Predicting neonatal perchlorate dose and inhibition of iodide uptake in the rat during lactation using physiologically-based pharmacokinetic modeling.

@article{Clewell2003PredictingNP,
  title={Predicting neonatal perchlorate dose and inhibition of iodide uptake in the rat during lactation using physiologically-based pharmacokinetic modeling.},
  author={Rebecca A. Clewell and Elaine A. Merrill and Kyung O. Yu and Deirdre A. Mahle and Teresa R Sterner and Jeffrey Fisher and Jeffery Gearhart},
  journal={Toxicological sciences : an official journal of the Society of Toxicology},
  year={2003},
  volume={74 2},
  pages={
          416-36
        }
}
  • R. Clewell, E. Merrill, +4 authors J. Gearhart
  • Published 1 August 2003
  • Medicine, Biology
  • Toxicological sciences : an official journal of the Society of Toxicology
Perchlorate (ClO4-), a contaminant in drinking water, competitively inhibits active uptake of iodide (I-) into various tissues, including mammary tissue. During postnatal development, inhibition of I- uptake in the mammary gland and neonatal thyroid and the active concentration ClO4- in milk indicate a potentially increased susceptibility of neonates to endocrine disruption. A physiologically based pharmacokinetic (PBPK) model was developed to reproduce measured ClO4- distribution in the… 
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The model's successful prediction of free and bound radioactive I- and perchlorate's interaction with free radioactive I - provide a basis for extending the structure to address the complex hypothalamic-pituitary-thyroid feedback system.
Perchlorate and Radioiodide Kinetics Across Life Stages in the Human: Using PBPK Models to Predict Dosimetry and Thyroid Inhibition and Sensitive Subpopulations Based on Developmental Stage
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Physiologically based pharmacokinetic/dynamic models for ClO4 − and its effect on thyroid iodide uptake were constructed for human gestation and lactation data, providing a framework for extrapolating from chemical exposure in laboratory animals to human response, and support a more quantitative understanding of life-stage-specific susceptibility to perchlorate.
Evaluation of iodide deficiency in the lactating rat and pup using a biologically based dose-response model.
A biologically based dose-response (BBDR) model for the hypothalamic-pituitary thyroid (HPT) axis in the lactating rat and nursing pup was developed to describe the perturbations caused by iodide…
Evidence for Competitive Inhibition of Iodide Uptake by Perchlorate and Translocation of Perchlorate into the Thyroid
TLDR
It is submitted that the simplest mode of action for ClO 4 − in the thyroid that remains consistent with all available data involves competitive inhibition of iodide transport into the thyroid follicle, transport of perchlorate into the Thyroid follicle against a concentration gradient, further transport intoThe thyroid lumen (where it may again interfere with iodide Transport), and, finally, passive diffusion back into the blood.
Revision of the affinity constant for perchlorate binding to the sodium‐iodide symporter based on in vitro and human in vivo data
A series of previously published physiologically based pharmacokinetic (PBPK) models describe the effect of perchlorate on iodide uptake by the thyroid, with the mechanism being competitive…
Use of a simple pharmacokinetic model to characterize exposure to perchlorate
  • M. Lorber
  • Medicine
    Journal of Exposure Science and Environmental Epidemiology
  • 2009
TLDR
A simple two-compartment first-order pharmacokinetic model that predicts concentrations of perchlorate in blood and urine was constructed and validated, and it was found that the consumption of foods, rather than ingestion of water, dominates background exposures.
Quantitative evaluation of dichloroacetic acid kinetics in human--a physiologically based pharmacokinetic modeling investigation.
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Variability analyses of the PBPK models support application of uncertainty factors (UF) of approximately 2 for intrahuman pharmacokinetic variability for the nasal effects and acute neurotoxicity.
Development of a rat and human PBPK model for bromate and estimation of human equivalent concentrations in drinking water
TLDR
The bromate PBPK model was used to assess the human equivalent drinking water concentration (HEC) consistent with average plasma concentrations in the rodent bioassays, and at drinking water concentrations <500 mg/L, the predicted HEC was two to three fold lower than the bioassay concentration.
Interspecies differences in susceptibility to perturbation of thyroid homeostasis: a case study with perchlorate.
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References

SHOWING 1-10 OF 101 REFERENCES
Predicting fetal perchlorate dose and inhibition of iodide kinetics during gestation: a physiologically-based pharmacokinetic analysis of perchlorate and iodide kinetics in the rat.
TLDR
A comparison of model-predicted internal dosimetrics in the adult male, pregnant, and fetal rat indicates that the fetal thyroid is more sensitive to inhibition than that of the adult.
PBPK predictions of perchlorate distribution and its effect on thyroid uptake of radioiodide in the male rat.
TLDR
A physiologically-based pharmacokinetic model for the adult male rat that successfully predicts perchlorate's interaction with iodide provides a sound basis for future incorporation of the complex hypothalamic-pituitary-thyroid feedback system.
The pharmacokinetics of perchlorate and its effect on the hypothalamus-pituitary-thyroid axis in the male rat.
TLDR
The results suggest that the typical homeostatic mechanisms of the thyroid may respond differently at high doses of perchlorate used in this rat study (above 1 mg/kg per day) or per chlorate may be acting on the HPT axis by mechanisms other than thyroidal (125)I(-) uptake inhibition.
Pharmacokinetics of toxic chemicals in breast milk: use of PBPK models to predict infant exposure.
TLDR
A recently developed P BPK model for perchlorate and iodide kinetics in the lactating and neonatal rat demonstrates the utility of PBPK modeling in predicting maternal and Neonatal distribution of these two compounds.
The use of physiologically based models to integrate diverse data sets and reduce uncertainty in the prediction of perchlorate and iodide kinetics across life stages and species
TLDR
Two approaches for calculating life stage-specific equivalent doses in a risk assessment for perchlorate are demonstrated: the direct combination of validated model predictions, and the development of preliminary PBPK models for the human-sensitive populations based on the relationship of the parameters in the validated rat and human models.
Two-generation reproduction study of ammonium perchlorate in drinking water in rats evaluates thyroid toxicity.
TLDR
Perchlorate is not a reproductive toxicant in rats when administered in the drinking water at doses up to 30 mg/kg-day, but it can affect the thyroid at doses > or =3 mg/ kg-day.
Physiologically based pharmacokinetic modeling of the lactating rat and nursing pup: a multiroute exposure model for trichloroethylene and its metabolite, trichloroacetic acid.
The mode of action of perchlorate ions on the iodine uptake of the thyroid gland.
A comparison between the inhibitory effect of perchlorate on iodide and pertechnetate concentrations in saliva in man.
TLDR
It was concluded that perchlorate is a more potent inhibitor of the salivary iodide concentrating mechanism than iodide given in molal equivalent doses.
Kinetics of the iodide trapping mechanism in normal and pathological human thyroid slices.
TLDR
The results suggest that the scattered trapping values observed in the different thyroid pathologies correspond to quantitative differences between them rather than to qualitative alterations in the thyroid iodide pump.
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