Abstract  Although an association between exposure to phthalates in house dust and childhood asthma or allergies has been reported in recent years, there have been no reports of these associations focusing on both adults and children. We aimed to investigate the relationships between phthalate levels in Japanese dwellings and the prevalence of asthma and allergies in both children and adult inhabitants in a cross-sectional study. The levels of seven phthalates in floor dust and multi-surface dust in 156 single-family homes were measured. According to a self-reported questionnaire, the prevalence of bronchial asthma, allergic rhinitis, allergic conjunctivitis, and atopic dermatitis in the 2 years preceding the study was 4.7%, 18.6%, 7.6%, and 10.3%, respectively. After evaluating the interaction effects of age and exposure categories with generalized liner mixed models, interaction effects were obtained for DiNP and bronchial asthma in adults (Pinteraction=0.028) and for DMP and allergic rhinitis in children (Pinteraction=0.015). Although not statistically significant, children had higher ORs of allergic rhinitis for DiNP, allergic conjunctivitis for DEHP, and atopic dermatitis for DiBP and BBzP than adults, and liner associations were observed (Ptrend<0.05). On the other hand, adults had a higher OR for atopic dermatitis and DEHP compared to children. No significant associations were found in phthalates levels collected from multi-surfaces. This study suggests that the levels of DMP, DEHP, DiBP, and BBzP in floor dust were associated with the prevalence of allergic rhinitis, conjunctivitis, and atopic dermatitis in children, and children are more vulnerable to phthalate exposure via household floor dust than are adults. The results from this study were shown by cross-sectional nature of the analyses and elaborate assessments for metabolism of phthalates were not considered. Further studies are needed to advance our understanding of phthalate toxicity.

Abstract  Background: Preterm birth is a significant public health problem, affecting over 1 in 10 live births and contributing largely to infant mortality and morbidity. Everyday exposure to environmental chemicals such as phthalates could contribute to prematurity, and may be modifiable. In the present study we examine variability in phthalate exposure across gestation and identify windows of susceptibility for the relationship with preterm birth. Methods: Women were recruited early in pregnancy as part of a prospective, longitudinal birth cohort at the Brigham and Women's Hospital in Boston, Massachusetts. Urine samples were collected at up to 4 time points during gestation for phthalate measurement, and birth outcomes were recorded at delivery. From this population we selected all 130 cases of preterm birth, defined as delivery before 37 weeks of completed gestation, as well as 352 random controls. Results: Urinary phthalate metabolite levels were moderately variable over pregnancy, but levels measured at multiple time points were associated with increased odds of preterm birth. Adjusted odds ratios (aOR) for spontaneous preterm birth were strongest in association with phthalate metabolite concentrations measured at the beginning of the third trimester (aOR for summed di-2-ethylhexyl phthalate metabolites [∑ DEHP] = 1.33, 95% confidence interval [CI] = 1.02, 1.73). Odds ratios for placental preterm birth, defined as delivery with presentation of preeclampsia or intrauterine growth restriction, were slightly elevated in the first trimester for DEHP metabolites (aOR for ∑ DEHP = 1.33, 95% CI = 0.99, 1.78). Conclusions: Pregnant women with exposure to phthalates both early and late in pregnancy are at an increased risk of delivering preterm, but mechanisms may differ based on etiology.

Abstract  Approximately 13 million U.S. children less than 6 years old spend some time in early childhood education (ECE) facilities where they may be exposed to potentially harmful chemicals during critical periods of development. We measured five phthalate esters in indoor dust (n = 39) and indoor and outdoor air (n = 40 and 14, respectively) at ECE facilities in Northern California. Dust and airborne concentrations were used to perform a probabilistic health risk assessment to compare estimated exposures with risk levels established for chemicals causing reproductive toxicity and cancer under California's Proposition 65. Di(2-ethylhexyl) phthalate (DEHP) and butyl benzyl phthalate (BBzP) were the dominant phthalates present in floor dust (medians = 172.2 and 46.8 μg/g, respectively), and dibutyl phthalate (DBP), diethyl phthalate (DEP), and diisobutyl phthalate (DIBP) were the dominant phthalates in indoor air (medians = 0.52, 0.21, and 0.10 μg/m(3), respectively). The risk assessment results indicate that 82-89% of children in California ECE had DBP exposure estimates exceeding reproductive health benchmarks. Further, 8-11% of children less than 2 years old had DEHP exposure estimates exceeding cancer benchmarks. This is the largest study to measure phthalate exposure in U.S. ECE facilities and findings indicate wide phthalate contamination and potential risk to developing children.

