Phthalate Diesters Research Articles

DISTRIBUTION AND EXPOSURE ASSESSMENT THROUGH INHALATION AND DERMAL PATHWAYS TO PHTHALATES IN INDOOR AIR COLLECTED FROM HANOI, VIETNAM

Phthalates (phthalic diesters) is one of endocrine disrupting compound groups which have been recently concerned of the occurrence and harmful effects to human health. In this report, ten common phthalates were analyzed in indoor air collected from hair salons and homes collected from Hanoi, Vietnam. Total concentrations of phthalates in indoor air ranged from 306 to 16000 ng/m3 (mean: 1140 ng/m3). High concentrations of phthalates were measured in indoor air collected from hair salons (mean: 4040 ng/m3). Among the studied phthalates, diethyl phthalate (DEP) was predominant compound and had the highest levels in indoor air. Based on the measured concentrations, the human exposure to phthalates through inhalation and dermal absorption were estimated for various age groups. Overall, the exposure doses decreased with increasing ages.

Endocrine disrupting chemicals in seminal plasma and couple fecundity

Growing evidence supports the importance of men's exposure to non-persistent endocrine disruptors (EDCs) and couple fecundability, as measured by time-to-pregnancy (TTP). This evolving literature contrasts with the largely equivocal findings reported for women's exposures and fecundity. While most evidence relies upon urinary concentrations, quantification of EDCs in seminal plasma may be more informative about potential toxicity arising within the testes. We analyzed 5 chemical classes of non-persistent EDCs in seminal plasma for 339 male partners of couples who were recruited prior to conception and who were followed daily until pregnant or after one year of trying. Benzophenones, bisphenols, parabens, and phthalate metabolites and phthalate diesters were measured using high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) except for phthalate diesters, which were analyzed using gas chromatography-mass spectrometry. Cox regression with discrete-time was used to estimate fecundability odds ratios (FORs) and 95% confidence intervals (CIs) for each chemical to estimate the probability of pregnancy. While most EDCs were detected in seminal plasma, concentrations were lower than urinary concentrations previously analyzed for the cohort. None of the EDCs were significantly associated with fecundability even after covariate adjustment, though benzophenones consistently yielded FORs <1.0 (ranging from 0.72 to 0.91) in couple-adjusted models suggestive of diminished fecundity (longer TTP). The findings underscore that a range of EDCs can be quantified in seminal plasma, but the lower concentrations may require a large cohort for assessing couple fecundability, as well as the need to consider other fecundity outcomes such as semen quality.

In utero combined di-(2-ethylhexyl) phthalate and diethyl phthalate exposure cumulatively impairs rat fetal Leydig cell development

Phthalate diesters, including di-(2-ethylhexyl) phthalate (DEHP) and diethyl phthalate (DEP), are chemicals to which humans are ubiquitously exposed. Humans are exposed simultaneously to multiple environmental chemicals, including DEHP and DEP. There is little information available about how each chemical may interact to each other if they were exposed at same time. The present study investigated effects of the combinational exposure of rats to DEP and DEHP on fetal Leydig cell development. The results showed that the gestational (GD12-20) exposure of DEP + DEHP resulted in synergistic and/or dose-additive effects on the development of fetal Leydig cell. The lowest observed adverse-effect levels (LOAEL) for fetal Leydig cell (aggregation and cell size), and StAR expressions were of 10 mg/kg and, lower than when these chemicals were exposed alone. Also, mathematical modeling the response curves supports the dose-addition model over integrated-addition model. Overall, these data demonstrate that individual phthalate with a similar mechanism of action can elicit cumulative, dose additive, and sometimes synergistic, effects on the development of male reproductive system when administered as a mixture.

