Elimination of Inhaled 3,3′-Dichlorobiphenyl and the Formation of the 4-Hydroxylated Metabolite

Abstract

The recent discovery of 3,3′-dichlorobiphenyl (CB11) as a byproduct of pigment manufacturing underscores the urgency to investigate its biological fate. The high level and ubiquity of atmospheric CB11 indicates that inhalation is the major route of exposure. However, few data on its uptake and elimination exist. A time course study was performed exposing male Sprague-Dawley rats to CB11 via nose-only inhalation with necropsy at 0, 4 and 8 h post exposure. An analytical method for CB11 and mono-hydroxylated metabolites employing pressurized liquid extraction and gas chromatography-mass spectrometry yielded efficient recovery of CB11 (73±9%) and its metabolite 3,3′-dichlorobiphenyl-4-ol (4-OH-CB11) (82±12%). Each rat was exposed to 106 μg/m3 vapor-phase CB11 for 2 h and received an estimated dose of 1.8 μg. Rapid apparent first-order elimination of CB11 was found in lung, serum and liver with half-lives of 1.9, 1.8 and 2.1 h, respectively. 4-OH-CB11 was detected in the liver but not the lung or serum of exposed animals and displayed apparent first-order elimination with a 2.4 h half-life. This study demonstrates rapid metabolism of CB11 and elimination of 4-OH-CB11 and suggests that the metabolite is not retained in the body but is susceptible to further biotransformation.

Hydroxylated polychlorinated biphenyls in human sera from adolescents and their mothers living in two U.S. Midwestern communities

“…Analytical artifacts cannot explain the low levels of these congeners because our laboratory was successful in measuring them in the Aroclors (Marek et al, 2013a) and our mono-tri homolog PCB standards showed good recoveries in our serum samples. Our animal inhalation studies have shown that these lower-chlorinated OH-PCBs are rapidly biotransformed to phase II metabolites (e.g., sulfated and glucuronidated conjugates) (Hu et al, 2013; Hu et al, 2014; Dhakal et al, 2012; Grimm et al, 2015). This suggests that other PCB metabolites may be better biomarkers for lower-chlorinated metabolites.…”

“…Recent studies also found OH-PCBs in sediments (Marek et al, 2013a) and human waste has been proposed as a source to surface waters (Ueno et al, 2007). Our group previously demonstrated that OH-PCBs are important metabolic products of PCB 11 and PCB 3 in rats and are excreted in urine and feces (Hu et al, 2013; 2014; Dhakal et al, 2014). OH-PCBs were present in the original Aroclors and this may have contributed OH-PCBs to sediments (Marek et al, 2013a).…”

Human Serum from Urban and Rural Adolescents and Their Mothers Shows Exposure to Polychlorinated Biphenyls Not Found in Commercial Mixtures

“…45 Our laboratory was the first to report PCB 11 in human serum 13, 14 and we know no other reports of PCB 11 in humans. Our group has performed the only inhalation studies of PCB 11 46 and 14 C-labelled PCB 11. 47 Our current study found that PCB 11 concentration was not age-dependent which suggests this compound does not biomagnify and its presence may be due to recent exposure.…”

Serum polychlorinated biphenyls and their hydroxylated metabolites are associated with demographic and behavioral factors in children and mothers

“…It is unclear why children’s sera did not demonstrate a significant correlation between PCBs and OH-PCBs, however, our prior work has shown that their congener profiles are skewed toward the lower-chlorinated PCBs compared to their mothers 33, 41 and these congeners are more rapidly >metabolized. 42 In addition, the limited availability of lower-chlorinated OH-PCB standards may have compromised the estimation of total OH-PCBs.…”