Abstract  BIOSIS COPYRIGHT: BIOL ABS. Following earlier work (Al-Omran & Preston, 1987) in which phthalate ester speciation was examined in laboratory studies, the present paper describes the results of an attempt to validate the results by field measurements in the River Mersey Estuary, Liverpool, UK. Samples of water, suspended solids and sediments were analysed for their phthalate ester content. Solid samples were also analysed for their carbon, organic carbon and lipid content. A comparison of the field and laboratory results confirms the association between diethylhexyl phthalate and small particles and shows that other phthalates tend to be associated with relatively coarse, lipid-rich particles. Partition coefficients between dissolved phthalate esters and suspended particles are calculated and compared with other laboratory studies.

Abstract  Despite its wide use in the manufacture of plastics, there is no published information on the developmental toxic potential of di-iso-butyl phthalate (DIBP). Its isomer, di-n-butyl phthalate, have been associated with developmental toxic effects in rodents, especially on the male reproductive system. This study was conducted to assess the effects of orally administered DIBP on the embryonic and fetal development in rats. Groups of 10–14 pregnant Sprague–Dawley rats were given DIBP by gavage (5 ml/kg), on Gestation Day (GD) 6 to 20, at doses of 0 (vehicle: olive oil), 250, 500, 750, or 1000 mg/kg/day. Maternal body weights and clinical signs were recorded. Dams were euthanized on GD 21, and the uterine contents were evaluated for the number of implantation sites, resorptions, fetal deaths, and live fetuses. All live fetuses were weighed and submitted to external examination. They were fixed in 10% neutral-buffered formalin, and internal gross examination of the reproductive tract was performed under a dissecting microscope. Sex was determined by examination of gonads. Maternal body weight gain was significantly depressed at 750 and 1000 mg/kg during the last days of treatment (GD 15–18, and GD 18–21). However, the weight gains during GD 6–21 corrected for uterine weight were comparable across groups (Table 1: see text). A significant increase in the mean percentage of resorptions per litter was observed in a doserelated manner at 500, 750 and 1000 mg/kg. The fetal body weight was significantly decreased at 750 and 1000 mg/kg. External malformations were observed in two fetuses from two different litters at 750 mg/kg: one fetus showed general oedema, and another exhibited multiple malformations including anal atresia, small genital tubercle, ectrodactyly, shortened hindlimbs. Because of their single occurrence and in the absence of a dose–response pattern, they could not be conclusively attributed to DIBP. Undescended testes were apparent in 56 and 70% of the male fetuses at 750 and 1000 mg/kg, respectively. There was no significant difference in the fetal sex ratio between the vehicle controls and the DIBP groups. This study demonstrates the developmental toxicity of DIBP administered to rats, by gavage, throughout the embryonic and fetal period. Further experiments are needed to characterize the full scale of DIBP developmental toxicity.

Abstract  We improved our previous analytical method to measure phthalate metabolites in urine as biomarkers for phthalate exposure by automating the solid-phase extraction (SPE) procedure and expanding the analytical capability to quantify four additional metabolites: phthalic acid, mono-3-carboxypropyl phthalate, mono-isobutyl phthalate (miBP), and monomethyl isophthalate. The method, which involves automated SPE followed by isotope dilution-high performance liquid chromatography (HPLC)-electrospray ionization (ESI)-tandem mass spectrometry (MS), allows for the quantitative measurement of 15 phthalate metabolites in urine with detection limits in the low ng/ml range. SPE automation allowed for the unattended sequential extraction of up to 100 samples at a time, and resulted in an increased sample throughput, lower solvent use, and better reproducibility than the manual SPE. Furthermore, the modified method permitted for the first time, the separation and quantification of mono-n-butyl phthalate (mBP) and its structural isomer miBP. The method was validated on spiked pooled urine samples and on pooled urine samples from persons with no known exposure to phthalates.