Abstract  Phthalate exposure during pregnancy has been linked to adverse birth outcomes such as preterm birth, and inflammation and oxidative stress may mediate these relationships. In a prospective cohort study of pregnant women recruited early in gestation in Northern Puerto Rico, we investigated the associations between urinary phthalate metabolites and biomarkers of inflammation, including C-reactive protein, IL-1β, IL-6, IL-10, and TNF-α, and oxidative stress, including 8-hydroxydeoxyguanosine (OHdG) and 8-isoprostane. Inflammation biomarkers were measured in plasma twice during pregnancy (N = 215 measurements, N = 120 subjects), and oxidative stress biomarkers in urine were measured three times (N = 148 measurements, N = 54 subjects) per woman. In adjusted linear mixed models, metabolites of di-2-ethylhexyl phthalate (DEHP) were associated with increased IL-6 and IL-10 but relationships were generally not statistically significant. All phthalates were associated with increases in oxidative stress markers. Relationships with OHdG were significant for DEHP metabolites as well as mono-n-butyl phthalate (MBP) and monoiso-butyl phthalate (MiBP). For 8-isoprostane, associations with nearly all phthalates were statistically significant and the largest effect estimates were observed for MBP and MiBP (49-50% increase in 8-isoprostane with an interquartile range increase in metabolite concentration). These relationships suggest a possible mechanism for phthalate action that may be relevant to a number of adverse health outcomes.

Abstract  The International Union against Tuberculosis and Lung Disease (IUATLD) Bronchial Symptoms Questionnaire (1984) was developed for use in studies of asthma and its reliability measured in an earlier survey in England. The association of the symptoms elicited by this questionnaire to bronchial response to histamine has also been described. This paper presents the results of studies of the questionnaire in four clinical centres in Europe. The reliability of the questionnaire and its ability to predict the bronchial response to histamine were compared for English, Finnish, French and German translations of the questionnaire in samples of diagnosed asthmatics and controls in Nottingham, Berlin, Helsinki and Paris. The answers to questions showed good repeatability, especially in Finland and Germany, particularly those questions on asthma and wheeze. The most sensitive symptom for predicting hyperresponsiveness was the question on wheeze, the most specific questions were those on waking at night with shortness of breath (Paris and Nottingham) and morning tightness (Helsinki and Berlin). This study shows that the IUATLD (1984) questionnaire may provide useful, valid and comparable data even in translation but these studies will need to be repeated in representative samples before such a possibility is accepted as fully demonstrated.

Abstract  In this research, a novel MgCl2-supported TiCl4 catalyst in conjunction with bifunctional internal donor was synthesized. The effects of internal donor on propylene polymerization behaviors and polymer properties (morphology, M (w) and MWD) were investigated. It was found that the activity of novel catalyst was higher than that of the traditional DIBP-based Ziegler-Natta catalyst, while the catalyst activity was less influenced by the ether group length of the bifunctional internal donor. It was also observed that the MWD of PP obtained by bifunctional internal donor-based catalyst was broader than that of PP made by DIBP-based Ziegler-Natta catalyst.

Abstract  Many diseases that manifest throughout the lifetime are influenced by factors affecting fetal development. Fetal exposure to xenobiotics, in particular, may influence the development of adult diseases. Established animal models provide systems for characterizing both developmental biology and developmental toxicology. However, animal model systems do not allow researchers to assess the mechanistic effects of toxicants on developing human tissue. Human fetal tissue xenotransplantation models have recently been implemented to provide human-relevant mechanistic data on the many tissue-level functions that may be affected by fetal exposure to toxicants. This review describes the development of human fetal tissue xenotransplant models for testis, prostate, lung, liver, and adipose tissue, aimed at studying the effects of xenobiotics on tissue development, including implications for testicular dysgenesis, prostate disease, lung disease, and metabolic syndrome. The mechanistic data obtained from these models can complement data from epidemiology, traditional animal models, and in vitro studies to quantify the risks of toxicant exposures during human development

