Genomes and Genes
Summary: An ester of phthalic acid. It appears as a light-colored, odorless liquid and is used as a plasticizer for many resins and elastomers.
- Reinsberg J, Wegener Toper P, van der Ven K, van der Ven H, Klingmueller D. Effect of mono-(2-ethylhexyl) phthalate on steroid production of human granulosa cells. Toxicol Appl Pharmacol. 2009;239:116-23 pubmed publisher..As the in vitro effective doses of MEHP are within the range of real environmental exposure levels an inhibitory effect on estrogen production in vivo seems to be possible. ..
- Erkekoglu P, Rachidi W, Yüzügüllü O, Giray B, Ozturk M, Favier A, et al. Induction of ROS, p53, p21 in DEHP- and MEHP-exposed LNCaP cells-protection by selenium compounds. Food Chem Toxicol. 2011;49:1565-71 pubmed publisher..Generated data also emphasized the critical role of Se in modulation of intracellular redox status, implicating the importance of the appropriate Se status in cellular response against testicular toxicity of phthalates. ..
- Eveillard A, Mselli Lakhal L, Mogha A, Lasserre F, Polizzi A, Pascussi J, et al. Di-(2-ethylhexyl)-phthalate (DEHP) activates the constitutive androstane receptor (CAR): a novel signalling pathway sensitive to phthalates. Biochem Pharmacol. 2009;77:1735-46 pubmed publisher..CAR-mediated effects of DEHP provide a new rationale for most endpoints of phthalates toxicity described previously, including endocrine disruption, hepatocarcinogenesis and the metabolic syndrome. ..
- Gillum N, Karabekian Z, Swift L, Brown R, Kay M, Sarvazyan N. Clinically relevant concentrations of di (2-ethylhexyl) phthalate (DEHP) uncouple cardiac syncytium. Toxicol Appl Pharmacol. 2009;236:25-38 pubmed publisher..The data indicate that DEHP, in clinically relevant concentrations, can impair the electrical and mechanical behavior of a cardiac cell network. Applicability of these findings to human patients remains to be established. ..
- Fan J, Traore K, Li W, Amri H, Huang H, Wu C, et al. Molecular mechanisms mediating the effect of mono-(2-ethylhexyl) phthalate on hormone-stimulated steroidogenesis in MA-10 mouse tumor Leydig cells. Endocrinology. 2010;151:3348-62 pubmed publisher..A model for the mechanism of MEHP action on MA-10 Leydig cell steroidogenesis is proposed...
- Carnevali O, Tosti L, Speciale C, Peng C, Zhu Y, Maradonna F. DEHP impairs zebrafish reproduction by affecting critical factors in oogenesis. PLoS ONE. 2010;5:e10201 pubmed publisher..Since there is a significant genetic similarity between D.rerio and humans, the harmful effects observed at oocyte level may be relevant for further molecular studies on humans. ..
- Maranghi F, Lorenzetti S, Tassinari R, Moracci G, Tassinari V, Marcoccia D, et al. In utero exposure to di-(2-ethylhexyl) phthalate affects liver morphology and metabolism in post-natal CD-1 mice. Reprod Toxicol. 2010;29:427-32 pubmed publisher..Our findings suggested that DEHP alters post-natal liver development delaying the programming of glycogen metabolism. ..
- Feige J, Gerber A, Casals Casas C, Yang Q, Winkler C, Bedu E, et al. The pollutant diethylhexyl phthalate regulates hepatic energy metabolism via species-specific PPARalpha-dependent mechanisms. Environ Health Perspect. 2010;118:234-41 pubmed publisher..b>Diethylhexyl phthalate (DEHP) is a widely used industrial plasticizer to which humans are widely exposed...
- Posnack N, Lee N, Brown R, Sarvazyan N. Gene expression profiling of DEHP-treated cardiomyocytes reveals potential causes of phthalate arrhythmogenicity. Toxicology. 2011;279:54-64 pubmed publisher..Exposure of neonatal rat cardiomyocytes to clinically relevant DEHP concentrations leads to global changes in mRNA expression. These changes help to explain the arrhythmogenic effects of phthalates on these cells. ..
- Preau J, Wong L, Silva M, Needham L, Calafat A. Variability over 1 week in the urinary concentrations of metabolites of diethyl phthalate and di(2-ethylhexyl) phthalate among eight adults: an observational study. Environ Health Perspect. 2010;118:1748-54 pubmed publisher..When collecting multiple spot urine samples, changing the time of collection may provide the most complete approach to assess exposure to diverse phthalates. ..
