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:

Persistent autism-relevant behavioral phenotype and social neuropeptide alterations in female mice offspring induced by maternal transfer of PBDE congeners in the commercial mixture DE-71.

Polybrominated diphenyl ethers (PBDEs) are ubiquitous persistent organic pollutants (POPs) that are known neuroendocrine disrupting chemicals with adverse neurodevelopmental effects. PBDEs may act as risk factors for autism spectrum disorders (ASD), characterized by abnormal psychosocial functioning, although direct evidence is currently lacking. Using a translational exposure model, we tested the hypothesis that maternal transfer of a commercial mixture of PBDEs, DE-71, produces ASD-relevant behavioral and neurochemical deficits in female offspring. C57Bl6/N mouse dams (F0) were exposed to DE-71 via oral administration of 0 (VEH/CON), 0.1 (L-DE-71) or 0.4 (H-DE-71) mg/kg bw/d from 3 wk prior to gestation through end of lactation. Mass spectrometry analysis indicated in utero and lactational transfer of PBDEs (in ppb) to F1 female offspring brain tissue at postnatal day (PND) 15 which was reduced by PND 110. Neurobehavioral testing of social novelty preference (SNP) and social recognition memory (SRM) revealed that adult L-DE-71 F1 offspring display deficient short- and long-term SRM, in the absence of reduced sociability, and increased repetitive behavior. These effects were concomitant with reduced olfactory discrimination of social odors. Additionally, L-DE-71 exposure also altered short-term novel object recognition memory but not anxiety or depressive-like behavior. Moreover, F1 L-DE-71 displayed downregulated mRNA transcripts for oxytocin (Oxt) in the bed nucleus of the stria terminalis (BNST) and supraoptic nucleus, and vasopressin (Avp) in the BNST and upregulated Avp1ar in BNST, and Oxtr in the paraventricular nucleus. Our work demonstrates that developmental PBDE exposure produces ASD-relevant neurochemical, olfactory processing and behavioral phenotypes that may result from early neurodevelopmental reprogramming within central social and memory networks.
Authors
Kozlova, EV; Valdez, MC; Denys, ME; Bishay, AE; Krum, JM; Rabbani, KM; Carrillo, V; Gonzalez, GM; Lampel, G; Tran, JD; Vazquez, BM; Anchondo, LM; Uddin, SA; Huffman, NM; Monarrez, E; Olomi, DS; Chinthirla, BD; Hartman, RE; Kodavanti, PRS; Chompre, G; Phillips, AL; Stapleton, HM; Henkelmann, B; Schramm, K-W; Curras-Collazo, MC
URI
https://scholars.duke.edu/individual/pub1499756
PMID
34687351
Source
pubmed
Published In
Arch Toxicol
Published Date
DOI
10.1007/s00204-021-03163-4

Beyond Cholinesterase Inhibition: Developmental Neurotoxicity of Organophosphate Ester Flame Retardants and Plasticizers.

<h4>Background</h4>To date, the toxicity of organophosphate esters has primarily been studied regarding their use as pesticides and their effects on the neurotransmitter acetylcholinesterase (AChE). Currently, flame retardants and plasticizers are the two largest market segments for organophosphate esters and they are found in a wide variety of products, including electronics, building materials, vehicles, furniture, car seats, plastics, and textiles. As a result, organophosphate esters and their metabolites are routinely found in human urine, blood, placental tissue, and breast milk across the globe. It has been asserted that their neurological effects are minimal given that they do not act on AChE in precisely the same way as organophosphate ester pesticides.<h4>Objectives</h4>This commentary describes research on the non-AChE neurodevelopmental toxicity of organophosphate esters used as flame retardants and plasticizers (OPEs). Studies in humans, mammalian, nonmammalian, and <i>in vitro</i> models are presented, and relevant neurodevelopmental pathways, including adverse outcome pathways, are described. By highlighting this scientific evidence, we hope to elevate the level of concern for widespread human exposure to these OPEs and to provide recommendations for how to better protect public health.<h4>Discussion</h4>Collectively, the findings presented demonstrate that OPEs can alter neurodevelopmental processes by interfering with noncholinergic pathways at environmentally relevant doses. Application of a pathways framework indicates several specific mechanisms of action, including perturbation of glutamate and gamma-aminobutyric acid and disruption of the endocrine system. The effects may have implications for the development of cognitive and social skills in children. Our conclusion is that concern is warranted for the developmental neurotoxicity of OPE exposure. We thus describe important considerations for reducing harm and to provide recommendations for government and industry decision makers. https://doi.org/10.1289/EHP9285.
Authors
Patisaul, HB; Behl, M; Birnbaum, LS; Blum, A; Diamond, ML; Rojello Fernández, S; Hogberg, HT; Kwiatkowski, CF; Page, JD; Soehl, A; Stapleton, HM
MLA Citation
Patisaul, Heather B., et al. “Beyond Cholinesterase Inhibition: Developmental Neurotoxicity of Organophosphate Ester Flame Retardants and Plasticizers.Environmental Health Perspectives, vol. 129, no. 10, Oct. 2021, p. 105001. Epmc, doi:10.1289/ehp9285.
URI
https://scholars.duke.edu/individual/pub1498678
PMID
34612677
Source
epmc
Published In
Environmental Health Perspectives
Volume
129
Published Date
Start Page
105001
DOI
10.1289/ehp9285

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