Cell Death Effects of the Phthalate 2-Ethyl-1-Hexanol on Human Linfoblast Cells

Abstract

Phthalates have been used in a wide variety of consumer goods. Their versatility as plasticizers has translated into worldwide use in a vast array of consumer products. These compounds can leach into matrices, such as food and liquids that can be routed for human exposure. One of the most used phthalates is Diethylhexyl phthalate (DEHP). Diethylhexyl phthalate and its metabolite 2-ethyl-1-hexanol (2-EH) have demonstrated biological effects which merit further evaluation. In this work, we expand on our previous work with DEHP and screen the 2-EH metabolite for different cell death endpoints such as growth inhibition, apoptosis, autophagy, caspase activation, DNA fragmentation, and cell cycle arrest using fluorophores and the NC3000 instrument. Significant results (p < 0.05) revealed higher toxicity for the 2-EH metabolite when compared to DEHP. Also, 2-EH presented apoptosis induction with characteristic hallmarks, such as loss of mitochondrial membrane potential, caspase activation, DNA fragmentation and cell cycle arrest at the S phase. In addition, the presence of autophagosome was detected through L3CB protein staining. We conclude that 2-EH presents differences in cell death endpoints that interestingly differ from the DEHP parent compound. Further studies are needed to establish the molecular pathways responsible for the observed effects.

Mechanism involved in cell death induced by DEHP (Di-ethylhexyl phthalate) on primary brain cells from Zebrafish (Danio rerio)

“…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-(2ethylhexyl) 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.…”