Human Milk Phthalate Diester Levels in Turkey

Introduction: Newborn and infants are among the most susceptible age groups to endocrine disruption due to potential environmental toxins like phthalates. Differing results have been found on phthalate exposure through human milk from different geographic parts of the world. In this study, we aim to evaluate six different phthalate diesters in human milk samples. Methods: In this part of the Human Milk Artificial Pollutants (HUMAP) study, human milk samples were analyzed using GC-MS to indicate the presence of bis (2-ethylhexyl) phthalate (DEHP), benzyl butyl phthalate (BBP), dibutyl phthalate (DBP), di-“isononyl” phthalate (DINP), di-“isodecyl” phthalate (DIDP), and di-n-octyl phthalate (DNOP). Results: This study included 72 mothers aged 18 to 41 years; human milk samples were taken from the mothers who gave their consent to participate within 7 to 79 days after birth (mean 34 ± 20 days). We did not detected phthalate esters as DEHP, BBP, DBP, DINP, DIDP, and DNOP in 72 human milk samples. Discussion: In this study, we did not find phthalate diesters in human milk samples in Turkey. Different results of previous studies about human milk phthalate levels might be related to geography, maternal factors, or analytical methods. In conclusion, potential further studies should continue for potential chemical contamination of human milk.

Determination of phthalate diesters and monoesters in human milk and infant formula by fat extraction, size-exclusion chromatography clean-up and gas chromatography-mass spectrometry detection

A sensitive and reliable analytical method was developed for the simultaneous determination of five phthalate diesters and corresponding monoesters in human milk samples and infant formulas. The method involved a liquid–liquid extraction with a CH2Cl2/CH3OH/NaCl 30% 2/1/0.5 (v/v/v) mixture, the clean-up of the extract by size-exclusion chromatography (swelling and elution solvent: cyclohexane/ethyl acetate 9/1v/v), the derivatization of monoesters by trimethylsilyl-diazomethane and instrumental analysis by gas chromatography coupled with mass spectrometry. Recovery was in the range of 83–115% and precision was found between 9% and 21%. For phthalate diesters, method detection limits (MDLs) ranged from hundreds of ng/kg to 4.2μg/kg on a fresh weight milk (f.w.) basis, depending on blank contribution evaluated in matrix. Lower MDLs (0.03-0.8μg/kg f.w.) were achieved for corresponding monoesters. The proposed method was applied to the determination of target compounds in nine human milk samples and four infant formulas, confirming their presence in all samples. However, a generally higher contamination was assessed in artificial milk than in breast milk samples.

Occurrence of phthalate diesters in indoor air from several Northern cities in Vietnam, and its implication for human exposure

Phthalates are used as plasticizers to impart flexibility of plastics. Because of their toxicity, human exposure to phthalates is a concern. Little is known on the occurrence of and inhalation exposure to phthalates in indoor air. In this study, ten phthalates were measured in 97 indoor air samples collected from Northern Vietnam during September 2016 to January 2017. The mean concentrations of total phthalates (i.e., sum of ten phthalates) in particulate and gas phases ranged from 95.2 to 13,100μgg−1 and from 57.0 to 14,900ngm−3, respectively. In bulk indoor air samples (i.e., gas plus particulate phase), the mean concentration of total phthalates ranged from 106 to 16,000ngm−3 (mean: 1040ngm−3). Diethyl phthalate (DEP) was found at the highest concentration in indoor air at a concentration range of below the method quantitation limit (MQL) to 12,400ngm−3 (mean: 376). Among various microenvironments, indoor air collected from hair salons contained the highest concentrations of phthalates (range: 596 to 16,000ngm−3). Among the four northern Vietnamese cities studied, the highest concentrations of phthalates were found in indoor air samples from Hanoi. The calculated mean inhalation exposure doses to phthalates for infants, toddlers, children, teenagers, and adults were 780, 485, 416, 292, and 213ngkg-bw−1d−1, respectively.

Prenatal and childhood exposure to phthalate diesters and sex steroid hormones in 2-, 5-, 8-, and 11-year-old children: A pilot study of the Taiwan Maternal and Infant Cohort Study.

