Mechanistic insights into the neurotoxicity of Isothiazolinone biocides in human neuronal cells 2026,

Sly Saint

Sly Saint

Senior Member (Voting Rights)

Abstract​

Isothiazolinones (ITs) are biocides with various biological properties and are hence used across different industries. They are commonly found in consumer products, disinfectants, and household cleaners. Although effective, ITs have been reported to exhibit neurotoxic effects in mouse- and rat-derived cells. However, the neurotoxicity of ITs in humans remains underexplored. In this study, we compared the neurotoxicity of four commonly used ITs—1,2-benzisothiazol-3(2H)-one (BIT), 2-methyl-4-isothiazolin-3-one (MIT), 2-n-octyl-4-isothiazolin-3-one (OIT), and 4,5-dichloro-2-octyl-4-isothiazolin-3-one (DCOIT)—in human-derived neuronal cells. The viability of cells exposed to these ITs decreased the most with DCOIT, followed by OIT, BIT, and MIT, respectively.

The ITs induced changes in neurite outgrowth and the expression of neurodevelopmental genes at concentrations considered noncytotoxic. RNA-sequencing revealed the regulation of the expression of genes associated with neurodevelopmental processes; ANXA2 and SYTL5 were upregulated following treatment with all four ITs, indicating their potential as biomarkers for IT-induced neurotoxicity.

A Kyoto Encyclopedia of Genes and Genomes pathway analysis indicated an association between all the tested ITs and neurodegenerative diseases. BIT caused the most pronounced changes in neurodevelopmental gene expression, with the highest potential for neurotoxicity. These findings provide insights into the potential neurotoxicity of ITs and highlight the need for revised safety assessments and regulatory strategies to address the risks associated with human exposure.

 
see also
In Vitro Neurotoxicity of Methylisothiazolinone, a Commonly Used Industrial and Household Biocide, Proceeds via a Zinc and Extracellular Signal-Regulated Kinase Mitogen-Activated Protein Kinase-Dependent Pathway

Abstract​

Neurodegenerative disorders in humans may be triggered or exacerbated by exposure to occupational or environmental agents. Here, we show that a brief exposure to methylisothiazolinone, a widely used industrial and household biocide, is highly toxic to cultured neurons but not to glia. We also show that the toxic actions of this biocide are zinc dependent and require the activation of p44/42 extracellular signal-regulated kinase (ERK) via a 12-lipoxygenase-mediated pathway. The cell death process also involves activation of NADPH oxidase, generation of reactive oxygen species, DNA damage, and overactivation of poly(ADP-ribose) polymerase, all occurring downstream from ERK phosphorylation. The toxic effects of methylisothiazolinone and related biocides on neurons have not been reported previously. Because of their widespread use, the neurotoxic consequences of both acute and chronic human exposure to these toxins need to be evaluated.



Neurotoxic Concerns Associated with Methylisothiazolinone​


When exploring the effects of chemicals on our health, we venture into a landscape of complex interactions and diverse outcomes. Methylisothiazolinone (MI) has come under scrutiny for its potential neurotoxic effects. This section dives into the neurotoxic concerns associated with MI, backed by research studies and expert analyses to provide a comprehensive understanding.

The crux of the neurotoxicity debate centers on how MI interacts with the nervous system. Neurotoxicity refers to damage to the brain or peripheral nervous system caused by exposure to natural or man-made toxic substances. These substances can disrupt the normal activity of the nervous system, leading to a multitude of adverse health effects ranging from acute symptoms like headaches and dizziness to long-term consequences like memory loss and reduced cognitive function.

Research Studies and Findings

One pivotal study that brought attention to the neurotoxic potential of MI was conducted by researchers at the University of Pittsburgh. In this study, published in the journal Toxicological Sciences, scientists discovered that MI could lead to neuronal cell death in rats, suggesting a possible mechanism through which MI could exert neurotoxic effects in humans. The study highlighted that even low levels of MI exposure could disrupt neuronal cells, which are critical for the functioning of the nervous system.

Further supporting this notion, a 2016 study in the journal Neurotoxicology investigated the effects of MI on the developing nervous system. It reported that prenatal exposure to MI resulted in altered neurodevelopmental outcomes in offspring, indicating the potential for MI to interfere with brain development.

Expert Opinions

Experts in the field of toxicology and neurology have weighed in on the findings, expressing concern over the potential for MI to cause neurotoxic effects. The consensus is that while more research is needed to fully understand the extent of MI's impact on the nervous system, the existing evidence warrants caution. Toxicologists advocate for minimizing exposure to MI, especially in vulnerable populations such as pregnant women and young children, to mitigate potential risks.
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Abnormal visual processing and increased seizure susceptibility result from developmental exposure to the biocide methylisothiazolinone​


Methylisothiazolinone, A Neurotoxic Biocide, Disrupts the Association of Src Family Tyrosine Kinases with Focal Adhesion Kinase in Developing Cortical Neurons​


 
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