Abstract  Indoor phthalate levels were investigated in 28 buildings, including 14 office and 14 residential buildings in Xi'an, China. Phthalate esters in the gas-, particle-, and dust- phase were measured separately. Four phthalates including dimethyl phthalate (DMP), diisobutyl phthalate (DiBP), di-n-butyl phthalate (DnBP) and di(2-ethylhexyl) phthalate (DEHP) were detected. The detection frequency of DnBP and DEHP was more than 90%. The concentrations of total phthalate esters ranged from 0.20 to 8.29 μg m−3 for the gas- phase, from 0.09 to 14.77 μg m−3 for the particle- phase and from 123 to 9504 μg g−1 for the dust- phase. The individual phthalate with the highest concentrations of 6.17 μg m−3, 7.97 μg m−3 and 7228 μg g−1 respectively for gas-, particle- and dust- phase in all investigated rooms is all DiBP. The median concentration of the gas- and particle-phase DiBP (0.52 and 0.72 μg m−3) and dust-phase DEHP (582 μg g−1) were the highest. It was also found that the average concentrations of individual phthalates in residential buildings were often higher than in office buildings, and correlation analysis indicated that DiBP, DnBP and DEHP might come from the same sources. Based on the gas- and particle-phase concentrations measured, the particle-air partition coefficients of phthalates were estimated, and their logarithm values were found to be linearly correlated with the logarithm values of their octanol-air partition coefficients. Finally, the total daily exposure to indoor phthalates in air and dust was calculated, and ranged from 2.6 μg kg−1 day−1 (for adults) to 7.4 μg kg−1 day−1 (for toddlers).

Abstract  Diisodecyl phthalate (DiDP) is an isomeric mixture of phthalates with predominantly 10-carbon branched-dialkyl chains, widely used as a plasticizer for polyvinyl chloride. The extent of human exposure to DiDP is unknown in part because adequate biomarkers of exposure to DiDP are not available. We identified several major metabolites of DiDP in urine of adult female Sprague–Dawley rats after a single oral administration of DiDP (300 mg/kg). These metabolites can potentially be used as biomarkers of exposure to DiDP. The metabolites extracted from urine were chromatographically resolved and identified by their chromatographic behavior and full scan negative ion electrospray ionization mass spectrum. The identity of metabolites with similar molecular weights was further examined in accurate mass mode. For some metabolites, unequivocal identification was done using authentic standards. Among these were the hydrolytic monoester of DiDP, monoisodecyl phthalate (MiDP), detected as a minor metabolite, and one ω oxidation product of MiDP, mono(carboxy-isononyl) phthalate (MCiNP), which was the most abundant urinary metabolite. We also tentatively identified other secondary metabolites of MiDP, mono(hydroxy-isodecyl) phthalate, mono(oxo-isodecyl) phthalate, mono(carboxy-isoheptyl) phthalate, mono(carboxy-isohexyl) phthalate, mono(carboxy-isopentyl) phthalate, mono(carboxy-isobutyl) phthalate, and mono(carboxy-ethyl) phthalate. Oxidative metabolites of diisoundecyl phthalate (DiUdP) and diisononyl phthalate (DiNP) were also detected suggesting the presence of DiUdP and DiNP in the DiDP formulation. The urinary concentrations of all these metabolites gradually decreased in the 4 days following the administration of DiDP. MCiNP and other DiDP secondary metabolites are more abundant in urine than MiDP, suggesting that these oxidative products are better biomarkers for DiDP exposure assessment than MiDP. Additional research on the toxicokinetics of these metabolites is needed to understand the extent of human exposure to DiDP from the urinary concentrations of MCiNP and other DiDP secondary metabolites.

Abstract  Part of the Water Environment Federation 1998 Literature Review. A literature review on the effects of pollutants on freshwater organisms is presented. The review is organized by pollutant category and by major receptor.

