"Environmental Perils: Pentachlorophenol, Tetrachlorohydroquinone, and Their Legacy"

Pentachlorophenol (PCP), a chlorinated aromatic organic compound, has served various agricultural purposes, including as a pesticide, fungicide, herbicide, and insecticide, since its introduction in 1936. However, its usage faced prohibition by the United States government in 1984 due to recognized carcinogenic and toxic properties. Despite this, approximately 36 million utility poles across the country remain treated with PCP, posing a continued risk of exposure. Exposure to PCP primarily occurs through direct volatilization from treated surfaces, leading to potential inhalation or skin contact. Its persistence in the environment, with a half-life of up to 200 days in water and varying durations in human tissue, contributes to its widespread presence. Recent studies have unveiled PCP's conversion into Tetrachlorohydroquinone (TCHQ), a more potent carcinogenic compound, through oxidative processes. TCHQ poses significant health risks, particularly evident in its heightened toxicity towards lung epithelial cells (A549) compared to PCP. Further investigations highlight TCHQ's activation of key cell death pathways, including apoptosis, pyroptosis, and necroptosis, along with increased expression of ZBP1, a regulator of PANoptosis. Additionally, TCHQ exposure prompts the upregulation of proinflammatory mediators like TLR-4, STAT3, CCL2, and IL-6. Our research aims to unravel the intricate molecular mechanisms underlying TCHQ-induced toxicity, particularly focusing on PANoptosome regulation in A549 cells. By gaining a thorough understanding of these pathways, we aim to reduce the health risks linked to PCP and TCHQ exposure and facilitate the development of safer alternatives for both humans and agricultural practices.