The toxicity and teratogenicity of mercuric mercury in the pregnant rat

Mercuric mercury (Hg2+), when injected IV into the pregnant Wistar rat, is retained mainly in the maternal compartment and uptake by the conceptuses is small. Thus if the dose is based on total body weight, the maternal body burden, particularly in late gestation, is greater than the whole body burden in the non-pregnant animal. The LD50 of Hg2+ (mg/kg total body weight), however, remains essentially constant (1.0-1.2 mg Hg2+/kg) throughout pregnancy. It seems, therefore, that the rat becomes more resistant to Hg2+ with increasing gestational age. This increased resistance does not correlate with differences in (a) the uptake of Hg2+ by the kidneys, the target organs of toxicity, (b) the severity of the histopathologically detected renal damage and (c) the inhibition of glomerular filtration. Biochemical measurements, however, suggest that kidney function may become less susceptible to Hg2+ as pregnancy advances from conception to near term. During mid-gestation the minimum effective teratogenic dose of Hg2+ (0.79 mg/kg total body weight) is high in relation to the maternal LD50 and the incidence of foetal malformations, mainly brain defects (23% in all live foetuses), is low. In rats of different gestational ages uptake of Hg2+ by the embryo/foetus at this dose level decreases sharply between day 12 and day 13. The teratogenic effects in the foetus and both the structural and functional damage to the maternal kidneys, however, are essentially the same in animals that are dosed with Hg2+ either immediately before, or immediately after these gestational ages.(ABSTRACT TRUNCATED AT 250 WORDS)