Health & Environmental Research Online (HERO)


Phthalates – Targeted Search for Epidemiological Studies

Show Project Details Hide Project Details
297 References Were Found:

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 crystal structure of human quinolinic acid phosphoribosyltransferase in complex with its inhibitor phthalic acid

Authors: Malik, SS; Patterson, DN; Ncube, Z; Toth, EA (In Press) HERO ID: 2215421

[Less] Quinolinic acid (QA), a biologically potent but neurodestructive metabolite is catabolized by quinolinic . . . [More] Quinolinic acid (QA), a biologically potent but neurodestructive metabolite is catabolized by quinolinic acid phosphoribosyltransferase (QPRT) in the first step of the de novo NAD(+) biosynthesis pathway. This puts QPRT at the junction of two different pathways, that is, de novo NAD(+) biosynthesis and the kynurenine pathway of tryptophan degradation. Thus, QPRT is an important enzyme in terms of its biological impact and its potential as a therapeutic target. Here, we report the crystal structure of human QPRT bound to its inhibitor phthalic acid (PHT) and kinetic analysis of PHT inhibition of human QPRT. This structure, determined at 2.55 Å resolution, shows an elaborate hydrogen bonding network that helps in recognition of PHT and consequently its substrate QA. In addition to this hydrogen bonding network, we observe extensive van der Waals contacts with the PHT ring that might be important for correctly orientating the substrate QA during catalysis. Moreover, our crystal form allows us to observe an intact hexamer in both the apo- and PHT-bound forms in the same crystal system, which provides a direct comparison of unique subunit interfaces formed in hexameric human QPRT. We call these interfaces "nondimeric interfaces" to distinguish them from the typical dimeric interfaces observed in all QPRTs. We observe significant changes in the nondimeric interfaces in the QPRT hexamer upon binding PHT. Thus, the new structural and functional features of this enzyme we describe here will aid in understanding the function of hexameric QPRTs, which includes all eukaryotic and select prokaryotic QPRTs. Proteins 2013; © 2013 Wiley Periodicals, Inc.

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

Bisphenol A and phthalate metabolite urinary concentrations: Daily and across pregnancy variability

Authors: Fisher, M; Arbuckle, TE; Mallick, R; Leblanc, A; Hauser, R; Feeley, M; Koniecki, D; Ramsay, T; Provencher, G; Bérubé, R; Walker, M (2015) Journal of Exposure Science and Environmental Epidemiology 25:231-239. HERO ID: 2718085

[Less] Phthalates and bisphenol A (BPA) are high production volume and ubiquitous chemicals that are quickly . . . [More] Phthalates and bisphenol A (BPA) are high production volume and ubiquitous chemicals that are quickly metabolized in the body. Traditionally, studies have relied on single spot urine analyses to assess exposure; ignoring variability in concentrations throughout a day or over a longer period of time. We compared BPA and phthalate metabolite results from urine samples collected at five different time points. Participants (n=80) were asked to collect all voids in a 24 h period on a weekday and then again on a weekend before 20 weeks of pregnancy. During the second and third trimesters and in the postpartum period, single spot urines were collected. Variability over time in urinary concentrations was assessed using intraclass correlation coefficients (ICCs) and the sensitivity to correctly classify a single sample as high or low versus the geometric mean (GM) of all samples was calculated. We found low reproducibility and sensitivity of BPA and all phthalate metabolites throughout pregnancy and into the postpartum period but much higher reproducibility within a day. Time of day when the urine was collected was a significant predictor of specific gravity adjusted exposure levels. We concluded that, if the interest is in average exposures across pregnancy, maternal/fetal exposure estimation may be more accurate if multiple measurements, collected across the course of the entire pregnancy, rather than a single spot measure, are performed.Journal of Exposure Science and Environmental Epidemiology advance online publication, 24 September 2014; doi:10.1038/jes.2014.65.

