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

Clewell, Rebecca A.; Merrill, Elaine A.; Gearhart, Jeffery M.; Robinson, Peter; Sterner, Teresa R; Mattie, David R.; Clewell, Harvey J.

doi:10.1080/15287390600755216

Cited by 64 publications

(87 citation statements)

References 78 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Driven by wide recognition that target tissue (or cell) dose is the most appropriate metric of dose for risk and safety assessment, there has been continued growth in the development of computational tools for estimating target tissue dose in vivo for a wide range of materials: volatile and non-volatile materials [42-44] organic chemicals [45,46], pharmaceuticals [47,48], and particulates and ultrafine particulates [49-53]. It is surprising, then, given the growing importance of in vitro studies to chemical and particle risk assessment [10] that few efforts [43,54-56] have been directed at developing computational models of dosimetry for in vitro systems.…”

Section: Discussionmentioning

confidence: 99%

ISDD: A computational model of particle sedimentation, diffusion and target cell dosimetry for in vitro toxicity studies

et al. 2010

View full text Add to dashboard Cite

BackgroundThe difficulty of directly measuring cellular dose is a significant obstacle to application of target tissue dosimetry for nanoparticle and microparticle toxicity assessment, particularly for in vitro systems. As a consequence, the target tissue paradigm for dosimetry and hazard assessment of nanoparticles has largely been ignored in favor of using metrics of exposure (e.g. μg particle/mL culture medium, particle surface area/mL, particle number/mL). We have developed a computational model of solution particokinetics (sedimentation, diffusion) and dosimetry for non-interacting spherical particles and their agglomerates in monolayer cell culture systems. Particle transport to cells is calculated by simultaneous solution of Stokes Law (sedimentation) and the Stokes-Einstein equation (diffusion).ResultsThe In vitro Sedimentation, Diffusion and Dosimetry model (ISDD) was tested against measured transport rates or cellular doses for multiple sizes of polystyrene spheres (20-1100 nm), 35 nm amorphous silica, and large agglomerates of 30 nm iron oxide particles. Overall, without adjusting any parameters, model predicted cellular doses were in close agreement with the experimental data, differing from as little as 5% to as much as three-fold, but in most cases approximately two-fold, within the limits of the accuracy of the measurement systems. Applying the model, we generalize the effects of particle size, particle density, agglomeration state and agglomerate characteristics on target cell dosimetry in vitro.ConclusionsOur results confirm our hypothesis that for liquid-based in vitro systems, the dose-rates and target cell doses for all particles are not equal; they can vary significantly, in direct contrast to the assumption of dose-equivalency implicit in the use of mass-based media concentrations as metrics of exposure for dose-response assessment. The difference between equivalent nominal media concentration exposures on a μg/mL basis and target cell doses on a particle surface area or number basis can be as high as three to six orders of magnitude. As a consequence, in vitro hazard assessments utilizing mass-based exposure metrics have inherently high errors where particle number or surface areas target cells doses are believed to drive response. The gold standard for particle dosimetry for in vitro nanotoxicology studies should be direct experimental measurement of the cellular content of the studied particle. However, where such measurements are impractical, unfeasible, and before such measurements become common, particle dosimetry models such as ISDD provide a valuable, immediately useful alternative, and eventually, an adjunct to such measurements.

show abstract

Section: Discussionmentioning

confidence: 99%

ISDD: A computational model of particle sedimentation, diffusion and target cell dosimetry for in vitro toxicity studies

et al. 2010

View full text Add to dashboard Cite

show abstract

“…Perchlorate can also form naturally through atmospheric reactions, and human exposure can occur via groundwater contamination and dietary intake of contaminated food crops [2]. In 2011 the United States Environmental Protection Agency (EPA) determined that perchlorate met the criteria for regulation as a drinking water contaminant, primarily based on the scientific evidence of perchlorate’s effects on thyroid function [3–4]. Perchlorate competes with iodide for transport into the thyroid via the sodium/iodide symporter (NIS), thus inhibiting iodide uptake into the thyroid and possibly reducing thyroid hormone production [5–6].…”

Section: Introductionmentioning

confidence: 99%

Association of prenatal perchlorate, thiocyanate, and nitrate exposure with neonatal size and gestational age

Evans

Rich

Weinberger

et al. 2015

Reproductive Toxicology

View full text Add to dashboard Cite

Background Perchlorate and similar anions compete with iodine for uptake into the thyroid by the sodium iodide symporter (NIS). This may restrict fetal growth via impaired thyroid hormone production. Methods We collected urine samples from 107 pregnant women and used linear regression to estimate differences in newborn size and gestational age associated with increases in perchlorate, thiocyanate, nitrate, and perchlorate equivalence concentrations (PEC; measure of total NIS inhibitor exposure). Results NIS inhibitor concentrations were not associated with newborn weight, length, or gestational age. Each 2.62 ng/µg creatinine increase in perchlorate was associated with smaller head circumference (0.32 cm; 95% CI: −0.66, 0.01), but each 3.38 ng/µg increase in PEC was associated with larger head circumference (0.48 cm; −0.01, 0.97). Conclusions These anions may have effects on fetal development (e.g. neurocognitive) that are not reflected in gross measures. Future research should focus on other abnormalities in neonates exposed to NIS inhibitors.

show abstract

“…Infants and children have the highest estimated intakes of perchlorate on a body weight basis (Murray et al, 2008). Fetus is predicted to receive the greatest dose (per kg body weight), because of dependence on the factors like placental sodium-iodide symporter activity and reduced maternal urinary clearance of perchlorate (Clewell et al, 2007). Higher levels of urinary perchlorate were found in children compared with adolescents and adults .…”

Section: Impacts In Humansmentioning

confidence: 98%

Review on Fate, Toxicity, and Remediation of Perchlorate

Sijimol

Jyothy

Pradeepkumar

et al. 2015

Environmental Forensics

View full text Add to dashboard Cite

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

Cited by 64 publications

References 78 publications

ISDD: A computational model of particle sedimentation, diffusion and target cell dosimetry for in vitro toxicity studies

ISDD: A computational model of particle sedimentation, diffusion and target cell dosimetry for in vitro toxicity studies

Association of prenatal perchlorate, thiocyanate, and nitrate exposure with neonatal size and gestational age

Review on Fate, Toxicity, and Remediation of Perchlorate

Contact Info

Product

Resources

About