The urinary metabolites of DINCH ® have an impact on the activities of the human nuclear receptors ERα, ERβ, AR, PPARα and PPARγ

Engel, Anika; Buhrke, Thorsten; Kasper, Stefanie; Behr, Anne‐Cathrin; Braeuning, Albert; Jessel, Sönke; Seidel, Albrecht; Völkel, Wolfgang; Lampen, Alfonso

doi:10.1016/j.toxlet.2018.02.006

Cited by 53 publications

(38 citation statements)

References 14 publications

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“…Several in vivo and in vitro toxicological studies have analyzed possible adverse effects of DINCH and contradictory results were obtained ( Campioli et al., 2015 ; Campioli et al., 2019 ; Campioli et al., 2017 ; David et al., 2015 ; EFSA, 2007 ; Eljezi et al., 2019 ; Engel et al., 2018 ; Nardelli et al., 2017 ; Vasconcelos et al., 2019 ). The in vivo toxicological studies of DINCH on rats have shown no effect on behavior, organ weight, serum chemistry ( David et al., 2015 ), and no evidence of reproductive toxicity or endocrine disruptive properties ( EFSA, 2007 ).…”

Section: Introductionmentioning

confidence: 99%

“…In another study, higher incidence of hemorrhagic testes was observed in the offspring of timed-pregnant Sprague-Dawley rats that were gavaged with 30 and 300 mg/kg/day of DINCH ( Nardelli et al., 2017 ). In a study, it has been shown that DINCH did not have any effect on the activity of human nuclear receptors ERα, ERβ, AR, PPARα and PPARγ in HEK293 cell line, while its metabolites, M2NCH, MINCH, OH-MINCH, oxo-MINCH, and cx-MINCH, were shown to activate these receptors ( Engel et al., 2018 ). Taken together, there is still a lack of information regarding toxicity and safety assessment of DINCH.…”

Section: Introductionmentioning

confidence: 99%

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

Saad

Bereketoğlu

Pradhan

2021

Heliyon

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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.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Saad

Bereketoğlu

Pradhan

2021

Heliyon

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“…Although underlying molecular mechanisms of health effects related to phthalate exposure during gestation are poorly understood, animal studies indicated that phthalate exposure can impair the function of Leydig di(isononyl)cyclohexane-1,2-dicarboxylate (DINCH), a nonphthalate plasticizer, has taken the place of phthalate due to the lower migration rate and toxicity (12). Although deemed safe by classical regulatory toxicological standards (13), DINCH and its metabolite cyclohexane-1,2-dicarboxylic acid monoisononylester would activate human ERα, ERβ, AR, PPARα, and PPARγ (14) and then affect disease processes (10,11). Because of the limited quantity of research on the effect of DINCH and its metabolite on pregnant women, this review did not cover the literature about DINCH and its metabolite.…”

Section: Introductionmentioning

confidence: 99%

The Endocrine Disruption of Prenatal Phthalate Exposure in Mother and Offspring

Qian

Shao

Ying

et al. 2020

Front. Public Health

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Phthalates are a group of ubiquitous synthetic endocrine-disrupting chemicals. Fetal and neonatal periods are particularly susceptible to endocrine disorders, which prenatal exposure to phthalates causes. There is increasing evidence concerning the potential endocrine disrupting for phthalate exposure during pregnancy. This article aims to review the endocrine impairment and potential outcomes of prenatal phthalate exposure. Prenatal exposure phthalates would disrupt the levels of thyroid, sex hormone, and 25-hydroxyvitamin D in pregnant women or offspring, which results in preterm birth, preeclampsia, maternal glucose disorders, infant cryptorchidism, infant hypospadias, and shorter anogenital distance in newborns, as well as growth restriction not only in infants but also in early adolescence and childhood. The relationship of prenatal phthalate exposure with maternal and neonatal outcomes in human beings was often sex-specific associations. Because of the potentially harmful influence of prenatal phthalate exposure, steps should be taken to prevent or reduce phthalate exposure during pregnancy.

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“…Although epidemiological studies of health effects related to DEHTP or DINCH exposure are extremely limited [34], recent animal studies suggest that gestational DINCH exposure can affect the function of Leydig cells, which produce testosterone and other androgens [35]. In addition, DINCH metabolites can activate human estrogen receptor (ER) α, ERβ, androgen receptor, peroxisome proliferator-activated receptor (PPAR) α, and PPARγ [36], which play key roles in metabolism, inflammation, and many other disease processes [37,38].…”

Section: Introductionmentioning

confidence: 99%

Determinants and characterization of exposure to phthalates, DEHTP and DINCH among pregnant women in the PROTECT birth cohort in Puerto Rico

Rodríguez‐Carmona

Ashrap

Calafat

et al. 2019

J Expo Sci Environ Epidemiol

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Background As a result of evidence suggesting phthalate toxicity, their use has decreased in recent years. However, new phthalates and non-phthalate replacements have emerged in their place, with unknown potential impacts on health. Methods We measured 15 phthalate, two di(2-ethylhexyl)terephthalate (DEHTP), and two di(isononyl)cyclohexane-1,2dicarboxylate (DINCH) urinary metabolites, collected up to three times during pregnancy from 994 women in Northern Puerto Rico (2011-2017). We used tests of linear trend to assess changes in concentrations over time and linear mixed models to identify predictors of exposure (sociodemographic characteristics, drinking water sources, diet, product use). Results Several phthalate metabolites decreased over the study period indicating decreased exposure, while the geometric mean of DEHTP metabolites (molecular sum) increased threefold between 2014 and 2017. Intraclass correlations revealed low to moderate reproducibility of these biomarkers across pregnancy. Several metabolites were associated with maternal age, income, education, pre-pregnancy BMI, drinking public water, use of cleaning and personal care products, and ice cream consumption. DINCH metabolite concentrations remained low throughout the study period. Conclusion Although exposure to some phthalates may be decreasing, exposure to replacements, such as DEHTP, is increasing. Additional studies are needed to further characterize sources of phthalate replacement chemicals and potential exposure-related health effects among vulnerable populations.

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The urinary metabolites of DINCH ® have an impact on the activities of the human nuclear receptors ERα, ERβ, AR, PPARα and PPARγ

Cited by 53 publications

References 14 publications

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

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

The Endocrine Disruption of Prenatal Phthalate Exposure in Mother and Offspring

Determinants and characterization of exposure to phthalates, DEHTP and DINCH among pregnant women in the PROTECT birth cohort in Puerto Rico

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