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 homogeneous assay principle for universal substrate quantification via hydrogen peroxide producing enzymes

Authors: Zscharnack, K; Kreisig, T; Prasse, AA; Zuchner, T (2015) Analytica Chimica Acta 854:145-152. HERO ID: 2718044

[Less] H2O2 is a widely occurring molecule which is also a byproduct of a number of enzymatic reactions. It . . . [More] H2O2 is a widely occurring molecule which is also a byproduct of a number of enzymatic reactions. It can therefore be used to quantify the corresponding enzymatic substrates. In this study, the time-resolved fluorescence emission of a previously described complex consisting of phthalic acid and terbium (III) ions (PATb) is used for H2O2 detection. In detail, glucose oxidase and choline oxidase convert glucose and choline, respectively, to generate H2O2 which acts as a quencher for the PATb complex. The response time of the PATb complex toward H2O2 is immediate and the assay time only depends on the conversion rate of the enzymes involved. The PATb assay quantifies glucose in a linear range of 0.02-10mmolL(-1), and choline from 1.56 to 100μmolL(-1) with a detection limit of 20μmolL(-1) for glucose and 1.56μmolL(-1) for choline. Both biomolecules glucose and choline could be detected without pretreatment with good precision and reproducibility in human serum samples and infant formula, respectively. Furthermore, it is shown that the detected glucose concentrations by the PATb system agree with the results of a commercially available assay. In principle, the PATb system is a universal and versatile tool for the quantification of any substrate and enzyme reaction where H2O2 is involved.

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

Comparative effects of di(n-butyl) phthalate exposure on fetal germ cell development in the rat and in human fetal testis xenografts

Authors: van Den Driesche, S; Mckinnell, C; Calarrão, A; Kennedy, L; Hutchison, GR; Hrabalkova, L; Jobling, MS; Macpherson, S; Anderson, RA; Sharpe, RM; Mitchell, RT (2015) Environmental Health Perspectives 123:223-230. HERO ID: 2718039

[Less] BACKGROUND: Phthalate exposure induces germ cell effects in the rat fetal testis. Whilst . . . [More] BACKGROUND: Phthalate exposure induces germ cell effects in the rat fetal testis. Whilst experimental models have shown that the human fetal testis is insensitive to the steroidogenic effects of phthalates, the effects on germ cells are less explored.

OBJECTIVES: To identify the effects of phthalate exposure on human fetal germ cells in a dynamic model and to establish if the rat is an appropriate model for investigating such effects.

METHODS: Immunohistochemistry, immunofluorescence and quantitative real-time PCR for Sertoli and germ cell markers on vehicle/di(n-butyl) phthalate (DBP)-exposed rat testes and human fetal testis xenografts. This included analysis of germ cell differentiation markers, proliferation markers and cell adhesion proteins.

RESULTS: In both rat and human fetal testes, DBP exposure induced similar germ cell effects, namely germ cell loss (predominantly undifferentiated), induction of multinucleated gonocytes (MNGs) and aggregation of differentiated germ cells, although the latter occurred rarely in the human. The mechanism for germ cell aggregation/MNG induction appears to be loss of Sertoli-germ cell membrane adhesion, probably due to Sertoli cell microfilament redistribution.

CONCLUSIONS: Our findings provide the first comparison of DBP effects in vivo on germ cell number, differentiation and aggregation in human and rat. They show comparable effects on germ cells in both species, but the effects in the human were muted compared with the rat. Nevertheless, phthalate effects on germ cells have potential implications for the next generation, which merits further study. Our results show that the rat is a human-relevant model in which to explore the mechanisms for germ cell effects.

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

Association between phthalates and externalizing behaviors and cortical thickness in children with attention deficit hyperactivity disorder

Authors: Park, S; Lee, JM; Kim, JW; Cheong, JH; Yun, HJ; Hong, YC; Kim, Y; Han, DH; Yoo, HJ; Shin, MS; Cho, SC; Kim, BN (2015) Psychological Medicine 45:1601-1612. HERO ID: 2718066

