Application of a human bronchoepithelial-air-liquid interface model to assess respiratory hazard of VOCs using a benchmark concentration modeling approach.

OBJECTIVE

Volatile organic compounds (VOCs) are prevalent in both indoor and outdoor environments and have been linked to health effects. This study aimed to assess VOC-induced effects on the respiratory epithelium using an in vitro human bronchial epithelial air-liquid interface (ALI) model.

METHODS

A human bronchial epithelial cell line, 16HBE, was cultured at ALI and exposed to relevant concentrations of two representative VOCs, acrolein or formic acid, and matched filtered air (control) in a CelTox exposure system for two hours to replicate an acute inhalation exposure. Cells were allowed to recover for 24 h before cell lysate and culture media were collected for analysis.

RESULTS

Cytotoxicity, based on LDH activity, significantly increased at the highest doses tested for both VOCs. A dose-dependent increase in barrier permeability was observed for confluent cells exposed to acrolein and formic acid. Acrolein and formic acid exposure induced IL-8, TNFα, and HMOX-1 expression, genes indicative of proinflammatory signaling and oxidative stress, respectively. Formic acid, but not acrolein, exposure also increased expression of PINK1, a gene indicative of mitophagy. Benchmark concentration (BMC) modeling of in vitro acrolein data yielded a BMCL (benchmark concentration lower confidence limit) that substantiates the stringency of OSHA's 8-hour permissible exposure limit (PEL). In contrast, BMC modeling of in vitro formic acid data produced BMCLs below existing regulatory exposure thresholds.

CONCLUSION

Collectively, these findings demonstrate that this model is a plausible in vitro tool to investigate VOC-induced effects on the airway and supports its utility in VOC safety evaluation.