Population toxicokinetic modeling of cadmium for health risk assessment.
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.
Amzal
Billy
B
Assessment Methodology Unit, European Food Safety Authority, Parma, Italy. Billy.AMZAL@efsa.europa.eu
Julin
Bettina
B
Vahter
Marie
M
Wolk
Alicja
A
Johanson
Gunnar
G
Akesson
Agneta
A
D000368:Aged; D002104:Cadmium / Q000493:pharmacokinetics* / Q000652:urine; D004032:Diet; D004781:Environmental Exposure; D005260:Female; D006801:Humans; D008875:Middle Aged; D008962:Models, Theoretical; D018570:Risk Assessment / Q000379:methods*; D014874:Water Pollutants, Chemical / Q000493:pharmacokinetics*
D014874:Water Pollutants, Chemical; D002104:Cadmium