Evaluation of Mixed-halogen Dioxins and Furans Generated by Combustion: Implications to First Responder Health
Open Access
- Author:
- Organtini, Kari Lynn
- Graduate Program:
- Biochemistry, Microbiology, and Molecular Biology
- Degree:
- Doctor of Philosophy
- Document Type:
- Dissertation
- Date of Defense:
- May 26, 2015
- Committee Members:
- Franklin Lewis Dorman Jr., Dissertation Advisor/Co-Advisor
Franklin Lewis Dorman Jr., Committee Chair/Co-Chair
Gary H Perdew, Committee Member
Squire J Booker, Committee Member
Ross Cameron Hardison, Committee Member
Andrew David Patterson, Committee Member - Keywords:
- dibenzo-p-dioxin
dibenzofuran
aryl hydrocarbon receptor
AHR
GCxGC-TOFMS
APGC-MS/MS - Abstract:
- Dibenzo-p-dioxins and dibenzofurans are well known as environmental contaminants of concern. With the increase in brominated flame retardants (BFRs) in modern consumer products, the polyhalogenated, or mixed bromo/chloro-, (PXDD/F) and polybromo- (PBDD/F) congeners are emerging as compounds of concern. A lot of research has been performed on the polychloro- analogs (PCDD/F), both analytically and biochemically, but the same is not true for both PXDD/Fs and PBDD/Fs. Since they are known to be byproducts of BFR combustion processes, there is a large potential for these compounds to be generated in fire debris. BFR combustion products become a concern when considering exposure risks of firefighters that frequently come into contact with this type of debris. Firefighters have been shown to experience an increase in certain cancers. One source which may be attributable to such long term health effects could be chronic exposure to BFR combustion products such as polyhalogenated dibenzo-p-dioxins and dibenzofurans generated in fire debris. The goal of these studies was two-fold; to characterize the range of PXDD/F and PBDD/F compounds generated in fire debris as well as begin to understand the toxicological implications of their exposure in a human system. Cell culture studies performed on HepG2 human liver cells were performed to determine the ability of PXDD/F compounds to induce AH receptor (AHR) mediated transcriptional activity. All compounds tested were determined to be AHR ligands, and response was AHR dependent. Potency levels of the PXDD/F compounds were similar in comparison to what is considered the most potent dibenzo-p-dioxin, 2,3,7,8-tetrachloro dibenzo-p-dioxin (TCDD). The similarity to TCDD suggests these compounds need to be addressed in toxicological and environmental screening methods, as they are currently overlooked. The results also indicate that, since TCDD is a probable human carcinogen, that firefighter exposure to these compounds may be detrimental to their health. Analytically, dioxin analysis has historically been performed using gas chromatography coupled to high resolution mass spectrometry (GC-HRMS). The present studies were conducted using different instrumental techniques to avoid the limitations of GC-HRMS analysis. Analytical characterization of fire debris samples was performed using two methods; comprehensive two dimensional gas chromatography coupled to time of flight mass spectrometry (GCxGC-TOFMS) and gas chromatography coupled to atmospheric pressure ionization triple quadrupole mass spectrometry (APGC-MS/MS). GCxGC-TOFMS analysis provided initial screening of samples to determine the range of compounds present. This technique was successful at resolving the compounds of interest away from the sample matrix allowing for non-targeted analysis of complex samples. The enhanced peak capacity and orthogonal separation of the GCxGC technique was beneficial for peak resolution of the halogenated dibenzo-p-dioxins and dibenzofuran isomers. Simulated household fire debris samples contained exclusively PBDFs, whereas, simulated electronics fire debris samples contained both PBDFs and PXDFs when analyzed on the GCxGC-TOFMS. Further sample analysis was performed using APGC-MS/MS, a much more sensitive technique that can detect dioxin compounds on the single femtogram level. The soft ionization technique and compound selective detection using multiple reaction monitoring mode (MRM) provided the sensitivity needed to fully characterize the fire debris samples. The results of these studies showed that APGC-MS/MS performed similarly, if not better, than GC-HRMS analysis for dioxin analysis and allowed for expansion of the list of dioxin compounds monitored for in the samples. Using the added sensitivity of APGC-MS/MS, the GCxGC-TOFMS data was confirmed, as well as allowed for identification of an expanded range of compounds. The polyhalogenated dibenzo-p-dioxin and dibenzofuran species were also identified in the fire debris samples using this technique. The analytical characterization of fire debris samples concluded that a range of PXDD/Fs (from di- through hexa- halogenated) and PBDD/Fs (Br through Br7) were present in fire debris samples that firefighters are typically exposed to. This data further supports the need to reconsider firefighter training and safety procedures, as well as the need to be aware of and monitor the types of compounds they are exposed to throughout a career. In addition, the results presented here also present implications to the general public through environmental exposure. Identification of PXDD/Fs in fire debris samples representing transportable particulate matter, such as the helmet wipe and wall foil samples, suggest these compounds have the potential to be transported and deposited into the environment. In addition, identification of these compounds in particulate matter suggests that the general population is also at risk of exposure to mixed halogenated dibenzo-p-dioxins and dibenzofurans. The potential occurrence of polybrominated and polyhalogenated dibenzo-p-dioxins and dibenzofurans calls for increased regulatory and environmental monitoring protocols to include PXDD/F compounds in routine procedures.