Halobenzoquinones (HBQs), a new class of disinfection byproducts (
DBPs), occur widely in treated
drinking water and recreational water. The main concern regarding human exposure to
DBPs stems from epidemiological studies that have consistently linked the consumption of chlorinated
drinking water with an increased risk of developing
bladder cancer. The U.S. Environmental Protection Agency and Health Canada have set regulations on the amount of
DBPs in
drinking water to minimize the risk. However, these regulated
DBPs do not account for the increased risk of
bladder cancer because they have different target organs or lower magnitudes of risk based on animal
carcinogenesis studies. Because of the pervasive exposure to
DBPs, identification of
DBPs relevant to human health has become one of the important research targets to address DBP-associated health concerns. Quantitative structure-toxicity relationship (QSTR) analysis has predicted HBQs to be potential bladder
carcinogens. Therefore, this perspective focuses on the chemical and toxicological characterization of HBQs. In vitro cytotoxicity experiments have shown that HBQs induce greater cytotoxicity and/or greater developmental toxicity than most of the regulated
DBPs. Cellular mechanistic studies indicate that HBQs are capable of producing
reactive oxygen species (ROS) either within cells or in
solution, depleting cellular
glutathione levels, and influencing cellular
antioxidant enzymes, which further induces oxidative stress and oxidative damage to cellular
proteins and
DNA. Oxidative damage to
DNA was demonstrated in the form of significant increases in cellular levels of
8-hydroxydeoxyguanosine (8-OHdG),
DNA strand breaks, and apurinic/apyrimidinic (AP) sites. HBQs can also form
DNA adducts, affect genome-wide DNA methylation, and inhibit
DNA repair enzymes. These findings demonstrate that HBQs are highly cytotoxic and potentially genotoxic and carcinogenic, although in vivo data corroborating this is not available. To fully understand the potential adverse health effects and
cancer risk due to HBQ exposure, multidisciplinary research is required regarding human exposure, health risk assessment, and toxicological mechanisms of HBQs.