Heather Stapleton

Overview:

Dr. Stapleton's research focuses on understanding the fate and transformation of organic contaminants in aquatic systems and in indoor environments. Her main focus has been on the bioaccumulation and biotransformation of brominated flame retardants, and specifically polybrominated diphenyl ethers,(PBDEs). Her current research projects explore the routes of human exposure to flame retardant chemicals and examine the way these compounds are photodegraded and metabolized using mass spectrometry to identify breakdown products/metabolites. She uses both in vivo techniques with fish, and in vitro techniques with cell cultures to examine metabolism of this varied class of chemicals. Also of interest to Dr. Stapleton is the study of the fate of PBDEs in the environment which may lead to bioaccumulation in aquatic systems and examining their bioavailability under different environmental conditions.

Positions:

Ronie-Richele Garcia-Johnson Distinguished Professor

Environmental Sciences and Policy
Nicholas School of the Environment

Professor

Environmental Sciences and Policy
Nicholas School of the Environment

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

B.S. 1997

Long Island University, Southhampton College

M.S. 2000

University of Maryland, College Park

Ph.D. 2003

University of Maryland, College Park

Grants:

Children Exposure to SVOC Mixtures Indoors and Associations with Obesity

Administered By
Environmental Sciences and Policy
Awarded By
National Institutes of Health
Role
Principal Investigator
Start Date
End Date

Mechanisms of Environmental-Mixture Induced Metabolic Disruption

Administered By
Environmental Sciences and Policy
Awarded By
National Institutes of Health
Role
Mentor
Start Date
End Date

The placenta: a novel target of sex specific neurotoxicity by fire retardants

Administered By
Environmental Sciences and Policy
Awarded By
North Carolina State University
Role
Principal Investigator
Start Date
End Date

Duke University Superfund Center - Development Exposures: Mechanisms, Outcomes and Remediation

Administered By
Environmental Sciences and Policy
Awarded By
National Institutes of Health
Role
Co-Principal Investigator
Start Date
End Date

MRI: Acquisition of a GC Hybrid Orbitrap High Resolution Tandem Mass Spectrometer for Environmental Science

Administered By
Environmental Sciences and Policy
Awarded By
National Science Foundation
Role
Principal Investigator
Start Date
End Date

Publications:

Characterizing azobenzene disperse dyes in commercial mixtures and children's polyester clothing.

Azobenzene disperse dyes are the fastest-growing class of dyestuffs, yet little is known about dye occurrences, sources, and transformations; azo dyes are also underrepresented in chemical standard catalogs, molecular databases, and mass spectral libraries. Many azo dyes are known to have sensitization, mutagenic, and carcinogenic properties. To fill these knowledge gaps, azo dyes were purified from dyestuffs by Soxhlet extraction and flash chromatography and characterized using ultra-high-performance liquid chromatography (UHPLC) coupled to a high resolution Orbitrap Fusion Lumos mass spectrometer operated in positive electrospray ionization mode, as well as by <sup>1</sup>H and <sup>13</sup>C NMR. Data were analyzed to identify likely chemical formulas and structures using a weight-of-evidence approach with multiple open-source, in silico computational mass spectrometry tools. Nineteen total azobenzene dyes were detected in dyestuffs via a non-targeted analysis approach; the azobenzene dyes Disperse Blue 79:1, Disperse Blue 183:1, Disperse Orange 44, Disperse Orange 73, Disperse Red 50, Disperse Red 73, and Disperse Red 354 were purified from raw dyestuffs. Samples of children's polyester clothing were then analyzed likewise. In clothing, 21 azobenzene disperse dyes were detected, 12 of which were confirmed and quantified via reference standards. Individual dyes in apparel were quantified at concentrations up to 9230 μg dye/g shirt, with geometric means ranging 7.91-300 μg dye/g shirt. Total dye load in apparel was quantified at up to 11,430 μg dye/g shirt. This research supported the development of reference standards and library mass spectra for azobenzene disperse dyes previously absent from standard and spectral libraries. By analyzing the scope and quantities of azo dyes in children's polyester apparel, this study will facilitate a more robust understanding of sources of these potentially allergenic and mutagenic compounds.
Authors
Overdahl, KE; Gooden, D; Bobay, B; Getzinger, GJ; Stapleton, HM; Ferguson, PL
MLA Citation
Overdahl, Kirsten E., et al. “Characterizing azobenzene disperse dyes in commercial mixtures and children's polyester clothing.Environmental Pollution (Barking, Essex : 1987), vol. 287, Oct. 2021, p. 117299. Epmc, doi:10.1016/j.envpol.2021.117299.
URI
https://scholars.duke.edu/individual/pub1482528
PMID
34023658
Source
epmc
Published In
Environmental Pollution (Barking, Essex : 1987)
Volume
287
Published Date
Start Page
117299
DOI
10.1016/j.envpol.2021.117299

