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Potential Antidotes to Phosphine Poisoning

Garrett, Kimberly K (2022) Potential Antidotes to Phosphine Poisoning. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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Abstract

Globally, phosphine gas released from metal phosphides is responsible for more poisonings (both intentional and accidental) than any other chemical agent. Metal phosphides (e.g. Ca3P2, AlP) produce phosphine through hydrolysis and can react with moisture in ambient air. Phosphine is used as a fumigant pesticide and is a workplace hazard in agriculture, shipping, pest control, and the semiconductor industry where it is used as a doping agent. However, the majority of phosphine exposures are suicidal in nature. No antidote to phosphine is currently available. Most purposeful phosphine poisonings occur through the ingestion of metal phosphides, which results in continuous exposure to phosphine gas. Therefore, an antidote with both prophylactic and therapeutic activity may be beneficial. Phosphine is associated with the inhibition of mitochondrial respiration at complex IV, cytochrome c oxidase, but the full implication of this inhibition as it relates to phosphine toxicity is not completely understood.
Because the mechanism is incomplete, a decorporation strategy, useful against two other mitochondrial poisons (cyanide and azide), was adopted. Based on inorganic principles, Au(I) and Ag(I) complexes were selected as potential decorporating antidotes against phosphine toxicity. In addition, some Co(II/III) complexes, shown to be effective against other complex IV inhibitors, were also tested. A novel method for screening potential antidotes to phosphine toxicity using Galleria mellonella larvae is described in this work. Antidotes that proved effective against phosphine toxicity in the larvae were subsequently examined in mice by a behavioral method. Methemoglobinemia, negatively associated with survival, and hemolysis have been reported in cases of phosphine poisoning. Murine blood exposed to phosphine was studied over the course of 1-2 hours, both in vivo and in vitro, for the presence of methemoglobin and potential hemolysis.


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Details

Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Garrett, Kimberly Kkkg12@pitt.edukkg120000-0003-2917-8040
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairLeikauf, George Dgleikauf@pitt.edugleikauf0000-0002-4514-7060
Committee MemberPeterson, Jamesjimmyp@pitt.edujimmyp0000-0002-7300-5887
Committee MemberPearce, Linda Llip10@pitt.edulip100000-0002-0940-965X
Committee MemberMillstone, Jilljem210@pitt.edujem2100000-0002-9499-5744
Date: 4 January 2022
Date Type: Publication
Defense Date: 10 August 2021
Approval Date: 4 January 2022
Submission Date: 15 December 2021
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Number of Pages: 178
Institution: University of Pittsburgh
Schools and Programs: Graduate School of Public Health > Environmental and Occupational Health
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: toxicology, spectroscopy, alternative model
Date Deposited: 04 Jan 2022 15:25
Last Modified: 04 Jan 2022 15:25
URI: http://d-scholarship.pitt.edu/id/eprint/42126

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