Integrated disinfection by-products research: assessing reproductive and developmental risks posed by complex disinfection by-product mixtures.

This article presents a toxicologically-based risk assessment strategy for identifying the individual components or fractions of a complex mixture that are associated with its toxicity. The strategy relies on conventional component-based mixtures risk approaches such as dose addition, response addition, and analyses of interactions. Developmental toxicity data from two drinking-water concentrates containing disinfection by-products (DBP) mixtures were used to illustrate the strategy. The results of this study showed that future studies of DBP concentrates using the Chernoff-Kavlock bioassay need to consider evaluating DBP that are concentrated more than 130-fold and using a rat strain that is more sensitive to chemically-induced pregnancy loss than Sprague-Dawley rats. The results support the planned experimental design of a multigeneration reproductive and developmental study of DBP concentrates. Finally, this article discusses the need for a systematic evaluation of DBP concentrates obtained from multiple source waters and treatment types. The development of such a database could be useful in evaluating whether a specific DBP concentrate is sufficiently similar to tested combinations of source waters and treatment alternatives so that health risks for the former may be estimated using data on the latter.