Health Risk of the Trihalomethanes Found in Drinking Water Carcinogenic Activity and InteractionsEPA Grant Number: R825384
Title: Health Risk of the Trihalomethanes Found in Drinking Water Carcinogenic Activity and Interactions
Investigators: Pereira, Michael A.
Institution: Medical College of Ohio
EPA Project Officer: Hiscock, Michael
Project Period: January 9, 1997 through January 8, 2000
Project Amount: $442,347
RFA: Drinking Water (1996) RFA Text | Recipients Lists
Research Category: Drinking Water , Water
Description:The use of chlorine to disinfect water for the purpose of drinking produces low levels of various disinfection by-products with the trihalomethanes and haloacetic acids being the most common. The trihalomethanes and haloacetic acids have demonstrated carcinogenic activity in laboratory animals. Numerous assumptions are needed in estimating the health hazard of exposure to trihalomethanes in drinking water when using results of their chronic bioassays that employed corn oil gavage as the vehicle. Hence, it will be determined whether the trihalomethanes administered in drinking water either promote or prevent liver cancer using an initiation-promotion bioassay. This will include comparison of the activity of the trihalomethanes administered in drinking water to that when administered by gavage in corn oil. The initiation-promotion bioassay will employ initiation of mice with N-methyl N-nitrosourea on day 15 of age followed by administering the trihalomethane starting at seven weeks of age. The livers will be evaluated for foci of altered hepatocytes, tumors, and various biological and molecular parameters to better understand the mechanism and pathogenesis of trihalomethanes in drinking water. Interactions among trihalomethanes and haloacetic acids will also be determined in mouse liver with respect to biological and molecular parameters and tumor promotion/prevention.
With respect to the colon carcinogenicity of the trihalomethanes, we will screen them when administered in the drinking water for the ability to initiate, promote or prevent colon cancer in rats. The azoxymethane-induced aberrant crypt foci and cancer model will be used. The relative activity of the trihalomethanes administered in drinking water will be compared to their activity when administered by gavage in corn oil. Observed activity of the trihalomethanes when administered in drinking water will be further evaluated using mechanism-related biological and molecular parameters.
Results of this grant will support the EPA in addressing: 1) whether the trihalomethanes in drinking water represent a carcinogenic hazard, and 2) interactions of trihalomethanes and haloacetic acids. Specifically, data will be supplied pertaining to the carcinogenic activity of trihalomethanes in rat colon and mouse liver when exposure is from drinking water. The results will decrease the uncertainties and assumptions in the estimation of the carcinogenic hazard of trihalomethanes in drinking water. Since the trihalomethanes and haloacetic acids are present as mixtures in drinking water, the project will determine interactions which might effect their carcinogenic activity in mouse liver and rat colon. In conclusion, the EPA will be supplied with data and new concepts that should reduce their reliance on default assumptions pertaining to the carcinogenic activity, mechanisms, interactions, and extrapolation of routes of administration in the hazard and risk assessment of the trihalomethanes and haloacetic acids found in drinking water.