Potential carcinogenic hazards of non-regulated disinfection by-products: Haloquinones, halo-cyclopentene and cyclohexene derivatives, N-halamines, halonitriles, and heterocyclic amines

Abstract

Drinking water disinfectants react with natural organic material (NOM) present in source waters used for drinking water to produce a wide variety of by-products. Several hundred disinfection by-products (DBPs) have been identified, but none have been identified with sufficient carcinogenic potency to account for the cancer risks projected from epidemiological studies. In a search for DBPs that might fill this risk gap, the present study projected reactions of chlorine and chloramine that could occur with substructures present in NOM to produce novel by-products. A review of toxicological data on related compounds, supplemented by use of a quantitative structure toxicity relationship (QSTR) program TOPKAT® identified chemicals with a high probability of being chronically toxic and/or carcinogenic among 489 established and novel DBPs. Classes of DBPs that were specifically examined were haloquinones (HQs), related halo-cyclopentene and cyclohexene (HCP&H) derivatives, halonitriles (HNs), organic N-chloramines (NCls), haloacetamides (HAMs), and nitrosamines (NAs). A review of toxicological data available for quinones suggested that HQs and HCP&H derivatives appeared likely to be of health concern and were predicted to have chronic lowest observed adverse effect levels (LOAELs) in the low μg/kg day-1 range. Several HQs were predicted to be carcinogenic. Some have now been identified in drinking water. The broader class of HNs was explored by considering current toxicological data on haloacetonitriles and extending this to halopropionitriles. 2,2-Dichloropropionitrile has been identified in drinking water at low concentrations, as well as the more widely recognized haloacetonitriles. The occurrence of HAMs has been previously documented. The very limited toxicological data on HAMs suggests that this class would have toxicological potencies similar to the dihaloacetic acids. Organic N-halamines are also known to be produced in drinking water treatment and have biological properties of concern, but no member has ever been characterized toxicologically beyond bacterial or in vitro studies of genotoxicity. The documented formation of several nitrosamines from secondary amines from both natural and industrial sources prompted exploration of the formation of additional nitrosamines. N-Diphenylnitrosamine was identified in drinking waters. Of more interest, however, was the formation of phenazine (and subsequently N-chorophenazine) in a competing reaction. These are the first heterocyclic amines that have been identified as chlorination by-products. Consideration of the amounts detected of members of these by-product classes and their probable toxicological potency suggest a prioritization for obtaining more detailed toxicological data of HQs > HCP&H derivatives > NCls > HNs. Based upon a ubiquitous occurrence and virtual lack of in vivo toxicological data, NCls are the most difficult group to assign a priority as potential carcinogenic risks. This analysis indicates that research on the general problem of DBPs re...

<b>Maternal and fetal toxicity of Wistar rats exposed to herbicide metolachlor

“…Pesticides, plasticizers, disinfection by-products, heavy metals and persistent organic pollutants have been related to carcinogenesis, chronic disease, endocrine disruption and congenital anomalies/malformations (Bull et al, 2011;Li & Ko, 2012;Nieuwenhuijsen, Dadvand, Grellier, Martinez, & Vrijheid, 2013;Magliano, Loh, Harding, Botton, & Shaw, 2014;Vested, Giwercman, Bonde, & Toft, 2014). The pesticides stand out in this scenario, considering their wide use in agriculture and consequential exposure of the general public and farm workers (Thulstrup & Bonde, 2006).…”

Aromatic Amines Sources, Environmental Impact and Remediation

“…Since the start of the industrial revolution, a wide variety of aromatic pollutants have also been introduced into the environment through anthropogenic activity (Bull et al 2011;Carmona et al 2009). The thermodynamic stability of the benzene ring, due to its resonance structure, has contributed to the widespread production and industrial use of natural and xenobiotic aromatic compounds, but has also contributed to the persistence of these compounds, many of which are toxic when released into the environment.…”

“…Therefore, they constitute an important and diversified class of pollutants. Many of them are toxic to most living organisms due to their genotoxic or cytotoxic properties (Bull et al 2011;Kim and Guengerich 2005).…”

Identification and ecotoxicity of degradation products of chloroacetamide herbicides from UV-treatment of water

“…In recent years, several reviews of the occurrence and fate of transformation by-products of manmade chemicals have been made (Richardson et al,, 2003;Richardson et al, 2007;Wei et al, 2010;Bull et al, 2011). Degradation products are generated during water treatment processes including oxidation.…”