Garrett, Kimberly K
(2022)
Potential Antidotes to Phosphine Poisoning.
Doctoral Dissertation, University of Pittsburgh.
(Unpublished)
This is the latest version of this item.
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
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| Status: |
Unpublished |
| Creators/Authors: |
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| ETD Committee: |
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| 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: |
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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Potential Antidotes to Phosphine Poisoning. (deposited 04 Jan 2022 15:25)
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