- Hayashi Y, Ito Y, Yamagishi N, Yanagiba Y, Tamada H, Wang D, et al. Hepatic peroxisome proliferator-activated receptor ? may have an important role in the toxic effects of di(2-ethylhexyl)phthalate on offspring of mice. Toxicology. 2011;289:1-10 pubmed publisher..Taken together, PPAR? expression is required for the toxicity of DEHP in fetuses and pups and altered plasma triglyceride levels, through regulation of MTP may be important in mPPAR? mice and not in hPPAR? mice. ..
- Meeker J, Calafat A, Hauser R. Urinary metabolites of di(2-ethylhexyl) phthalate are associated with decreased steroid hormone levels in adult men. J Androl. 2009;30:287-97 pubmed publisher..In conclusion, these results suggest that urinary metabolites of DEHP are inversely associated with circulating steroid hormone levels in adult men. However, additional research is needed to confirm these findings. ..
- Camann D, Schultz S, Yau A, Heilbrun L, Zuniga M, Palmer R, et al. Acetaminophen, pesticide, and diethylhexyl phthalate metabolites, anandamide, and fatty acids in deciduous molars: potential biomarkers of perinatal exposure. J Expo Sci Environ Epidemiol. 2013;23:190-6 pubmed publisher..Validation studies are necessary to verify that each detected chemical in molars provides a biomarker of perinatal exposure. ..
- Zhang X, Zhang L, Li L, Feng Y, Chen B, Ma J, et al. Diethylhexyl phthalate exposure impairs follicular development and affects oocyte maturation in the mouse. Environ Mol Mutagen. 2013;54:354-61 pubmed publisherb>Diethylhexyl phthalate (DEHP) is an estrogen-like compound widely used as a commercial plasticizer and present in medical devices, tubing, food containers and packaging...
- Martinelli M, Mocchiutti N, Bernal C. Effect of di(2-ethylhexyl) phthalate (DEHP) on lipolysis and lipoprotein lipase activities in adipose tissue of rats. Hum Exp Toxicol. 2010;29:739-45 pubmed publisher..More research is needed to achieve a comprehensive understanding of the potential mechanisms by which DEHP causes, among others, a reduced body fat retention. ..
- Petersen J, Jensen L. Phthalates and food-contact materials: enforcing the 2008 European Union plastics legislation. Food Addit Contam Part A Chem Anal Control Expo Risk Assess. 2010;27:1608-16 pubmed publisher..All findings of phthalates were associated with the use of plasticized polyvinylchloride (PVC). ..
- Anderson W, Castle L, Hird S, Jeffery J, Scotter M. A twenty-volunteer study using deuterium labelling to determine the kinetics and fractional excretion of primary and secondary urinary metabolites of di-2-ethylhexylphthalate and di-iso-nonylphthalate. Food Chem Toxicol. 2011;49:2022-9 pubmed publisher..These robust fractional excretion values for the main primary and secondary phthalate metabolites along with estimates of their uncertainty can be used in future surveys of human exposure to DEHP and DINP. ..
- Huang L, Lee C, Hsu P, Shih T. The association between semen quality in workers and the concentration of di(2-ethylhexyl) phthalate in polyvinyl chloride pellet plant air. Fertil Steril. 2011;96:90-4 pubmed publisher..To investigate potential associations between semen quality in workers and the concentrations of di(2-ethylhexyl) phthalate (DEHP) in personal air collected from polyvinyl chloride (PVC) plants...
- Lin Y, Wei J, Li Y, Chen J, Zhou Z, Song L, et al. Developmental exposure to di(2-ethylhexyl) phthalate impairs endocrine pancreas and leads to long-term adverse effects on glucose homeostasis in the rat. Am J Physiol Endocrinol Metab. 2011;301:E527-38 pubmed publisher..DEHP exposure in critical periods of development can be a potential risk factor, at least in part, for developing diabetes. ..
- Wang W, Craig Z, Basavarajappa M, Gupta R, Flaws J. Di (2-ethylhexyl) phthalate inhibits growth of mouse ovarian antral follicles through an oxidative stress pathway. Toxicol Appl Pharmacol. 2012;258:288-95 pubmed publisher..Collectively, these data suggest that DEHP inhibits follicle growth by inducing production of ROS and by decreasing the expression and activity of SOD1. ..
- Piché C, Sauvageau D, Vanlian M, Erythropel H, Robaire B, Leask R. Effects of di-(2-ethylhexyl) phthalate and four of its metabolites on steroidogenesis in MA-10 cells. Ecotoxicol Environ Saf. 2012;79:108-15 pubmed publisher..Overall, the study suggests the involvement of multiple active metabolites in the testicular toxicity of DEHP. ..