BackgroundPhthalate diesters are commonly used and have been well established as environmental endocrine disruptors. However, few studies have examined their effects on sex steroid hormones in children. We followed children over time to examine the association between pre- and post-natal phthalate exposure and sex steroid hormone levels at 2, 5, 8, and 11 years of age.MethodsWe recruited 430 pregnant women from central Taiwan from 2000 to 2001 and assessed their children at birth, 2, 5, 8, and 11 years of age. We studies children with at least one measurement for both phthalate and hormone levels during each any of the follow-up time point (n = 193). Estradiol, free testosterone, testosterone, and progesterone were measured from venous blood. Three monoesters of di-2-ethylhexyl phthalate (DEHP), mono-benzyl phthalate, mono-n-butyl phthalate, mono-ethyl phthalate, and mono-methyl phthalate were measured in maternal urine collected during the 3rd trimester and child urine collected at each follow-up point. The sum of mono-2-ethylhexyl phthalate (∑MEHP) was calculated by summing the concentrations of the three DEHP monoesters. Generalized estimating equation regression analysis with repeated measures was used to estimate associations between phthalate metabolites and hormone levels.ResultsAfter adjustment for potential confounders, maternal ∑MEHP level was associated with decreased levels of progesterone in girls (β = −0.309 p = 0.001). The child ∑MEHP concentration was associated with decreased levels of progesterone for girls (β = −0.194, p = 0.003) and with decreased levels of free testosterone for boys (β = −0.124, p = 0.004).ConclusionsEarly-life DEHP exposure may alter sex steroid hormones of children over time, which may pose potential reproductive health risks.

Children with atopic dermatitis and frequent emollient use have increased urinary levels of low-molecular-weight phthalate metabolites and parabens.

Parabens may be added to cosmetic and personal care products for preservation purposes. Low-molecular weight (LMW) phthalate diesters function as plasticizers, fixatives or solvents in such products, but may also be found in small quantities as contaminants from plastic containers. To evaluate the association between emollient use, atopic dermatitis and FLG mutations, respectively, with urinary concentrations of phthalate metabolites and parabens in Danish children. Eight hundred and forty-five Danish children 4-9years of age were studied. Urinary concentrations of phthalate metabolites and parabens were determined, and children were genotyped for common FLG loss-of-function mutations. Information about atopic dermatitis and use of emollients was obtained from questionnaires completed by parents. The prevalence of atopic dermatitis was 16.1%. Phthalate metabolite and paraben levels were generally higher in children with frequent use of emollients compared to uncommon users, reaching statistical significance for some LMW phthalates and parabens. While there was no association with common FLG mutations, children with atopic dermatitis had significantly higher urinary levels of one LMW phthalate and two parabens, respectively, when compared to children without atopic dermatitis. Emollient use and atopic dermatitis were associated with modestly increased internal LMW phthalate and paraben exposure in 4-9year old children. It is unknown whether the difference is explained by increased use of the specific emollients that are used to treat pruritic and inflamed skin, and/or whether the impaired skin barrier allows chemicals to penetrate more easily. Moreover, the putative toxicological burden is unknown.

