Cyclohexane-1,2-dicarboxylic acid diisononyl ester and metabolite effects on rat epididymal stromal vascular fraction differentiation of adipose tissue

Campioli, Enrico; Duong, Tam B.; Deschamps, François; Papadopoulos, Vassilios

doi:10.1016/j.envres.2015.03.036

Cited by 43 publications

(43 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Indeed, the extensive knowledge generated with the work performed for the last two decades on the biological assessment of phthalate plasticizers paved the way of what needs to be performed to assess newer ones. Recent findings that next‐generation safer plasticizers, such as the diisononyl cyclohexane‐1,2‐dicarboxylate (DINCH) which has been in the market for few years now, unveiled that DINCH and its metabolite cyclohexane‐1,2‐dicarboxylic acid mono isononyl ester (MINCH) are bioactive in different settings (Campioli et al ., ; Nardelli et al ., ), although deemed safe by classical regulatory toxicological standards (Bhat et al ., ).…”

Section: Discussionmentioning

confidence: 98%

Prenatal phthalate exposure: epigenetic changes leading to lifelong impact on steroid formation

Martinez–Arguelles

Papadopoulos

2016

Andrology

View full text Add to dashboard Cite

SUMMARYEndocrine disruptors (ED) are environmental pollutants that mimic endogenous hormonal signals. Exposure to EDs during fetal and early life is a public health concern because these are periods characterized by high cellular plasticity that influence the physiology and development of disease later in life. Phthalates are plasticizers used in the industry to manufacture polyvinyl chloride products and several consumer products. Di(2-ethylhexyl) phthalate (DEHP) is one of the most produced plasticizers; it is ubiquitously found contaminating the environment, and has been shown to be an ED. Human exposure to phthalates starts during fetal development and continues after birth through contact of the newborn with the environment and contaminated food sources. We used a rat model in which pregnant dams are gavaged with DEHP from gestational day 14 until birth to study the long-term effects of DEHP. This window of fetal exposure results in decreased circulating testosterone and aldosterone levels in adult male offspring and estradiol in the female. The observed steroid changes are likely of an epigenetic origin as DEHP is rapidly cleared after birth. Here, we review the long-term effects of fetal exposure to DEHP with a focus on the molecular and epigenetic changes, including DNA methylation, which may mediate long-term endocrine dysfunction.

show abstract

Section: Discussionmentioning

confidence: 98%

Prenatal phthalate exposure: epigenetic changes leading to lifelong impact on steroid formation

Martinez–Arguelles

Papadopoulos

2016

Andrology

View full text Add to dashboard Cite

show abstract

“…Campioli and colleagues reported that DINCH itself had no toxicological effect; however, MINCH, a minor DINCH metabolite, promoted differentiation in a primary culture model of rat preadipocytes, which is mediated by PPAR-α in its first stage. Therefore, if MINCH acts as a potential PPAR-α agonist and is able to alter hormone signaling, it may be considered a metabolic disruptor interfering with the endocrine system (Campioli et al 2015). However, they did not study MHiNCH and it is unknown if this metabolite has similar activities as MINCH.…”

Section: Discussionmentioning

confidence: 99%

“…Similarly, a recent in vitro experimental study by Boisvert and colleagues has shown no consistent effect of DINCH on Leydig and spermatogonial mouse testicular cell lines (Boisvert et al 2016). In addition, based on another recent in vitro study using rat preadipocytes, Campioli and coworkers also found no effect of DINCH itself, but they suggested that cyclohexane-1,2-dicarboxylic acid monoisononyl ester (MINCH), a minor metabolite of DINCH (Koch et al 2013), is a potent peroxisome proliferator-activated receptor (PPAR)-α agonist and a metabolic disruptor capable of inducing stromal vascular fraction preadipocyte differentiation, which may interfere with the endocrine system (Campioli et al 2015). Whether DINCH behaves as an endocrine disruptor and has toxicological effects on reproduction is unclear due to the scarce data on experimental animals (Boisvert et al 2016, Campioli et al 2015, Campioli and Papadopoulos 2016, Otter 2016).…”

Section: Introductionmentioning

confidence: 99%

Urinary concentrations of cyclohexane-1,2-dicarboxylic acid monohydroxy isononyl ester, a metabolite of the non-phthalate plasticizer di(isononyl)cyclohexane-1,2-dicarboxylate (DINCH), and markers of ovarian response among women attending a fertility center