Abstract  An anaerobic gas production test was used for determining the potential biodegradation of 22 organic chemicals under methanogenic conditions. Nine of the examined chemicals were extensively mineralized ( > 75%) both in sewage sludge and in a freshwater swamp indicating good agreement between biodegradation potentials in these habitats. Samples from a marine sediment showed a less extensive mineralization of most of the test chemicals, and lag periods of several weeks often preceded net gas production. As marine sediments usually contain sulfate at the time of collection, the assessment of biodegradation potentials in such environments is probably more reliable when using a method based on sulfate reduction instead of methanogenic gas production. The results of the tests indicate that the commonly recommended washing of sludge solids can be eliminated by applying a more diluted inoculum.

Abstract  Studies have been carried out on the simultaneous determination of 8 phthalates, i. e. di-ethyl phthalate (DEP) , di-propyl phthalate (DPP) , di-isobutyl phthalate (DIBP) , dibutyl phthalate (DBP) , benzyl butyl phthalate ( BBP) , di-cyclohexyl phthalate (DCHP) , di-(2-ethylhexyl) phthalate (DEHP), di-octyl phthalate (DOP) and 4 parabens, i. e. methylparaben (MPB), ethylparaben (EPB), propyl paraben (PPB), and butyl paraben (BPB) by gas chromatography in combination with mass spectrometry (GC/MS) in electron ionisation mode (EI) with selected-ion monitoring (SIM) acquisition method. The phthalates and parabens in 15 cosmetic products, including hair sprays, perfumes, deodorants, cream, lotion, etc. were determined. The determination of the samples were performed after sonication-assisted extraction with methanol, cleaned up with an LC-C18 column (3 mL) and analyzed by GC/MS method. The base peak (m/z 149) of the phthalates and the base peak (m/z 121) of the parabens were selected for the screening studies. The characteristic ions, m/z 121, 149, 177, 222 for DEP; m/z 149, 191, 209 for DPP; m/z 57, 149, 223 for DIBP; m/z 104, 149 for DBP; m/z 91, 132, 149, 206 for BBP; m/z 55, 149, 167 for DCHP; m/z 113, 149, 167, 279 for DEHP; m/z 149, 279 for DOP; m/z 65, 93, 121, 152 for MPB; m/z 93, 121, 138, 166 for EPB; m/z 93, 121, 138, 180 for PPB; and m/z 93, 121, 138, 194 for BPB were chosen for quantitative studies. These techniques are capable to detect phthalates and parabens at the level of 0. 1 -5. 0 microg/kg. Overall recoveries were 80% - 100% with relative standard deviations (RSDs) less than 10%. Only one of the 15 examined samples was free from phthalates and parabens. The rest 14 samples were found to contain at least 3 or more of these phthalates and/or parabens. The predominant phthalates detected in the studied samples were MPB, PPB, DPP, DCHP and DEHP. The residue levels were at 1. 42 -4 278 mg/kg.

Abstract  The genotoxicity of phthalates, widely used plasticizers, has been shown previously for di-butyl-phthalate (DBP) and di-iso-butyl-phthalate (DiBP) in human mucosal cells of the upper aerodigestive tract in a previous study using the Comet assay. Furthermore, higher genotoxic sensitivities of patients with squamous cell carcinomas of either the larynx or the oropharynx compared to non-tumor patients were described. Other authors have demonstrated DNA damage by a different phthalate in human hymphocytes. It was the aim of the present study to determine whether there is a correlation between the genotoxic sensitivities to DBP and its isomer DiBP in either mucosal cells or lymphocytes. The single-cell microgel electrophoresis assay (Comet assay) was applied to detect DNA strand breaks in human epithelial cells of the upper aerodigestive tract (n=132 specimens). Human mucosa was harvested from the oropharynx in non-tumor pateints and patients with squamous cell carcinomas of the oropharynx. Laryngeal mucosa of patients with laryngeal squamous cell carcinomas was harvested as well. Peripheral lymphocytes (n=49 speciments) were separated from peripheral blood. Xenobiotics investigated were DBP, DiBP, and N'methyl-N'-nitro-N-nitrosoguanidine (MNNG) as positive control, respectively. For statistical analysis, the SPSS correlation analysis according to Pearson and the Wilcoxon test were performed. Genotoxicity was found for DBP and DiBP in epithelial cells and lymphocytes (P<0.001). MNNG caused severe DNA damage. In analyzing DPB and DiBP results, genotoxic impacts in mucosal cells showed an intermediate correlation (r=0.570) Correlation in lymphocytes was the same (r=0.570). Phthalates have been investigated as a potential health hazard for a variety of reasons, including the possible xenoestrogenic impact, peroxisome proliferation, and membrane destabilization. The present investigation suggests a correlated DNA-damaging impact of DBP and DiBP in human mucosal cells and in lymphocytes, respectively.

