Health & Environmental Research Online (HERO)


Print Feedback Export to File
730423 
Journal Article 
Abstract 
Low-dose trichloroethylene exposure during valvuloseptal morphogenesis causes ventricular septal defects in hatched chicks 
Rufer, ES; Hacker, T; Lough, J; Smith, SM 
2008 
1 
Toxicologist
ISSN: 0731-9193 
102 
S-1 
314 
English 
Trichloroethylene (TCE) is a common groundwater contaminant in the U.S.
Several studies associate gestational TCE exposure with congenital heart defects;
however, this conclusion is controversial and the basis for TCE’s cardiac teratogenicity
is not well understood. We previously showed that chick embryos exposed
to an in ovo concentration of ~8 ppb TCE during valvuloseptal morphogenesis
have reduced cardiac output, hyperplastic cushions and increased mortality; exposure
during the earlier cardiac specification period had little adverse effect. To further
narrow this critical window, we exposed in ovo embryos during valvuloseptal
morphogenesis to a single TCE level (mean egg concentration 0.4 – 4000 ppb) applied
at a single developmental time point (stages 13, 15, 17, 20 or 24; 2-4.25 days’
incubation). Stages 15 and 17 were the most sensitive to TCE and those embryos
had <57% survival to stage 30 (6.5 days’ incubation), suggesting that the early
cushion period represents the critical window of TCE sensitivity. These embryos
had a biphasic dose response to TCE with the greatest mortality at ~8 ppb, a level
just above the maximum contaminant level for TCE in human drinking water.
Exposure at the other stages had lesser effects on mortality. Hatched chicks exposed
to ~8 ppb TCE at stage 17 had a significant incidence (38%; p<0.01; n=16) of high
ventricular septal defects (VSDs) as detected by transthoracic echocardiography
and confirmed by dissection; control injected chicks had no VSDs (n=14). These
data independently confirm that TCE is a cardiac teratogen for chick and identify
early valvuloseptal morphogenesis as a critical window for this common groundwater
contaminant. (Supported by NIH award ES11738 and T32 ES07015) 
Society of Toxicology 47th Annual Meeting 
Seattle, WA 
March 16-20, 2008