Formaldehyde neurotoxicity: Effects on the mammalian brain, cognitive function, and neurodegenerative risk. A scoping review

Aqueous formaldehyde (FA) solution, known as formalin, is currently the primary agent used for preserving tissue samples and anatomical specimens. Formaldehyde is widely used in laboratories and the chemical industry; it also occurs as an air pollutant and endogenous cellular metabolite. The potential carcinogenic effects of formalin on the respiratory tract are well documented. A less recognized consequence of occupational exposure to FA is its detrimental effect on the central nervous system (CNS) and brain function. A literature review was conducted to investigate the effects of FA on the brain. Five databases were searched: PubMed, Web of Science (WoS), Embase, ScienceDirect, and Google Scholar. To describe the effects of FA exposure and endogenous FA generation, 35 relevant publications were collected and analyzed. The literature review demonstrated that inhalation is the most common route of FA exposure. Several studies have shown that FA may cause hippocampal damage, disrupt melatonin secretion, and induce a wide range of cognitive disorders with varying characteristics and severity. These disorders include memory impairment, disturbances in balance and spatial orientation, learning difficulties, sleep disturbances, impaired judgment, and prolonged reaction times to stimuli. Increased endogenous FA concentration has also been associated with a higher risk of neurodegenerative diseases, such as Alzheimer's disease (AD) and amyotrophic lateral sclerosis. The literature analysis demonstrated the high neurotoxicity of FA, which may lead to numerous neuropsychiatric disorders. We aim to draw attention to the risks associated with the routine use of formalin, particularly among anatomists and pathologists, and to encourage consideration of less harmful alternative preservation agents.