Welcome to the Cadmium Reverse Dosimetry App.
This app accompanies the manuscript titled “Cadmium physiologically based pharmacokinetic (PBPK) models for forward and reverse dosimetry: Review, evaluation, and adaptation to the U.S. population” published in Toxicology letters (DOI: 10.1016/j.toxlet.2022.07.812).
Access to the app is provided to readily illustrate the output of the models, quickly compare estimates and conduct forward and reverse dosimetry analyses. The tool also allows the user to freely change PBPK parameter assumptions. In the manuscript, we provide an example of using the tool for forward and reverse dosimetry analyses and the results when using the different models evaluated given a set of chosen input values. In the tool, the user can assume a constant exposure to Cd from birth until the age under evaluation or can provide the data as intake per kg BW for each year of age.
Please refer to the manuscript for a full description of the methods, results, limitations and conclusions of the analysis.
DisclaimerThe U.S. Food and Drug Administration (FDA) have taken all reasonable precautions in creating this application. FDA is not responsible for errors, omissions or deficiencies regarding the application. The application is being made available “as is” and without warranties of any kind, either expressed or implied, including, but not limited to, warranties of performance, merchantability, and fitness for a particular purpose. FDA in not making a commitment in any way to regularly update the system. Responsibility for the interpretation and use of the application lies solely with the user. In no event shall FDA be liable for direct, indirect, special, incidental, or consequential damages resulting from the use, misuse, or inability to use the application. “Third parties” use of or acknowledgment of the application and its accompanying documentation, including through the suggested citation, does not in any way represent that FDA endorses such third parties or expresses any opinion with respect to their statements.
Suggested citationRégis Pouillot, Sofia Santillana Farakos, Judith Spungen, Heather R Schaefer, Brenna Flannery, Jane M Van Doren. 2022.
Cadmium physiologically based pharmacokinetic (PBPK) models for forward and reverse dosimetry: Review, evaluation, and adaptation to the U.S. population.
Toxicology letters 10.1016/j.toxlet.2022.07.812.
Note from the authors: in Figure 1 of this manuscript, the legends of the arrows starting from the “Daily uptake” compartment to Blood 1 and Blood 3 compartments were reversed and the unit of C8 should have been “μg”. A corrected version is provided below. The original KN model (Kjellstrom and Nordberg, 1978). Blood 1 is the plasma compartment where Cd may bind to plasma components (i.e., albumin and other organic constituents). Blood 2 is the red-blood cell compartment, which represents the accumulation of Cd in erythrocytes. Blood 3 represents the binding of Cd to metallothionein. For mass balance purposes, an arrow from GI tract Intake to Faeces was added as well as the “exhaled” excretion route.
Upload a csv file with two columns. First column is age (from 0 to at least tested age by step of one year); second column is dose in μg/kg BW/day.
All plots: Cadmium in each compartment in μg (i.e. not per volume or mass unit, with the exception of renal cortex (in μg/g), feces and urine (μg/day)).
OutputCadmium in each compartment in μg (i.e. not per volume or mass unit, with the exception of renal cortex (in μg/g), feces and urine (μg/day)).
that is, POD in μg/day
The creatinine excretion per day can be evaluated using Equation D from Ix et al, 2011 (CKD model): CE = (879.89 + 12.51 × BW (kg) - 6.19 × Age (year) + (34.51 if Black) - (379.42 if Female))/1000, validated for age > 20.
Alternatively, provide the age and gender of the population on which the POD was estimated and we'll provide an estimated daily creatinine excretion using the body weight and creatinine model specified on the side panel, applied to the US population.
The POD (μg/g cortex) will be converted to kidney burden K (μg) using the equation K = POD × kw / 1.5, with kw the kidney weight evaluated as kw = kwa × (BW / BWa)0.84. kwa is the average weight of the kidneys in adults (310g for men, 275g for women, ICRP(1981)), BWa the average weight of adults and BW the body weight, both estimated using the growth model specified on the side panel.