Environmental Phthalate Diesters as hMT1 and hMT2 Melatonin Receptor Ligands

Phthalates esters are commonly used plasticizers that have been linked to endocrine disruption and developmental alterations. Humans are exposed to these ubiquitous synthetic compounds via inhalation of ambient air, dermal contact with consumer products, and ingestion through food and drinking water. It is estimated from urinary metabolite levels that in the US, median adult daily exposure values for phthalate levels are about 8.5–16.8 μg/kg bw/day (Wittassek et al., Mol Nutr Food Res. 55:7–31, 2011). Using integrated pharmacoinformatics‐molecular docking approaches we discovered that several phthalate diesters show structural similarities to melatonin receptor ligands and bind with relatively high docking scores to melatonin binding pockets on in silico hMT1 and hMT2 melatonin receptor models. An assortment of phthalates including three monoesters and ten diesters with alkyl and/or aromatic substituents were tested for competition with 2‐[125I]‐iodomelatonin (100 nM) binding to hMT1 and hMT2 receptors stably expressed in CHO cells to assess binding affinity (Ki) as well as apparent intrinsic efficacy in the presence of GTP (100 μM). In GPCR binding assays, GTP decouples G proteins from receptors causing decreased affinity (rightward shift) for agonists but not for antagonists. Phthalate diesters with aromatic substituents (BBzP: Benzyl Butyl Phthalate; DPP: Diphenyl Phthalate) exhibited the highest affinities toward both hMT1 (BBzP Ki: 2.6 ± 0.3 μM, n=8; DPP Ki: 2.9 ± 0.7 μM, n=8) and hMT2 (BBzP Ki: 1.3 ± 0.2 μM, n=9; DPP Ki: 0.66 ± 0.10 μM, n=9) receptors. Among phthalates with alkyl substituents, four carbon (C4; DBP: Dibutyl Phthalate) and six carbon (C6; DHP: Dihexyl Phthalate) chain length diesters best competed for binding to hMT1 receptors with affinities ranging from 5 to 8 μM. hMT2 receptors did not show any preference to chain lengths of C6 or shorter (DEP: Diethyl Phthalate; DMP: Dimethyl Phthalate; DPrP: Dipropyl Phthalate; DBP; DHP), as all Ki values were between 2 and 7 μM. DBP and BBzP bound to melatonin receptors with affinities in the low micromolar range, however their respective monoester metabolites, MBP (Monobutyl Phthalate) and MBzP (Monobenzyl Phthalate), did not compete for binding to either receptor. The presence of GTP caused a leftward shift of the binding competition curves for both BBzP and DPP at hMT1 melatonin receptors (BBzP KiGTP/KiControl: 3.8; DPP KiGTP/KiControl: 2.6) suggesting inverse agonist efficacy. Little or no shift (BBzP KiGTP/KiControl: 1.3; DPP KiGTP/KiControl: 1.5) on competition curves for hMT2 melatonin receptors suggests antagonist efficacy. Together these data suggest that phthalate diesters could interact with hMT1 and hMT2 receptors to disrupt melatonin receptor‐mediated signaling processes in target tissues.Support or Funding InformationSupported by ES 023684 to MLD and RVR.

Environmental Chemicals Compete for 2‐[125I]‐Iodomelatonin Binding to Melatonin Receptors in Brain Slices from C3H/HeN Mice

Melatonin binds to MT1 and MT2 G protein‐coupled receptors to modulate physiological responses. In‐silico molecular modeling and in‐vitro bioassays support that a common carbamate pesticide, carbaryl, acts as a putative melatonin receptor antagonist at MT1 and agonist at MT2 (Popovska‐Gorevski et al., FASEB J 2014; 28: 662.12) while common plasticizers (phthalate esters) act as inverse agonists at MT1 and antagonists at MT2 (Jones et al. EB Abstract 2017). Due to the persistent and widespread use of phthalates (plastic, vinyl, and leather products) and carbaryl (agriculture), humans are exposed daily to low levels of these compounds in household, food, and water products. Evidence indicates that environmental exposure to pesticides or phthalates are linked to metabolic disorders, though it is not clear which biological targets contribute to disease pathology (Montgomery et al., Am J Epidemiol. 2008, 167[10]: 1235–1246; James‐Todd et al., Environ Int. 2016, 96:118–126). This study assessed the ability and specificity of carbaryl and several commonly used phthalate esters to compete for 2‐[125I]‐iodomelatonin binding in adjacent coronal brain slices (20μm) from C3H/HeN mice using quantitative receptor autoradiography following in‐vitro or ex‐vivo treatment. Optical density (OD) values and specific binding were determined from autoradiograms in brain regions of interest (suprachiasmatic nucleus [SCN] and paraventricular nucleus of the thalamus [PVNT]) known to modulate circadian rhythms, metabolic, behavioral, and cardiovascular responses through actions at melatonin receptors. Environmental chemicals (dibutyl phthalate [DBP], carbaryl, diphenyl phthalate [DPP], benzyl butyl phthalate [BzBP], and diethyl phthalate [DEP]; 1, 10, 100 μM) competed in a concentration dependent manner for 2‐[125I]‐iodomelatonin (75pM) binding to melatonin receptors in brain slices in vitro. The concentrations of environmental chemicals inhibiting binding by 50% (IC50) were 1.31, 1.71, 1.82, 3.76, and 42.1 μM in the SCN and 1.52, 3.75, 1.60, 1.99, and 28.8 μM in the PVNT respectively. In‐vivo administration of carbaryl (10mg/kg, ip) significantly reduced specific 2‐[125I]‐iodomelatonin binding (50pM) OD in SCN brain slices processed ex‐vivo at 30 (mean ± SEM = 1.7 ± 0.12, n=5, p&lt;0.01), 60 (1.5 ± 0.10, n=6, p&lt;0.001), and 120 (1.8 ± 0.06, n=4, p&lt;0.05) minutes post administration compared to vehicle treated mice (2.4 ± 0.15, n=6, One‐Way ANOVA [F5,22=10.14], p&lt;0.05; Dunnet's Post Test), which recovered by 240 minutes (2.5 ± 0.16, n=4). Phthalate diesters (DBP, DPP, BzBP, and DEP) competed for melatonin receptor binding in the SCN and PVNT in a concentration dependent manner, however a phthalate monoester (monobenzyl phthalate) did not (IC50 &gt; 100 μM). Carbaryl competed both in‐vitro (SCN and PVNT) and ex‐vivo (SCN) for melatonin receptor binding in brain slices from C3H/HeN mice demonstrating the ability to reach target areas in the brain responsible for the control of circadian rhythms. Environmental exposure to phthalates or carbaryl may disrupt time of day messages conveyed by endogenous melatonin to its receptors in target tissues such as the SCN and PVNT.Support or Funding InformationSupported by ES 023684 and JSMBS funds to MLD and RVR.

