Description
TitleDisposition and molecular actions of organophosphate flame retardants
Date Created2019
Other Date2019-05 (degree)
Extent1 online resource (xiv, 186 pages) : illustrations
DescriptionOrganophosphate 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.
NotePh.D.
NoteIncludes bibliographical references
Genretheses, ETD doctoral
LanguageEnglish
CollectionSchool of Graduate Studies Electronic Theses and Dissertations
Organization NameRutgers, The State University of New Jersey
RightsThe author owns the copyright to this work.
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