Mínguez-Alarcón

Souter

Chiu

et al. 2016

Environmental Research

View full text Add to dashboard Cite

Di(isononyl)cyclohexane-1,2-dicarboxylate (DINCH), a non-phthalate plasticizer, was introduced commercially in 2002 as an alternative to ortho-phthalate esters because of its favorable toxicological profile. However, the potential health effects from DINCH exposure remain largely unknown. We explored the associations between urinary concentrations of metabolites of DINCH on markers of ovarian response among women undergoing in vitro fertilization (IVF) treatments. Between 2011 and 2015, 113 women enrolled a prospective cohort study at the Massachusetts General Hospital Fertility Center and provided up to two urine samples prior to oocyte retrieval. The urinary concentrations of two DINCH metabolites, cyclohexane-1,2-dicarboxylic acid monohydroxy isononyl ester (MHiNCH) and cyclohexane-1,2-dicarboxylic acid monocarboxyisooctyl ester (MCOCH), were quantified by isotope dilution tandem mass spectrometry. We used generalized linear mixed models to evaluate the association between urinary metabolite concentrations and markers of ovarian response, accounting for multiple IVF cycles per woman via random intercepts. On average, women with detectable urinary MHiNCH concentrations, as compared to those below LOD, had a lower estradiol levels (−325 pmol/l, p=0.09) and number of retrieved oocytes (−1.8, p=0.08), with a stronger association among older women. However, urinary MHiNCH concentrations were unrelated to mature oocyte yield and endometrial wall thickness. In conclusion, we found suggestive negative associations between urinary MHiNCH concentrations and peak estradiol levels and number of total oocyte yields. This is the first study evaluating the effect of DINCH exposure on human reproductive health and raises the need for further experimental and epidemiological studies to better understand the potential effects of this chemical on health.

show abstract

“…Franken et al (2017) reported the high occurrence of asthma in Belgian teenagers (especially girls) associated with high DEHP and DnBP exposure 32 . DEHT and DINCH administration to rodents revealed no signs of DEHP-like toxicity [33][34][35] . However, DINCH in utero exposure has been associated with signs of impaired liver metabolism and premature testicular aging such as decreased testosterone secretion, physical changes in seminal glands and testicular atrophy in rats and their young offspring 36 .…”

Section: Introductionmentioning

confidence: 89%

In Vitro Inhalation Bioaccessibility of Phthalate Esters and Alternative Plasticizers Present in Indoor Dust Using Artificial Lung Fluids

Kademoglou

Giovanoulis

Palm-Cousins

et al. 2018

Environ. Sci. Technol. Lett.

View full text Add to dashboard Cite

Phthalate esters (PEs) are plasticiser additives imparting durability, elasticity and flexibility to consumer products. The low migration stability of PEs along with their ubiquitous character and adverse health effects to humans and especially children has resulted in their classification as major indoor contaminants. This study assesses inhalation exposure to PEs via indoor dust using an in vitro inhalation bioaccessibility test (i.e. uptake) for of dimethyl phthalate (DMP), diethyl phthalate (DEP) and di-(2-ethylhexyl) phthalate (DEHP) and the alternative non phthalate plasticisers bis(2-ethylhexyl) terephthalate (DEHT) and cyclohexane-1,2-dicarboxylic acid diisononyl ester (DINCH), exposure. Using artificial lung fluids, which mimicktwo distinctively different pulmonary environments, namely artificial lysosomal fluid (ALF, pH = 4.5) representing the fluid that inhaled particles would contact after phagocytosis by alveolar and interstitial macrophages within the lung and Gamble's solution (pH = 7.4), the fluid for deep dust deposition within the pulmonary environment. Low molecular weight (MW) PEs such as DMP and DEP were highly bioaccessible (> 75 %) in both artificial pulmonary media, whereas highly hydrophobic compounds such as DEHP, DINCH and DEHT were < 5 % bioaccessible via the lung. Our findings show that the in vitro pulmonary uptake of PEs is primarily governed by their hydrophobicity and water solubility, highlighting thus the need for the establishment of a unified and biologically relevant inhalation bioaccessibility test format, employed within the risk assessment framework for volatile and semi-volatile organic pollutants.

show abstract

Cyclohexane-1,2-dicarboxylic acid diisononyl ester and metabolite effects on rat epididymal stromal vascular fraction differentiation of adipose tissue

Cited by 43 publications

References 36 publications

Prenatal phthalate exposure: epigenetic changes leading to lifelong impact on steroid formation

Prenatal phthalate exposure: epigenetic changes leading to lifelong impact on steroid formation

Urinary concentrations of cyclohexane-1,2-dicarboxylic acid monohydroxy isononyl ester, a metabolite of the non-phthalate plasticizer di(isononyl)cyclohexane-1,2-dicarboxylate (DINCH), and markers of ovarian response among women attending a fertility center

In Vitro Inhalation Bioaccessibility of Phthalate Esters and Alternative Plasticizers Present in Indoor Dust Using Artificial Lung Fluids

Contact Info

Product

Resources

About