Functional impairment of blood-brain barrier following pesticide exposure during early development in rats

1 The effect of certain pesticides on the functional integrity of the devel oping blood-brain barrier (BBB) was studied following single and repeated e xposure, and after subsequent withdrawal in rats. 2 Ten-day-old rat pups exposed orally to quinalphos (QP, organophosphate), cypermethrin (CM, pyrethroid) and lindane (LD, organochlorine) at a dose of 1/50th of LD50, showed a significant increase in the brain uptake index (B UI) for a micromolecular tracer, sodium fluorescein (SF), by 97, 37 and 72% , respectively, after 2 h, Residual increases in the BUI were found even af ter 3 days of the single treatment of QP (28%) and LD (23%). 3 Repeated exposure for 8 days (postnatal days (PND) 10-17) with QP, CM and LD increased the BBB permeability by 130, 80 and 50%, respectively. Recove ry from these changes was complete in QP and LD-treated animals after 13 da ys (PND 18-30) of withdrawal. However, CM showed persistent effects that we re normalized only after 43 days (PND 18-60) of withdrawal. 4 A single dose reduced to 1/100th of LD50 also increased BUI in 10-day-old rat pups following QP (20%) and CM (28%) exposure at 2 h, 5 An age-dependent effect of these pesticides was evident from the study sh owing higher magnitude of BUI changes in 10-day-old rats as compared to tha t in 15-day-old rats. Furthermore, adult rats did not show any effect on BB B permeability even at a higher dose (1/25th of LD50) of these pesticides g iven alone or in combination with piperonyl butoxide (600 mg/kg, i.p.) for 3 consecutive days. 6 This study showed that developing BBB is highly vulnerable to single or r epeated exposure of certain pesticides, The observed persistent effects dur ing brain development even after withdrawal of the treatment may produce so me neurological dysfunction at later life as well.