A Feasibility Study of Cumulative Risk Assessment Methods for Drinking Water Disinfection By-Product Mixtures

Abstract

Humans are exposed daily to complex mixtures of chemicals, including drinking water disinfection by-products (DBPs) via oral, dermal, and inhalation routes. Some positive epidemiological and toxicological studies suggest reproductive and developmental effects and cancer are associated with consumption of chlorinated drinking water. Thus, the U.S. Environmental Protection Agency (EPA) conducted research to examine the feasibility of evaluating simultaneous exposures to multiple DBPs via all three exposure routes. A cumulative risk assessment approach was developed for DBP mixtures by combining exposure modeling and physiologically based pharmacokinetic modeling results with a new mixtures risk assessment method, the cumulative relative potency factors (CRPF) approach. Internal doses were estimated for an adult female and an adult male, each of reproductive age, and for a child (age 6 yr) inclusive of oral, dermal, and inhalation exposures. Estimates of the daily internal doses were made for 13 major DBPs, accounting for activity patterns that affect the amount of human contact time with drinking water (e.g., tap water consumed, time spent showering), building characteristics (e.g., household air volumes), and physicochemical properties of the DBPs (e.g., inhalation rates, skin permeability rates, blood:air partition coefficients). A novel cumulative risk assessment method, the CRPF approach, is advanced that integrates the principles of dose addition and response addition to produce multiple-route, chemical mixture risk estimates using total absorbed doses. Research needs to improve this approach are presented.

Notes

*The terms mechanism of toxicity (or mechanism of toxic action) and mode of action represent a continuum of understanding regarding a toxicodynamic process (U.S. EPA, 2002a). A toxicologic outcome is considered to be damaging to the organism at any level of biological organization (i.e., molecular, cellular, tissue, etc.). Knowledge of a chemical's mechanism of toxicity or mechanism of toxic action implies that the molecular and cellular events leading to a toxicologic outcome are described and well understood. Knowledge of a chemical's mode of action implies a general understanding of key toxicodynamic events, but not a detailed description of these events. Mode of action is defined as the set of key biological events leading to a toxicologic outcome.

*The ICED has the same mathematical interpretation as the dioxin toxicity equivalents (TEQ). TEQ refers to the quantification of dioxin concentrations based on the congeners’ equivalent 2,3,7,8-TCDD toxicity (U.S. EPA, 1989). ICED is applied to mixtures other than dioxins.

*Note that the TEM and ERDEM modeling results were done for different time periods, 24 and 48 h, respectively. Given this was a feasibility study, these efforts were conducted independently; the time periods were therefore not coordinated to be the same.