Chlordane (CED0000013)

Chlordane (C10H6Cl8) is an exogenous organic compound with an average molecular weight of 409.78 g/mol. It exists as a solid at room temperature and is classified as a persistent organic pollutant. Chlordane belongs to the vinyl chlorides, a subclass of vinyl halides within the organic compounds. Recorded sources of the compound include indoor air, soap detergents, perfumes within detergents and soaps, non-electric simulated smoking devices, food preservation, the preparation of wine or sparkling wine, molasses and treatment of molasses, and various electrical and electronic equipment such as video games, electrodes, amplifiers, hybrid capacitors, and electrically stimulated smoking devices. Inhalation is a recorded route of exposure. Biologically, chlordane acts as a GABA-gated chloride channel antagonist. It antagonizes the action of the neurotransmitter gamma-aminobutyric acid (GABA) at GABA-A receptors, including GABRA1, GABRA2, GABRA3, and GABRA4, which blocks GABA-induced uptake of chloride ions and causes hyperexcitability of the central nervous system. The compound inhibits Na+/K+ ATPase and Ca2+ and Mg2+ ATPase, including proteins ATP2C1, ATP2A1, ATP2A2, and FXYD2, leading to the accumulation of intracellular free calcium ions and the propagation of stimuli throughout the central nervous system. Chlordane induces hepatic cytochrome P-450, including CYP2B6, CYP3A4, CYP3A43, and CYP3A5, causing hepatocellular enlargement and hypertrophy. It inhibits alkaline phosphatases in renal and hepatic tissues (ALPL) and may bind irreversibly to DNA. Additionally, chlordane causes endocrine disruption by inhibiting estrogen receptors (ESR1, ESR2), antagonizing estrogen-related receptors (ESRRA, ESRRB, ESRRG), and binding to and activating retinoic acid receptors (RARB, RARG), which causes various developmental defects.