Chemical and Toxicological Characterization of Halobenzoquinones, an Emerging Class of Disinfection Byproducts

Abstract

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.

Impact of Water Heaters on the Formation of Disinfection By‐products

“…Some of the nonregulated DBPs have shown greater developmental toxicity and growth inhibition than the regulated ones (Li et al 2015, Liu & Zhang 2014, Yang & Zhang 2013, Plewa et al 2004). However, assessing human exposure to DBPs is a challenging task because of the high degree of temporal and spatial variability and the multiple routes of exposure.…”

Perturbation of xenobiotic metabolism in Dreissena polymorpha model exposed in situ to surface water (Lake Trasimene) purified with various disinfectants

“…Cellular mechanistic studies indicate that halogenated DBPs are capable of producing reactive oxygen species either within cells or in solution, depleting cellular glutathione levels, and influencing cellular antioxidant enzymes, which further induce oxidative stress and oxidative damage to cellular proteins and DNA. These findings, although not corroborated by in vivo data, demonstrate that halogenated DBPs are highly cytotoxic, genotoxic and potentially carcinogenic (Li et al, 2015).…”

The Unexpected and Exceptionally Facile Chemical Modification of the Phenolic Hydroxyl Group of Tyrosine by Polyhalogenated Quinones under Physiological Conditions

“…25−27 Recently several polyhalogenated quinones were also identified as disinfection byproducts in drinking and swimming pool water, which are suspected bladder carcinogens. 28 It is well-known that the toxicity of quinone metabolites is mainly through their swift covalent binding to thiol groups. 8,13 Here our findings that TXBQs can modify tyrosine with high reactivity may provide some unexpected new insight into their potential toxicity.…”