An Adverse Outcome Pathway Linking Organohalogen Exposure to Mitochondrial Disease
Joint Authors
McMinn, Brooke
Duval, Alicia L.
Sayes, Christie M.
Source
Issue
Vol. 2019, Issue 2019 (31 Dec. 2019), pp.1-24, 24 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2019-04-01
Country of Publication
Egypt
No. of Pages
24
Main Subjects
Abstract EN
Adverse outcome pathways (AOPs) are pragmatic tools in human health hazard characterization and risk assessment.
As such, one of the main goals of AOP development is to provide a clear, progressive, and linear mechanistic representation of pertinent toxicological key events (KEs) occurring along the different levels of biological organization.
Here, we present an AOP framework that depicts how exposure to organohalogens can lead to mitochondrial disease.
Organohalogens are disinfectant by-products (DBPs) found in our drinking water.
Chloroform, trichloroacetic acid, and trichlorophenol were selected to represent specific types of organohalogens for the development of this AOP.
Although each of these compounds contains chlorine atoms, they differ in aromaticity and solubility, which have a significant impact on their potency.
This AOP consists of two main pathways, both of which are triggered by the molecular initiating event (MIE) of excessive reactive oxygen species generation.
Pathway 1 details the downstream consequences of oxidative stress, which include mitochondrial DNA damage, protein aggregation, and depolarization of the mitochondrial membrane.
Pathway 2 shows the KEs that result from inadequate supply of glutathione, including calcium dysregulation and ATP depletion.
Pathways 1 and 2 converge at a common KE: opening of the mitochondrial membrane transition pore (mPTP).
This leads to the release of cytochrome c, caspase activation, apoptosis, and mitochondrial disease.
This AOP was developed according to the Organisation for Economic Co-operation and Development guidance, including critical consideration of the Bradford Hill criteria for Weight of Evidence assessment and key questions for evaluating confidence.
The presented AOP is expected to serve as the basis for designing new toxicological tests as well as the characterization of novel biomarkers for disinfectant by-product exposure and adverse health effects.
American Psychological Association (APA)
McMinn, Brooke& Duval, Alicia L.& Sayes, Christie M.. 2019. An Adverse Outcome Pathway Linking Organohalogen Exposure to Mitochondrial Disease. Journal of Toxicology،Vol. 2019, no. 2019, pp.1-24.
https://search.emarefa.net/detail/BIM-1192295
Modern Language Association (MLA)
McMinn, Brooke…[et al.]. An Adverse Outcome Pathway Linking Organohalogen Exposure to Mitochondrial Disease. Journal of Toxicology No. 2019 (2019), pp.1-24.
https://search.emarefa.net/detail/BIM-1192295
American Medical Association (AMA)
McMinn, Brooke& Duval, Alicia L.& Sayes, Christie M.. An Adverse Outcome Pathway Linking Organohalogen Exposure to Mitochondrial Disease. Journal of Toxicology. 2019. Vol. 2019, no. 2019, pp.1-24.
https://search.emarefa.net/detail/BIM-1192295
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1192295