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The toxicokinetics cell demography model to explain metal kinetics in terrestrial invertebrates.

Argasinski K, Bednarska A, Laskowski R - Ecotoxicology (2012)

Bottom Line: At low constant toxicant concentrations in food, the model predicts that toxicant-driven cell mortality is moderate and the total amount of toxicant in the intestine increases slowly up to the level resulting from the gradual increase of the cell replacement rate.The increased cell death rate results in reduced toxicant absorption, which in turn brings its body load down.The resulting pattern of toxicokinetic trajectory for high metal concentration closely resemble that found in empirical studies, indicating that the model probably describes the actual phenomenon.

View Article: PubMed Central - PubMed

Affiliation: Institute of Environmental Sciences, Jagiellonian University, Gronostajowa 7, 30-387, Kraków, Poland. argas1@wp.pl

ABSTRACT
Metal toxicokinetics in invertebrates are usually described by one-compartment first-order kinetic model. Although the model gives an adequate description of the toxicokinetics in certain cases, it has been shown to fail in some situations. It also does not seem acceptable on purely theoretical grounds as accumulation and excretion rates may change depending on instantaneous toxicant concentration in the gut. We postulate that the mechanism behind such changes is connected with the toxic effect of metals on gut epithelial cells. Based on published data, we have constructed a mechanistic model assuming a dynamic rate of replacement of epithelial cells with increasing contamination. We use a population-type modeling, with a population of gut epithelial cells characterized by specific death and birth rates, which may change depending on the metal concentration in food. The model shows that the equilibrium concentration of a toxicant in an organism is the net result of gut cell death and replacement rates. At low constant toxicant concentrations in food, the model predicts that toxicant-driven cell mortality is moderate and the total amount of toxicant in the intestine increases slowly up to the level resulting from the gradual increase of the cell replacement rate. At high constant concentration, total toxicant amount in the gut increases very fast, what is accompanied by massive cell death. The increased cell death rate results in reduced toxicant absorption, which in turn brings its body load down. The resulting pattern of toxicokinetic trajectory for high metal concentration closely resemble that found in empirical studies, indicating that the model probably describes the actual phenomenon.

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Model predictions for moderate toxicity ( = 9, b = 10) show ca. 16 % loss of cells (upper panel) and a marked increase in the amount of the toxicant (nominal value 45) accumulated in gut epithelial cells, with only a slight decrease after ca. 15 time units (lower panel);  number of toxic particles introduced to the organism during interval , b number of new cells produced during
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Fig2: Model predictions for moderate toxicity ( = 9, b = 10) show ca. 16 % loss of cells (upper panel) and a marked increase in the amount of the toxicant (nominal value 45) accumulated in gut epithelial cells, with only a slight decrease after ca. 15 time units (lower panel); number of toxic particles introduced to the organism during interval , b number of new cells produced during

Mentions: The model’s performance was tested using a range of constant concentration/toxicity values (Figs. 1, 2, 3). So far the model has been tested whether it can follow real experimental data on metal TK. Since the TKCD model is mechanistic rather than phenomenological or statistical regression model, fitting its parameters, such as cell mortalities, to the observed data is not methodologically correct. Technically this is possible but the estimated parameter values would be not scientifically plausible. The TKCD model predictions for high toxicity were compared with results of the empirical study on Pterostichus oblongopunctatus exposed to 2,500 mg Ni/kg dry food (Bednarska et al. 2011)—the only Ni concentration used by the authors. Figure 3 shows that the model produces pattern similar to the empirical observations despite its simplicity. Accordingly, laboratory studies gathering TK of different metals at different concentrations in food would be invaluable in testing the model’s performance. As stated by Forbes et al. (2009), models can identify important data gaps which can be used to guide further study designs—and that is exactly what results from the model presented herein.Fig. 1


The toxicokinetics cell demography model to explain metal kinetics in terrestrial invertebrates.

Argasinski K, Bednarska A, Laskowski R - Ecotoxicology (2012)

Model predictions for moderate toxicity ( = 9, b = 10) show ca. 16 % loss of cells (upper panel) and a marked increase in the amount of the toxicant (nominal value 45) accumulated in gut epithelial cells, with only a slight decrease after ca. 15 time units (lower panel);  number of toxic particles introduced to the organism during interval , b number of new cells produced during
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3475973&req=5

Fig2: Model predictions for moderate toxicity ( = 9, b = 10) show ca. 16 % loss of cells (upper panel) and a marked increase in the amount of the toxicant (nominal value 45) accumulated in gut epithelial cells, with only a slight decrease after ca. 15 time units (lower panel); number of toxic particles introduced to the organism during interval , b number of new cells produced during
Mentions: The model’s performance was tested using a range of constant concentration/toxicity values (Figs. 1, 2, 3). So far the model has been tested whether it can follow real experimental data on metal TK. Since the TKCD model is mechanistic rather than phenomenological or statistical regression model, fitting its parameters, such as cell mortalities, to the observed data is not methodologically correct. Technically this is possible but the estimated parameter values would be not scientifically plausible. The TKCD model predictions for high toxicity were compared with results of the empirical study on Pterostichus oblongopunctatus exposed to 2,500 mg Ni/kg dry food (Bednarska et al. 2011)—the only Ni concentration used by the authors. Figure 3 shows that the model produces pattern similar to the empirical observations despite its simplicity. Accordingly, laboratory studies gathering TK of different metals at different concentrations in food would be invaluable in testing the model’s performance. As stated by Forbes et al. (2009), models can identify important data gaps which can be used to guide further study designs—and that is exactly what results from the model presented herein.Fig. 1

Bottom Line: At low constant toxicant concentrations in food, the model predicts that toxicant-driven cell mortality is moderate and the total amount of toxicant in the intestine increases slowly up to the level resulting from the gradual increase of the cell replacement rate.The increased cell death rate results in reduced toxicant absorption, which in turn brings its body load down.The resulting pattern of toxicokinetic trajectory for high metal concentration closely resemble that found in empirical studies, indicating that the model probably describes the actual phenomenon.

View Article: PubMed Central - PubMed

Affiliation: Institute of Environmental Sciences, Jagiellonian University, Gronostajowa 7, 30-387, Kraków, Poland. argas1@wp.pl

ABSTRACT
Metal toxicokinetics in invertebrates are usually described by one-compartment first-order kinetic model. Although the model gives an adequate description of the toxicokinetics in certain cases, it has been shown to fail in some situations. It also does not seem acceptable on purely theoretical grounds as accumulation and excretion rates may change depending on instantaneous toxicant concentration in the gut. We postulate that the mechanism behind such changes is connected with the toxic effect of metals on gut epithelial cells. Based on published data, we have constructed a mechanistic model assuming a dynamic rate of replacement of epithelial cells with increasing contamination. We use a population-type modeling, with a population of gut epithelial cells characterized by specific death and birth rates, which may change depending on the metal concentration in food. The model shows that the equilibrium concentration of a toxicant in an organism is the net result of gut cell death and replacement rates. At low constant toxicant concentrations in food, the model predicts that toxicant-driven cell mortality is moderate and the total amount of toxicant in the intestine increases slowly up to the level resulting from the gradual increase of the cell replacement rate. At high constant concentration, total toxicant amount in the gut increases very fast, what is accompanied by massive cell death. The increased cell death rate results in reduced toxicant absorption, which in turn brings its body load down. The resulting pattern of toxicokinetic trajectory for high metal concentration closely resemble that found in empirical studies, indicating that the model probably describes the actual phenomenon.

Show MeSH
Related in: MedlinePlus