Phthalate release in leachate from municipal landfills of central Poland.

Phthalate diesters (PAEs) are used as plasticizer additives to polymer chains to make the material more flexible and malleable. PAEs are bonded physically, not chemically, to the polymeric matrix and can migrate to and leach from the product surface, posing a serious danger to the environment and human health. There have been a number of studies on PAE concentrations in landfill leachate conducted in the EU and around the world, though few in Poland. In the present study, the leachate of five municipal landfills was analyzed for the presence of PAEs. Raw leachate was sampled four times over the period of one year in 2015/16. It was the first large study on this subject in Poland. PAEs were detected in the leachate samples on all of the landfills, thereby indicating that PAEs are ubiquitous environmental contaminants. The following PAEs were detected in at least one sample: Di(2-ethylhexyl) phthalate (DEHP), Diethyl phthalate (DEP), Dimethyl phthalate (DMP), Di-n-butyl phthalate (DBP), Di-isobutylphthalate (DIBP). Out of all ten PAEs, DEHP was the most predominant, with concentrations up to 73.9 μg/L. DEHP was present in 65% of analyzed samples (in 100% of samples in spring, 80% in winter, and 40% in summer and autumn). In only 25% of all samples DEHP was below the acceptable UE limit for surface water (1.3 μg/L), while 75% was from 1.7 to 56 times higher than that value. On the two largest landfills DEHP concentrations were observed during samples from all four seasons, including on a landfill which has been remediated and closed for the last 5 years.

Wastewater-Based Epidemiology as a New Tool for Estimating Population Exposure to Phthalate Plasticizers.

This study proposes the monitoring of phthalate metabolites in wastewater as a nonintrusive and economic alternative to urine analysis for estimating human exposure to phthalates. To this end, a solid-phase extraction-liquid chromatography-tandem mass spectrometry method was developed, allowing for the determination of eight phthalate metabolites in wastewater (limits of quantification between 0.5 and 32 ng L-1). The analysis of samples from the NW region of Spain showed that these substances occur in raw wastewater up to ca. 1.6 μg L-1 and in treated wastewater up to ca. 1 μg L-1. Concentrations in raw wastewater were converted into levels of exposure to six phthalate diesters. For two of them, these levels were always below the daily exposure thresholds recommended by the U.S. Environmental Protection Agency and the European Food Safety Authority. For the other four, however, estimates of exposure surpassed such a threshold (especially the toddler threshold) in some cases, highlighting the significance of the exposure to phthalates in children. Finally, concentrations in wastewater were also used to estimate metabolite concentrations in urine, providing a reasonable concordance between our results and the data obtained in two previous biomonitoring studies.