- Swan S, Liu F, Hines M, Kruse R, Wang C, Redmon J, et al. Prenatal phthalate exposure and reduced masculine play in boys. Int J Androl. 2010;33:259-69 pubmed publisher..Our findings suggest that these ubiquitous environmental chemicals have the potential to alter androgen-responsive brain development in humans. ..
- Peck J, Sweeney A, Symanski E, Gardiner J, Silva M, Calafat A, et al. Intra- and inter-individual variability of urinary phthalate metabolite concentrations in Hmong women of reproductive age. J Expo Sci Environ Epidemiol. 2010;20:90-100 pubmed publisher..g., metabolites of DEHP). ..
- Dalman A, Eimani H, Sepehri H, Ashtiani S, Valojerdi M, Eftekhari Yazdi P, et al. Effect of mono-(2-ethylhexyl) phthalate (MEHP) on resumption of meiosis, in vitro maturation and embryo development of immature mouse oocytes. Biofactors. 2008;33:149-55 pubmed..05). These results indicate that MEHP could negatively modulate mouse oocyte meiotic maturation in vitro and embryo development, suggesting possible risks for human and other mammalians reproductive health. ..
- Vo T, Jung E, Dang V, Jung K, Baek J, Choi K, et al. Differential effects of flutamide and di-(2-ethylhexyl) phthalate on male reproductive organs in a rat model. J Reprod Dev. 2009;55:400-11 pubmed
- Tanida T, Warita K, Ishihara K, Fukui S, Mitsuhashi T, Sugawara T, et al. Fetal and neonatal exposure to three typical environmental chemicals with different mechanisms of action: mixed exposure to phenol, phthalate, and dioxin cancels the effects of sole exposure on mouse midbrain dopaminergic nuclei. Toxicol Lett. 2009;189:40-7 pubmed publisher..These results indicate that ED mixtures as pollution have unique and elusive effects. Thyroid hormones and/or aryl hydrocarbon receptor-related mechanisms may be responsible for this counteraction. ..
- Erkekoglu P, Giray B, Kizilgun M, Rachidi W, Hininger Favier I, Roussel A, et al. Di(2-ethylhexyl)phthalate-induced renal oxidative stress in rats and protective effect of selenium. Toxicol Mech Methods. 2012;22:415-23 pubmed publisher..These findings emphasized the critical role of Se as an effective redox regulator and the importance of Se status in protecting renal tissue from the oxidant stressor activity of DEHP. ..
- Klinefelter G, Laskey J, Winnik W, Suarez J, Roberts N, Strader L, et al. Novel molecular targets associated with testicular dysgenesis induced by gestational exposure to diethylhexyl phthalate in the rat: a role for estradiol. Reproduction. 2012;144:747-61 pubmed publisher..Pregnant dams were dosed orally from gestation day (GD) 13-19 with 0, 10, or 100 mg diethylhexyl phthalate (DEHP)/kg body weight per day. Each endpoint was represented by 16l...
- Xu Y, Hubal E, Clausen P, Little J. Predicting residential exposure to phthalate plasticizer emitted from vinyl flooring: a mechanistic analysis. Environ Sci Technol. 2009;43:2374-80 pubmed
- Shen O, Du G, Sun H, Wu W, Jiang Y, Song L, et al. Comparison of in vitro hormone activities of selected phthalates using reporter gene assays. Toxicol Lett. 2009;191:9-14 pubmed publisher..0x10(-4)M. Together, the findings demonstrate that the three phthalates could simultaneously disrupt the function of two or more hormonal receptors. Therefore, these phthalates should be considered in risk assessments for human health. ..
- Han S, Lee H, Han S, Lim D, Jung K, Kwack S, et al. An exposure assessment of di-(2-ethylhexyl) phthalate (DEHP) and di-n-butyl phthalate (DBP) in human semen. J Toxicol Environ Health A. 2009;72:1463-9 pubmed publisher..These findings suggest the detection of phthalates in healthy human semen might require further investigation for effects on human fertility. ..
- Erkekoglu P, Rachidi W, Yuzugullu O, Giray B, Favier A, Ozturk M, et al. Evaluation of cytotoxicity and oxidative DNA damaging effects of di(2-ethylhexyl)-phthalate (DEHP) and mono(2-ethylhexyl)-phthalate (MEHP) on MA-10 Leydig cells and protection by selenium. Toxicol Appl Pharmacol. 2010;248:52-62 pubmed publisher
- Durmaz E, Ozmert E, Erkekoglu P, Giray B, Derman O, Hincal F, et al. Plasma phthalate levels in pubertal gynecomastia. Pediatrics. 2010;125:e122-9 pubmed publisher..DEHP, which has antiandrogenic or estrogenic effects, may be an etiologic factor in pubertal gynecomastia. These results may pioneer larger-scale studies on the etiologic role of DEHP in pubertal gynecomastia. ..
