Abstract
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.
The views expressed in this article are those of the authors and do not necessarily reflect the views and policies of the U.S. Environmental Protection Agency. Mention of trade names or commercial products does not constitute endorsement or recommendation for use.
Notes
1Based on CitationNarotsky et al. (1997b), P(Effect) = 1/[1 + exp(11.7 – 2.5 × ln(dosage))].
2To conduct a risk assessment, rather than an illustrative analysis, other more statistically robust comparisons, such as an ED10 or dose-response slopes, would have been evaluated to calculate RPF. The modes of toxic action associated with reproductive toxicity of the DBP also would have been thoroughly explored to determine if they were similar to the toxic mode of action of BDCM.