honey bee colonies deployed fields pollination. was conducted over six-year period (2009–2014) both field laboratory. Field surveys (2009–2011) measured residues on flowers 41 commercial across growing region. A two-year (2010–2011) determined decay rate after application. laboratory contact LD50 workers (2013). exposure/effect three years (2011–2013). study, 8–18 previously unexposed were randomly assigned one two treatments, (1) isolated that treated prior bloom with fungicide, propiconazole, but no other pesticides, or (2) not any pesticides. measures taken evaluate effects monitored each year estimation colonies, as flowers, workers, pollen brought back hives; colony population size (workers brood); (3) queen status presence; (4) oviposition rate; (5) supersedure (6) egg hatch success; (7) mortality developing larvae pupae; (8) royal jelly deposition wax comb cells; (9) worker longevity; (10) foraging activity; (11) repellency foragers; (12) overwintering (13) hypopharyngeal gland acini size; (14) pathogen parasite incidence intensity. results these experiments showed 24,747 ppb. Residues found be abundant application mean concentration 2083.8 ± 851.3 (se). non-detectable levels took about 40 days three-year hive deployment detected pollen, bees, demonstrating occurs even though applied before bloom. Also evidence reduced populations, increased supersedure, decreased rate, intensity, loss due found. However, exposed exhibited longevity (17.3%), hypertrophy 5 d old nurse (8.3%), 3.5 h foragers

Language: Английский

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Cumulative Risk Meets Inter-Individual Variability: Probabilistic Concentration Addition of Complex Mixture Exposures in a Population-Based Human In Vitro Model

Toxics, Journal Year: 2022, Volume and Issue: 10(10), P. 549 - 549

Published: Sept. 20, 2022

Although humans are continuously exposed to complex chemical mixtures in the environment, it has been extremely challenging investigate resulting cumulative risks and impacts. Recent studies proposed use of “new approach methods,” particular vitro assays, for hazard dose−response evaluation mixtures. We previously found, using five human cell-based that concentration addition (CA), usual default calculate risk, is mostly accurate within an order magnitude. Here, we extend these findings further how data can be used quantify inter-individual variability CA. Utilizing from testing 42 Superfund priority chemicals separately 8 defined a population-wide model, applied CA predict effective concentrations cytotoxicity each individual, “typical” (median) “sensitive” (first percentile) members population, median-to-sensitive individual ratio (defined as toxicodynamic factor, TDVF). quantified accuracy with Loewe Additivity Index (LAI). found LAI varies more between different than individuals, predictions population median generally or TDVF. Moreover, values were <1, indicating potent predicted by Together our previous studies, posit new methods including multiple phenotypes diverse cell types fill critical gaps risk assessment, but sophisticated models mixture additivity bioavailability may needed. In meantime, because simple underestimate potency magnitude more, either whole-mixture or, alternatively, stringent benchmarks indices (e.g., lower index) needed ensure public health protection.

Language: Английский

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Toxicokinetic–Toxicodynamic Model to Assess Thermal Stress

Environmental Science & Technology, Journal Year: 2023, Volume and Issue: 57(50), P. 21029 - 21037

Published: Dec. 8, 2023

Temperature is a crucial environmental factor affecting the distribution and performance of ectothermic organisms. This study introduces new temperature damage model to interpret their thermal stress. Inspired by ecotoxicological in General Unified Threshold for Survival (GUTS) framework, assumes that depends on balance between temperature-dependent accumulation constant repair. Mortality due stress driven level exceeding threshold. Model calibration showed good agreement with measured survival Gammarus pulex exposed different temperatures. Further, simulations, including temperatures, daily fluctuations, heatwaves, demonstrated model's ability predict effects various scenarios. With this, present contributes mechanistic understanding as single stressor while facilitating incorporation an additional alongside chemicals multistressor effect models.

Language: Английский

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Utilizing Ec50 for Average Swimming Speed as a Basis for Mixture Toxicity Studies with Triazole Fungicides in Behavioral Ecotoxicology

Published: Jan. 1, 2024

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Language: Английский

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