- Pant N, Pant A, Shukla M, Mathur N, Gupta Y, Saxena D. Environmental and experimental exposure of phthalate esters: the toxicological consequence on human sperm. Hum Exp Toxicol. 2011;30:507-14 pubmed publisher..There are a significant correlation between phthalate ester diethylhexyl phthalate, di-n-butyl phthalate (DEHP and DBP) and sperm motility both in vitro and in vivo conditions...
- Matsuda T, Kurohane K, Imai Y. Di-(2-ethylhexyl) phthalate enhances skin sensitization to isocyanate haptens in mice. Toxicol Lett. 2010;192:97-100 pubmed publisher..The results suggested that the combination of a hapten and a phthalate ester significantly affects the outcome of CHS. ..
- Martinez Arguelles D, Guichard T, Culty M, Zirkin B, Papadopoulos V. In utero exposure to the antiandrogen di-(2-ethylhexyl) phthalate decreases adrenal aldosterone production in the adult rat. Biol Reprod. 2011;85:51-61 pubmed publisher..Moreover, these results suggest the existence of a DEHP-sensitive adrenal-testis axis regulating androgen formation. ..
- Christiansen S, Boberg J, Axelstad M, Dalgaard M, Vinggaard A, Metzdorff S, et al. Low-dose perinatal exposure to di(2-ethylhexyl) phthalate induces anti-androgenic effects in male rats. Reprod Toxicol. 2010;30:313-21 pubmed publisher..The results provide new evidence of low-dose effects of DEHP and are consistent with the EU NOAEL of 5 mg/kg for DEHP. Our results also indicate a reason for concern about human exposure to DEHP. ..
- Hannas B, Lambright C, Furr J, Howdeshell K, Wilson V, Gray L. Dose-response assessment of fetal testosterone production and gene expression levels in rat testes following in utero exposure to diethylhexyl phthalate, diisobutyl phthalate, diisoheptyl phthalate, and diisononyl phthalate. Toxicol Sci. 2011;123:206-16 pubmed publisher
- Schmidt J, Schaedlich K, Fiandanese N, Pocar P, Fischer B. Effects of di(2-ethylhexyl) phthalate (DEHP) on female fertility and adipogenesis in C3H/N mice. Environ Health Perspect. 2012;120:1123-9 pubmed publisher..Although F1 mice were exposed to DEHP only in utero and during lactation, we observed metabolic changes in the offspring of diet-exposed females. ..
- Ellero Simatos S, Claus S, Benelli C, Forest C, Letourneur F, Cagnard N, et al. Combined transcriptomic-(1)H NMR metabonomic study reveals that monoethylhexyl phthalate stimulates adipogenesis and glyceroneogenesis in human adipocytes. J Proteome Res. 2011;10:5493-502 pubmed publisher..Altogether, these results indicate that MEHP promoted the differentiation of human preadipocytes to adipocytes. These mechanisms might contribute to the suspected obesogenic effect of MEHP. ..
- Takatori S, Akutsu K, Kondo F, Ishii R, Nakazawa H, Makino T. Di(2-ethylhexyl)phthalate and mono(2-ethylhexyl)phthalate in media for in vitro fertilization. Chemosphere. 2012;86:454-9 pubmed publisher..The concentrations of DEHP and MEHP in PS were <10-982 and 47.0-1840 ng mL(-1), respectively. The DEHP and MEHP detected in these media were derived from PS. This is the first study on the chemical contamination of IVFM, SWM, and PS. ..
- Kim B, Cho S, Kim Y, Shin M, Yoo H, Kim J, et al. Phthalates exposure and attention-deficit/hyperactivity disorder in school-age children. Biol Psychiatry. 2009;66:958-63 pubmed publisher..The present study showed a strong positive association between phthalate metabolites in urine and symptoms of ADHD among school-age children. ..
- Andrade A, Grande S, Talsness C, Grote K, Chahoud I. A dose-response study following in utero and lactational exposure to di-(2-ethylhexyl)-phthalate (DEHP): non-monotonic dose-response and low dose effects on rat brain aromatase activity. Toxicology. 2006;227:185-92 pubmed..To our knowledge, this is the first study to report biological effects of DEHP at doses that overlap with the estimated exposure of the general human population. ..