[Less] Background. Previous studies have implicated the relationship between environmental phthalate exposure . . . [More] Background. Previous studies have implicated the relationship between environmental phthalate exposure and attention deficit hyperactivity disorder (ADHD) symptoms of childhood, but no studies have been conducted in children who have a confirmed diagnosis of ADHD obtained through meticulous diagnostic testing. We aimed to determine whether phthalate metabolites in urine would be higher in children with ADHD than in those without ADHD and would correlate with symptom severity and cortical thickness in ADHD children. Method. A cross-sectional examination of urine phthalate metabolite concentrations was performed; scores for ADHD symptoms, externalizing problems, and continuous performance tests were obtained from 180 children with ADHD, and brain-imaging data were obtained from 115 participants. For the control group, children without ADHD (N = 438) were recruited. Correlations between phthalate metabolite concentrations and clinical measures and brain cortical thickness were investigated. Results. Concentrations of phthalate metabolites, particularly the di(2-ethylhexyl) phthalate (DEHP) metabolite, were significantly higher in boys with ADHD than in boys without ADHD. Concentrations of the di-n-butyl phthalate (DBP) metabolite were significantly higher in the combined or hyperactive-impulsive subtypes compared to the inattentive subtype, and the metabolite was positively correlated with the severity of externalizing symptoms. Concentrations of the DEHP metabolite were negatively correlated with cortical thickness in the right middle and superior temporal gyri. Conclusions. The results of this study suggest an association between phthalate concentrations and both the diagnosis and symptom severity of ADHD. Imaging findings suggest a negative impact of phthalates on regional cortical maturation in children with ADHD.

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 negative correlation between insulin-like peptide 3 and bisphenol A in human cord blood suggests an effect of endocrine disruptors on testicular descent during fetal development

Authors: Chevalier, N; Brucker-Davis, F; Lahlou, N; Coquillard, P; Pugeat, M; Pacini, P; Panaïa-Ferrari, P; Wagner-Mahler, K; Fénichel, P (2015) Human Reproduction 30:447-453. HERO ID: 2718038

[Less] STUDY QUESTION: Does a relationship exist between insulin-like peptide 3 (INSL3) and . . . [More] STUDY QUESTION: Does a relationship exist between insulin-like peptide 3 (INSL3) and selected environmental endocrine disruptors (EEDs) in human cord blood (cb)?

SUMMARY ANSWER: In the whole population (cryptorchid and control boys) cbINSL3 correlated negatively with cb free bisphenol A (BPA) providing indirect evidence for an impact of EEDs on fetal Leydig cell INSL3 production.

WHAT IS KNOWN ALREADY: INSL3 is a major regulator of testicular descent. This hormone has been shown to be decreased in cord blood from boys with idiopathic cryptorchidism, the most frequent male malformation. Fetal exposure to several EEDs has been suspected to be involved in the occurrence of idiopathic cryptorchidism.

STUDY DESIGN, SIZE, DURATION: Correlations between cb INSL3 or testosterone and cb free bioactive BPA and maternal milk polychlorinated biphenyls (PCB153), dichlorodiphenyldichloroethylene (DDE), and monobutyl phthalate (mBP) were assessed in newborn boys in a prospective case-control study. All boys (n = 6246) born after 34 weeks of gestation were systematically screened at birth for cryptorchidism over a 3-year period (2002-2005), and a diagnosis of cryptorchidism confirmed by a senior paediatrician.

PARTICIPANTS/MATERIALS, SETTING, METHODS: We studied 52 cryptorchid (26 transient, 26 persistent) and 128 control boys born at two hospitals in southern France. INSL3 was assayed in CB by a modified validated enzyme-linked immunosorbent assay. Testosterone was measured in CB after diethyl-ether extraction by means of ultra-pressure liquid chromatography-tandem mass spectrometry. Free cbBPA was measured after an extraction step with a radioimmunoassay validated after comparison of values obtained by high-pressure liquid chromatography-mass spectrometry. The xenobiotic analysis in mothers' milk was performed after fat extraction by gas chromatography-mass spectrometry.

MAIN RESULTS AND THE ROLE OF CHANCE: EED concentrations were not increased in the cryptorchid versus control group although a trend for increased mBP (P = 0.09) was observed. In the whole study population, cb levels of BPA correlated negatively with INSL3 (P = 0.01; R(2) = 0.05) but not with testosterone. No other EED correlated with INSL3 or with testosterone.

LIMITATIONS, REASONS FOR CAUTION: The levels of BPA and INSL3 in cb may not reflect chronic fetal exposure to EEDs. The deleterious impact of EEDs on fetal testicular descent during specific windows of development has yet to be demonstrated.

