Funding Agency: National Institute of Environmental Health Sciences (NIEHS)
Collaborators: James Olson (University at Buffalo)
During the past decade both animal and human studies have supported an association between polybrominated diphenyl ether (PBDE) flame retardants and neurobehavioral/neurodevelopmental disorders, particularly following in utero and postnatal exposure. Recently, hydroxylated metabolites of PBDEs (OH-BDEs) have been found to accumulate in human serum at levels similar to and in some cases greater than that of the parent PBDEs. The significance of this finding is heightened by mechanistic studies showing that mono-hydroxylated metabolites of 2,2',4,4'-tetrabromodiphenyl ether (PBDE-47)1, the most abundant PBDE detected in human serum, and 2,2’,4,4’,6-pentabromodiphenyl ether (PBDE-100)2, can be greater endocrine disruptors than the parent compounds.
Similarly, children can exhibit higher levels of PBDEs, OH-BDEs, and MeO-BDEs in serum levels compared to their mothers, which is a concern for the neurological impact of developing newborns. Thus, there is a critical need to further our understanding of PBDE metabolism in humans; along with understanding the transfer of BDEs to children.
The overall objectives of this research are to:
1. Characterize the in vitro metabolism of PBDE-47 and -100 in humans by investigating their metabolic differences and genetic variability of key biotransforming enzymes, such as Cytochrome P450 enzymes.
2. Develop a simultaneous, “one-shot” sample preparation method for the quantification of PBDEs, OH-BDEs and MeO-BDEs in human serum and breast milk using gas chromatography tandem mass spectrometry for high throughput analysis3. Investigation of paired breast milk and serum samples from a subset of female volunteers will help explain the partitioning patterns of these BDEs in the human body. With knowledge of the individuals’ CYP-P450 enzyme activity, metabolic processes can be further elucidated to describe their fate and pathways in humans and the biological environment.