Age-Dependency of Blood-Brain Barrier Penetration by cis- and trans-Permethrin in the Rat

Permethrin (PER), a Type I pyrethroid, is the most widely used insecticide in domestic settings in the U.S. The overall objective of this study was to assess the efficiency of the blood-brain barrier (BBB) as an obstacle to the cis (CIS) and trans (TRANS) isomers of PER, and to determine whether its barrier function changes during maturation of the rat. Experiments were conducted to quantify brain uptake of CIS and TRANS in postnatal day (PND) 14, 21 and 90 Sprague-Dawley rats. The common carotid artery of anesthetized rats was perfused for 2 or 4 min with 1, 10 or 50 μM 14C-CIS or 14C-TRANS in 4% albumin. Brain deposition of each isomer was inversely related to age, with levels in the youngest animals >5 times those in adults. Brain uptake was linear over the 50-fold range of pyrethroid concentrations, indicative of passive, non-saturable BBB permeation. The extent of uptake of toxicologically-relevant concentrations of CIS and TRANS was quite similar. Thus, dissimilar BBB permeation does not contribute to the greater acute neurotoxic potency of CIS, but greater permeability of the immature BBB to CIS and TRANS may contribute to the increased susceptibility of pre-weanling rodents to the insecticides.