Polychlorinated biphenyls (PCBs) are synthetic organic chlorinated compounds used in industries for decades until their ban in 1979. PCBs were originally developed in the late 1800′s, and began to be used more widely commercially in the 1930′s (Markowitz, 2018). Their beneficial industrial properties, such as low water solubility, low ability to conduct current, low flammability, and very high chemical stability, made them ideal components of electrical insulators and plasticizers. PCBs were found in a large proportion of electrical transformers across the U.S. and contributed to the expansion of the U.S. electrical grid. Because of their low flammability, they have been incorporated into many building materials, particularly in schools and were heavily used during school building booms during the 1960s (Thomas, 2012). Most schools in the U.S. were built during the period of heavy use of PCBs in building materials (Rowand, 1999).

Concerns about human toxicity of environmental exposures to PCBs emerged in the 1960s. Two major epidemics of PCB poisoning due to the consumption of contaminated rice-bran cooking oil have been documented. The first occurred in Japan in 1968, affecting approximately 1700 individuals, and is known as the "Yusho" incident (Kuratsune et al., 1972). A second, similar outbreak occurred in Taiwan between 1978 and 1979, with over 2000 reported cases, referred to as the "Yu-Cheng" (oil disease) incident (Chen et al., 1980). In addition, accumulating reports of PCBs acting as carcinogens, endocrine disrupters, and causing neurodevelopmental and reproductive disorders led the Environmental Protection Agency (EPA) to ban their production in 1979 under the Toxic Substances Control Act (TSCA). Unfortunately, given their very high chemical stability (half-life in sediment of aquatic ecosystems can be many decades), PCBs persist in the environment and their high lipid solubility has made them difficult to contain leading to their continued presence in air, soil, water and continued incorporation into the food chain (Beyer and Biziuk, 2009; Hens and Hens, 2017).

209 individual chemical congeners of PCBs exist, each composed of two linked benzene rings with varying numbers and positions of chlorine atoms. These congeners are broadly classified based on their structural and toxicological properties into dioxin-like and non-dioxin-like PCBs. Dioxin-like PCBs bind the aryl hydrocarbon receptor (AhR), thereby triggering a cascade of gene regulatory events that can lead to oxidative stress, immunotoxicity, and neurotoxicity (Jin et al., 2020; Shen et al., 2016; Zhang et al., 2012). Dioxin-like activity is typically associated with a coplanar configuration. In contrast, non-dioxin-like PCBs are in a noncoplanar conformation, reducing AhR binding. These two classes of PCBs likely have different mechanisms of toxicity, though many toxic exposures involve a blend of congeners, therefore involving a mixture of both classes of PCBs (Imamoglu and Christensen, 2002; Jursa et al., 2006).

A major route of human exposure to PCBs is via fish consumption as PCBs make their way into aquatic ecosystems. PCBs bio-accumulate, and larger predator fish often consumed by humans contain higher concentrations of PCBs (Porte and Albaigés, 1994). The fetus and neonate are especially susceptible to the toxic effects of these compounds due to exposure during critical windows of nervous system development. PCBs readily cross the placenta, resulting in fetal exposure during gestation, while PCBs are additionally transferred to the neonate through breastfeeding (Aliyu et al., 2010; Rogan et al., 1986a, 1986b). Their lipid solubility leads them to reach the brain leading to an impact on nervous system development. A more recently-recognized form of exposure to PCBs is the airborne route. PCBs are often spontaneously produced as byproducts during the synthesis of pigments that are still in wide use in paints. Thus, in addition to legacy industrial PCBs that continue to persist in the environment, there is continued production and release of PCBs from certain organic pigments, and high levels continue to be found in schools (Herrick et al., 2011; Marek et al., 2017). Therefore, PCB exposure continues to be an ongoing health issue.

This review is focused on the effects of PCBs on hearing. We provide a comprehensive examination of how PCBs affect the auditory system, encompassing both the peripheral components (cochlea and auditory nerve) and central auditory pathways (brainstem through auditory cortex). We discuss the possible mechanisms of PCB ototoxicity, behavioral and functional outcomes of PCB exposure on hearing. We present key findings from animal models and human studies.