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John S. Reif,¹ Maureen C. Hatch,² Michael Bracken,³ Lewis B. Holmes,⁴ Bernard A. Schwetz,⁵ and Philip C. Singer⁶

¹Department of Environmental Health, Colorado State University, Fort Collins, CO 80523 USA; ²Division of Epidemiology, Columbia University, New York, NY 10032 USA; ³Department of Epidemiology and Public Health, Yale University, New Haven, CT 06510 USA; ⁴Genetics and Teratology Unit, Massachusetts General Hospital, Boston, MA 02114 USA; ⁵Environmental Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709 USA; ⁶Department of Environmental Sciences and Engineering, University of North Carolina, Chapel Hill, NC 27599 USA.

Abstract

Recent epidemiologic studies have reported associations between the consumption of chlorinated drinking water and reproductive and developmental effects. Here we review the available epidemiologic data, assess the hazard potential posed by exposure to disinfection by-products, identify critical data gaps, and offer recommendations for further research. The epidemiologic evidence supporting associations between exposure to water disinfection by-products (DBPs) and adverse pregnancy outcomes is sparse, and positive findings should be interpreted cautiously. The methods used during the early stages of research in this area have been diverse. Variability in exposure assessment and endpoints makes it difficult to synthesize or combine the available data. Exposure misclassification and unmeasured confounding may have lead to bias in risk estimation. Future studies of reproductive outcome and exposure to chlorinated water should use improved methods for exposure assessment to 1) assure selection of appropriate exposure markers, 2) assess seasonal and annual fluctuations in DBPs, 3) assess variability within the distribution system, and 4) assess exposure through multiple routes such as bathing and showering, as well as consumption. Population-based studies should be conducted to evaluate male and female fertility, conception delay, growth retardation, and specific birth defects. The reproductive and developmental effects of exposure to DBPs could be efficiently explored in ongoing investigations by incorporating valid exposure markers and relevant questionnaire information. Future studies should make use of naturally occurring variability in the concentrations of DBPs and may incorporate biomarkers of exposure and effect in their design. Epidemiologic investigations should be conducted in parallel with laboratory-based and animal studies in a coordinated, multidisciplinary approach. Key words: birth defects, chlorination, drinking water, epidemiology, low birth weight, prematurity, reproduction, teratogens, trihalomethanes. Environ Health Perspect 104:1056-1061 (1996)

Address correspondence to D. Robinson, Risk Science Institute, ILSI, 1126 16th St. NW, Washington, DC 20036 USA. M. C. Hatch is currently at Mount Sinai School of Medicine, New York, NY 10029 USA ; B. A. Schwetz is currently at the National Center for Toxicological Research, Food and Drug Administration, Jefferson, AR 72079 USA.

Adapted from the Report of the Panel on Reproductive Effects of Disinfection By-products in Drinking Water, Health Effects Research Laboratory, U.S. Environmental Protection Agency and International Life Sciences Institute, Risk Science Institute.

The panel of authors was convened through collaboration between the Health Effects Research Laboratory (HERL) , U.S. Environmental Protection Agency (EPA) and International Life Sciences Institute (ILSI) , Risk Science Institute. Support was provided through a cooperative agreement between the Office of Research and Development, Office of Health and Environmental Assessment (HERL) , EPA and the ILSI Risk Science Institute. The authors thank R. Calderon and D. Robinson for organizing and directing this effort. The panel gratefully acknowledges J. White for assistance with the preparation of the report and S. Carter for coordinating the workshop and the production of the panel report.

Received 6 February 1996 ; accepted 18 June 1996.