Di(isononyl) cyclohexane-1,2-dicarboxylate (DINCH) alters transcriptional profiles, lipid metabolism and behavior in zebrafish larvae

Noha Saad,Ceyhun Bereketoglu,Ajay Pradhan

doi:10.1016/j.heliyon.2021.e07951

Abstract

Plasticizers are commonly used in different consumer goods and personal care products to provide flexibility, durability and elasticity to polymers. Due to their reported toxicity, the use of several plasticizers, including phthalates has been regulated and/or banned from the market. Di(isononyl) cyclohexane-1,2-dicarboxylate (DINCH) is an alternative plasticizer that was introduced to replace toxic plasticizers. Increasing global demand and lack of toxicity data and safety assessment of DINCH have raised the concern to human and animal health. Hence, in the present study, we investigated the adverse effects of DINCH (at concentrations ranging from 0.01 to 10 μM) in early developmental stages of zebrafish using different endpoints such as hatching rate, developmental abnormalities, lipid content, behavior analysis and gene expression. We found that DINCH caused hatching delay in a dose-dependent manner and altered the expression of genes involved in stress response. Lipid staining using Oil Red O stain showed a slight lipid accumulation around the yolk, brain, eye and neck with increasing concentration. Genes associated with lipid transport such as fatty acid synthesis, β-oxidation, elongation, lipid transport were significantly altered by DINCH. Genes involved in cholesterol biosynthesis and homeostasis were also affected by DINCH indicating possible developmental neurotoxicity. Behavioral analysis of larvae demonstrated a distinct locomotor activity upon exposure to DINCH. The present data shows that DINCH could induce physiological and metabolic toxicity to aquatic organisms. Hence, further analyses and environmental monitoring of DINCH should be conducted to determine its safety and toxicity levels.

Highlights

Plasticizers are multifunctional chemicals that provide flexibility, durability and elasticity to polymers by reducing their glass transition temperature, melt viscosity and elastic modulus (Bui et al, 2016; Wypych, 2004)
DINCH is one such alternative plasticizers that was introduced into the market in 2002 and it is of great importance to determine its biological effects
DINCH is one of the alternative plasticizers whose use is increasing in the European market

Summary

Introduction

Plasticizers are multifunctional chemicals that provide flexibility, durability and elasticity to polymers by reducing their glass transition temperature, melt viscosity and elastic modulus (Bui et al, 2016; Wypych, 2004). Phthalates do not have covalent interaction with the products, they leach out and contaminate the environment (Crinnion, 2010). Their high and widespread use has resulted in the detection of their metabolites in urine samples of the general population from the U.S, Europe and Canada (de Renzy-Martin et al, 2014; Mínguez-Alarcon et al, 2016; Saravanabhavan et al, 2013; Zota et al, 2014). Several alternative plasticizers are in the market and their production is gradually increasing (Bui et al, 2016)

Objectives

Methods

Results

Discussion

Conclusion