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Dibutyl Phthalate (DBP)

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The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Plastics derived endocrine disruptors (BPA, DEHP and DBP) induce epigenetic transgenerational inheritance of obesity, reproductive disease and sperm epimutations : Supplemental materials

Authors: Manikkam, M; Tracey, R; Guerrero-Bosagna, C; Skinner, MK (2013) PLoS ONE 8:e55387. [Supplemental Data] HERO ID: 3229882

[Less] Environmental compounds are known to promote epigenetic transgenerational inheritance of adult onset . . . [More] Environmental compounds are known to promote epigenetic transgenerational inheritance of adult onset disease in subsequent generations (F1-F3) following ancestral exposure during fetal gonadal sex determination. The current study was designed to determine if a mixture of plastic derived endocrine disruptor compounds bisphenol-A (BPA), bis(2-ethylhexyl)phthalate (DEHP) and dibutyl phthalate (DBP) at two different doses promoted epigenetic transgenerational inheritance of adult onset disease and associated DNA methylation epimutations in sperm. Gestating F0 generation females were exposed to either the "plastics" or "lower dose plastics" mixture during embryonic days 8 to 14 of gonadal sex determination and the incidence of adult onset disease was evaluated in F1 and F3 generation rats. There were significant increases in the incidence of total disease/abnormalities in F1 and F3 generation male and female animals from plastics lineages. Pubertal abnormalities, testis disease, obesity, and ovarian disease (primary ovarian insufficiency and polycystic ovaries) were increased in the F3 generation animals. Kidney and prostate disease were only observed in the direct fetally exposed F1 generation plastic lineage animals. Analysis of the plastics lineage F3 generation sperm epigenome previously identified 197 differential DNA methylation regions (DMR) in gene promoters, termed epimutations. A number of these transgenerational DMR form a unique direct connection gene network and have previously been shown to correlate with the pathologies identified. Observations demonstrate that a mixture of plastic derived compounds, BPA and phthalates, can promote epigenetic transgenerational inheritance of adult onset disease. The sperm DMR provide potential epigenetic biomarkers for transgenerational disease and/or ancestral environmental exposures.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Inhibin B response to testicular toxicants hexachlorophene, ethane dimethane sulfonate, di-(n-butyl)-phthalate, nitrofurazone, DL-ethionine, 17-alpha ethinylestradiol, 2,5-hexanedione, or carbendazim following short-term dosing in male rats

Authors: Erdos, Z; Pearson, K; Goedken, M; Menzel, K; Sistare, FD; Glaab, WE; Saldutti, LP (2013) Birth Defects Research, Part B: Developmental and Reproductive Toxicology 98:41-53. HERO ID: 1639209

[Less] BACKGROUND: Inhibin B is a heterodimer glycoprotein that downregulates follicle-stimulating . . . [More] BACKGROUND: Inhibin B is a heterodimer glycoprotein that downregulates follicle-stimulating hormone and is produced predominantly by Sertoli cells. The potential correlation between changes in plasma Inhibin B and Sertoli cell toxicity was evaluated in male rats administered testicular toxicants in eight studies. Inhibin B fluctuations over 24 hr were also measured.

METHODS: Adult rats were administered one of eight testicular toxicants for 1 to 29 days. The toxicants were DL-ethionine, dibutyl phthalate, nitrofurazone, 2,5-hexanedione, 17-alpha ethinylestradiol, ethane dimethane sulfonate, hexachlorophene, and carbendazim. In a separate study plasma was collected throughout a 24-hr period via an automatic blood sampler.

RESULTS: Histomorphologic testicular findings included seminiferous tubule degeneration, round and elongate spermatid degeneration/necrosis, seminiferous tubule vacuolation, aspermatogenesis, and interstitial cell degeneration. There was a varying response of plasma Inhibin B levels to seminiferous tubule toxicity, with three studies showing high correlation, three studies with a response only at a certain time or dose, and two studies with no Inhibin B changes. In a receiver operating characteristics exclusion model analysis, where treated samples without histopathology were excluded, Inhibin B showed a sensitivity of 70% at 90% specificity in studies targeting seminiferous tubule toxicity.