- Borch J, Metzdorff S, Vinggaard A, Brokken L, Dalgaard M. Mechanisms underlying the anti-androgenic effects of diethylhexyl phthalate in fetal rat testis. Toxicology. 2006;223:144-55 pubmedb>Diethylhexyl phthalate (DEHP) is widely used as a plasticizer in consumer products and is known to disturb the development of the male reproductive system in rats...
- Stroheker T, Regnier J, Lassurguere J, Chagnon M. Effect of in utero exposure to di-(2-ethylhexyl)phthalate: distribution in the rat fetus and testosterone production by rat fetal testis in culture. Food Chem Toxicol. 2006;44:2064-9 pubmed..Thus, DEHP and/or its metabolites appear to cross the placental barrier, reach the fetal gonads. In vitro, neither DEHP nor its main metabolites decreased the testosterone production. ..
- Mazzeo P, di Pasquale D, Ruggieri F, Fanelli M, D Archivio A, Carlucci G. HPLC with diode-array detection for the simultaneous determination of di(2-ethylhexyl)phthalate and mono(2-ethylhexyl)phthalate in seminal plasma. Biomed Chromatogr. 2007;21:1166-71 pubmed..The limits of detection were 0.010 and 0.015 microg/mL, for DEHP and MEHP, respectively. This method was used to analyze real samples in support of clinical studies on these potential endocrine disruptors. ..
- Lee J, Park J, Jang B, Knudsen T. Altered expression of genes related to zinc homeostasis in early mouse embryos exposed to di-2-ethylhexyl phthalate. Toxicol Lett. 2004;152:1-10 pubmed..9 mg/kg for MT-II, and 6.6 mg/kg for ZnT-1. We conclude that DEHP exposure to pregnant dams at reasonably low levels during organogenesis stages can alter the expression of several key genes in embryonic zinc homeostasis. ..
- David R, Moore M, Cifone M, Finney D, Guest D. Chronic peroxisome proliferation and hepatomegaly associated with the hepatocellular tumorigenesis of di(2-ethylhexyl)phthalate and the effects of recovery. Toxicol Sci. 1999;50:195-205 pubmed
- Koch H, Preuss R, Angerer J. Di(2-ethylhexyl)phthalate (DEHP): human metabolism and internal exposure-- an update and latest results. Int J Androl. 2006;29:155-65; discussion 181-5 pubmed..Premature neonates (n = 45) were exposed to DEHP up to 100 times above the limit values depending on the intensity of medical care (median: 42 microg/kg/day; 95th percentile: 1,780 microg/kg/day). ..
- Li H, Kim K. Effects of mono-(2-ethylhexyl) phthalate on fetal and neonatal rat testis organ cultures. Biol Reprod. 2003;69:1964-72 pubmed..These results suggest that MEHP adversely affects the gonocytes, which are mitotically active and undergoing migration and differentiation in neonatal testes, but it has no effect on fetal gonocytes that are mitotically quiescent. ..
- Takano H, Yanagisawa R, Inoue K, Ichinose T, Sadakane K, Yoshikawa T. Di-(2-ethylhexyl) phthalate enhances atopic dermatitis-like skin lesions in mice. Environ Health Perspect. 2006;114:1266-9 pubmed..DEHP could be at least partly responsible for the recent increase in atopic dermatitis. ..
- Kambia K, Dine T, Azar R, Gressier B, Luyckx M, Brunet C. Comparative study of the leachability of di(2-ethylhexyl) phthalate and tri(2-ethylhexyl) trimellitate from haemodialysis tubing. Int J Pharm. 2001;229:139-46 pubmed..In view of several biological effects previously reported, it is time to reconsider the use of DEHP only as a plasticizer. ..
- Kanki K, Nishikawa A, Masumura K, Umemura T, Imazawa T, Kitamura Y, et al. In vivo mutational analysis of liver DNA in gpt delta transgenic rats treated with the hepatocarcinogens N-nitrosopyrrolidine, 2-amino-3-methylimidazo[4,5-f]quinoline, and di(2-ethylhexyl)phthalate. Mol Carcinog. 2005;42:9-17 pubmed..Our data also indicate that analysis of specific in vivo mutational responses with transgenic animal models can provide crucial information for understanding the molecular mechanisms underlying chemical carcinogenesis. ..
- Ma M, Kondo T, Ban S, Umemura T, Kurahashi N, Takeda M, et al. Exposure of prepubertal female rats to inhaled di(2-ethylhexyl)phthalate affects the onset of puberty and postpubertal reproductive functions. Toxicol Sci. 2006;93:164-71 pubmed..These data suggest that inhaled DEHP may advance the onset of puberty and alter postpubertal reproductive functions. ..