Developmental Exposure to Chlorpyrifos Modulates Pulmonary Function in Adult Rats

Abstract

Acute OP intoxication is well known to cause bronchoconstriction and increase airway secretions via inhibition of acetylcholinesterase (AChE). However, occupational and environmental exposures to organophosphorus pesticides (OP) at levels not expected to significantly inhibit AChE are associated with increased incidence of asthma and other pulmonary diseases. In support of the epidemiological data, acute exposure of adult guinea pigs and rats to OPs at levels that do not inhibit AChE in the lung, blood or brain have been shown to cause airway hyperreactivity (AHR). More recently, epidemiologic studies have suggested that exposure to OPs during development is also associated with increased risk of asthma. To address whether developmental OP exposures are also causally linked to AHR, we measured respiratory physiology in young adult rats exposed to the OP chlorpyrifos (CPF) at 0, 0.1, 0.3 and 1 mg/kg/d (sc) from postnatal days 1–4. Using a Flexivent mechanical ventilator, airway responsiveness to electrical stimulation of the vagus nerves was quantified. Preliminary findings suggest that adult female rats exposed developmentally to CPF exhibit significantly decreased airway resistance and elastance in response to electrical vagal stimulation relative to vehicle controls. In contrast, male rats exposed developmentally to CPF did not exhibit any changes in airway resistance and elastance in response to electrical vagal stimulation relative to vehicle controls. These results suggest that early life exposure to CPF triggers atypical expansion of the large and small conducting airways in the lungs of female, but not male rats. These findings will significantly advance our understanding of the role of OPs in respiratory diseases, and ultimately, inform risk assessments used to protect human health and safety. The United States Environmental Protection Agency currently uses acetylcholinesterase inhibition as a biomarker of OP toxicity; however, OPs modulate lung function at levels significantly lower than those that inhibit AChE. The findings of this research could potentially provide a scientifically rational basis for reassessment of exposure limits for OPs as well as help direct future research on therapeutic agents for treating/respiratory disorders in OP‐exposed children and adolescents.Support or Funding InformationWork was supported by the NIH (R01 ES017592 to PL and pilot project funding to ACG from P30 ES023513).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.