Exposing the Airway Surface to the Neonicotinoid Clothianidin Alters the Electrophysiological Properties of Human Airway Epithelia

The neonicotinoid clothianidin is used indoors and outdoors as an insecticide and extensively as a seed coating in agriculture where working solutions are prepared at 4000 ppm. Health effects of clothianidin are often studied under the assumption that ingestion is the exposure route, yet inhalation exposures are likely, given that clothianidin is sprayed and dust is resuspended. We studied the effect of airway exposure to clothianidin using human donor epithelia. Acute clothianidin doses greater than 50 ppm applied to the apical (airway-facing) surface resulted in decreased ion transport properties, specifically, decreased activity of the surface sodium channel, ENaC. During a 6 h 500 ppm clothianidin exposure, the permeability of airway epithelia to clothianidin rose from ∼4.2 × 10^-6 to ∼13.5 × 10^-6 cm·s^-1 without an increase in cell death, indicating a loss of barrier integrity. Respiratory precautions should be considered for those in proximity to aerosol-generating clothianidin application.