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Population toxicokinetic modeling of cadmium for health risk assessment.

Amzal B, Julin B, Vahter M, Wolk A, Johanson G, Akesson A - Environ. Health Perspect. (2009)

Bottom Line: The one-compartment population model appeared to be an adequate modeling option to link cadmium intake to urinary cadmium and to describe the population variability.We estimated the cadmium half-life to be about 11.6 years, with about 25% population variability.Population toxicokinetic models can be robust and useful tools for risk assessment of chemicals, because they allow quantification and integration of population variability in toxicokinetics.

View Article: PubMed Central - PubMed

Affiliation: Assessment Methodology Unit, European Food Safety Authority, Parma, Italy. Billy.AMZAL@efsa.europa.eu

ABSTRACT

Background: Cadmium is a widespread environmental pollutant that has been shown to exert toxic effects on kidney and bones in humans after long-term exposure. Urinary cadmium concentration is considered a good biomarker of accumulated cadmium in kidney, and diet is the main source of cadmium among nonsmokers.

Objective: Modeling the link between urinary cadmium and dietary cadmium intake is a key step in the risk assessment of long-term cadmium exposure. There is, however, little knowledge on how this link may vary, especially for susceptible population strata.

Methods: We used a large population-based study (the Swedish Mammography Cohort), with repeated dietary intake data covering a period of 20 years, to compare estimated dietary cadmium intake with urinary cadmium concentrations on an individual basis. A modified version of the Nordberg-Kjellström model and a one-compartment model were evaluated in terms of their predictions of urinary cadmium. We integrated the models and quantified the between-person variability of cadmium half-life in the population. Finally, sensitivity analyses and Monte Carlo simulations were performed to illustrate how the latter model could serve as a robust tool supporting the risk assessment of cadmium in humans.

Results: The one-compartment population model appeared to be an adequate modeling option to link cadmium intake to urinary cadmium and to describe the population variability. We estimated the cadmium half-life to be about 11.6 years, with about 25% population variability.

Conclusions: Population toxicokinetic models can be robust and useful tools for risk assessment of chemicals, because they allow quantification and integration of population variability in toxicokinetics.

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Related in: MedlinePlus

Comparison of individual urinary cadmium (U-Cd) predictions using the one-compartment model and the eight-compartment model.
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f2-ehp-117-1293: Comparison of individual urinary cadmium (U-Cd) predictions using the one-compartment model and the eight-compartment model.

Mentions: The mean predictions of urinary cadmium using the two models were very close (Figure 2). This finding is consistent with a similar conclusion in WHO/IPCS (1992) regarding model comparison between a one-compartment model and a PBTK model (the Kjellström and Nordberg model in that case). Because the two models result in essentially the same predictions, the eight-compartment cannot be said to have a substantially better prediction power. Therefore, we chose the one-compartment model in the subsequent calculations.


Population toxicokinetic modeling of cadmium for health risk assessment.

Amzal B, Julin B, Vahter M, Wolk A, Johanson G, Akesson A - Environ. Health Perspect. (2009)

Comparison of individual urinary cadmium (U-Cd) predictions using the one-compartment model and the eight-compartment model.
© Copyright Policy - public-domain
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2721875&req=5

f2-ehp-117-1293: Comparison of individual urinary cadmium (U-Cd) predictions using the one-compartment model and the eight-compartment model.
Mentions: The mean predictions of urinary cadmium using the two models were very close (Figure 2). This finding is consistent with a similar conclusion in WHO/IPCS (1992) regarding model comparison between a one-compartment model and a PBTK model (the Kjellström and Nordberg model in that case). Because the two models result in essentially the same predictions, the eight-compartment cannot be said to have a substantially better prediction power. Therefore, we chose the one-compartment model in the subsequent calculations.

Bottom Line: The one-compartment population model appeared to be an adequate modeling option to link cadmium intake to urinary cadmium and to describe the population variability.We estimated the cadmium half-life to be about 11.6 years, with about 25% population variability.Population toxicokinetic models can be robust and useful tools for risk assessment of chemicals, because they allow quantification and integration of population variability in toxicokinetics.

View Article: PubMed Central - PubMed

Affiliation: Assessment Methodology Unit, European Food Safety Authority, Parma, Italy. Billy.AMZAL@efsa.europa.eu

ABSTRACT

Background: Cadmium is a widespread environmental pollutant that has been shown to exert toxic effects on kidney and bones in humans after long-term exposure. Urinary cadmium concentration is considered a good biomarker of accumulated cadmium in kidney, and diet is the main source of cadmium among nonsmokers.

Objective: Modeling the link between urinary cadmium and dietary cadmium intake is a key step in the risk assessment of long-term cadmium exposure. There is, however, little knowledge on how this link may vary, especially for susceptible population strata.

Methods: We used a large population-based study (the Swedish Mammography Cohort), with repeated dietary intake data covering a period of 20 years, to compare estimated dietary cadmium intake with urinary cadmium concentrations on an individual basis. A modified version of the Nordberg-Kjellström model and a one-compartment model were evaluated in terms of their predictions of urinary cadmium. We integrated the models and quantified the between-person variability of cadmium half-life in the population. Finally, sensitivity analyses and Monte Carlo simulations were performed to illustrate how the latter model could serve as a robust tool supporting the risk assessment of cadmium in humans.

Results: The one-compartment population model appeared to be an adequate modeling option to link cadmium intake to urinary cadmium and to describe the population variability. We estimated the cadmium half-life to be about 11.6 years, with about 25% population variability.

Conclusions: Population toxicokinetic models can be robust and useful tools for risk assessment of chemicals, because they allow quantification and integration of population variability in toxicokinetics.

Show MeSH
Related in: MedlinePlus