Is dieldrin-induced congenital inviability mediated by central nervous system hyperstimulation or by altered carbohydrate metabolism

Carbohydrate metabolism and central nervous sytem (CNS) intoxication were investigated as causes of dieldrin-induced congenital inviability. The 24-h LD50 was calculated using 5-day-old normal mice (CD-1 strain), fasted for 24 h, and gavaged with dieldrin. The LD50, 27 mg/kg, was 5% of the cumulative dose received by the dieldrin-treated, pregnant females. Acutely poisoned pups convulsed and tremored, inviable pups do not. Inviable pups were caesarian delivered on day 18 from dieldrin-treated females (p.o., 2 mg/kg per day, from day 6 to day 18), and aspects of carbohydrate metabolism were measured 0, 19, and 24 h postdelivery. Inviable and control pups weighed the same at all times but the liver weight of inviable pups was reduced by 0, 8, and 21%, at 0, 19, and 24 h, respectively (control: 61, 48, and 41 mg/g body weight). The inviable pups were hypoglycemic at delivery (0.69 vs. 0.95 mg/mL plasma in the controls), at 19 h (0.53 vs. control values of 0.94 mg/mL), and were aglycemic at 24 h (normal pups: 0.32 mg/mL). Liver glycogen, normal in inviable pups at birth (control: 71 mg/g liver), was reduced by 38% at 19 h (control: 19 mg/g) and by 77% at 24 h (control: 4.5 mg/g). Cardiac glycogen was reduced in treated pups only at 24 h (5.5 mg/g vs. control levels of 11.0 mg/g). Muscle glycogen was also reduced only at 24 h (2.2 mg/g vs. control levels of 5.4 mg/g). Prenatal dieldrin did not affect blood lactate, pyruvate, or urea, nor did it alter hepatic lactate dehydrogenase (LDH) or fructose diphosphatase (FDPase) activities. It is concluded that the inviability is not caused by CNS stimulation; it is associated with congenital hypoglycemia, enhanced glycogenolysis, and apparently normal gluconeogenesis.