Cardiac teratogenesis of trichloroethylene and dichloroethylene in a mammalian model.
Recent epidemiologic studies have demonstrated a greater than expected number of pediatric patients with congenital heart disease in areas where drinking water was contaminated by halogenated aliphatic hydrocarbons. Trichloroethylene, trichloroethane and dichlorethylene were the principal contaminants in the groundwater. A previous study of chick embryos demonstrated that when injected into the air sacs of fertilized eggs trichloroethylene produced more than three times the number of cardiac defects that are found in control embryos. This mammalian study demonstrates similar effects of trichloroethylene and dichloroethylene when applied under provocative circumstances (that is, solutions delivered through a catheter into the gravid uterus from an intraperitoneal osmotic pump) to the developing rat fetus in utero during the period of organ differentiation and development. Furthermore, the effect is dose dependent for both agents. Although only a very small number of congenital heart anomalies (3%) were found in the control group, 9% and 12.5% were found in the lower dose trichloroethylene and dichloroethylene groups and 14% and 21% in the higher dose groups, respectively (p less than 0.05). A variety of cardiac defects were found. Dichloroethylene appears to be at least as great a cardiac teratogen as trichloroethylene even though it was administered at a 10-fold lower concentration. These agents appear to be specific cardiac teratogens because only a single noncardiac anomaly was found. This study in a rat model demonstrates a dose-dependent relation between fetal exposure to trichloroethylene and dichloroethylene in utero during the period of organogenesis and the appearance of a variety of congenital cardiac defects.
Dawson
B V
BV
Department of Internal Medicine, University of Arizona Health Sciences Center, Tucson.
Johnson
P D
PD
Goldberg
S J
SJ
Ulreich
J B
JB
D000014:Abnormalities, Drug-Induced; D000818:Animals; D004000:Dichloroethylenes / Q000008:administration & dosage / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005318:Fetal Heart / Q000187:drug effects; D006330:Heart Defects, Congenital / Q000139:chemically induced*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D014241:Trichloroethylene / Q000008:administration & dosage / Q000633:toxicity*
D004000:Dichloroethylenes; D014241:Trichloroethylene