Achromobacter denitrificans SP1 efficiently utilizes 16 phthalate diesters and their downstream products through protocatechuate 3,4-cleavage pathway

This study provides physical and analytical evidences for the efficient utilization of most of the commercially available phthalate diesters by Achromobacter denitrificans SP1, coupled with the demonstration of a plausible degradation pathway. We tested 17 phthalate diesters [viz., ditridecyl phthalate, diisodecyl phthalate (DIDP), di(2-ethylhexyl)phthalate (DEHP), di-n-octyl phthalate (DOP), bis(2-ethylhexyl)isophthalate (BEIP), dihexyl phthalate (DHP), dibutyl phthalate (DBP), dicyclohexyl phthalate (DCHP), diphenyl phthalate (DPP), benzyl butyl phthalate (BBP), diamyl phthalate (DAmP), diisobutyl phthalate, dipropyl phthalate, dially phthalate (DAlP), diethyl phthalate, diethyl terephthalate and dimethyl phthalate (DMP)], and their major degradation products for the degradation efficiency of A. denitrificans SP1 in Wx medium. It efficiently utilized 16 phthalate diesters (except DAlP), and showed general preference toward phthalate diesters with longer side chains (utilized ~10mM in 48h) than those with shorter side chains and with cyclic structures (utilized ~5mM in 48h) accompanied by a sharp decline of pH to ~5 from initial 7. In a detailed study, about 37mM (~15g/L) DEHP was utilized in 48h. Moreover, A. denitrificans SP1 produced reddish-pink pigment when DIDP, DEHP, DOP, DHP, DBP, DIBP, BBP, DAmP, DCHP, DPP or DMP was supplied in the medium. From the available evidences, it seems that its putative phthalate diester degradation pathway contains the following check points: phthalate diesters, phthalate monoesters, phthalate (4,5-dioxygenase), protocatechuate (3,4-dioxygenase), and TCA cycle. Nonspecificity toward utilization of phthalate diesters, especially with greater specificity to phthalate diesters having longer side chain, and the characteristic sticky reddish-pink (or colorless) cell clump formation in the presence of phthalate diesters makes A. denitrificans SP1 a very attractive candidate to be employed as an efficient biofactory in waste water treatment processes.

Prenatal and postnatal phthalate exposure and sex hormone changes in a 12-year follow-up birth cohort study

Introduction: Phthalate diesters are well-known environmental endocrine disruptors. However, few studies have examined their effects on children’s sex hormones using a birth cohort follow-up approa...

Exposure to phthalates during pregnancy and thyroid hormones in pregnant women and newborns

Introduction: Phthalates are endocrine disrupting chemicals found in many consumer products. Prior evidence suggests that some phthalates may disrupt thyroid function, but the effect of phthalates on thyroid hormones in pregnant women and neonates has not been thoroughly investigated. Methods: We measured nine phthalate metabolites representing exposure to six parent phthalate diesters in urine collected at ~16 and 26 weeks gestation in a prospective pregnancy and birth cohort. We calculated the mean of 16 and 26 week metabolite concentrations and created exposure quartiles. We measured thyroid stimulating hormone (TSH), free and total thyroxine (FT4, TT4), and triiodothyronine (FT3, TT3) concentrations in maternal serum at ~16 weeks (n=184) and in cord serum (n=275). We estimated the associations of phthalates with maternal or cord thyroid hormones by multivariable linear regression. Results: Mothers in the 4th quartile of urinary monoethyl phthalate (MEP) had 0.05 ng/dL lower FT4 (95%CI -0.09, -0.01) compared to those in the 1st quartile (p-trend=0.02). Cord TSH was 19.8% lower among infants born to women in the 4th quartile of monobenzyl phthalate (MBzP) (95%CI: -34.1, -2.3), compared to those in the 1st quartile (p-trend 0.03). Infants born to mothers in the 4th quartile of di(2-ethylhexyl) phthalate (DEHP) metabolites had decreased cord FT3 [-0.09 pg/mL (95%CI: -0.19, 0.01); p-trend=0.04] versus those in the 1st quartile. We observed marginally significant inverse trends of both MEP (p-trend=0.06) and monoisobutyl phthalate (MiBP) (p-trend=0.06) with cord TT4. Conclusions: In this cohort, maternal urinary MEP was inversely associated with maternal FT4. Maternal urinary concentrations of MBzP, DEHP metabolites, MEP, and MiBP were inversely associated with cord thyroid hormones. These results suggest that maternal exposure to phthalates during pregnancy may disrupt maternal and cord thyroid hormones necessary for normal growth and neurodevelopment.

