US EPA

Humans are exposed daily to complex mixtures of drinking water disinfection by-products (DBPs) via oral, dermal, and inhalation routes. Some positive epidemiological studies suggest reproductive and developmental effects and cancer are associated with consumption of chlorinated drinking water. However, the results of current single-chemical DBP toxicology studies fail to corroborate these findings. Assuming additivity, human health risk estimates based on rodent bioassay data and oral exposures alone do not indicate the same magnitude of risks found in positive epidemiological studies. Thus, it is hypothesized that this difference may be accounted for by evaluating simultaneous exposures to multiple DBPs via multiple exposure routes.

EPA conducted research to examine the feasibility of performing a cumulative risk assessment 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) inclusive of oral, dermal and inhalation exposures. Exposure estimates were developed for 13 major DBPs, accounting for physicochemical properties of the DBPs (inhalation rates, skin permeability rates, blood:air partition coefficients, etc.) and activity patterns that affect the amount of human contact time with drinking water (e.g., tap water consumed, time spent showering, building characteristics). 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.

U.S. EPA. The Feasibility Of Performing Cumulative Risk Assessments For Mixtures Of Disinfection By-Products (DBPs) In Drinking Water. U.S. Environmental Protection Agency, Washington, DC, EPA/600/R-03/051.