Dried Blood Spots as a Matrix for Biomonitoring of Polyhalogenated Biphenyls Open Access

Abstract

Polychlorinated biphenyls (PCBs) and polybrominated biphenyls (PBBs) are classes of persistent organic pollutants that are known endocrine disruptors and have been shown to cause neurodevelopmental toxicity and increased cancer risk. Biomonitoring of chemicals such as PCBs and PBBs has become an increasingly popular and important tool for exposure assessment. Historically, serum or plasma have been used as the primary matrices for biomonitoring of exposures, but various limitations associated with the use of these matrices have led to the research and development of simpler and more cost effective tools for exposure assessment. Dried blood spots (DBS), drops of whole blood collected on pieces of filter paper are a simpler and more cost effective tool for the future of biomonitoring, yet little has been done in the way of method testing and development due to the extremely low blood volume of each spot (~65 µL). The objective of this study was to measure levels of PBB-153, PCB-118, PCB-138, PCB- 153, and PCB-180 in DBS collected through the Michigan PBB registry using a newly developed method utilizing gas chromatography-electron impact ionization-tandem mass spectrometry (GC-MS/MS). The results of the DBS analysis were compared to participant matched serum, analyzed using the same method. Extraction recoveries using DBS ranged from 90.0%-93.7%, accuracies for all five target compounds ranged from 80.0%-110.5%, and inter-day precisions ranged from 2.4%-16.4%, all of which fall within the recommended acceptable standards. Statistical analysis showed strong positive correlations between the DBS and serum methods, and Bland-Altman analysis indicated strong agreement between methods. Our study was the first to use GC/MS-MS for the analysis of these compounds in DBS, and has provided a cost effective, selective, and robust method for biomonitoring of PCBs and PBBs.

Table of Contents

Introduction & Background

Biomonitoring

Polybrominated Biphenyls

Polychlorinated Biphenyls

Biomarker Research

PBB Contamination Incident of the Early 1970s

Current Study

Public Health Relevance

Study Design & Methods

Study Population

Sample Collection and Shipment

Chemicals Used in Present Study

Preparation of Standards Solution and Quality Control Measures

PBB and PCB Extraction from Serum and DBS

GC-MS/MS Analysis

Data Processing

Method Validation and Data Analysis

Extraction Recovery

Limit of Detection

Accuracy

Precision

Results

Extraction Recovery of DBS

Chromatographic Separation

Minimum Detectible Limit

Accuracy and Precision

Statistical Analysis

Correlation Analysis

Bland-Altman Analysis

Discussion

Analytic methods

Limitations

Extension to other analytes

Conclusions

Funding

References

Tables and Figures

Table 1: MRM transitions and related parameters by target compound

Table 2: Fortified DBS validation

Table 3: Fortified Serum Validation

Table 4: Spearman's correlation analysis using DBS and serum concentrations

Figure 1: General structure of PBBs

Figure 2: General structure of PCBs

Figure 3: Extracted ion chromatogram of a 0.05 ng/mL equivalent calibrant (S4)

Figure 4: Extracted ion chromatogram of a 0.05 ng/mL fortified in-house DBS (DBS-QCH)

Figure 5-1: Extracted ion chromatogram from unknown DBS sample (99990026)

Figure 5-2 : Extracted ion chromatogram from unknown serum sample (99990026)

Figure 6: Bland-Altman plot PBB-153

Figure 7: Bland-Altman plot PBB-118

Figure 8: Bland-Altman plot PCB-138

Figure 9: Bland-Altman plot PCB-153

Figure 10: Bland-Altman plot PCB-180

About this Master's Thesis

Rights statement

• Permission granted by the author to include this thesis or dissertation in this repository. All rights reserved by the author. Please contact the author for information regarding the reproduction and use of this thesis or dissertation.

School	Rollins School of Public Health
Department	Environmental Health
Degree	MPH
Submission	Master's Thesis
Language	English
Research Field	Health Sciences, Public Health Environmental Health Health Sciences, Toxicology
Keyword	Michigan PBB Registry Dried Blood Spots PBBs Biomarkers Biomonitoring PCBs
Committee Chair / Thesis Advisor	Barr, Dana Boyd, Emory University
Committee Members	Tolbert, Paige, Emory University
Partnering Agencies	US (Federal) agency other than CDC

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