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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.


Related in: MedlinePlus

Measured reduction of fish weight [“●” (each dot represents one fish); mean, “−”] and predictions including model uncertainty (Materials and Methods: Linking cell population growth to whole organism growth) based on in vitro cell population growth data (“”) for different chemical concentrations.(A and B) Results for cyproconazole (A) and for propiconazole (B). Weight reduction is presented as percent of weight of control samples after 62-day exposure for cyproconazole and 31-day exposure for propiconazole. We assumed that the total mass of all fish cells is the same as fish weight. For cyproconazole, all tested concentrations caused a significant effect on fish weight, whereas for propiconazole, the three highest concentrations caused significant effect on fish weight [P < 0.05, analysis of variance (ANOVA) and Dunnett’s multiple comparison test, performed in GraphPad Prism].
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Figure 3: Measured reduction of fish weight [“●” (each dot represents one fish); mean, “−”] and predictions including model uncertainty (Materials and Methods: Linking cell population growth to whole organism growth) based on in vitro cell population growth data (“”) for different chemical concentrations.(A and B) Results for cyproconazole (A) and for propiconazole (B). Weight reduction is presented as percent of weight of control samples after 62-day exposure for cyproconazole and 31-day exposure for propiconazole. We assumed that the total mass of all fish cells is the same as fish weight. For cyproconazole, all tested concentrations caused a significant effect on fish weight, whereas for propiconazole, the three highest concentrations caused significant effect on fish weight [P < 0.05, analysis of variance (ANOVA) and Dunnett’s multiple comparison test, performed in GraphPad Prism].

Mentions: The close correspondence between inhibited cell proliferation (in vitro) and reduced fish growth (in vivo) supports our hypothesis that the modeled inhibition of cell population growth under chemical stress can be taken as proxy for chemical effects on fish growth (Table 1 and Fig. 3; for model parameters and equations, see Materials and Methods). The impact of four concentrations of cyproconazole on the growth of rainbow trout (62 days) and five concentrations of propiconazole on the growth of fathead minnow (31 days) were predicted on the basis of in vitro data. The predictions agreed very well with the observed reduction in fish growth, especially when considering the variation in fish growth data (Fig. 3).


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

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

Measured reduction of fish weight [“●” (each dot represents one fish); mean, “−”] and predictions including model uncertainty (Materials and Methods: Linking cell population growth to whole organism growth) based on in vitro cell population growth data (“”) for different chemical concentrations.(A and B) Results for cyproconazole (A) and for propiconazole (B). Weight reduction is presented as percent of weight of control samples after 62-day exposure for cyproconazole and 31-day exposure for propiconazole. We assumed that the total mass of all fish cells is the same as fish weight. For cyproconazole, all tested concentrations caused a significant effect on fish weight, whereas for propiconazole, the three highest concentrations caused significant effect on fish weight [P < 0.05, analysis of variance (ANOVA) and Dunnett’s multiple comparison test, performed in GraphPad Prism].
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 3: Measured reduction of fish weight [“●” (each dot represents one fish); mean, “−”] and predictions including model uncertainty (Materials and Methods: Linking cell population growth to whole organism growth) based on in vitro cell population growth data (“”) for different chemical concentrations.(A and B) Results for cyproconazole (A) and for propiconazole (B). Weight reduction is presented as percent of weight of control samples after 62-day exposure for cyproconazole and 31-day exposure for propiconazole. We assumed that the total mass of all fish cells is the same as fish weight. For cyproconazole, all tested concentrations caused a significant effect on fish weight, whereas for propiconazole, the three highest concentrations caused significant effect on fish weight [P < 0.05, analysis of variance (ANOVA) and Dunnett’s multiple comparison test, performed in GraphPad Prism].
Mentions: The close correspondence between inhibited cell proliferation (in vitro) and reduced fish growth (in vivo) supports our hypothesis that the modeled inhibition of cell population growth under chemical stress can be taken as proxy for chemical effects on fish growth (Table 1 and Fig. 3; for model parameters and equations, see Materials and Methods). The impact of four concentrations of cyproconazole on the growth of rainbow trout (62 days) and five concentrations of propiconazole on the growth of fathead minnow (31 days) were predicted on the basis of in vitro data. The predictions agreed very well with the observed reduction in fish growth, especially when considering the variation in fish growth data (Fig. 3).

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.


Related in: MedlinePlus