Potential health effects of drinking water disinfection by-products using quantitative structure toxicity relationship

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...

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“…Moudgal et al (2000) were identified as likely to be a moderately active multispecies/target carcinogen at low doses.…”

Section: Discussionmentioning

confidence: 99%

“…Moudgal et al (2000) were fell into a intermediate category identified as likely to be a moderately active multispecies/target carcinogen at low doses. Thus, the findings of our analysis were generally consistent with those of Woo et al (2002).…”

Section: Discussionmentioning

confidence: 99%

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

Bull¹,

et al. 2011

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“…However, in 1974, it was discovered that the chlorination of drinking waters resulted in the production of chloroform and other trihalomethanes (THMs) due to the reaction of chlorine with the organics in the water. Since then hundreds of additional disinfection by-products (DBPs) have been identified, including haloacetic acids and haloacetonitriles (Moudgal et al, 2000;Bellar et al, 1974;Rook, 1976). Since 1980's DBPs have raised significant concern due to evidence of their adverse human health effects, in particular cancer and reproductive disorders (Cantor et al, 1988;Graves et al, 2002).…”

Section: Disinfection By-products and Thmsmentioning

confidence: 99%

Environmental Engineering

Olson¹

2015

Environmental Science

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“…A positive prediction is indicated when the probability is greater than 0.7. The details of the assessment process using the TOPKAT software have been previously published (Moudgal et al, 2000;Ruiz et al, 2008;Pohl et al, 2010;Ruiz et al, 2011). …”

Section: Qsar Identification Of Chemicals That Have a Potential For Dmentioning

confidence: 99%

Joint toxicity of alkoxyethanol mixtures: Contribution of in silico applications

Pohl

Ruíz

Scinicariello

et al. 2012

Regulatory Toxicology and Pharmacology

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Exposure to chemicals occurs often as mixtures. Presented in this paper is information on alkoxyethanols and the impact they might have on human health in combination with some commonly found aliphatic and aromatic compounds. Our studies to evaluate the joint toxicity of these chemicals among themselves and in combination with other chemicals reveal a variety of possible outcomes depending on the exposure scenario. The interactions are predominantly based on metabolic pathways and are common among several solvents and organic compounds. Quantitative structure activity relationship (QSAR) analysis can be used with high confidence to identify chemicals that will interact to influence overall joint toxicity. Potential human exposure to a combination of alkoxyethanol, toluene and substituted benzenes may increase reproductive and developmental disease conditions. Inheritable gene alterations result in changes in the enzyme function in different subpopulations causing variations in quantity and/or quality of particular isoenzymes. These changes are responsible for differential metabolism of chemicals in species, genders, and life stages and are often the basis of a population's susceptibility. Unique genotypes introduced as a function of migration can alter the genetic makeup of any given population. Hence special consideration should be given to susceptible populations while conducting chemical health risk assessments.

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Potential health effects of drinking water disinfection by-products using quantitative structure toxicity relationship

Cited by 62 publications

References 20 publications

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

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

Environmental Engineering

Joint toxicity of alkoxyethanol mixtures: Contribution of in silico applications

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