Abstract  BIOSIS COPYRIGHT: BIOL ABS. RRM NOTE MOUSE RAT DIBUTYLPHTHALATE

Abstract  BIOSIS COPYRIGHT: BIOL ABS. Recently, a new procedure was developed to estimate total body residues (TBRS) in biota after exposure to complex mixtures of organic chemicals in water. The procedure is based on a simulation of bioconcentration using a hydrophobic phase and on the measurement of total molar concentrations on this hydrophobic phase via vapor pressure osmometry and gas chromatography-mass spectrometry. In this paper, the results of the application of this procedure to effluents and surface water are presented. Estimated TBRs (TBRests) give information on the potential total bioaccumulation of complex mixtures. Moreover, using these estimated total body burdens, baseline toxicity effects can be predicted, including the contributions of chemicals with specific modes of action to the overall baseline toxicity. The advantage of the parameter TBRest is that it determines total molar concentrations of organic chemicals, including those chemicals that are usually not measured because they cann

Abstract  The relation between a dynamic and a thermodynamic temperature, glass transition Tg and boiling point Tb, is investigated for various glass-forming liquids, with emphasis on monohydroxy alcohols. As is well known, Tb and Tg are positively correlated across a large variety of liquids. However, we found that the same quantities show a negative correlation within an isomeric series, i.e., Tb decreases with increasing Tg for different isomers of the same chemical formula. For the alcohol series, CnH2n+1OH with 3 < or = n < or = 10, a master curve of the negative Tg - Tb correlation is obtained if the temperatures are normalized to the respective values of the n-alkanols. This Tg - Tb dependence of isomeric liquids is linked to entropic effects and responsible for much of the scatter of the correlation observed for a large number of molecular organic glass-formers with 45 < Tg < 250 K. Dielectric relaxation is measured for three groups of isomers: (a) 3-methoxyl-1-butanol and 2-iso-propoxyethanol, (b) 1,4-, 1,2-, and 2,4-pentanediol, and (c) di-n- and di-iso-butyl phthalate. Two key parameters of the dynamics, fragility m and stretching exponent beta, are found to be indistinguishable within isomers of moderately different Tgs. Larger fragility differences are readily expected with pronounced structural change, but no systematic trend is observed within an isomer series. The results provide a useful tool for assessing Tg, m, and beta for marginal glass formers on the basis of their isomers.

