Occurrence and distribution of PCB metabolites in blood and their potential health effects in humans: a review

Abstract

In recent years, attention has been directed to chemicals with possible endocrine-disrupting properties. Polychlorinated biphenyls (PCBs) and their metabolites belong to one group of environmental contaminants that have been shown to interact with the endocrine system in mammals, including humans. Although recent developments have been made in terms of determination of PCB metabolites in blood samples, still limited number of studies have been able to elucidate their profiles and toxicological and health effects in humans. This review aims to evaluate and compare the levels of hydroxylated PCBs (OH-PCBs) and methyl sulfone PCBs (MeSO2-PCBs) in blood and their relationship to parent compounds and also address the potential risks and adverse health effects in humans. Levels of OH-PCBs varied between 0.0002 and 1.6 ng g(-1) w/w in human serum/plasma from the selected literature, correlating well with ∑PCBs. In contrast, ∑OH-PCB/∑PCB ratio in animals did not show a significant correlation, which might suggest that the bioaccumulation plays an even more important role in the concentration of OH-PCBs compared to PCB metabolism. Highest levels of MeSO2-PCBs were reported in marine mammals with high selectivity retention in the liver. Health effects of PCB metabolites included carcinogenicity, reproductive impairment, and developmental neurotoxicity, being more efficiently transferred to the brain and across the placenta from mother to fetus in comparison to the parent PCBs. Based on the lack of knowledge on the occurrence and distribution of lower chlorinated OH-PCBs in humans, further studies to identify and assess the risks associated to human exposure are essential.

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

“…OH-PCB congeners bearing a para -substituted hydroxyl group and adjacent chlorine on meta or ortho position of the biphenyl rings are more likely to cause alteration of thyroid hormone levels (Quinete et al, 2014; Tehrani and Van Aken, 2014). Some OH-PCBs decrease serum retinol transport (Brouwer and Vandenberg, 1986) and are potential endocrine disruptors (Meerts et al, 2004) and neurotoxicants (Shimokawa et al, 2006; Londono et al, 2010; Lesmana et al, 2014; Kimura-Kuroda et al, 2007).…”

Differential neurotoxic effects of <i>in utero</i> and lactational exposure to hydroxylated polychlorinated biphenyl (OH-PCB 106) on spontaneous locomotor activity and motor coordination in young adult male mice

“…Results suggest that the neurotoxic effects of OH-PCB 106 could vary according to the period of OH-PCB 106 exposure. Indeed, OHPCBs are thought to be excreted more rapidly from the body compared with parent PCBs (Malmberg et al, 2004;Soechitram et al, 2004;Quinete et al, 2014), as hydroxylated metabolites are generally more hydrophilic than parent compounds, which are lipophilic and mainly accumulate in adipose tissue. Thus, it is considered that the duration of exposure to OH-PCB 106 may be shorter than that of a parent PCB.…”

“…In addition to PCB congeners, their metabolites, hydroxylated PCBs (OH-PCBs), are also suspected to have endocrine-disrupting and neurotoxic effects because their chemical structures are similar to those of the thyroid hormone (TH) (Kimura- Kuroda et al, 2007;Quinete et al, 2014). In addition, OH-PCBs can be transferred to the fetus/neonate via the placenta and lactation (Fängström et al, 2002;Lesmana et al, 2014;Meerts et al, 2002;Park et al, 2008;Sandau et al, 2002;Sinjari and Darnerud, 1998;Soechitram et al, 2004).…”

Evaluation of Relationship Between Obesity and Endocrine Disrupting Chemicals-II: Polychlorinated Biphenyls: Review

“…Bu basamakta oluşan MeSO 2 -PCB merkaptürik asit yolağı ile metabolize olur. 29,41,42 Yüksek lipofilik özellikleri nedeni ile yağ oranı yüksek dokularda birikme eğilimi gös-termektedirler. Karaciğer, adipoz doku, deri ve anne sütünde yüksek miktarlarda bulunmaktadırlar.…”

“…Yine bu bileşiklere maruziyetle inflamatuar sitokinlerin (IL-6 ve TNF-α) transkripsiyonunda artış olduğu ve bu bileşiklerin pregnan X reseptörü (PXR), konstitütif androstan reseptörü (CAR), karaciğer-X-reseptör-α (LXRα) ve farnesoid-X-reseptörlerini (FXR) etkilediği de düşünülmektedir. 31,33,[42][43][44] Ancak, bu bileşiklerin çok daha farklı mekanizmalarla ve farklı birçok proteini hedefleyerek obeziteye neden olabilecekleri önerilmektedir. Diğer taraftan, PCB'lerin obezite dışında da gelişimsel bozukluklar, kanser ve endokrin bozukluklar gibi farklı hastalıklara yol aça-bileceği yapılan çalışmalarla gösterilmektedir.…”