Oral mucosa changes associated with chronic oral and inhalation exposure to 2,4-dichlorophenoxiacetic acid (2,4-D) in Wistar rats

Toxicol Res (Camb). 2020 Nov 24;9(6):746-757. doi: 10.1093/toxres/tfaa085. eCollection 2020 Dec.

Abstract

The respiratory tract and the oral mucosa are the first areas contaminated by pesticides. The herbicide dichlorophenoxyacetic acid (2,4-D) is a widely used pesticide across the world for both crops and gardens. The aim of this study was to evaluate oral mucosal damage after an experimental simulation of chronic oral and inhalational environmental exposure to 2,4-D formulation. Eighty male Wistar rats were exposed to three distinct concentrations of 2,4-D formulation (low-187.17 mg/m3; medium-313.31 mg/m3; and high-467.93 mg/m3). Oral exposure (through contaminated feed) or inhalation exposure lasted 6 months. Rat tongues were collected for cyto- and histopathology. There was a difference between exposure groups in the intensity of tissue congestion. Most rats exposed to 2,4-D presented mucosal inflammation at both cytology and histology (P < 0.05). Hyperkeratosis only occurred in rats exposed orally at the high concentration. There was an increase in the number of nucleoli-organizing regions in the dorsal epithelium as the 2,4-D concentration increased (P < 0.001). The inhalation route was more associated with increased mitosis figures and nucleoli-organizing region count (P < 0.05). Chronic oral and inhalation exposure to high concentrations of 2,4-D formulation caused an increase in the proliferation rate and thickness of the tongue epithelium and stimulated the inflammatory response in the tissue.

Keywords: environmental exposure; leukoplakia; oral; oral mucosa; oral neoplasms; pesticide exposure.