Environmental Sorption Behavior of Ionic and Ionizable Organic Chemicals

Henneberger, Luise; Goss, Kai‐Uwe

doi:10.1007/398_2019_37

Cited by 9 publications

(17 citation statements)

References 123 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Prediction models for the partitioning of ionized molecules are still widely missing. 12 The development of such models is also complicated by the fact that ions undergo more complex sorption processes like ion exchange or ion pair partitioning compared to neutral molecules and often show nonlinear sorption isotherms. 12,13 The aim of this work was to experimentally determine the exposure of 15 chemicals, 14 IOCs and one neutral chemical, in two in vitro cell-based bioassays, testing for oxidative stress response and activation of the peroxisome proliferatoractivated receptor gamma (PPARγ), respectively.…”

Section: ■ Introductionmentioning

confidence: 99%

“…12 The development of such models is also complicated by the fact that ions undergo more complex sorption processes like ion exchange or ion pair partitioning compared to neutral molecules and often show nonlinear sorption isotherms. 12,13 The aim of this work was to experimentally determine the exposure of 15 chemicals, 14 IOCs and one neutral chemical, in two in vitro cell-based bioassays, testing for oxidative stress response and activation of the peroxisome proliferatoractivated receptor gamma (PPARγ), respectively. The selected test chemicals were chosen to represent different exposure scenarios from nearly completely freely dissolved (e.g., caffeine) to highly protein-bound chemicals (e.g., naproxen and ibuprofen), explicitly including chemicals that showed nonlinear binding isotherms to medium proteins 14 and consequently concentration-variable exposure in previous studies (e.g., diclofenac).…”

Section: ■ Introductionmentioning

confidence: 99%

“…Many toxicologically and environmentally relevant chemicals like surfactants, pharmaceuticals, and pesticides are ionic and ionizable organic chemicals (IOCs). − Exposure assessment is especially challenging for IOCs, because these chemicals can be present in different forms (e. g., neutral, cationic, anionic, or with multiple charges) depending on the pH value of the medium. Prediction models for the partitioning of ionized molecules are still widely missing . The development of such models is also complicated by the fact that ions undergo more complex sorption processes like ion exchange or ion pair partitioning compared to neutral molecules and often show nonlinear sorption isotherms. , …”

Section: Introductionmentioning

confidence: 99%

“…Prediction models for the partitioning of ionized molecules are still widely missing . The development of such models is also complicated by the fact that ions undergo more complex sorption processes like ion exchange or ion pair partitioning compared to neutral molecules and often show nonlinear sorption isotherms. , …”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Experimental Exposure Assessment of Ionizable Organic Chemicals in In Vitro Cell-Based Bioassays

Huchthausen

Mühlenbrink

König

et al. 2020

Chem. Res. Toxicol.

Self Cite

View full text Add to dashboard Cite

Exposure assessment in in vitro cell-based bioassays is challenging for ionizable organic chemicals (IOCs), because they are present as more than one chemical species in the bioassay medium. Furthermore, compared to neutral organic chemicals, their binding to medium proteins and lipids is driven by more complex molecular interactions. Total medium concentrations (C total,medium ) and/or freely dissolved medium concentrations (C free,medium ) were determined for one neutral chemical and 14 IOCs (acids, bases, multifunctional) at concentrations relevant for determination of cytotoxicity and effect. C free,medium was measured in two in vitro bioassays at the time of dosing and after 24 h of incubation using solid-phase microextraction. C free,medium was maximally 1.7 times lower than the nominal concentrations (C nom ) for the hydrophilic chemicals (caffeine and lamotrigine). For the organic acids (naproxen, ibuprofen, warfarin, and diclofenac), C free,medium was by a factor of 4 lower than C nom at high concentrations, but the ratio was much higher at low concentrations, indicating a nonlinear binding behavior. The experimental C free,medium was also compared with C free,medium predicted with a mass balance model accounting for binding to medium proteins and lipids. The mass balance model performed well for five of the test chemicals (within a factor of 10), but it underestimated C free,medium by up to a factor of 1200 for chemicals that showed nonlinear binding to medium components. These findings emphasize that experimental exposure assessment is required for improved understanding of in vitro toxicity data.

show abstract

Section: ■ Introductionmentioning

confidence: 99%

Section: ■ Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Experimental Exposure Assessment of Ionizable Organic Chemicals in In Vitro Cell-Based Bioassays

Huchthausen

Mühlenbrink

König

et al. 2020

Chem. Res. Toxicol.