Phthalate Esters in Indoor Window Films in a Northeastern Chinese Urban Center: Film Growth and Implications for Human Exposure.

Indoor window film samples were collected in buildings during 2014-2015 for the determination of six phthalate diesters (PAEs). Linear regression analysis suggested that the film mass was positively and significantly correlated with the duration of film growth (from 7 to 77 days). PAEs were detected in all window film samples (n = 64). For all the samples with growth days ranged from 7 to 77 days, the median concentrations of total six PAEs (∑6PAEs) in winter and summer window film samples were 9900 ng/m(2) film (2000 μg/g film) and 4700 ng/m(2) film (650 μg/g film), respectively. Among PAEs analyzed, di-2-ethyl-hexyl phthalate (DEHP) was the major compound (71 ± 9.7%), followed by di-n-butyl phthalate (DBP; 20 ± 7.4%) and diisobutyl phthalate (DiBP; 5.1 ± 2.2%). Positive correlations among PAEs suggested their common sources in the window film samples. Room temperature and relative humidity were negatively and significantly correlated with PAEs concentations (in ng/m(2)). Poor ventilation in cold winter in Noreastern China significantly influenced the concentrations of PAEs in window film which suggested higher inhalation exposure dose in winter. The median hazard quotient (HQ) values from PAEs exposure were below 1, suggesting that the intake of PAEs via three exposure pathways was considered as acceptable.

프탈레이트류와 그 대체물질의 내분비계 교란독성: 에스트로겐성과 안드로겐성을 중심으로

Objectives: Although information on the toxicity of phthalate diesters is readily available, little is known about phthalate alternatives. The present article provides a summary of available information on the toxicity of phthalate diesters and their alternatives, with a special focus on estrogenicity and androgenicity. Methods: We collected a battery of in vitro and in vivo assay data from the literature to assess the estrogenicity/anti-estrogenicity and androgenicity/anti-androgenicity of 15 phthalate diesters and 21 phthalate alternatives. Results: A number of in vitro studies show that certain phthalate diesters can bind to estrogen receptors and have a weak estrogenic potential. However, this potential was not seen in in vivo studies. Phthalate diesters produced anti-androgenic effects in animals by reducing testosterone production. Among them, di-(2-ethyl-hexyl) phthalate (DEHP) was the most potent. While almost all phthalate alternatives have a lower toxic potential than does DEHP, evidence of reproductive toxicity and estrogenic potential were found in several substances. Conclusion: Significant data gaps exist for phthalate alternatives regarding reproductive endocrine disruption, requiring further investigation.

Lethal and sublethal effects of phthalate diesters in Silurana tropicalis larvae.