CONCLUSION: Decreases in Inhibin B correlated with Sertoli cell toxicity in the majority of studies evaluated, demonstrating the value of Inhibin B as a potential biomarker of testicular toxicity. There was no correlation between decreases in Inhibin B and interstitial cell degeneration. In addition, a pattern of Inhibin B secretion could not be identified over 24 hr.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Di-n-butyl phthalate disrupts the expression of genes involved in cell cycle and apoptotic pathways in mouse ovarian antral follicles

Authors: Craig, ZR; Hannon, PR; Wang, W; Ziv-Gal, A; Flaws, JA (2013) Biology of Reproduction 88:23. HERO ID: 1639213

[Less] Di-n-butyl phthalate (DBP) is present in many consumer products, such as infant, beauty, and medical . . . [More] Di-n-butyl phthalate (DBP) is present in many consumer products, such as infant, beauty, and medical products. Several studies have shown that DBP causes reproductive toxicity in rodents, but no studies have evaluated its effects on ovarian follicles. Therefore, we used a follicle culture system to evaluate the effects of DBP on antral follicle growth, cell cycle and apoptosis gene expression, cell cycle staging, atresia, and 17β-estradiol (E(2)) production. Antral follicles were isolated from adult CD-1 mice and exposed to DBP at 1, 10, 100, and 1000 μg/ml for 24 or 168 h. Follicles treated with vehicle or DBP at 1-100 μg/ml grew over time, but DBP at 1000 μg/ml significantly suppressed follicle growth. Regardless of effect on follicle growth, DBP-treated follicles had decreased mRNA for cyclins D2, E1, A2, and B1 and increased p21. Levels of the proapoptotic genes Bax, Bad, and Bok were not altered by DBP treatment, but DBP 1000 μg/ml increased levels of Bid and decreased levels of the antiapoptotic gene Bcl2. DBP-treated follicles contained significantly more cells in G(1) phase, significantly less cells in S, and exhibited a trend for fewer cells in G(2). Although DBP did not affect E(2) production and atresia at 24 h, follicles treated with DBP had reduced levels of E(2) at 96 h and underwent atresia at 168 h. These data suggest that DBP targets antral follicles and alters the expression of cell cycle and apoptosis factors, causes cell cycle arrest, decreases E(2), and triggers atresia, depending on dose.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

The immunotoxicity of dibutyl phthalate on the macrophages in mice

Authors: Li, L; Li, HS; Song, NN; Chen, HM (2013) Immunopharmacology and Immunotoxicology 35:272-281. HERO ID: 1639203

[Less] OBJECTIVE: Dibutyl phthalate (DBP), a widely used phthalate chemical, is commonly used . . . [More] OBJECTIVE: Dibutyl phthalate (DBP), a widely used phthalate chemical, is commonly used as plasticizer. It is well known that DBP causes reproductive and developmental diseases, but the effect of DBP on the immune system remains to be determined. We assessed the effect of DBP on immune functions of murine macrophages, which constitute a key component in the immune response.

MATERIALS AND METHODS: Murine peritoneal exudate macrophages (PEMs) were treated with 0, 1, 5, 10, 50 or 100 μM DBP in vitro for 24 h and then the viability of PEMs were measured by flow cytometry (FCM) and trypan blue count. To investigate the effect of DBP on the functions of PEMs, we treated the PEMs with moderate dose of DBP (0, 1, 5 or 10 μM) in vitro for 24 h. The phenotypes, phagocytosis and cytokine production of PEMs were measured by FCM or real-time PCR. The immunogenicity and antigen presenting capacity of PEMs treated with DBP in vitro were assessed both by the mixed lymphocytereaction (MLR) in vitro assay and through the injection of exposed cells in mice by the delayed-type hypersensitivity (DTH) assay.

