Identification of a sulfate metabolite of PCB 11 in human serum

Abstract

Despite increasing evidence for a major role for sulfation in the metabolism of lower-chlorinated polychlorinated biphenyls in vitro and in vivo, and initial evidence for potential bioactivities of the resulting sulfate ester metabolites, the formation of PCB sulfates in PCB exposed human populations had not been explored. The primary goal of this study was to determine if PCB sulfates, and potentially other conjugated PCB derivatives, are relevant classes of PCB metabolites in the serum of humans with known exposures to PCBs. In order to detect and quantify dichlorinated PCB sulfates in serum samples of 46 PCB-exposed individuals from either rural or urban communities, we developed a high-resolution mass spectrometry-based protocol using 4-PCB 11 sulfate as a model compound. The method also allowed the preliminary analysis of these 46 human serum extracts for the presence of other metabolites, such as glucuronic acid conjugates and hydroxylated PCBs. Sulfate ester metabolites derived from dichlorinated PCBs were detectable and quantifiable in more than 20 % of analyzed serum samples. Moreover, we were able to utilize this method to detect PCB glucuronides and hydroxylated PCBs, albeit at lower frequencies than PCB sulfates. Altogether, our results provide initial evidence for the presence of PCB sulfates in human serum. Considering the inability of previously employed analytical protocols for PCBs to extract these sulfate ester metabolites and the concentrations of these metabolites observed in our current study, our data support the hypothesis that total serum levels of PCB metabolites in exposed individuals may have been underestimated in the past.

Cardiovascular Effects of Polychlorinated Biphenyls and Their Major Metabolites

“…continued environmental release has been associated with paint and pigment manufacturing (Hu and Hornbuckle 2010). Both parent PCB 11 and its hydroxylated, glucuronidated, and sulfated metabolites have been detected in blood samples of exposed individuals (Grimm et al 2017;Sethi et al 2017Sethi et al , 2019Zhu et al 2013). Nonlegacy PCBs, also called unintentionally produced PCBs, now represent the major source of PCBs in the atmosphere of China (Zhao et al 2020).…”

“…Characterization of the margins of exposure for PCBs and their metabolites was achieved by cell type-specific comparison of measured bioactivity, i.e., calculated POD values, and human serum concentrations of selected PCBs, hydroxylated metabolites of PCBs (OHPCBs), and PCB sulfates. PCB and OHPCB serum concentrations were based on the data from the Airborne Exposure to Semi-Volatile Organic Pollutants study (Ampleman et al 2015;Grimm et al 2017;Koh et al 2016aKoh et al , 2016b.…”

“…To facilitate the interpretation of the observed in vitro effects in a risk assessment context, margins of exposure were determined for each of the assessed PCBs and metabolites (Figure 7). We used human exposure data, where available (Ampleman et al 2015;Grimm et al 2017;Koh et al 2016aKoh et al , 2016b, to estimate serum concentration ranges for exposed subjects. As an initial risk characterization approach, POD values for each cell type were combined into one box-and-whiskers plot per chemical tested, plotted as nominal in vitro concentrations, and compared with the ranges of total human serum-free fractions, shown separately for parent PCBs ( Figure 7A) and their hydroxylated ( Figure 7B) or sulfated ( Figure 7C) metabolites.…”

“…For hydroxylated PCBs, the margins varied from over three orders of magnitude to less than one ( Figure 7B). For the sulfated PCBs, even though human biomonitoring data suggested that their serum concentrations were generally higher than those of parent molecules or hydroxylated metabolites (Ampleman et al 2015;Grimm et al 2017;Koh et al 2016aKoh et al , 2016b, MOEs were generally over one order of magnitude ( Figure 7C).…”

Mono-, di-, and trichlorinated biphenyls (PCB 1-PCB 39) in the indoor air of office rooms and their relevance on human blood burden

“…The concentration in plasma or urine was too low for correlation analysis in the other lower chlorinated biphenyls. Grimm et al measured 4‐PCB 11 sulfate in 20% in the serum samples of a study population (n = 46) from urban and rural communities. PCB 11 was used in the United States as a by‐product in commercial paint and pigment production.…”