WIDER IMPLICATIONS OF THE FINDINGS: The negative correlation between cb free BPA and INSL3 provides indirect evidence for an impact of EEDs on human fetal Leydig cell INSL3 production and points to cbINSL3 as a possible target of EED action during fetal testis development.

STUDY FUNDING/COMPETING INTERESTS: This project was sponsored by the Clinical Research Board of Nice University Hospital and supported by a grant from the French Research Ministry and from the Department of Hormonology and Metabolic Disorders, Hôpital Cochin, APHP, Paris-Descartes University, France. There are no conflicts of interest to declare.

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

Amniotic fluid phthalate levels and male fetal gonad function

Authors: Jensen, MS; Anand-Ivell, R; Nørgaard-Pedersen, B; Jönsson, BA; Bonde, JP; Hougaard, DM; Cohen, A; Lindh, CH; Ivell, R; Toft, G (2015) Epidemiology 26:91-99. HERO ID: 2718067

[Less] BACKGROUND: Prenatal exposure to phthalates may pose a threat to human male reproduction. . . . [More] BACKGROUND: Prenatal exposure to phthalates may pose a threat to human male reproduction. However, additional knowledge about the in vivo effect in humans is needed, and reported associations with genital abnormalities are inconclusive. We aimed to study prenatal di(2-ethylhexyl) phthalate (DEHP) and diisononyl phthalate (DiNP) exposure in relation to cryptorchidism, hypospadias, and human fetal Leydig cell function.

METHODS: We studied 270 cryptorchidism cases, 75 hypospadias cases, and 300 controls. Second-trimester amniotic fluid samples were available from a Danish pregnancy-screening biobank (n = 25,105) covering 1980-1996. We assayed metabolites of DEHP and DiNP (n = 645) and steroid hormones (n = 545) by mass spectrometry. We assayed insulin-like factor 3 by immunoassay (n = 475) and analyzed data using linear or logistic regression.

RESULTS: Mono(2-ethyl-5-carboxypentyl) phthalate (5cx-MEPP, DEHP metabolite) was not consistently associated with cryptorchidism or hypospadias. However, we observed an 18% higher (95% confidence interval [CI] = 5%-33%) testosterone level, and a 41% lower (-56% to -21%) insulin-like factor 3 level in the highest 5cx-MEPP tertile compared with the lowest. Mono(4-methyl-7-carboxyheptyl) phthalate (7cx-MMeHP, DiNP metabolite) showed elevated odds ratio point estimates for having cryptorchidism (odds ratio = 1.28 [95% CI = 0.80 to 2.01]) and hypospadias (1.69 [0.78 to 3.67]), but was not consistently associated with the steroid hormones or insulin-like factor 3.

CONCLUSIONS: Data on the DEHP metabolite indicate possible interference with human male fetal gonadal function. Considering the DiNP metabolite, we cannot exclude (nor statistically confirm) an association with hypospadias and, less strongly, with cryptorchidism.

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

Urinary phthalate metabolites and biomarkers of oxidative stress in pregnant women: A repeated measures analysis

Authors: Ferguson, KK; Mcelrath, TF; Chen, YH; Mukherjee, B; Meeker, JD (2015) Environmental Health Perspectives 123:210-216. HERO ID: 2718064

[Less] BACKGROUND: Phthalate exposure occurs readily in the environment and has been associated . . . [More] BACKGROUND: Phthalate exposure occurs readily in the environment and has been associated with an array of health endpoints, including adverse birth outcomes. Some of these may be mediated by oxidative stress, a proposed mechanism for phthalate action.

OBJECTIVES: In the present study we explore the associations between phthalate metabolites and biomarkers of oxidative stress measured in urine samples from multiple time points during pregnancy.

METHODS: Women were participants in a nested case-control study of preterm birth (N=130 cases, N=352 controls). Each was recruited early in pregnancy and followed until delivery, providing urine samples at up to 4 visits. Nine phthalate metabolites were measured to assess exposure, and 8-hydroxydeoxyguanosine and 8-isoprostane were also measured in urine as markers of oxidative stress. Associations were assessed using linear mixed models to account for intra-individual correlation, with inverse selection probability weightings based on case status to allow for greater generalizability.