Abstract  Phthalate esters are found in a wide variety of consumer and food packing products. Hence there is widespread exposure of the human population to these chemicals. Some of the phthalate esters are known to be toxic to the developing male reproductive system. This paper derives a reference dose (RfD) for each of the phthalate esters (dibutyl phthalate, diisobutyl phthalate, butylbenzyl phthalate, diethylhexyl phthalate, dipentyl phthalate, and diisononyl phthalate) that cause these effects. As these phthalate esters cause similar adverse biological effects and have the same mechanism of action, it is appropriate in a risk assessment to consider the potential adverse effects from cumulative exposure to these chemicals using a dose addition model. This paper provides examples of a cumulative risk assessment using the hazard index and relative potency approaches from the RfDs derived from studies in laboratory animals and exposure information in people. The results of the cumulative risk assessments for both a US and a German population show that the hazard index is below one. Thus it is unlikely that humans are suffering adverse developmental effects from current environmental exposure to these phthalate esters.

Abstract  Carcinogenesis in the upper aerodigestive tract is influenced by multiple factors. Besides tobacco and alcohol consumption, specific pollutants such as phthalates, nitrosamines, and polycyclic aromatic carbohydrates may be important in tumor initiation. Genetic factors related to mutagen sensitivity and DNA repair capacity also play a role. The aim of this study was to investigate whether human peripheral blood lymphocytes and mucosal epithelium of the upper aerodigestive tract, the target for volatile and liquid xenobiotics, are equally sensitive to genotoxic agents. The Comet assay was used to detect for DNA damage induced by genotoxic agents in mucosal epithelial cells and peripheral blood lymphocytes of 60 volunteers. Mucosa was harvested from larynx, oropharynx, and inferior nasal turbinates. Xenobiotics investigated were dibutylphthalate (DBP), diisobutylphthalate (DiBP), N'-nitrosodiethylamine (NDELA), benzo[a]pyrene (B[a]P), and N'-methyl-N'-nitro-N-nitrosoguanidine (MNNG). DBP, DiBP, B[a]P, NDELA and MNNG induced a significant increase in DNA migration in both cell populations. Peripheral blood lymphocytes were more sensitive than mucosal cells to DBP and DiBP, but not to NDELA and B[a]P. The correlation, in terms of DNA migration, between lymphocytes and mucosal cells among volunteers was relatively poor. Based on the poor correlation in response between the two cell types, the sensitivity of peripheral blood lymphocytes to genotoxic agents appears to be a poor predictor of sensitivity in the target cells of the upper aerodigestive tract. Further attention should be focused on intra-individual mutagen sensitivities and inter-individual genetic differences as regards susceptibility to upper aerodigestive tract cancer.

Abstract  BACKGROUND: Phthalates are widely used chemicals, and human exposure is extensive. Recent studies have indicated that phthalates may have thyroid-disrupting properties. OBJECTIVE: We aimed to assess concentrations of phthalate metabolites in urine samples from Danish children and to investigate the associations with thyroid function, insulin-like growth factor I (IGF-I), and growth. METHODS: In 845 children 4-9 years of age, we determined urinary concentrations of 12 phthalate metabolites and serum levels of thyroid-stimulating hormone, thyroid hormones, and IGF-I. RESULTS: Phthalate metabolites were detected in all urine samples, of which monobutyl phthalate was present in highest concentration. Phthalate metabolites were negatively associated with serum levels of free and total triiodothyronine, although statistically significant primarily in girls. Metabolites of di(2-ethylhexyl) phthalate and diisononyl phthalate were negatively associated with IGF-I in boys. Most phthalate metabolites were negatively associated with height, weight, body surface, and height gain in both sexes. CONCLUSIONS: Our study showed negative associations between urinary phthalate concentrations and thyroid hormones, IGF-I, and growth in children. Although our study was not designed to reveal the mechanism of action, the overall coherent negative associations between urine phthalate and thyroid and growth parameters may suggest causative negative roles of phthalate exposures for child health.