Monitoring Human Exposure to Organophosphate Esters: Comparing Silicone Wristbands with Spot Urine Samples as Predictors of Internal Dose

Silicone wristbands present a noninvasive exposure assessment tool and an alternative to traditional biomonitoring; however, questions about their utility remain as validation studies are limited. We sought to determine if wristbands provide quantitative estimates of internal organophosphate ester (OPE) exposure. We evaluated internal dose by measuring metabolite masses excreted in 24-h urine samples collected over five days among 10 adults. We compared internal dose to OPE concentrations in paired wristbands worn during collection and, as a comparison, evaluated metabolite levels in spot urine samples. Three of six OPE metabolites evaluated were detected in greater than 98% of urine samples, and 24 of 34 assessed OPEs were detected in at least one wristband. OPE uptake in wristbands was linear over time (range = 0.54-61.8 ng/g/day). OPE concentrations in spot urine and wristbands were not correlated with total diphenyl phosphate (DPHP) excreted in urine, which may be due to the range of possible DPHP parent compounds or dietary exposure. However, for tris(1,3-dichloro-2-propyl)phosphate (TDCIPP) and tris(2-chloroisopropyl)phosphate (TCIPP), wristbands and spot urine samples were both moderately to strongly correlated with internal dose (allrs> 0.56 andp< 0.1), suggesting both perform well as integrated exposure estimates. Given the potential advantages of silicone wristbands, further studies investigating additional compounds are warranted.
Authors
Hoffman, K; Levasseur, JL; Zhang, S; Hay, D; Herkert, NJ; Stapleton, HM
MLA Citation
Hoffman, K., et al. “Monitoring Human Exposure to Organophosphate Esters: Comparing Silicone Wristbands with Spot Urine Samples as Predictors of Internal Dose.” Environmental Science and Technology Letters, vol. 8, no. 9, Sept. 2021, pp. 805–10. Scopus, doi:10.1021/acs.estlett.1c00629.
URI
https://scholars.duke.edu/individual/pub1497107
Source
scopus
Published In
Environmental Science & Technology Letters
Volume
8
Published Date
Start Page
805
End Page
810
DOI
10.1021/acs.estlett.1c00629

Reproducibility of adipogenic responses to metabolism disrupting chemicals in the 3T3-L1 pre-adipocyte model system: An interlaboratory study.

The 3T3-L1 murine pre-adipocyte line is an established cell culture model for screening Metabolism Disrupting Chemicals (MDCs). Despite a need to accurately identify MDCs for further evaluation, relatively little research has been performed to comprehensively evaluate reproducibility across laboratories, assess factors that might contribute to varying degrees of differentiation between laboratories (media additives, plastics, cell source, etc.), or to standardize protocols. As such, the goals of this study were to assess interlaboratory variability of efficacy and potency outcomes for triglyceride accumulation and pre-adipocyte proliferation using the mouse 3T3-L1 pre-adipocyte cell assay to test chemicals. Ten laboratories from five different countries participated. Each laboratory evaluated one reference chemical (rosiglitazone) and three blinded test chemicals (tributyltin chloride, pyraclostrobin, and bisphenol A) using: 1) their Laboratory-specific 3T3-L1 Cells (LC) and their Laboratory-specific differentiation Protocol (LP), 2) Shared 3T3-L1 Cells (SC) with LP, 3) LC with a Shared differentiation Protocol (SP), and 4) SC with SP. Blinded test chemical responses were analyzed by the coordinating laboratory. The magnitude and range of bioactivities reported varied considerably across laboratories and test conditions, though the presence or absence of activity for each tested chemical was more consistent. Triglyceride accumulation activity determinations for rosiglitazone ranged from 90 to 100% across test conditions, but 30-70 % for pre-adipocyte proliferation; this was 40-80 % for triglyceride accumulation induced by pyraclostrobin, 80-100 % for tributyltin, and 80-100 % for bisphenol A. Consistency was much lower for pre-adipocyte proliferation, with 30-70 % active determinations for pyraclostrobin, 30-50 % for tributyltin, and 20-40 % for bisphenol A. Greater consistency was observed for the SC/SP assessment. As such, working to develop a standardized adipogenic differentiation protocol represents the best strategy for improving consistency of adipogenic responses using the 3T3-L1 model to reproducibly identify MDCs and increase confidence in reported outcomes.
Authors
Kassotis, CD; Hoffman, K; Völker, J; Pu, Y; Veiga-Lopez, A; Kim, SM; Schlezinger, JJ; Bovolin, P; Cottone, E; Saraceni, A; Scandiffio, R; Atlas, E; Leingartner, K; Krager, S; Tischkau, SA; Ermler, S; Legler, J; Chappell, VA; Fenton, SE; Mesmar, F; Bondesson, M; Fernández, MF; Stapleton, HM
MLA Citation
Kassotis, Christopher D., et al. “Reproducibility of adipogenic responses to metabolism disrupting chemicals in the 3T3-L1 pre-adipocyte model system: An interlaboratory study.Toxicology, vol. 461, Sept. 2021, p. 152900. Epmc, doi:10.1016/j.tox.2021.152900.
URI
https://scholars.duke.edu/individual/pub1494543
PMID
34411659
Source
epmc
Published In
Toxicology
Volume
461
Published Date
Start Page
152900
DOI
10.1016/j.tox.2021.152900

