Excretion and disposition of [¹⁴C]carbaryl in pregnant, non-pregnant and foetal tissues of the rat after acute administration

Abstract

1. Non-pregnant or pregnant Sprague-Dawley rats on the 18th and 19th days of gestation were injected i.p. with a tracer dose (2.8 μCi/kg) of either [ring-¹⁴C]carbaryl or [carbonyl-¹⁴C]carbaryl. Distribution of total ¹⁴C was examined in foetal, maternal and nonpregnant rat tissues. Pregnancy alters the disposition and excretion of carbaryl.

2. Carbaryl crossed the placenta and was rapidly distributed in all foetal tissues. Highest concentrations were seen in foetal kidney. At 8h after injection, foetal brain, heart and lung all contained more ¹⁴C, on a weight basis, than their maternal organ counterparts. Elimination from the whole foetus was biphasic, and after 8h approx. 3% of the dose was still present in the whole foetus.

3. Significantly more ¹⁴CO₂ was exhaled by the pregnant rat during 8h than by nonpregnant. Urinary excretion of ¹⁴C after dosage with [ring-¹⁴C]carbaryl was significantly less in pregnant than in non-pregnant rats.

4. Kinetically, the tissue distribution of ¹⁴C from carbaryl or metabolites was biphasic in pregnant and non-pregnant animals. [¹⁴C]carbaryl concn. declined rapidly for 1 to 2h. After 2h the ¹⁴C levels from animals dosed with [ring-¹⁴C]carbaryl declined more slowly.

5. The pattern of ¹⁴C distribution was more complicated after injection of [carbonyl-¹⁴C]carbaryl. The ¹⁴C activity increased in the animal tissues after 2 h, in contrast to animals dosed with [ring-¹⁴C]carbaryl. Non-pregnant animals treated with [carbonyl-¹⁴C]carbaryl did not show a similar pattern of distribution. Carbamylated tissue proteins may, after time, release some bound carbonyl-¹⁴C label, causing the increase in ¹⁴C activity seen between 2 and 8 h. However, this does not necessarily imply uptake of the intact carbamate.