Self Cite

View full text Add to dashboard Cite

show abstract

“…In an aquatic environment, toltrazuril will bioconcentrate to a lesser extent than the other compounds. 66 Ionic species feature different sorption preferences than neutral organic compounds, as they increasingly partition into phospholipids and structural protein, 67 and they are susceptible to an ion-trapping effect if the pH of the exposure medium is lower than the internal pH of the organism. 66 …”

Section: Resultsmentioning

confidence: 99%

Modeling Bioavailable Concentrations in Zebrafish Cell Lines and Embryos Increases the Correlation of Toxicity Potencies across Test Systems

Lungu-Mitea

Vogs

Carlsson

et al. 2020

Environ. Sci. Technol.

View full text Add to dashboard Cite

Linking cellular toxicity to low-tier animal toxicity and beyond is crucial within the adverse outcome pathway concept and the 3R framework. This study aimed to determine and compare the bioavailable effect concentrations in zebrafish cell lines and embryos. Acute, short-term toxicity (48 h) of eight veterinary pharmaceuticals was measured in two zebrafish cell lines (hepatocytes, fibroblasts) and zebrafish embryos. Seven endpoints of cytotoxicity were recorded. The fish embryo acute toxicity test was modified by adding sublethal endpoints. Chemical distribution modeling (mass balance) was applied to compute the bioavailable compound concentrations in cells ( C free ) and embryos ( C int;aq ) based on nominal effect concentrations ( C nom ). Effect concentration ratios were calculated (cell effects/embryo effects). A low correlation was observed between cytotoxicity and embryo toxicity when nominal concentrations were used. Modeled bioavailable effect concentrations strongly increased correlations and placed regression lines close to the line of unity and axis origin. Cytotoxicity endpoints showed differences in sensitivity and predictability. The hepatocyte cell line depicted closer proximity to the embryo data. Conclusively, the high positive correlation between the cell- and embryo-based test systems emphasizes the appropriate modulation of toxicity when linked to bioavailable concentrations. Furthermore, it highlights the potential of fish cell lines to be utilized in integrated testing strategies.

show abstract

Predicting the Accumulation of Ionizable Pharmaceuticals and Personal Care Products in Aquatic and Terrestrial Organisms

Carter

Armitage

Brooks

et al. 2022

Enviro Toxic and Chemistry

View full text Add to dashboard Cite

The extent to which chemicals bioaccumulate in aquatic and terrestrial organisms represents a fundamental consideration for chemicals management efforts intended to protect public health and the environment from pollution and waste. Many chemicals, including most pharmaceuticals and personal care products (PPCPs), are ionizable across environmentally relevant pH gradients, which can affect their fate in aquatic and terrestrial systems. Existing mathematical models describe the accumulation of neutral organic chemicals and weak acids and bases in both fish and plants. Further model development is hampered, however, by a lack of mechanistic insights for PPCPs that are predominantly or permanently ionized. Targeted experiments across environmentally realistic conditions are needed to address the following questions: (1) What are the partitioning and sorption behaviors of strongly ionizing chemicals among species? (2) How does membrane permeability of ions influence bioaccumulation of PPCPs? (3) To what extent are salts and associated complexes with PPCPs influencing bioaccumulation? (4) How do biotransformation and other elimination processes vary within and among species? (5) Are bioaccumulation modeling efforts currently focused on chemicals and species with key data gaps and risk profiles? Answering these questions promises to address key sources of uncertainty for bioaccumulation modeling of ionizable PPCPs and related contaminants. Environ Toxicol Chem 2022;00:1–11. © 2022 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

show abstract

Environmental Sorption Behavior of Ionic and Ionizable Organic Chemicals

Cited by 9 publications

References 123 publications

Experimental Exposure Assessment of Ionizable Organic Chemicals in In Vitro Cell-Based Bioassays

Experimental Exposure Assessment of Ionizable Organic Chemicals in In Vitro Cell-Based Bioassays

Modeling Bioavailable Concentrations in Zebrafish Cell Lines and Embryos Increases the Correlation of Toxicity Potencies across Test Systems

Predicting the Accumulation of Ionizable Pharmaceuticals and Personal Care Products in Aquatic and Terrestrial Organisms

Contact Info

Product

Resources

About