RESULTS: Interquartile range increases in phthalate metabolites were associated with significantly higher concentrations of both biomarkers. Estimated differences were greater in association with mono-benzyl phthalate (MBzP), mono-n-butyl phthalate (MBP), and mono-iso-butyl phthalate (MiBP), compared with di-2-ethylhexyl (DEHP) metabolites.

CONCLUSIONS: Urinary phthalate metabolites were associated with increased oxidative stress biomarkers in our study population of pregnant women. These relationships may be particularly relevant to the study of birth outcomes linked to phthalate exposure. Although replication is necessary in other populations, these results may also be of great importance for a range of other health outcomes associated with phthalates.

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

Analysis of PAEs in semen of infertile men

Authors: Wang, SY; Wang, Y; Xie, FQ; Li, YX; Wan, XL; Ma, WW; Wang, DC; Wu, YH (2015) International Journal of Occupational and Environmental Health 21:40-48. HERO ID: 2718068

[Less] Objectives: Phthalates are environmental chemicals with reproductive toxicity and estrogenic effects . . . [More] Objectives: Phthalates are environmental chemicals with reproductive toxicity and estrogenic effects in animals. They are of increasing concern to human health. Aim: To determine whether phthalate levels in semen were associated with infertility. Methods: Using semen samples from 107 infertile and 94 fertile men, the presence and quantity of five phthalate esters were measured using high-performance liquid chromatography (HPLC). Using data collected from questionnaires and clinical examinations, the correlation between phthalate exposure and semen quality was analyzed. Results: The cumulative levels of the measured phthalate esters were significantly higher in the infertility group compared to the control group (P<0·05). Concentrations of the five phthalate esters in men varied by age with older men showing higher cumulative levels. Conclusions: The presence of phthalates may contribute to male infertility in our study population.

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

Glucocorticoid-like activity of propylparaben, butylparaben, diethylhexyl phthalate and tetramethrin mixtures studied in the MDA-kb2 cell line

Authors: Klopčič, I; Kolšek, K; Dolenc, MS (2015) Toxicology Letters 232:376-383. HERO ID: 5608155

[Less] Endocrine-disrupting compounds can interfere with the endocrine organs or hormone system and cause tumors, . . . [More] Endocrine-disrupting compounds can interfere with the endocrine organs or hormone system and cause tumors, birth defects and developmental disorders in humans. The estrogen-like activity of compounds has been widely studied but little is known concerning their possible modulation of the glucocorticoid receptor. Steroidal (synthetic and natural) and non-steroidal endocrine-active compounds commonly occur as complex mixtures in human environments. Identification of such molecular species, which are responsible for modulating the glucocorticoid receptor are necessary to fully assess their risk. We have used the MDA-kb2 cell line, which expresses endogenous glucocorticoid receptor and a stably transfected luciferase reporter gene construct, to quantify the glucocorticoid-like activity of four compounds present in products in everyday use - propylparaben (PP), butylparaben (BP), diethylhexyl phthalate (DEHP) and tetramethrin (TM). We tested all possible combinations of these compounds at two concentrations (1 μM and 10 nM) and compared their glucocorticoid-like activity. At the concentration of 1 μM seven mixtures were identified to have glucocorticoid-like activity except: DEHP+TM, BP+TM, DEHP+PP+TM, BP+PP+TM. At the concentration of 10 nM only three mixtures have glucocorticoid modulatory activity: DEHP+PP, BP+PP, DEHP+BP+PP+TM. Identified glucocorticoid-like activities were between 1.25 and 1.51 fold at the concentration of 1 μM and between 1.23 and 1.44 fold at the concentration of 10 nM in comparison with the solvent control. Individually BP, PP, and DEHP had glucocorticoid-like activity of 1.60, 1.57 and 1.50 fold over the solvent control at the concentration of 1 μM. On the other hand PP and DEHP, at the concentration of 10nM, showed no glucocorticoid-like activity, while BP showed 1.44 fold. The assertion that individual glucocorticoid-like compounds do not produce harm because they are present at low, ineffective levels in humans may be irrelevant when we include mixed exposures. This study emphasizes that risk assessment of compounds should take mixture effects into account.