Cardiac teratogenesis of halogenated hydrocarbon-contaminated drinking water

Department of Internal Medicine, University of Arizona Health Sciences Center, Tucson.

OBJECTIVES. The purpose of this study was to test the hypothesis that administration of trichloroethylene and dichloroethylene to pregnant rats during organogenesis would produce a significant fetal cardiac teratogenic effect. It was also hypothesized that administration of these compounds only before pregnancy would not be associated with fetal cardiac teratogenesis. BACKGROUND. Epidemiologic observations demonstrated an increased number of congenital cardiac defects in children whose mother resided in an area with drinking water contaminated by trichloroethylene and dichloroethylene. A prior provocative intrauterine exposure study in rats established a positive link between these contaminants and an increased number of fetal hearts with congenital cardiac defects. METHODS. Sprague-Dawley rats were given pure tap drinking water (control subjects) or water contaminated with high or low dose of trichloroethylene or dichloroethylene (experimental groups) during prepregnancy only, prepregnancy and pregnancy or during pregnancy alone. RESULTS. A total of 2,045 fetuses were examined. Trichloroethylene or dichloroethylene delivered exclusively in the period before pregnancy caused no increase in congenital cardiac malformations over the control level. Compared with the control group, rats exposed to these agents both before and during pregnancy, had a significantly greater number of fetuses with cogenital cardiac malformations. Trichloroethylene (high dose only) administered only during pregnancy produced a significant increase in cardiac defects. Other fetal variables, including noncardiac congenital abnormalities, showed no significant difference between control and treated groups. CONCLUSIONS. Trichloroethylene and dichloroethylene administered during organogenesis are cardiac, but not general, teratogens. The data indicate that these agents administered in drinking water to pregnant rats caused an increased number of congenital cardiac defects in rat fetuses.

This article has been cited by other articles:

				V. J. Drake, S. L. Koprowski, N. Hu, S. M. Smith, and J. Lough Cardiogenic Effects of Trichloroethylene and Trichloroacetic Acid Following Exposure during Heart Specification of Avian Development Toxicol. Sci., November 1, 2006; 94(1): 153 - 162. [Abstract] [Full Text] [PDF]

				M. A. Peraza, A. D. Burdick, H. E. Marin, F. J. Gonzalez, and J. M. Peters The Toxicology of Ligands for Peroxisome Proliferator-Activated Receptors (PPAR) Toxicol. Sci., April 1, 2006; 90(2): 269 - 295. [Abstract] [Full Text] [PDF]

				S. M. Mone, M. W. Gillman, T. L. Miller, E. H. Herman, and S. E. Lipshultz Effects of Environmental Exposures on the Cardiovascular System: Prenatal Period Through Adolescence Pediatrics, April 1, 2004; 113(4/S1): 1058 - 1069. [Abstract] [Full Text] [PDF]

				J. W. Fisher, S. R. Channel, J. S. Eggers, P. D. Johnson, K. L. MacMahon, C. D. Goodyear, G. L. Sudberry, D. A. Warren, J. R. Latendresse, and L. J. Graeter Trichloroethylene, Trichloroacetic Acid, and Dichloroacetic Acid: Do They Affect Fetal Rat Heart Development? International Journal of Toxicology, September 1, 2001; 20(5): 257 - 267. [Abstract] [PDF]

				M. J Nieuwenhuijsen, M. B Toledano, N. E Eaton, J. Fawell, and P. Elliott Chlorination disinfection byproducts in water and their association with adverse reproductive outcomes: a review Occup. Environ. Med., February 1, 2000; 57(2): 73 - 85. [Abstract] [Full Text] [PDF]

				A. S. Boyer, W. T. Finch, and R. B. Runyan Trichloroethylene Inhibits Development of Embryonic Heart Valve Precursors in Vitro Toxicol. Sci., January 1, 2000; 53(1): 109 - 117. [Abstract] [Full Text] [PDF]

				P. D. Johnson, B. V. Dawson, and S. J. Goldberg Cardiac teratogenicity of trichloroethylene metabolites J. Am. Coll. Cardiol., August 1, 1998; 32(2): 540 - 545. [Abstract] [Full Text] [PDF]