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

Disinfection by-products (DBPs) are produced as a result of disinfecting wa ter using various treatment methods, Over the years, chlorine has remained the most popular disinfecting agent due to its ability to kill pathogens. H owever, in 1974, it was discovered that the superchlorination of drinking w ater resulted in the production of chloroform and other trihalomethanes. Si nce then hundreds of additional DBPs have been identified, including haloac etic acids and haloacetonitriles with very little or no toxicological data available, thus necessitating the use of additional methods for hazard esti mation. Quantitative Structure Toxicity Relationship (QSTR) is one such met hod and utilizes a computer-based technology to predict the toxicity of a c hemical solely from its molecular attributes. The current research was cond ucted utilizing the TOPKAT (R)/QSTR software package which is comprised of robust, cross-validated QSTR models for assessing mutagenicity, rodent carc inogenicity (female/male; rat/mouse), developmental toxicity, skin sensitiz ation, lowest-observed-adverse-effect level (LOAEL), fathead minnow LC50, r at oral LD50 and Daphia magna EC50. A total of 252 DBPs were analyzed for t he likelihood that they would produce tumors and developmental effects usin g the carcinogenicity and developmental toxicity submodels of TOPKAT (R). T he model predictions were evaluated to identify generalizations between the functional groups (e.g. alcohols,acids, etc.) and specific toxic endpoints . Developmental toxicity was identified as an endpoint common to the majori ty of aliphatic mono- and dicarboxylic acids, aliphatic halogenated and non -halogenated ketones, and aliphatic haloacetonitriles. In the case of the c arcinogenicity submodels, most aliphatic aldehydes were identified as carci nogens only in the female mouse submodel. The majority of the aliphatic and aromatic dicarboxylic acids were identified as carcinogens in the female r at submodel. All other functional groups examined were largely predicted as non-carcinogens in all the cancer submodels (i.e. male/female rats and mic e). The QSTR results should aid in the prioritization for evaluation of tox ic endpoints in the absence of in vivo bioassays. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.