Submit Manuscript | http://medcraveonline.com Introduction Modern manufacturing practices have relied on plastics to improve the physical properties of consumer goods. In turn, plastic manufacturing technologies have evolved to modify the characteristics of their products. Phthalates are widely used as plasticizers to increase the fexibility and durability of plastic products. Among the most commonly used phthalates in consumer products, are di-(2- ethylhexyl) phthalate (DEHP), diisononyl phthalate (DINP), dibutyl phthalate (DBP), diisodecyl phthalate (DIDP), di-n-octyl phthalate (DnOP), and benzyl butyl phthalate (BBP or BzBP). DEHP being the most used phthalate, which has been widely employed in a variety of items, including construction materials, fooring, pipes, food packaging, and medical devices. 1-3 In addition, using microwaves to prepare food or drinks can increase the leaching of phthalates from containers. 4 Furthermore, they are frequently released by industrial waste, manufacturing runoff, solid waste, sewage drainage, and the degradation of phthalate-containing items. 5 These chemicals are commonly found to have poor water solubility and diffculty evaporating, as well as low to moderate mobility in soils and aquatic environments, allowing them to stay in surrounding environments for prolonged periods of time. 6 Individual molecules can spread in a variety of ways after entering the environment; for example, they can bind to dust particles and travel large distances through the air. A considerable portion of particles, however, falls into bodies of water, posing the biggest threat to aquatic life. 5 In terms of health impact, these compounds have been shown to breach the placental barrier and have an effect on human development, particularly the reproductive and endocrine systems. Due to its ubiquity in the environment, DEHP has raised concerns pertaining to continuous exposure on the human population and the formation of toxic metabolites such as 2-ethyl-1-hexanol (2EH) and mono-(2- ethylhexyl) phthalate (MEHP) during the degradation of DEHP. 7 Some microorganisms that can degrade di-ester plasticizers can also be sources of 2-EH. 4 The brain has been determined to be at risk of DEHP exposure. This phthalate can affect neurodevelopment and lead to teratogenic anomalies by disrupting normal fetal brain development, as DEHP can cross the placenta and enter the fetal circulation. 8-10 In postnatal rats, post-DEHP exposure was found to be harmful to the development of the hippocampus (large part of the brain that is involved in memory and spatial navigation) in males but not females. 11 In addition to rats, DEHP neurotoxicity has been observed in Caenorhabditis elegans, a nematode. DEHP exposure can result in an intracellular accumulation of ROS, which causes neurotoxicity, it can also inhibit the expression of many genes required for AFD sensory neuron differentiation and function (necessary for the thermosensory response). 11 Given the high sensitivity of zebrafsh for the analysis of novel compounds, as well as a screening model for detecting toxicity and drug effcacy, the zebrafsh model is being commonly used as a neurotoxicological model. 12-14 Pharm Pharmacol Int J. 2022;10(6):218‒223. 218 ©2022 Acevedo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and build upon your work non-commercially. Mechanism involved in cell death induced by DEHP (Di-ethylhexyl phthalate) on primary brain cells from Zebrafsh (Danio rerio) Volume 10 Issue 6 - 2022 Andy Acevedo, 1 Alejandra Rivera, 2 Karoline Ríos, 1 Roland González, 3 Aysha Díaz, 1 Beatriz Zayas 1 1 School Science, Technology & Environment, Ana G. Méndez University, USA 2 Morningside Graduate School of Biomedical Sciences, UMASS Chan Medical School, USA 3 Department of Biological Sciences, Toxicology Graduate Program, North Carolina State University, USA Correspondence: Beatriz Zayas, Ana G. Méndez University, School Science, Technology & Environment, San Juan, Puerto Rico, USA, Email Received: December 01, 2022 | Published: December 15, 2022 Abstract Human and ecological exposure to chemical contaminants continue to increase given anthropogenic activities and sources. Phthalates are among the most persistent toxic chemicals found in aquatic systems. Phthalates belong to a family of chemical compounds that are heavily used in global manufacturing, distinguished for being able to provide durability and elasticity to plastic products, with poor water solubility and low evaporation. In terms of health impact, these compounds have been shown to breach the placental barrier having effect on human development and neurodegeneration. The main purpose of our study has been to assess the neurotoxicity of phthalates implementing the zebrafsh (Danio rerio) model to determine the cell death induction of DEHP on brain cells. For many years, the zebrafsh embryonic model has been used to study vertebrate development. Our study, in contrast, used adult zebrafsh to resemble mature species that can be continuously exposed to low concentrations of DEHP. To assess the neurotoxicity, brain tissue from zebrafsh was extracted via dissection, and primary neural cells dissociated to obtain primary cell subcultures. The neural cells where subsequently exposed to DEHP (Di-ethylhexyl phthalate) at concentrations from 10µM to 100µM for 48 hours to observe cell growth inhibition (GI50). The results indicate neural cell death at a GI50 of 62.9 µM. Apoptosis induction, caspase activation, mitochondrial membrane damage as well as autophagy cell death were analyzed to identify DEHP cell death mechanism at the GI50 concentration. In conclusion, this study clearly demonstrated that DEHP can induce apoptosis cell death on zebrafsh neural brain cells in culture through the activation of an intrinsic apoptotic pathways with caspases 3 and 7 activation as well as autophagic pathway and mitochondrial damage. The presence of phthalates as well as other chemical contaminants on aquatic environments needs to be earnestly controlled in order to reduce neurotoxicity to aquatic species as well as human. Keywords: neurotoxicity, ecotoxicology, phthalates, cell death mechanism, zebrafsh, apoptosis Pharmacy & Pharmacology International Journal Research Article Open Access