RESULTS: High dose of DBP (50-100 μM) showed cytotoxicity on PEMs, whereas after the treatment with moderate dose of DBP (1-10 μM) in vitro, PEMs expressed low level of CD36, CD80 and MHC-II molecules, and showed significantly decreased phagocytosis on apoptotic cells and Escherichia coli. In addition, DBP treatment exhibited a decrease in the cytokine production, immunogenicity and antigen-presenting capacity of PEMs.

CONCLUSIONS: The present study shows the effects of DBP on macrophages, demonstrating immunogenicity and decreased antigen presentation in vitro.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Identification of transcription factors and coactivators affected by dibutylphthalate interactions in fetal rat testes

Authors: Plummer, SM; Dan, D; Quinney, J; Hallmark, N; Phillips, RD; Millar, M; Macpherson, S; Elcombe, CR (2013) Toxicological Sciences 132:443-457. HERO ID: 1639208

[Less] Previous analysis of in utero dibutylphthalate (DBP)-exposed fetal rat testes indicated that DBP's antiandrogenic . . . [More] Previous analysis of in utero dibutylphthalate (DBP)-exposed fetal rat testes indicated that DBP's antiandrogenic effects were mediated, in part, by indirect inhibition of steroidogenic factor 1 (SF1), suggesting that peroxisome proliferator-activated receptor alpha (PPARα) might be involved through coactivator (CREB-binding protein [CBP]) sequestration. To test this hypothesis, we have performed chromatin immunoprecipitation (ChIP) microarray analysis to assess the DNA binding of PPARα, SF1, CBP, and RNA polymerase II in DBP-induced testicular maldevelopment target genes. Pathway analysis of expression array data in fetal rat testes examined at gestational day (GD) 15, 17, or 19 indicated that lipid metabolism genes regulated by SF1 and PPARα, respectively, were overrepresented, and the time dependency of changes to PPARα-regulated lipid metabolism genes correlated with DBP-mediated repression of SF1-regulated steroidogenesis genes. ChIP microarrays were used to investigate whether DBP-mediated repression of SF1-regulated genes was associated with changes in SF1 binding to genes involved in DBP-induced testicular maldevelopment. DBP treatment caused reductions in SF1 binding in CYP11a, StAR, and CYP17a. Follicle-stimulating hormone receptor (FSHR), regulated by SF1 but unaffected by DBP-treatment, also contained SF1-binding peaks, but DBP did not change this compared with control. GD15 and GD19 fetal testes contained PPARα protein-binding peaks in CYP11a, StAR, and CYP17a regulatory regions. In contrast to its repressive effect on SF1, DBP treatment caused increases in these peaks compared with control. PPARα-binding peaks in the FSHR promoter were not detected in GD15 samples. Hence, the repressive effect of DBP on SF1-regulated steroidogenic genes correlates with inhibition of SF1-DNA binding and increased PPARα-DNA binding. The data indicate that PPARα may act as an indirect transrepressor of SF1 on steroidogenic genes in fetal rat testes in response to DBP treatment.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Di(2-ethylhexyl)phthalate (DEHP) and di-n-butylphthalate (DBP) exposure through diet in hospital patients

Authors: Cirillo, T; Fasano, E; Esposito, F; Montuori, P; Amodio Cocchieri, R (2013) Food and Chemical Toxicology. HERO ID: 1332531

