Trichloroethylene, trichloroacetic acid, and dichloroacetic acid: do they affect fetal rat heart development?
Trichloroethylene (TCE), trichloroacetic acid (TCA), and dichloroacetic acid (DCA) are commonly found as groundwater contaminants in many regions of the United States. Cardiac birth defects in children have been associated with TCE, and laboratory studies with rodents report an increased incidence of fetal cardiac malformations resulting from maternal exposures to TCE, TCA, and DCA. The objective of this study was to orally treat pregnant CDR(CD) Sprague-Dawley rats with large bolus doses of either TCE (500 mg/kg), TCA (300 mg/kg), or DCA (300 mg/kg) once per day on days 6 through 15 of gestation to determine the effectiveness of these materials to induce cardiac defects in the fetus. All-trans retinoic acid (RA) dissolved in soybean oil was used as a positive control. Soybean oil is commonly used as a dosing vehicle for RA teratology studies and was also used in this study as a dosing vehicle for TCE. Water was used as the dosing vehicle for TCA and DCA. Fetal hearts were examined on gestation day (GD) 21 by an initial in situ, cardiovascular stereomicroscope examination, and then followed by a microscopic dissection and examination of the formalin-fixed heart. The doses selected for TCA and DCA resulted in a modest decrease in maternal weight gain during gestation (3% to 8%). The fetal weights on GD 21 in the TCA and DCA treatment groups were decreased 8% and 9%, respectively, compared to the water control group and 21% in the RA treatment group compared to soybean oil control group. The heart malformation incidence for fetuses from the TCE-, TCA-, and DCA-treated dams did not differ from control values on a per fetus or per litter basis. The rate of heart malformations, on a per fetus basis, ranged from 3% to 5% for TCE, TCA, and DCA treatment groups compared to 6.5% and 2.9% for soybean oil and water control groups. The RA treatment group was significantly higher with 33% of the fetuses displaying heart defects. For TCE, TCA, and DCA treatment groups 42% to 60% of the litters contained at least one fetus with a heart malformation, compared to 52% and 37% of the litters in the soybean oil and water control groups. For the RA treatment group, 11 of 12 litters contained at least one fetus with a heart malformation. Further research is needed to quantify the spontaneous rates of heart defects for vehicle control rats and to explain the disparity between findings in the present study and other reported findings on the fetal cardiac teratogenicity of TCE, TCA, and DCA.
Fisher
J W
JW
Air Force Research Laboratory, Human Effectiveness Directorate, Wright-Patterson Air Force Base, Ohio, USA.
Channel
S R
SR
Eggers
J S
JS
Johnson
P D
PD
MacMahon
K L
KL
Goodyear
C D
CD
Sudberry
G L
GL
Warren
D A
DA
Latendresse
J R
JR
Graeter
L J
LJ
D000818:Animals; D003999:Dichloroacetic Acid / Q000008:administration & dosage / Q000633:toxicity*; D005260:Female; D005318:Fetal Heart / Q000002:abnormalities / Q000187:drug effects*; D020567:Fetal Weight / Q000187:drug effects; D008098:Litter Size / Q000187:drug effects; D008297:Male; D009929:Organ Size / Q000187:drug effects; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D014238:Trichloroacetic Acid / Q000008:administration & dosage / Q000633:toxicity*; D014241:Trichloroethylene / Q000008:administration & dosage / Q000633:toxicity*; D014874:Water Pollutants, Chemical / Q000633:toxicity
D014874:Water Pollutants, Chemical; D014241:Trichloroethylene; D014238:Trichloroacetic Acid; D003999:Dichloroacetic Acid