Critical review of the epidemiologic literature regarding the association between congenital heart defects and exposure to trichloroethylene

The most recent Integrated Risk Information System review of trichloroethylene (TCE; CAS# 79-01-6) has suggested that congenital heart defects (CHD) are a critical endpoint associated with exposure to this solvent. This conclusion was drawn, at least partly, from epidemiologic data, including several relatively recent studies. The current article critically reviews this epidemiologic literature, focusing on study quality and consistency. Literature searches uncovered approximately a dozen studies that specifically addressed associations between TCE and congenital malformations in eight populations. Four of these reported positive associations between TCE and heart defects, with significant relative risks as high as 5-6 in some subgroups. However, each of the positive studies had substantial design or analytical flaws that could easily explain the results, thereby limiting the conclusions that can be drawn. Five studies found no positive association with TCE, and several of these reported substantially fewer cases than expected despite similar/higher exposures compared to positive studies, further detracting from causal conclusions. Overall, this epidemiologic literature provides no substantive or consistent evidence linking TCE to CHD.