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CLINICAL STUDIES

Cardiac teratogenicity of trichloroethylene metabolites

^a Department of Pediatrics, Steele Memorial Children’s Research Center, Southwest Environmental Health Science Center, University of Arizona, Tucson, Arizona, USA
^* Department of Internal Medicine, Steele Memorial Children’s Research Center, Southwest Environmental Health Science Center, University of Arizona, Tucson, Arizona, USA

Manuscript received February 17, 1997; revised manuscript received April 14, 1998, accepted April 29, 1998.

Address for correspondence: Dr. Paula D. Johnson, Department of Pediatrics, Section of Cardiology, University of Arizona Health Sciences Center, 1501 N. Campbell Avenue, PO Box 245073, Tucson, Arizona 85724
pdj{at}peds.arizona.edu

Objectives. The hypothesis of this study was that metabolites of trichloroethylene (TCE), dichloroethylene (DCE) and related compounds were responsible for fetal cardiac teratogenic effects seen when TCE or DCE is consumed by pregnant rats during organogenesis. Identification of teratogenic metabolites would allow more accurate assessment of environmental contaminants and public health risks from contaminated water or possibly municipal water supplies which, when chlorinated, may produce these potentially dangerous chemicals.

Background. Human epidemiologic studies and previous teratogenic studies using chick embryos and fetal rats have shown an increased incidence of congenital cardiac lesions in animals exposed to TCE and DCE.

Methods. Metabolites and compounds studied in drinking water exposure included: trichloroacetic acid (TCAA), monochloroacetic acid (MCAA), trichloroethanol (TCEth), carboxy methylcystine (CMC), trichloroacetaldehyde (TCAld), dichloroacetaldehyde (DCAld), and dichlorovinyl cystine (DCVC). Compounds were administered to pregnant rats during fetal heart development.

Results. Fetuses of rats receiving 2,730 ppm TCAA in drinking water were the only group that demonstrated a significant increase in cardiac defects (10.53%) compared with controls (2.15%) on a per fetus basis (p = 0.0001, Fischer’s exact test), and a per litter basis (p = 0.0004, Wilcoxon and p = 0.0015, exact permutation tests). Trichloroacetic acid also demonstrated an increased number of implantation and resorption sites (p < 0.05) over controls. Other maternal and fetal variables showed no statistically significant differences between treated and untreated groups.

Conclusions. Of the metabolites tested, only TCAA appeared to be a specific cardiac teratogen in the fetus when imbibed by the maternal rat.

Abbreviations and Acronyms   CMC = carboxy methylcystine   DCAA = dichloroacetic acid   DCAld = dichloroacetaldehyde   DCE = dichloroethylene   DCVC = dichlorovinyl cystine   MCAA = monochloroacetic acid   TCAA = trichloroacetic acid   TCAld = trichloroacetaldehyde   TCE = trichloroethylene   TCEth = trichloroethanol

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