Role of the blood‐brain barrier in limiting CNS uptake of pyrethroid insecticides: findings with hCMEC cells as a proxy (1064.14)

Abstract

Pyrethroids, the most widely‐used insecticides in the U.S., generally exhibit low neurotoxicity in humans and other mammals. Kinetic studies of the pyrethroid deltamethrin (DLM) have revealed that levels of the hydrophobic, neurotoxic parent compound are <20% of blood levels in rats. Experiments with hCMEC cells, a human brain endothelial cell line, were undertaken as part of an effort to understand the BBB’s role in limited CNS deposition of DLM. hCMEC cells were grown in EGM‐2 medium, seeded in T‐75 flasks, and allowed to grow to confluency within 3‐4 days. DLM uptake by the cells was concentration‐dependent, indicating a saturable process. Cyclosporin inhibited uptake, suggesting an active influx transport process. Increasing the amount of human serum albumin reduced the free/unbound fraction of DLM, which correlated with decreased cellular uptake. In conclusion: DLM’s pronounced plasma protein/lipoprotein binding (~90+%) appears to limit its availability for BBB passage; and a BBB influx transporter of low capacity and low affinity contributes to hCMEC uptake.Grant Funding Source: Council for the Advancement of Pyrethroid human Risk Assessment (CAPHRA)