Abstract  BIOSIS COPYRIGHT: BIOL ABS. RRM JAPAN

Abstract  Studies have shown that phthalate esters traverse the food web and can be found as the original ester in fish. However, concentrations are not expected to be magnified across the food web to a great extent since fish appear more capable of F degrading them than do in- vertebrates. Under conditions of continuous exposure, respiratory and dietary factors influence phthalate ester accumulation. Effects: Lethality: One of the major problems in testing the biological effects of phthalate esters in aqueous systems is their initial or sustained solubility in water The methodological details given in the studies reported allow few definitive statements concerning the actual ester concentrations used. Six phthalate esters have been studied for lethality, detailed studies for most of the organisms involved only DnBP. Lethal concentrations (LC50) for all the aquatic or- ganisms investigated range from 1 to 10 mg/1. The only noted lethal threshold is at a DnBP concentration of 0.5 mg/1 for rainbow trout (Salmo gairdneri). The data on the lethality of dimethylphthalate (DMP), diethylphthalate (DEP) and din-propylphthalate (DnPP) seem generally to fall within the same range as that for DnBP. In contrast, the values for DEHP lethal concentrations (LC50) are at least an order of magnitude higher than those for DnBP. The data for di-n-octylphthalate (DnOP) suggest that it is even less toxic than DEHP. Studies on the mortality of aquatic organisms exposed chroni- cally to phthalate esters are limited in number and difficult to interpret. The data for DnBP indicate that no threshold exists. Several effects of phthalate esters have been reported to occur at what may be considered an acutely lethal range of concentrations. Such effects cannot be truly classified as sublethal but are most probably manifestations of toxicity prior to actual death. Hence, effects such as suppression of respiration, failure of reproduction and survival of young, growth impairment,and depression of heartbeat, although usually considered as sublethal effects, were noted in experiments using acutely lethal concentrations of phthalate esters. Although the mechanisms are not known, DnOP, DEHP and di-iso-butylphthalate (DiBP) were found to suppress respira- tion in a soil not preincubated with phthalate esters. However, soil that had been preincubated did not undergo respiration suppression even at very high ester con- centrations. No variation in either the number of species of microorganisms or other responses, such as respiration, was found after the introduction of DEHP, phthalic acid, or 2-ethylhexanol into an intermittent flow-through hydrosoil. The number of larvae of brine shrimp (Artemia salina) hatched over 24 hours was reduced by 20 and 40 percent because of DEP and DnBP, respectively. No reduction was caused by DMP. There was a sufficient dosage (either in concentration or time) of these phthalate esters to allow for significant mortality in the early-hatching larvae. It has been reported that dietary phthalate esters have an effect upon the survival of zebrafish (Brachydamio rerio) fry. However, it is unclear whether the reduction in survival was due to the parent or the fry feeding on the DEHP in the diet. In addition, the variation in spawns and eggs per spawn may have been within the expected range of the species and the relationship to DEHP concentration was probably coincidental. The only studies that have examined the effects of phthalate esters on growth were carried out with some micro- organisms. The concentrations that inhibit growth are high, been shown to act as heartbeat depressors in goldfish (Cra- ssius auratus). Reductions of approximately 60% were recorded for 12 mg/l DnBP and 200 mg/l benzylbutylphthalate (BBP), respectively. A reduction of 33% was recorded for 200 mg/l DEHP. Sublethal Effects: Very little information is available on the sublethal effects of phthalate esters on aquatic organisms. Depression of reproduction in the water flea (Daphnia magna) has been observed. Di-(2-ethylhexyl)phthalate, in concentrations of 3, 10 an 30 ug/l, reduced egg laying over a 3-week period by 60, 70 and 80% respectively. The growth of rainbow trout fry, adult brook trout (Sulvelinus fontinalis) and fathead minnow fry was not sig- nificantly affected when the fish were exposed to low levels of DEHP; however, vertebral collagen content of bone and hydroxylproline content of collagen were altered. Steroid hormone biosynthesis in male Atlantic cod (Gradus morhus) was affected by DEHP at concentrations as low as 1 ug/g of tissue. The present criteria describing the sublethal effects of phthalate esters on aquatic organisms do not form an adequate scientific base on which to develop water quality objectives for the protection of aquatic life. (Shortened)

Abstract  An extensive body of animal studies has demonstrated that prenatal phthalate exposure, by lowering fetal testicular testosterone, can cause testicular, epididymal, and gubernacular cord agenesis, as well as shortened anogenital distance (AGD). This cluster of abnormalities has been termed the "phthalate syndrome". We present data from the first study to examine AGD and related endpoints in relation to in utero phthalate exposure in humans. Methods: A standardized measure of AGD and some of the genital measurements used to identify the phthalate syndrome in rodents were obtained in boys 2-30 months of age. Alternative methods for adjusting AGD and body weight at examination were compared. Markers of genital development were examined in relation to phthalate metabolite levels in stored prenatal urine samples. These phthalate levels were compared to those measured in a national sample and to those causing phthalate syndrome in rodents. Results: Four phthalate metabolites [monoethyl phthalate (MEP), mono-n-butyl phthalate (MBP), monobenzyl phthalate (MBzP), and mono-isobutyl phthalate (MiBP)] were inversely related to AGD (p-values from 0.012 (MEP) to 0.055 (MBzP). Comparing concentration in the highest to the lowest quartiles, the odds ratio for a shorter-than-predicted AGD ranged from 3.8 to 10.2 (all p-values < 0.05). AGD was more strongly related to a measure of joint exposure to these four phthalate metabolites. Shorter AGD was correlated with a measure of testicular descent and penile volume. The urinary phthalate concentrations associated with shorter AGD were consistent with those that have been measured in one-quarter of the female population of the United States. The median intake estimates associated with reduced AGD are two orders of magnitude below the USEPA reference doses for these chemicals. Discussion: We demonstrated associations between phthalates and genital development that are consistent with the anti-androgenic action of phthalates and the development of the phthalate syndrome previously identified in rodents at higher doses. This study supports the hypothesis that prenatal phthalate exposure can adversely affect reproductive development in male infants and that current regulatory levels may not be adequately protective.

