Mechanisms of Neurotoxicity Associated with Exposure to the Herbicide Atrazine

Abstract

Atrazine is an herbicide commonly used on crops to prevent broadleaf weeds. Atrazine is an endocrine-disrupting chemical mainly targeting the neuroendocrine system and associated axes, especially as a reproductive toxicant through attenuation of the luteinizing hormone (LH). Current regulatory levels for chronic exposure are based on no observed adverse effect levels (NOAELs) of these LH alterations in rodent studies. Atrazine has also been studied for its effects on the central nervous system and neurotransmission. The European Union (EU) recognized the health risks of atrazine exposure as a public health concern with no way to contain contamination of drinking water. As such, the EU banned atrazine use in 2003. The United States recently reapproved atrazine’s use in the fall of 2020. Research has shown that there is a wide array of adverse health effects that are seen across multiple models, exposure times, and exposure periods leading to dysfunction in many different systems in the body with most pointing to a neuroendocrine target of toxicity. There is evidence of crosstalk between systems that can be affected by atrazine exposure, causing widespread dysfunction and leading to changes in behavior even with no direct link to the hypothalamus. The hypothetical mechanism of toxicity of atrazine endocrine disruption and neurotoxicity can therefore be described as a web of pathways that are influenced through changes occurring in each and their multiple feedback loops with further research needed to refine NOAELs for neurotoxic outcomes.

DNA Double-Strand Breaks Induced in Human Cells by 6 Current Pesticides: Intercomparisons and Influence of the ATM Protein

“…Here, we examined whether a model based on the nucleo-shuttling of the ATM protein is also relevant for the exposure to pesticide. To this aim, human skin fibroblast and brain astrocyte cells from different RIANS statuses were exposed to six current pesticides of domestic and environmental interest, namely gamma-hexachlorocyclohexane (lindane, HCH) [ 30 , 31 ], atrazine (ATR) [ 32 ], glyphosate (GBH) [ 33 ], permethrin (PER) [ 34 ], pentachlorophenol (PCP) [ 35 , 36 ], and thiabendazole (TBZ) [ 37 ] ( Table 1 ), and subjected to immunofluorescence, with the RIANS biomarkers as endpoints. The general objective of this paper is to better identify, document, and quantify the molecular steps of the individual response to pesticides that may lead to cellular death, whatever its form.…”

Occurrence of Banned and Currently Used Herbicides, in Groundwater of Northern Greece: A Human Health Risk Assessment Approach

“…Recent studies showed that ATR is an endocrine disruptor causing disfunctions at normal human reproduction and development for both genders [ 16 ]. Furthermore, ATR was correlated to potential neurological and liver problems [ 5 , 17 ].…”

Effects of Subtoxic Concentrations of Atrazine, Cypermethrin, and Vinclozolin on microRNA-Mediated PI3K/Akt/mTOR Signaling in SH-SY5Y Cells

“…Gonadal hormones are fundamental for the CNS’ activity during maturity and even senescence not only for their role in the neurogenesis processes, but also because they can exert a protective activity counteracting the insurgence of neurodegenerative disorders [ 14 ]. Moreover, EDC exposure may impact neurotransmitters also outside of the hypothalamus, which is known as a neuroendocrine structure [ 15 ]. Exposure to EDCs, as atrazine, may deregulate numerous pathways resulting in the multiple different health outcomes including neurotoxicity, which has been waived from inclusion in the most recent human health risk assessments [ 16 ].…”