Abstract  A large number of phthalate esters were screened for estrogenic activity using a recombinant yeast screen. a selection of these was also tested for mitogenic effect on estrogen-responsive human breast cancer cells. A small number of the commercially available phthalates tested showed extremely weak estrogenic activity. The relative potencies of these descended in the order butyl benzyl phthalate (BBP) > dibutyl phthalate (DBP) > diisobutyl phthalate (DIBP) > diethyl phthalate (DEP) > diisiononyl phthalate (DINP). Potencies ranged from approximately 1 x 10(6) to 5 x 10(7) times less than 17beta-estradiol. The phthalates that were estrogenic in the yeast screen were also mitogenic on the human breast cancer cells. Di(2-ethylhexyl) phthalate (DEHP) showed no estrogenic activity in these in vitro assays. A number of metabolites were tested, including mono-butyl phthalate, mono-benzyl phthalate, mono-ethylhexyl phthalate, mon-n-octyl phthalate; all were wound to be inactive. One of the phthalates, ditridecyl phthalate (DTDP), produced inconsistent results; one sample was weakly estrogenic, whereas another, obtained from a different source, was inactive. analysis by gel chromatography-mass spectometry showed that the preparation exhibiting estrogenic activity contained 0.5% of the ortho-isomer of bisphenol A. It is likely that the presence of this antioxidant in the phthalate standard was responsible for the generation of a dose-response curve--which was not observed with an alternative sample that had not been supplemented with o,p'-bisphenol A--in the yeast screen; hence, DTDP is probably not weakly estrogenic. The activities of simple mixtures of BBP, DBP, and 17beta-estradiol were assessed in the yeast screen. No synergism was observed, although the activities of the mixtures were approximately additive. In summary, a small number of phthalates are weakly estrogenic in vitro. No data has yet been published on whether these are also estrogenic in vitro. No data has yet been published on whether these are also estrogenic in vivo; this will require tests using different classes of vertebrates and different routes of exposure.

Abstract  We investigated the relationship between prenatal maternal urinary concentrations of phthalate metabolites and neonatal behavior in their 295 children enrolled in a multiethnic birth cohort between 1998 and 2002 at the Mount Sinai School of Medicine in New York City. Trained examiners administered the Brazelton Neonatal Behavioral Assessment Scale (BNBAS) to children within 5 days of delivery. We measured metabolites of 7 phthalate esters in maternal urine that was collected between 25 and 40 weeks' gestation. All but two phthalate metabolites were over 95% detectable. We summed metabolites on a molar basis into low and high molecular weight phthalates. We hypothesized the existence of sex-specific effects from phthalate exposure a priori given the hormonal activity of these chemicals. Overall we found few associations between individual phthalate metabolites or their molar sums and most of the BNBAS domains. However, we observed significant sex-phthalate metabolite interactions (p<0.10) for the Orientation and Motor domains and the overall Quality of Alertness score. Among girls, there was a significant linear decline in adjusted mean Orientation score with increasing urinary concentrations of high molecular weight phthalate metabolites (B=-0.37, p=0.02). Likewise, there was a strong linear decline in their adjusted mean Quality of Alertness score (B=-0.48, p<0.01). In addition, boys and girls demonstrated opposite patterns of association between low and high molecular weight phthalate metabolite concentrations and motor performance, with some indication of improved motor performance with increasing concentration of low molecular weight phthalate metabolites among boys. This is the first study to report an association between prenatal phthalate exposure and neurological effects in humans or animals, and as such requires replication.

