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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

Time-dependent chemical concentration-response curves.(A and B) Results for cyproconazole (A) and for propiconazole (B). Symbols, measured values; solid lines, values described by sigmoidal concentration-response curves. Data points for 120-hour exposure (dashed lines) were predicted by the GUTS-SD model, and the sigmoidal concentration-response curve was fitted to these values. CIs are given in table S8.
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Figure 1: Time-dependent chemical concentration-response curves.(A and B) Results for cyproconazole (A) and for propiconazole (B). Symbols, measured values; solid lines, values described by sigmoidal concentration-response curves. Data points for 120-hour exposure (dashed lines) were predicted by the GUTS-SD model, and the sigmoidal concentration-response curve was fitted to these values. CIs are given in table S8.

Mentions: At the same time, the lowest chemical concentrations used in experiments for cell survival (1.5 mg/liter for cyproconazole and 2.3 mg/liter for propiconazole) were the highest concentrations used in the cell proliferation experiments, which are then corresponding to the highest concentrations used in the FELS test (Table 1). These concentrations did not cause any effect on cell survival within 120 hours [see Fig. 1 and table S8; confidence intervals (CIs) for these concentrations included 100% cell survival]. In support of these experimental data, the threshold values for the initiation of cell death were 1063 mg/kg wet weight for cyproconazole (corresponding to 16.9 mg/liter in exposure medium) and 713.6 mg/kg wet weight for propiconazole (corresponding to 6.78 mg/liter in exposure medium) according to the GUTS-SD model.


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

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

Time-dependent chemical concentration-response curves.(A and B) Results for cyproconazole (A) and for propiconazole (B). Symbols, measured values; solid lines, values described by sigmoidal concentration-response curves. Data points for 120-hour exposure (dashed lines) were predicted by the GUTS-SD model, and the sigmoidal concentration-response curve was fitted to these values. CIs are given in table S8.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 1: Time-dependent chemical concentration-response curves.(A and B) Results for cyproconazole (A) and for propiconazole (B). Symbols, measured values; solid lines, values described by sigmoidal concentration-response curves. Data points for 120-hour exposure (dashed lines) were predicted by the GUTS-SD model, and the sigmoidal concentration-response curve was fitted to these values. CIs are given in table S8.
Mentions: At the same time, the lowest chemical concentrations used in experiments for cell survival (1.5 mg/liter for cyproconazole and 2.3 mg/liter for propiconazole) were the highest concentrations used in the cell proliferation experiments, which are then corresponding to the highest concentrations used in the FELS test (Table 1). These concentrations did not cause any effect on cell survival within 120 hours [see Fig. 1 and table S8; confidence intervals (CIs) for these concentrations included 100% cell survival]. In support of these experimental data, the threshold values for the initiation of cell death were 1063 mg/kg wet weight for cyproconazole (corresponding to 16.9 mg/liter in exposure medium) and 713.6 mg/kg wet weight for propiconazole (corresponding to 6.78 mg/liter in exposure medium) according to the GUTS-SD model.

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