Neurotoxicity of Persistent Organic Pollutants: Possible Mode(S) of Action and Further Considerations

Abstract

Persistent organic pollutants (POPs) are long-lived toxic organic compounds and are of major concern for human and ecosystem health. Although the use of most POPs is banned in most countries, some organochlorine pesticides are still being used in several parts of the world. Although environmental levels of some POPs such as polychlorinated biphenyls (PCBs) have declined, newly emerging POPs such as polybrominated diphenyl ethers (PBDEs) have been increasing considerably. Exposure to POPs has been associated with a wide spectrum of effects including reproductive, developmental, immunologic, carcinogenic, and neurotoxic effects. It is of particular concern that neurotoxic effects of some POPs have been observed in humans at low environmental concentrations. This review focuses on PCBs as a representative chemical class of POPs and discusses the possible mode(s) of action for the neurotoxic effects with emphasis on comparing dose-response and structure-activity relationships (SAR) with other structurally related chemicals. There is sufficient epidemiological and experimental evidence showing that PCB exposure is associated with motor and cognitive deficits in humans and animal models. Although several potential mode(s) of actions were postulated for PCB-induced neurotoxic effects, changes in neurotransmitter systems, altered intracellular signalling processes, and thyroid hormone imbalance are predominant ones. These three potential mechanisms are discussed in detail in vitro and in vivo. In addition, SAR was conducted on other structurally similar chemicals to see if they have a common mode(s) of action. Relative potency factors for several of these POPs were calculated based on their effects on intracellular signalling processes. This is a comprehensive review comparing molecular effects at the cellular level to the neurotoxic effects seen in the whole animal for environmentally relevant POPs.

The presence of polychlorinated biphenyls in yellow pigment products in China with emphasis on 3,3′-dichlorobiphenyl (PCB 11)

“…And PCB 11 was reported as a dominant component in some places (King et al, 2002;Rodenburg et al, 2010;Baek et al, 2013;Grossman, 2013), even made the total PCBs concentration exceed the local standard in the Delaware River (Rodenburg et al, 2010). Some studies suggested that PCB 11 had some potentially toxic activities like calcium, dopamine, and thyroid hormone interference (Shain et al, 1991;Kodavanti, 2005).…”

Permanently compromised NADPH-diaphorase activity within the osmotically activated supraoptic nucleus after in utero but not adult exposure to Aroclor 1254

“…Since NO participates in synaptic plasticity, neurite outgrowth and extension, synaptogenesis, neuronal proliferation and maturation (Holscher, 1997;Sanchez-Islas and Leon-Olea, 2004;Wu et al, 1994), the early PCB-induced changes in NOS activity may be associated with altered nervous system development and function (Kodavanti, 2005). Others have suggested that PCB-induced disruption of thyroid hormone signaling in PCB-exposed animals may explain the long-term effects of developmental PCB exposure on nervous system structure and function (Yang et al, 2009).…”

“…Polychlorinated biphenyls (PCBs) are persistent organohalogen compounds of which chronic exposure can lead to endocrine disruption and neurotoxicity (Kodavanti, 2005;Kodavanti and Curras-Collazo, 2010). Although the manufacture of PCBs (including the high production industrial mixture, Aroclor 1254), was discontinued in 1977, PCBs are still found in significant quantities in the environment and human tissues including human breast milk (Lang, 1992;She et al, 2007).…”

Endocrine Disruptors Are a Novel Direction of Endocrinologic Scientific Investigation

“…ПХБ -эндокринные дизрапторы. Они нару-шают функциональную деятельность щитовидной железы, снижая продукцию тиреоидных гормонов, печени и про-цессы обмена веществ, наиболее выраженные в прена-тальном периоде развития особи с последующим разви-тием детского ожирения и риском возникновения сахарного диабета [31,32]. Воздействие ПХБ в пренатальном периоде развития организма приводит к нарушениям половой диф-ференцировки гипоталамуса [33].…”