Phthalates are compounds used in polymers to increase their flexibility and are now ubiquitous in the environment as a result of widespread use. Because few studies have focused on the adverse effects of these chemicals in aquatic species, the present study aimed to determine the effects of phthalate diesters in amphibians. Western clawed frog (Silurana tropicalis) tadpoles were acutely exposed to water spiked with monomethyl phthalate (MMP; 1.3-1595.5 mg/L), dimethyl phthalate (DMP; 0.03-924.0 mg/L), or dicyclohexyl phthalate (DCHP; 0.3-99.3 mg/L). Because few studies have addressed the toxicity of these specific phthalates in most organisms, the present study used higher concentrations of these chemicals to determine their toxicity pathways in amphibians and at the same time investigate a suite of genes known to be altered by the well-studied phthalates. Both DMP and DCHP increased larval mortality (9.1-924.0 mg/L DMP and 4.1-99.3 mg/L DCHP), increased frequency of malformations in tadpoles (0.1-34.1 mg/L DMP and 4.1-19.0 mg/L DCHP), and up-regulated cellular stress-related messenger-RNA (mRNA) levels (4.1 mg/L DCHP). To characterize the molecular toxicity pathway of these phthalates in tadpoles, transcriptome analysis was conducted using a custom microarray. Parametric analysis of gene set enrichment revealed important changes in the expression of genes related to drug metabolism and transport, liver metabolism, xenobiotic clearance, and xenobiotic metabolism after DMP and DCHP treatments, although these responses were less pronounced with MMP (the metabolite of DMP). The present study is one of the few studies that demonstrated complementarity between gene expression analysis and organismal effects. Environ Toxicol Chem 2016;35:2511-2522. © 2016 SETAC.

Prenatal phthalate exposure and infant size at birth and gestational duration

BackgroundPhthalate exposure is widespread. Prior research suggests that prenatal phthalate exposure may influence birth size and gestational duration, but published results have been inconsistent. ObjectiveWe quantified the relationship between maternal urinary phthalate concentrations and infant birth weight z-scores, length, head circumference, and gestational duration. MethodsIn a cohort of 368 women from the HOME Study, based in Cincinnati, OH, we measured nine phthalate metabolites representing exposure to six parent phthalate diesters in urine collected at approximately 16 and 26 weeks gestation. Infant birth size and gestational duration were abstracted from medical records. We used multivariable linear regression to estimate covariate adjusted associations between urinary phthalate metabolite concentrations and infant outcomes. ResultsIn unadjusted models, we observed a negative association between monoethyl phthalate (MEP) and birth weight z-scores, while mono-3-carboxypropyl phthalate (MCPP) was positively associated with gestational duration. After covariate adjustment, phthalate metabolite concentrations were no longer associated with birth size or gestational duration. ConclusionsIn this cohort, urinary phthalate metabolite concentrations during pregnancy were not associated with infant birth size or gestational duration. Additional research is needed to determine if exposures during earlier periods of fetal development are associated with infant health.

Dibutyl Phthalate Exposure Disrupts Evolutionarily Conserved Insulin and Glucagon-Like Signaling in Drosophila Males.

Phthalate diesters are commonly used as industrial plasticisers, as well as in cosmetics and skin care products, as a result people are constantly exposed to these xenobiotics. Recent epidemiological studies have found a correlation between circulating phthalate levels and type 2 diabetes, whereas animal studies indicate that phthalates are capable of disrupting endocrine signaling. Nonetheless, how phthalates interfere with metabolic function is still unclear. Here, we show that feeding Drosophila males the xenobiotic dibutyl phthalate (DBP) affects conserved insulin- and glucagon-like signaling. We report that raising flies on food containing DBP leads to starvation resistance, increased lipid storage, hyperglycemia, and hyperphagia. We go on to show that the starvation-resistance phenotype can be rescued by overexpression of the glucagon analogue adipokinetic hormone (Akh). Furthermore, although acute DBP exposure in adult flies is able to affect insulin levels, only chronic feeding influences Akh expression. We establish that raising flies on DBP-containing food or feeding adults DBP food affects the expression of homologous genes involved in xenobiotic and lipid metabolism (AHR [Drosophila ss], NR1I2 [Hr96], ABCB1 [MDR50], ABCC3 [MRP], and CYP3A4 [Cyp9f2]). Finally, we determined that the expression of these genes is also influenced by Akh. Our results provide comprehensive evidence that DBP can disrupt metabolism in Drosophila males, by regulating genes involved in glucose, lipid, and xenobiotic metabolism.