Abstract  BACKGROUND: The ubiquitous use of phthalate esters in plastics, personal care products and food packaging materials results in widespread general population exposure. In this report, we extend our preliminary study on the relationship between urinary concentrations of phthalate metabolites and sperm DNA damage among a larger sample of men and include measurements of mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) and mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), two oxidative metabolites of di-(2-ethylhexyl) phthalate (DEHP). METHODS: Among 379 men from an infertility clinic, urinary concentrations of phthalate metabolites were measured using isotope-dilution high-performance liquid chromatography-tandem mass spectrometry. Sperm DNA damage measurements, assessed with the neutral comet assay, included comet extent (CE), percentage of DNA in tail (Tail%) and tail distributed moment (TDM). RESULTS: Monoethyl phthalate (MEP), a metabolite of diethyl phthalate, was associated with increased DNA damage, confirming our previous findings. Mono-(2-ethylhexyl) phthalate (MEHP), a metabolite of DEHP, was associated with DNA damage after adjustment for the oxidative DEHP metabolites. After adjustment for MEHHP, for an interquartile range increase in urinary MEHP, CE increased 17.3% [95% confidence interval (CI) = 8.7-25.7%], TDM increased 14.3% (95% CI = 6.8-21.7%) and Tail% increased 17.5% (95% CI = 3.5-31.5%). CONCLUSIONS: Sperm DNA damage was associated with MEP and with MEHP after adjusting for DEHP oxidative metabolites, which may serve as phenotypic markers of DEHP metabolism to 'less toxic' metabolites. The urinary levels of phthalate metabolites among these men were similar to those reported for the US general population, suggesting that exposure to some phthalates may affect the population distribution of sperm DNA damage.

Abstract  BACKGROUND: Phthalates may pose a risk for perinatal developmental effects. An important question relates to the choice of suitable biological matrices for assessing exposure during this period. OBJECTIVES: This study was designed to measure the concentrations of phthalate diesters or their metabolites in breast milk, blood or serum, and urine and to evaluate their suitability for assessing perinatal exposure to phthalates. METHODS: In 2001, 2-3 weeks after delivery, 42 Swedish primipara provided breast milk, blood, and urine samples at home. Special care was taken to minimize contamination with phthalates (e.g., use of a special breast milk pump, heat treatment of glassware and needles, addition of phosphoric acid). RESULTS: Phthalate diesters and metabolites in milk and blood or serum, if detected, were present at concentrations close to the limit of detection. By contrast, most phthalate metabolites were detectable in urine at concentrations comparable to those from the general population in the United States and in Germany. No correlations existed between urine concentrations and those found in milk or blood/serum for single phthalate metabolites. Our data are at odds with a previous study documenting frequent detection and comparatively high concentrations of phthalate metabolites in Finnish and Danish mothers' milk. CONCLUSIONS: Concentrations of phthalate metabolites in urine are more informative than those in milk or serum. Furthermore, collection of milk or blood may be associated with discomfort and potential technical problems such as contamination (unless oxidative metabolites are measured). Although urine is a suitable matrix for health-related phthalate monitoring, urinary concentrations in nursing mothers cannot be used to estimate exposure to phthalates through milk ingestion by breast-fed infants.

Abstract  Background: High exposure to phthalates, which are ubiquitous contaminants, has been shown in animal studies to produce detrimental effects on male reproductive functions. A recent study in humans reported dose–response relations between low phthalate levels in urine and human semen parameters, which raises the question whether humans are more sensitive to phthalate exposure than animals. Methods: Urine, serum, and semen samples were collected from 234 young Swedish men at the time of their medical conscript examination. Semen volume, sperm concentration, and motility were measured, together with sperm chromatin integrity (sperm chromatin structure assay) and biochemical markers of epididymal and prostatic function. We analyzed reproductive hormones in serum, and mono ethyl phthalate (MEP), mono ethylhexyl phthaltale (MEHP), mono benzyl phthalate (MBzP), mono butyl phthalate (MBP), and phthalic acid in urine. Results: For MBP, MBzP, and MEHP, no clear pattern of associations were observed with any of the reproductive biomarkers. Subjects within the highest quartile for MEP had fewer motile sperm (mean difference = 8.8%; 95% confidence interval = 0.8–17), more immotile sperms (8.9%; 0.3–18), and lower luteinizing hormone values (0.7 IU/L; 0.1–1.2), but there was no suggestion of harmful effects for most other endpoints. Phthalic acid actually was associated with improved function, as measured by several markers. Conclusions: The observed weak associations between 1 phthalate biomarker and impairment of a few aspects of reproductive function biomarkers were not consistent with results from a recent U.S. study. It is not yet possible to conclude whether phthalate exposure may reflect a hazard for human male reproduction.

