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Disposition and molecular actions of organophosphate flame retardants
Descriptive
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Title
Disposition and molecular actions of organophosphate flame retardants
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Marco
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Stephanie Michelle
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Stephanie Michelle Marco
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author
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Buckley
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Brian T
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Brian T Buckley
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Advisory Committee
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chair
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Aleksunes
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Lauren M
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Lauren M Aleksunes
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Advisory Committee
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internal member
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Richardson
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Jason R
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Jason R Richardson
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Advisory Committee
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internal member
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Roepke
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Troy A
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Troy A Roepke
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Advisory Committee
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internal member
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Lee
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Jeehiun
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Jeehiun Lee
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Advisory Committee
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outside member
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Rutgers University
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School of Graduate Studies
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theses
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2019
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2019-05
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2019
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English
Abstract
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Organophosphate flame retardants (OPFRs) are a class of chemicals applied to clothing, electronics, plastics, furniture, and building materials to reduce the flammability of commercial products. Over the past 15 years, global use of OPFRs has increased significantly, as they replace other persistent bioaccumulative compounds such as polybrominated diphenyl ethers. OPFRs are chemicals of emerging toxicological and environmental concern due to reports of endocrine disruption, neurotoxicity, and reproductive and developmental toxicity in animals; as well as their environmental persistence. Although research on the adverse effects of OPFR exposure has increased over the past decade, there are still several gaps in our understanding of their behavior in vivo and their potential toxicity, especially in mammals. The purpose of this dissertation was to investigate whether OPFRs interact with molecular targets (acetylcholinesterase, AChE), metabolic enzymes (carboxylesterase, CES), and transporters (multi-drug resistance protein 1, MDR1) that influence their overall disposition and potential for neurotoxicity. The findings in this dissertation demonstrate that OPFRs do not behave like the structurally similar organophosphate pesticides in terms of inhibiting enzyme activity and that OPFRs are more effective inhibitors of CES than AChE. Although, the OPFRs did not demonstrate adverse effects on brain and liver enzymatic activity in vitro, the brain and liver, as well as the kidneys, placenta, and fetus, were identified as targets of toxicity due to their preferential accumulation of OPFRs. Finally, MDR1 was shown to potentially influence the in vivo disposition of TPP in the brain suggesting that MDR1 may protect the brain from TPP accumulation. The results of this study will help guide future research into OPFR-induced organ-specific adverse effects, especially in the brain and in the developing fetus.
Subject
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Topic
Toxicology
Subject
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Topic
Fireproofing agents -- Toxicology
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Rutgers University Electronic Theses and Dissertations
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ETD_9855
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1 online resource (xiv, 186 pages) : illustrations
Note
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Ph.D.
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Includes bibliographical references
Subject
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Topic
Phosphates -- Toxicology
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School of Graduate Studies Electronic Theses and Dissertations
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rucore10001600001
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doi:10.7282/t3-mkgv-1p84
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ETD doctoral
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Rights
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The author owns the copyright to this work.
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Name
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Marco
GivenName
Stephanie
MiddleName
Michelle
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Permission or license
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2019-04-12 16:24:14
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Stephanie Marco
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Affiliation
Rutgers University. School of Graduate Studies
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Author Agreement License
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I hereby grant to the Rutgers University Libraries and to my school the non-exclusive right to archive, reproduce and distribute my thesis or dissertation, in whole or in part, and/or my abstract, in whole or in part, in and from an electronic format, subject to the release date subsequently stipulated in this submittal form and approved by my school. I represent and stipulate that the thesis or dissertation and its abstract are my original work, that they do not infringe or violate any rights of others, and that I make these grants as the sole owner of the rights to my thesis or dissertation and its abstract. I represent that I have obtained written permissions, when necessary, from the owner(s) of each third party copyrighted matter to be included in my thesis or dissertation and will supply copies of such upon request by my school. I acknowledge that RU ETD and my school will not distribute my thesis or dissertation or its abstract if, in their reasonable judgment, they believe all such rights have not been secured. I acknowledge that I retain ownership rights to the copyright of my work. I also retain the right to use all or part of this thesis or dissertation in future works, such as articles or books.
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2019-05-31
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2021-05-30
Detail
Access to this PDF has been restricted at the author's request. It will be publicly available after May 30th, 2021.
Copyright
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Copyright protected
Availability
Status
Open
Reason
Permission or license
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