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Toxicology across scales: Cell population growth in vitro predicts reduced fish growth.

Stadnicka-Michalak J, Schirmer K, Ashauer R - Sci Adv (2015)

Bottom Line: We show that tests using cell cultures, combined with modeling of toxicological effects, can replace tests with juvenile fish.Our model predicts reduced fish growth in two fish species in excellent agreement with measured in vivo data of two pesticides.This promising step toward alternatives to fish toxicity testing is simple, inexpensive, and fast and only requires in vitro data for model calibration.

View Article: PubMed Central - PubMed

Affiliation: Eawag, Swiss Federal Institute of Aquatic Science and Technology, 8600 Dübendorf, Switzerland. ; School of Architecture, Civil and Environmental Engineering, École Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland.

ABSTRACT
Environmental risk assessment of chemicals is essential but often relies on ethically controversial and expensive methods. We show that tests using cell cultures, combined with modeling of toxicological effects, can replace tests with juvenile fish. Hundreds of thousands of fish at this developmental stage are annually used to assess the influence of chemicals on growth. Juveniles are more sensitive than adult fish, and their growth can affect their chances to survive and reproduce. Thus, to reduce the number of fish used for such tests, we propose a method that can quantitatively predict chemical impact on fish growth based on in vitro data. Our model predicts reduced fish growth in two fish species in excellent agreement with measured in vivo data of two pesticides. This promising step toward alternatives to fish toxicity testing is simple, inexpensive, and fast and only requires in vitro data for model calibration.

No MeSH data available.


Interpolation of the predicted fish weight reduction to other chemical concentrations.Symbols represent predictions with model uncertainty (Materials and Methods: Linking cell population growth to whole-organism growth) obtained on the basis of measured in vitro data and the von Bertalanffy growth model, and lines represent fitted model with 95% CIs (Materials and Methods: Interpolation to other chemical concentrations).
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Figure 2: Interpolation of the predicted fish weight reduction to other chemical concentrations.Symbols represent predictions with model uncertainty (Materials and Methods: Linking cell population growth to whole-organism growth) obtained on the basis of measured in vitro data and the von Bertalanffy growth model, and lines represent fitted model with 95% CIs (Materials and Methods: Interpolation to other chemical concentrations).

Mentions: Next, the von Bertalanffy growth model (22) was implemented to predict the inhibition of cell proliferation caused by the chemicals during long-term exposure. In this model, organism growth is presented as body length over time; however, we focused on the increase of fish weight and not length because it was shown that the former is more sensitive to chemical exposure (23). The model was also used to interpolate fish weight reduction to other chemical concentrations (Fig. 2; Materials and Methods: Interpolation to other chemical concentrations), so that the inhibition of cell population growth could be compared with the inhibition of fish growth caused by the chemical concentrations in the FELS tests. The comparisons were made for the exposure times used in the FELS tests at the only time points available, which were 31 days for fathead minnow (Pimephales promelas) and 62 days for rainbow trout (O. mykiss).


Toxicology across scales: Cell population growth in vitro predicts reduced fish growth.

Stadnicka-Michalak J, Schirmer K, Ashauer R - Sci Adv (2015)

Interpolation of the predicted fish weight reduction to other chemical concentrations.Symbols represent predictions with model uncertainty (Materials and Methods: Linking cell population growth to whole-organism growth) obtained on the basis of measured in vitro data and the von Bertalanffy growth model, and lines represent fitted model with 95% CIs (Materials and Methods: Interpolation to other chemical concentrations).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4643812&req=5

Figure 2: Interpolation of the predicted fish weight reduction to other chemical concentrations.Symbols represent predictions with model uncertainty (Materials and Methods: Linking cell population growth to whole-organism growth) obtained on the basis of measured in vitro data and the von Bertalanffy growth model, and lines represent fitted model with 95% CIs (Materials and Methods: Interpolation to other chemical concentrations).
Mentions: Next, the von Bertalanffy growth model (22) was implemented to predict the inhibition of cell proliferation caused by the chemicals during long-term exposure. In this model, organism growth is presented as body length over time; however, we focused on the increase of fish weight and not length because it was shown that the former is more sensitive to chemical exposure (23). The model was also used to interpolate fish weight reduction to other chemical concentrations (Fig. 2; Materials and Methods: Interpolation to other chemical concentrations), so that the inhibition of cell population growth could be compared with the inhibition of fish growth caused by the chemical concentrations in the FELS tests. The comparisons were made for the exposure times used in the FELS tests at the only time points available, which were 31 days for fathead minnow (Pimephales promelas) and 62 days for rainbow trout (O. mykiss).

Bottom Line: We show that tests using cell cultures, combined with modeling of toxicological effects, can replace tests with juvenile fish.Our model predicts reduced fish growth in two fish species in excellent agreement with measured in vivo data of two pesticides.This promising step toward alternatives to fish toxicity testing is simple, inexpensive, and fast and only requires in vitro data for model calibration.

View Article: PubMed Central - PubMed

Affiliation: Eawag, Swiss Federal Institute of Aquatic Science and Technology, 8600 Dübendorf, Switzerland. ; School of Architecture, Civil and Environmental Engineering, École Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland.

ABSTRACT
Environmental risk assessment of chemicals is essential but often relies on ethically controversial and expensive methods. We show that tests using cell cultures, combined with modeling of toxicological effects, can replace tests with juvenile fish. Hundreds of thousands of fish at this developmental stage are annually used to assess the influence of chemicals on growth. Juveniles are more sensitive than adult fish, and their growth can affect their chances to survive and reproduce. Thus, to reduce the number of fish used for such tests, we propose a method that can quantitatively predict chemical impact on fish growth based on in vitro data. Our model predicts reduced fish growth in two fish species in excellent agreement with measured in vivo data of two pesticides. This promising step toward alternatives to fish toxicity testing is simple, inexpensive, and fast and only requires in vitro data for model calibration.

No MeSH data available.