Abstract  BACKGROUND: Rates of preterm birth have been rising over the past several decades. Factors contributing to this trend remain largely unclear, and exposure to environmental contaminants may play a role. OBJECTIVE: We investigated the relationship between phthalate exposure and preterm birth. METHODS: Within a large Mexican birth cohort study, we compared third-trimester urinary phthalate metabolite concentrations in 30 women who delivered preterm (< 37 weeks of gestation) with those of 30 controls (> or = 37 weeks of gestation). RESULTS: Concentrations of most of the metabolites were similar to those reported among U.S. females, although in the present study mono-n-butyl phthalate (MBP) concentrations were higher and monobenzyl phthalate (MBzP) concentrations lower. In a crude comparison before correcting for urinary dilution, geometric mean urinary concentrations were higher for the phthalate metabolites MBP, MBzP, mono(3-carboxylpropyl) phthalate, and four metabolites of di(2-ethyl-hexyl) phthalate among women who subsequently delivered preterm. These differences remained, but were somewhat lessened, after correction by specific gravity or creatinine. In multivariate logistic regression analysis adjusted for potential confounders, elevated odds of having phthalate metabolite concentrations above the median level were found. CONCLUSIONS: We found that phthalate exposure is prevalent among this group of pregnant women in Mexico and that some phthalates may be associated with preterm birth.

Abstract  OBJECTIVE: To monitor the level of phthalates in human semen samples and to analyze the relationship between phthalate levels and semen parameters. METHODS: Concentrations of three kinds of commonly used phthalates (di-ethyl phthalate, DEP; di-n-butyl phthalate, DBP; di-2-ethylhexyl phthalate, DEHP) were measured using reversed-phase HPLC. Semen parameters were measured by computer aided sperm analysis (CASA). RESULTS: The three phthalates were detected in most of the biological samples, with median levels of 0.30 mg/L (0.08-1.32 mg/L) in semen specimens. There was a significant positive association between liquefied time of semen and phthalate concentrations of semen. The correlation coefficient was 0.456 for DEP, 0.475 for DBP, and 0.457 for DEHP, respectively. There was no significant difference between phthalate concentrations of semen and sperm density or livability, though the correlation coefficients were negative. CONCLUSION: These results suggest that people who reside in Shanghai are exposed to phthalates, especially to DBP and DEHP. Although the level of phthalates is relatively mild, an association of phthalate levels and reduced quality of human semen has been shown in the present study.

Abstract  BACKGROUND: Widespread human exposure to phthalates, some of which are developmental and reproductive toxicants in experimental animals, raises concerns about potential human health risks. Underappreciated sources of exposure include phthalates in the polymers coating some oral medications. OBJECTIVE: The objective of this study was to evaluate whether users of phthalate-containing medications have higher urinary concentrations of phthalate metabolites than do nonusers. METHODS: We used publically available files from the National Health and Nutrition Examination Survey for the years 1999-2004. For certain survey periods, participants were asked to recall use of prescription medication during the past 30 days, and for a subsample of individuals, the urinary concentrations of phthalate metabolites were measured. We a priori identified medications potentially containing phthalates as inactive ingredients and then compared the mean urinary concentration of phthalate metabolites between users and nonusers of those medications. RESULTS: Of the 7,999 persons with information on urinary phthalate concentrations, 6 reported using mesalamine formulations, some of which may include dibutyl phthalate (DBP); the mean urinary concentration of monobutyl phthalate, the main DBP metabolite, among these mesalamine users was 50 times higher than the mean for nonusers (2,257 microg/L vs. 46 microg/L; p < 0.0001). Users of didanosine, omeprazole, and theophylline products, some of which may contain diethyl phthalate (DEP), had mean urinary concentrations of monoethyl phthalate, the main DEP metabolite, significantly higher than the mean for nonusers. CONCLUSION: Select medications might be a source of high exposure to some phthalates, one of which, DBP, shows adverse developmental and reproductive effects in laboratory animals. These results raise concern about potential human health risks, specifically among vulnerable segments of the general population and particularly pregnant women and children.