Trichloroethylene in Drinking Water throughout Gestation Did Not Produce Congenital Heart Defects in Sprague Dawley Rats

Birth Defects Research

July 30, 2019

Dr. John DeSesso, DABFM, DABFE, FACFEI, DABCHS, Fellow ATS, principal scientist at Exponent, Dr. James Bus, DABT, Fellow ATS, senior managing scientist at Exponent, and external colleagues have recently published an article in the journal Birth Defects Research. The article details a large study demonstrating that trichloroethylene (TCE), a widespread hydrocarbon contaminant, does not cause heart defects in offspring of pregnant rats exposed to TCE concentrations in water up to the aqueous solubility limit.  The study also measured blood levels of trichloroethylene (TCE) and metabolites in pregnant rats.  The data is important because the Environmental Protection Agency is re-evaluating the permissible exposure limits for TCE and several controversial studies have suggested that drinking TCE-contaminated water by pregnant rats causes heart defects in offspring.  The new study affirms the absence of cardiac defects associated with maternal consumption of water containing TCE nearly as high as the aqueous solubility limit of TCE.  These new data align with negative results of other large studies that exposed pregnant rats to TCE by inhalation or by oral intubation.


Background: Trichloroethylene (TCE) was negative for developmental toxicity after inhalation and oral gavage exposure of pregnant rats but fetal cardiac defects were reported following drinking water exposure throughout gestation. Because of the deficiencies in this latter study, we performed another drinking water study to evaluate whether TCE causes heart defects.

Methods: Groups of 25 mated Sprague Dawley rats consumed water containing 0, 0.25, 1.5, 500, or 1,000 ppm TCE from gestational day 1 — 21. TCE concentrations were measured at daily formulation, when placed into water bottles each day and when water bottles were removed from cages. Four additional mated rats per group were used for plasma measurements. At termination, fetal hearts were carefully dissected fresh and examined.

Results: All TCE concentrations were >90% of target when initially placed in water bottles and when bottles were placed on cages. All dams survived with no clinical signs. Rats in the two higher dose groups consumed less water/day than other groups but showed no changes in maternal or fetal weights. The only fetal cardiac observation was small (<1 mm) membranous ventricular septal defect occurring in all treated and water control groups; incidences were within the range of published findings for naive animals. TCE was not detected in maternal blood, but systemic exposure was confirmed by detecting its primary oxidative metabolite, trichloroacetic acid, although only at levels above the quantitation limit in the two higher dose groups.

Conclusions: Ingesting TCE in drinking water ≤1,000 ppm throughout gestation does not cause cardiac defects in rat offspring.

To read the full article, click here.