[Less] Ready-to-eat packed meals intended to hospital patients were studied over a two-weeks period to measure . . . [More] Ready-to-eat packed meals intended to hospital patients were studied over a two-weeks period to measure the contents of di-(2-ethylhexyl) phthalate (DEHP) and di-n-butylphthalate (DBP) and to evaluate their daily intake by total diet. The packaging consisted of polyethylene terephthalate (PET) dishes sealed with polypropylene (PP) foil. The DEHP mean concentrations in total meals varied from 0.061±0.028 to 0.307±0.138μg/gwetweight (wet wt.); the DBP mean levels varied from 0.025±0.018 to 0.174±0.091μg/gwetwt. Highest levels of concentration for DEHP and DBP were found in bread with mean values of 0.307±0.138μg/gwetwt. and 0.174±0.091μg/gwetwt. for DEHP and DBP, respectively. The daily intake for DEHP was 3.1±0.9μg/kgbw and 1.5±0.5μg/kgbw for DBP. The mean±sd incidence of DEHP and DBP intake via hospital meals on the respective EFSA TDI was 6±2% (range 4-11%), and 15±5% (range 8-24%), respectively. Even if for hospital patients the major route of exposure may be represented by medical devices, the influence of the diet could have a significant value on TDI.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

A dose response study to assess effects after dietary administration of diisononyl phthalate (DINP) in gestation and lactation on male rat sexual development

Authors: Clewell, RA; Thomas, A; Willson, G; Creasy, DM; Andersen, ME (2013) Reproductive Toxicology 35:70-80. HERO ID: 1325348

[Less] Male rat sexual development was evaluated after dietary administration of 0, 760, 3800, 11,400ppm diisononyl . . . [More] Male rat sexual development was evaluated after dietary administration of 0, 760, 3800, 11,400ppm diisononyl phthalate (DiNP) and 7600ppm dibutyl phthalate (DBP) from gestation day (GD) 12 to postnatal day (PND) 14. Maternal weight was reduced on GD 20, PND 2 and 14 at 11,400ppm DiNP. Pup weight was reduced on PND 2 and 14 at 11,400 and 3800ppm DiNP. DBP induced multinucleated germ cells (MNGs) and Leydig cell aggregates (LCAs) in PND 2 testes. 7600ppm DBP reduced anogenital distance (AGD) on PND 2 and 14, and increased nipple retention and reproductive tract malformations on PND 49. DiNP induced MNGs (3800ppm) and LCAs (11,400ppm) on PND 2, and reduced AGD (11,400ppm) on PND 14. DiNP did not alter AGD, nipple retention or reproductive tract malformations on PND 49. Global endpoint analysis showed no evidence of a rat "phthalate syndrome" on PND 49 with DiNP administration.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Disposition of diiosononyl phthalate and its effects on sexual development of the male fetus following repeated dosing in pregnant rats

Authors: Clewell, RA; Sochaski, M; Edwards, K; Creasy, DM; Willson, G; Andersen, ME (2013) Reproductive Toxicology 35:56–69. HERO ID: 1325350

[Less] Pregnant Sprague-Dawley rats received 50, 250, and 500mg/kg/day diisononyl phthalate (DiNP) from GD . . . [More] Pregnant Sprague-Dawley rats received 50, 250, and 500mg/kg/day diisononyl phthalate (DiNP) from GD 12 to 19 via corn oil gavage to study the dose response for effects on fetal male rat sexual development as well as metabolite disposition in the dam and fetus. Monoisononyl phthalate (MiNP), mono(carboxy-isooctyl) phthalate (MCiOP), mono(hydroxyl-isononyl) phthalate (MHiNP), mono(oxo-isononyl) phthalate (MOiNP), and monoisononyl phthalate glucuronide (MiNP-G) were found in all measured tissues. MCiOP was the major metabolite, followed in decreasing order by MiNP, MHiNP, MOiNP, and MiNP-G. Percentage of dose absorbed decreased at 750mg/kg/day. Testosterone concentration in the fetal testes was reduced at 250 and 750mg/kg/day. Multinucleated germ cells were increased in the testes of rats at 250 and 750mg/kg/day. The no observed effect level (NOEL) for this study was 50mg/kg/day based on increased MNGs and reduced testes testosterone concentration in the fetal rat.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Urine phthalates concentrations are higher in people with stroke: United States National Health and Nutrition Examination Surveys (NHANES), 2001-2004

Author: Shiue, I (2013) European Journal of Neurology 20:728-731. HERO ID: 1290636

[Less] BACKGROUND AND PURPOSE: Associations between plastic-associated chemicals, such as bisphenol A, and . . . [More] BACKGROUND AND PURPOSE: Associations between plastic-associated chemicals, such as bisphenol A, and cardiovascular disease have begun to emerge in the current century. However, the relationship between urine phthalates and risk of stroke is unclear. It was aimed to study the relationship between urine phthalates concentrations and risk of stroke in a national population-based cross-sectional study.

