HISTOLOGICAL-CHANGES IN RAT EMBRYONIC BLOOD-CELLS AS A POSSIBLE MECHANISM FOR VENTRICULAR SEPTAL-DEFECTS PRODUCED BY AN N-PHENYLIMIDE HERBICIDE

An N-phenylimide herbicide, S-53482, inhibits protoporphyrinogen oxida se, an enzyme common to chlorophyll and heme biosynthesis, and produce s embryolethality, teratogenicity [mainly ventricular septal defects ( VSD) and wavy ribs], and growth retardation in rats. In order to eluci date the mechanism of the developmental toxicity, in particular VSD, e ffects of the herbicide on rat embryonic blood cells were investigated histologically at the light and electron microscopic levels at 6, 12, 24, 36, and 48 h after oval administration of the chemical to pregnan t rats on day 12 of gestation, the most sensitive day for toxicity. El ectron and light microscopy demonstrated mitochondrial lesions, includ ing abnormal iron deposits that were probably due to inhibition of hem e biosynthesis, in erythroblasts derived from the yolk sac, Subsequent ly, degeneration of these erythroblasts occurred followed by erythroph agocytosis. Histologically hearts from exposed embryos had a thin vent ricular wall, which may reflect a compensatory reaction to a loss of e mbryonic blood cells. Thus, the herbicide may induce VSD due to hemato logical dysfunction caused by the inhibition of heme biosynthesis rath er than by direct injurious effects on the heart. (C) 1997 Wiley-Liss, Inc.