Sex-specific Disruption of the Prairie Vole Hypothalamus by Developmental Exposure to a Flame Retardant Mixture.

Prevalence of neurodevelopmental disorders (NDDs) with social deficits is conspicuously rising, particularly in boys. Flame retardants (FRs) have long been associated with increased risk, and prior work by us and others in multiple species has shown that developmental exposure to the common FR mixture Firemaster 550 (FM 550) sex-specifically alters socioemotional behaviors including anxiety and pair bond formation. In rats, FRs have also been shown to impair aspects of osmoregulation. Because vasopressin (AVP) plays a role in both socioemotional behavior and osmotic balance we hypothesized that AVP and its related nonapeptide oxytocin (OT) would be vulnerable to developmental FM 550 exposure. We used the prairie vole (Microtus ochrogaste) to test this because it is spontaneously prosocial. Using siblings of prairie voles used in a prior study that assessed behavioral deficits resulting from developmental FM 550 exposure across 3 doses, here we tested the hypothesis that FM 550 sex-specifically alters AVP and OT neuronal populations in critical nuclei, such as the paraventricular nucleus (PVN), that coordinate those behaviors, as well as related dopaminergic (determined by tyrosine hydroxylase (TH) immunolabeling) populations. Exposed females had fewer AVP neurons in the anterior PVN and more A13 TH neurons in the zona incerta than controls. By contrast, in FM 550 males, A13 TH neuron numbers in the zona incerta were decreased but only in 1 dose group. These results expand on previous work showing evidence of endocrine disruption of OT/AVP pathways, including to subpopulations of PVN AVP neurons that coordinate osmoregulatory functions in the periphery.
Authors
Gillera, SEA; Marinello, WP; Cao, KT; Horman, BM; Stapleton, HM; Patisaul, HB
MLA Citation
Gillera, Sagi Enicole A., et al. “Sex-specific Disruption of the Prairie Vole Hypothalamus by Developmental Exposure to a Flame Retardant Mixture.Endocrinology, vol. 162, no. 8, Aug. 2021. Epmc, doi:10.1210/endocr/bqab100.
URI
https://scholars.duke.edu/individual/pub1482979
PMID
34038511
Source
epmc
Published In
Endocrinology
Volume
162
Published Date
DOI
10.1210/endocr/bqab100

Gestational Exposure to Perfluorooctanoic Acid (PFOA) or Its Replacement GenX Induces Adverse Pregnancy Outcomes and Disrupts the Placenta

Authors
Blake, BE; Cope, H; Hall, S; Keys, R; Mahler, B; Mccord, J; Scott, B; Stapleton, H; Strynar, M; Elmore, S; Fenton, S
MLA Citation
URI
https://scholars.duke.edu/individual/pub1453860
Source
wos-lite
Published In
Birth Defects Research
Volume
112
Published Date
Start Page
823
End Page
823