METHODS: Data were retrieved from United States National Health and Nutrition Examination Surveys, 2001-2004 including demographics, self-reported medical conditions (stroke status) and urine phthalates concentrations. Analyses involved t-test and logistic regression models.

RESULTS: Of 13 phthalates concentrations, the mean values of mono-n-butyl phthalate (2001-2002: 131.27 ± 685.62 and 43.02 ± 117.70, P = 0.0001; 2003-2004: 114.36 ± 555.41 and 49.48 ± 153.53, P = 0.008) and mono-(3-carboxypropyl) phthalate (2001-2002: 13.60 ± 37.05 and 5.48 ± 10.55, P < 0.001; 2003-2004: 10.56 ± 38.37 and 5.94 ± 14.76, P = 0.038) concentrations were found significantly higher in people with stroke. It was also observed that low doses of mono-n-butyl phthalate (OR 1.0009, 95%CI 0.999-1.003, P = 0.266 in 2001-2002 and OR 1.0010, 95%CI 1.0001-1.0019, P = 0.028 in 2003-2004, respectively) and mono-(3-carboxypropyl) phthalate (OR 1.03, 95%CI 1.00-1.05, P = 0.055 in 2001-2002 and OR 1.004, 95%CI 1.00-1.01 P = 0.240 in 2003-2004, respectively) were associated with higher risk of stroke after full adjustments.

CONCLUSIONS: Urine phthalates concentrations are potentially associated with increased risk of stroke, although the causality cannot be established in the current cross-sectional study design. Future longitudinal cohort studies and/or clinical trials are warranted to understand the biological mechanism along the pathway before drawing a firm conclusion on the relationship between phthalates and risk of stroke in humans.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Combined subchronic toxicity of bisphenol A and dibutyl phthalate on male rats

Authors: Zhang, WZ; Yong, L; Jia, XD; Li, N; Fan, YX (2013) Biomedical and Environmental Sciences 26:63-69. HERO ID: 1639212

[Less] OBJECTIVE: To evaluate the combined subchronic toxicity of bisphenol A (BPA) and dibutyl . . . [More] OBJECTIVE: To evaluate the combined subchronic toxicity of bisphenol A (BPA) and dibutyl phthalate (DBP) in male Sprague Dawley (SD) rats.

METHODS: Forty 4-week-old male rats weighing 115-125 g were randomly divided into BPA-treated, DBP-treated group, BPA+DBP-treated and control groups and fed with a soy- and alfalfa-free diet containing 285.4 ppm BPA, 285.4 ppm DBP, 285.4 ppm BPA plus 285.4 ppm DBP, and a control diet, respectively, for 90 consecutive days. At the end of the study, the animals were sacrificed by exsanguination via the carotid artery under diethyl etherane aesthesia and weighed. Organs, including liver, kidneys, spleen, thymus, heart, brain, and testis underwent pathological examination. The androgen receptor (AR), gonadotropin-releasing hormone receptor (GNRHR), and progesterone hormone receptor (PR) genes from the hypothalamus were detected by real-time PCR. The biomedical parameters were analyzed.

RESULTS: No significant difference was found in food intake, body weight, tissue weight, organ/brain weight ratio, and biomedical parameters among the four groups (P>0.05). However, BPA and DBP up-regulated AR, PR and GNRHR expression levels in rats and showed a synergistic or an additive effect in the BPA+DBP group.

CONCLUSION: The combined subchronic toxicity of BPA and DBP is synergistic or additive in male SD rats.