Trichloroethylene in drinking water throughout gestation did not produce congenital heart defects in Sprague Dawley rats

Abstract

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.

Keywords: TCE; toxicokinetics; trichloroacetic acid; ventricular septal defects.

Figure 1

An 11.5 L amber glass bottle used for batch formulation preparation is shown fitted with a fabricated siphon valve to ensure that formulations are prepared in a closed system (a). The bottle was purged with nitrogen; it was then capped and sealed with a foil liner and silicone septum. Note the two cannulas, each with its own siphon valve. Each siphon valve had an inlet and an outlet outfitted with a spigot (b), whereby the inlet valve pumped nitrogen into the bottle while the TCE‐containing water formulation was removed via the outlet valve. TCE, trichloroethylene

Figure 2

Mean water consumption during gestation. Values based on measured concentrations of TCE in dosing formulations prior to transfer to water bottles and the amount of water consumed; it does not account for the loss of TCE from the drinking water when given to the animals in water bottles over the 24‐hr exposure period. TCE, trichloroethylene

Figure 3

Mean body weights during gestation

Figure 4

Mean body weight gains during gestation

Figure 5

This diagram illustrates a coronal section through a postnatal heart. The muscular ventricular septum, shown in section, forms the medial walls of the right and left ventricles. Note that the muscular septum (pink) contributes more than 90% of the vertical height of the ventricular septum. The membranous portion of the ventricular septum (red) is the small thin‐walled structure near the floor of the atria. In the present study, the reported VSDs in the TCE exposed groups were all located in the membranous ventricular septum and were smaller than 1 mm in diameter. The right and left atria are separated by the interatrial septum (yellow), which is attached to the floor of the atria. TCE, trichloroethylene; VSDs, ventricular septal defects