Skip to Content


The Feasibility of Performing Cumulative Risk Assessments for Mixtures of Disinfection By-Products in Drinking Water

Document Details

Information about this document as published in the Federal Register.

Published Document

This document has been published in the Federal Register. Use the PDF linked in the document sidebar for the official electronic format.

Start Preamble


Environmental Protection Agency.


Notice of availability.


This notice announces the availability of a final report titled, “The Feasibility of Performing Cumulative Risk Assessments for Mixtures of Disinfection By-Products in Drinking Water (EPA/600/R-03-051F),” which was prepared by the U.S. Environmental Protection Agency's (EPA) National Center for Environmental Assessment (NCEA) of the Office of Research and Development (ORD).


This document will be available on or about January 7, 2004.


The document will be made available electronically through the NCEA Web site (​ncea). A limited number of paper copies will be available from the EPA's National Service Center for Environmental Publications (NSCEP), P.O. Box 42419, Cincinnati, OH 45242; telephone: 1-800-490-9198 or 513-489-8190; facsimile: 513-489-8695. Please provide your name, your mailing address, the title and the EPA number of the requested publication.

Start Further Info


The Technical Information Staff, National Center for Environmental Assessment/Cincinnati, Ohio office (MS-117), U.S. Environmental Protection Agency, 26 W. Martin Luther King Drive, Cincinnati, OH 45268. Telephone: 513-569-7257; fax: 513-569-7475; e-mail:

End Further Info End Preamble Start Supplemental Information


In 1996, the Safe Drinking Water Act Amendments were passed, requiring the EPA to consider the risk assessment of contaminant mixtures in drinking water and prompting this current research on disinfection by-product (DBP) mixtures. Humans are exposed daily to hundreds of DBPs via oral, dermal, and inhalation routes. Some positive epidemiologic studies suggest cancer and reproductive/developmental effects are associated with consumption of chlorinated drinking water. However, in other epidemiologic studies significant health effects have not been observed, and current single-chemical toxicology studies fail to corroborate epidemiologic findings. Furthermore, human health risk estimates made using animal data based only on oral exposures do not reflect the same magnitude of risks found in positive epidemiologic studies. Thus, it is hypothesized that this difference can be accounted for by evaluating simultaneous exposures to multiple DBPs via all three exposure routes. This report addresses the feasibility of such an assessment, yielding the following interim results:

  • Exposure estimates are made for an adult female and an adult male, each of reproductive age, and for a child (age 6) of total absorbed doses inclusive of exposures via oral, dermal and inhalation routes.
  • Estimates are made for 13 major DBPs, accounting for human activity patterns that affect contact time with drinking water (e.g., tap water consumed, time spent showering, building characteristics) and physicochemical properties of the DBPs (inhalation rates, skin permeability rates, blood:air partition coefficients, etc.). Start Printed Page 920
  • A novel cumulative risk assessment method, Cumulative Relative Potency Factors, is advanced that integrates the principles of dose addition and response addition to produce multiple-route, chemical mixture risk estimates using total absorbed doses.

The report acknowledges the need for additional research, such as, to conduct a more complete uncertainty and sensitivity analysis on the exposure estimates, and to conduct a more comprehensive analysis of toxic mode of action for the DBPs. This report makes two significant contributions to the science. First, external exposure modeling is conducted and linked with physiologically-based pharmacokinetic modeling to produce internal dose measures of drinking water disinfection by-products (DBPs) for multiple route exposures to be used in mixture risk assessments. Thus, a comprehensive exposure estimate is made for 13 of the major DBPs of concern, including the four trihalomethanes and five haloacetic acids that are currently regulated. Second, a mixtures risk assessment method, based on additivity concepts is proposed to logically evaluate human health risks using total internal doses and oral toxicology dose-response data based on knowledge or assumptions regarding toxic mode of action. This new method is a novel approach to evaluating multiple route exposures that can be generalized for the evaluation of other environmental mixtures.

Start Signature

Dated: December 23, 2003.

Peter W. Preuss,

Director, National Center for Environmental Assessment.

End Signature End Supplemental Information

[FR Doc. 04-322 Filed 1-6-04; 8:45 am]