Assessment of the developmental toxicity and placental transfer of 1,2-dichloroethane in rats.
This study evaluates the developmental toxicity and placental transfer of 1,2-dichloroethane (DCE) in rats. Sprague-Dawley rats were given 0-2.4 mmol DCE kg-1 day-1 by gavage, or were exposed for 6 hr per day to 0-300 ppm DCE by inhalation, from Day 6 to 20 of gestation. Maternal toxicity was observed after inhalation exposure to 300 ppm DCE and oral administration of 2.0 or 2.4 mmol DCE kg-1. There was no evidence of altered growth nor teratogenic effects after either inhalation or oral administration of DCE at any concentration tested. The time course disposition of 14C was examined over a 48-hr period in 12- and 18-day pregnant rats after a single oral dose of 1.6 mmol [14C]DCE kg-1. Peak concentrations of radiocarbon occurred between 2 and 4 hr postdose. Conceptus (Day 12) and fetal (Day 18) tissues accounted for 0.06 and 0.4% of the administered dose, respectively. Up to 4 hr, levels of radiocarbon in placenta and fetus were slightly less than in maternal plasma of 18-day pregnant rats and were two to five times higher at later periods. At 2 hr, unchanged DCE accounted for most of radioactivity (78-86%) recovered in maternal plasma, placenta, and fetus. Acidic metabolites and radioactivity bound to macromolecules increased up to 24 hr (0.01 mumol-eq DCE g-1) in either placental or fetal tissues. Thereafter, their levels declined more slowly than those in the maternal plasma. Results from this developmental toxicity study in rats confirm embryonic exposure to radiocarbon associated with [14C]DCE and/or its metabolites and has demonstrated the lack of observable teratogenic effects.
Payan
J P
JP
Institut National de Recherche et de Sécurité, Vandoeuvre, France.
Saillenfait
A M
AM
Bonnet
P
P
Fabry
J P
JP
Langonne
I
I
Sabate
J P
JP
D000280:Administration, Inhalation; D000284:Administration, Oral; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D004622:Embryo, Mammalian / Q000737:chemistry; D005314:Embryonic and Fetal Development / Q000187:drug effects*; D005025:Ethylene Dichlorides / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics / Q000633:toxicity*; D005260:Female; D005333:Fetus / Q000002:abnormalities / Q000737:chemistry; D008297:Male; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D011849:Radioactive Tracers; D051381:Rats; D017207:Rats, Sprague-Dawley; D012098:Reproduction / Q000187:drug effects; D014018:Tissue Distribution
D005025:Ethylene Dichlorides; D011849:Radioactive Tracers