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

Karoline Rios,Christian Vélez,Beatriz Zayas

doi:10.4236/ojapo.2019.81001

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.

Highlights

We expand on our previous work with Diethylhexyl phthalate (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
The growth inhibition dose of 4.4 μM for 2-EH and 76 μM for DEHP on TK6 cells were determined after a 24-hour exposure (Table 1)
Mitochondrial health was assessed after exposure to the phthalates and the Compound DEHP 2-EH

Summary

Introduction

Modern manufacturing practices have relied on plastics to improve the physical. Plastic manufacturing technologies have evolved to modify the characteristics of their products. Phthalates are widely used as plasticizers to increase the flexibility and durability of plastic products. Since the 1920s with the introduction of Diethylhexyl phthalate (DEHP) phtalate ester, compounds have been used extensively in different types of products such as building materials, flooring, piping, food packaging, and medical devices, among others [1] [2] [3]. Exposure to phthalates can occur from food, water air, fabrics, dust, medications, cosmetics, and any plastic-made products. The preparation of food or drink, using microwaves, can promote the leaching of phthalates from containers [4]

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