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  The ultraviolet (UV) absorption spectra, aqueous solubility, and distribution coefficients for partitioning between octanol (111875) and water were determined for phthalate esters. The compounds studied were dimethyl-phthalate (131113), diethyl-phthalate (84662), diisopropyl-phthalate (605458), dipropyl-phthalate (131168), diisobutyl-phthalate (84695), dibutyl-phthalate (84742), dipentyl-phthalate (131180), diallyl-phthalate (131179), butyl-benzyl-phthalate (85687), and diethylhexyl-phthalate (117817). The aqueous solubilities and distribution coefficients were determined at 20 degrees-C using gas chromatography or UV spectrophotometry. UV spectra were obtained in aqueous or octanol solutions using 1 centimeter cells in a UV visible spectrophotometer. The UV absorption spectra of aqueous solutions of the compounds coincided within experimental error. The absorption maxima occurred at wavelengths of 198.5, 229.5, 275.5, and 281 nanometers. The corresponding molar absorptivities were 4.54, 3.90, 3.14, and 3.1. The logarithms of the aqueous solubility data were correlated with the logarithms of the octanol and water distribution coefficients for all compounds except dipentyl-phthalate. A linear regression equation was obtained. The UV absorption maximum at 198.5 nanometers has not been previously reported.

Abstract  Rhodococcus erytropolis and Pseudomonas sp. rapidly degrade many kinds of polycyclic aromatic hydrocarbon (PAH) compounds such as phenanthrene and phthalate esters such as di(2-ethylhexyl) phthalate, used as plasticizers. These compounds were efficiently removed from wastewater by inoculating viable cells of Rhodococcus erythropolis and Pseudomonas sp. into activated sludge as a biological treatment system. The rapid PCR method and fluorescent antibody techniques were successfully applied for tracing the specified microorganisms, which were inoculated into a mixed culture system. The relationship of microflora to the removal rate of these compounds such as phthalate esters in inoculated biological treatment systems was examined. The metabolic pathway was investigated and enzymes were purified.

Abstract  In the past it has been demonstrated that small quantities of phthalates may be released from polyvinyl chloride items to physiological solutions. To ascertain the effect these plasticizers might have upon the fetus, a teratogenic study was undertaken in rats using eight phthalate esters. Six of the phthalates, whose acute, i.p. LD50 values were below 10 ml/Kg., were administered to rats at doses representing 1/10, 1/5 and 1/3 of the acute LD50 dose on the 5th, 10th and 15th day of gestation. while the two less toxic compounds were injected at a level of 5 and 10 ml/Kg. Distilled water and normal saline were tested at 10 ml/Kg., and cottonseed oil at 5 and 10 ml/Kg. Untreated animals were used for control values. The number of corpora lutea ranged from 52 to 65 per group of 5 rats. with no apparent distribution according to treatment. Embryo-fetal toxicity ranged from 0% to a high of 98.2%. Petal malformations ranged from 0% to 100%. both for gross and skeletal abnormalities, with skeletal defects generally being more common. Fetuses from all phthalate-treated groups were smaller (P = 0.01) than the untreated controls. Absence of tail, anophthalmia and twisted hind legs were the most common gross abnormalities, while elongated and fused ribs and abnormal skull bones were the most common deformities found in stained skeletal specimens.

Abstract  BIOSIS COPYRIGHT: BIOL ABS. RRM AIR POLLUTION MONITORING

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.