Abstract  Phthalic acid esters (PAE) are commonly found in the sludge generated in the wastewater treatment plants. Anaerobic digestion followed by land application is a common treatment and disposal practice of sludge. To date, many studies exist on the anaerobic biodegradation rates of PAE, especially of the easily biodegradable ones, whereas the higher molecular weight PAE have reported to be non-biodegradable under methanogenic conditions. Furthermore, there is no information on the effect of the PAE on the performance of the anaerobic digesters treating sludge. In this study, the anaerobic biodegradation of di-n-butyl phthalate (DBP), di-ethyl phthalate (DEP) and di-ethylhexyl phthalate (DEHP) was investigated and their relative rates of anaerobic degradation were calculated. Also, the biological removal of PAE during the anaerobic digestion of sludge in bench-scale digesters was investigated using DBP and DEHP as model compounds of one biodegradable and one recalcitrant PAE respectively. The degradation of all the PAE tested in this study (DEP, DBP and DEHP) is adequately described by first-order kinetics. Batch and continuous experiments showed that DEP and DBP present in sludge are rapidly degraded under mesophilic anaerobic conditions (a first-order kinetic constant of 8.04 x 10(-2) and 13.69 x 10(-2)-4.35 day(-1) respectively) while DEHP is degraded at a rate between one to two orders of magnitude lower (0.35 x 10(-2)-3.59 x 10(-2) day(-1)). It is of high significance that experiments with anaerobic sludge of different origin (US and Europe) showed that degradation of DEHP occurs under methanogenic conditions. Accumulation of high levels of DEHP (more than 60 mg/l) in the anaerobic digester has a negative effect on DBP and DEHP removal rates as well as on the biogas production

Abstract  Of the many compounds that leach from respiratory therapy tubing into air passing through it, we selected five compounds to analyze. The five compounds are known to be potentially carcinogenic, toxic or known to induce estrogenic activity. Parts-per-million and parts-per-billion concentrations of these species were found in the air passing through the tubing: the plasticizers di-(2-ethylhexyl) phthalate (DEHP) and di-ethyl phthalate (DEP), the antioxidants butylated hydroxy toluene (BHT) and p-nonylphenol (p-NP), and the contaminant (from commercial preparation of DEHP) 2-ethylhexanol (2-EH). These levels are high enough to cause some concern about exposure for patients who use oxygen on a long-term basis, those sensitive or allergic to these species, or those with asthma. A method was developed for analysis of solid tubing samples, showing great variability in concentrations of small, volatile molecules from sample to sample. A method was also developed for pre-concentration of small molecules onto Tenax adsorbants from air passing through the tubing. Both solid samples and adsorbant loaded with analyte were analyzed by direct dynamic thermal desorption gas chromatography mass spectrometry (GCMS). This study does not imply that adverse reactions by patients to chemical compounds leaching from respiratory medical tubing will occur but that further investigation is warranted

Abstract  For screening chemicals possessing endocrine disrupting potencies, the uterotrophic assay has been placed in a higher level in the OECD testing framework than the ER binding assay to detect ER-mediated activities. However, there are no studies that can demonstrate a clear relationship between these assays. In order to clarify the relationship between the in vitro ER binding and in vivo uterotrophic assays and to determine meaningful binding potency from the ER binding assay, we compared the results from these assays for 65 chemicals spanning a variety of chemicals classes. Under the quantitative comparison between logRBAs (relative binding affinities) and logLEDs (lowest effective doses), the log RBA was well correlated with both logLEDs of estrogenic and anti-estrogenic compounds at r(2)=0.67 (n=28) and 0.79 (n=23), respectively. The RBA of 0.00233% was found to be the lowest ER binding potency to elicit estrogenic or anti-estrogenic activities in the uterotrophic assay, accordingly this value is considered as the detection limit of estrogenic or anti-estrogenic activities in the uterotrophic assay. The usage of this value as cutoff provided the best concordance rate (82%). These findings are useful in a tiered approach for identifying chemicals that have potential to induce ER-mediated effects in vivo.

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  The authors investigated the inhibitory effects of phthalate esters and alkylphenols on steroidogenesis by human adrenocortical H295R cells, a model of human steroidogenic cells. Dicyclohexyl phthalate (DCHP) at a concn. of 30 ?M produced a significant decrease in the dibutyryl cAMP-stimulated cortisol secretion (76% redn.). 4-t-Pentylphenol (4-t-PP), 4-t-octylphenol (4-t-OP) and 4-nonylphenol (4-NP) also produced significant decreases in the dibutyryl cAMP-stimulated cortisol secretion by 58, 34 and 40%, resp. at 50 ?M. Redns. in cortisol secretion by these chems. were dose-dependent. To elucidate the inhibitory effects of DCHP, 4-t-PP, 4-t-OP and 4-NP on cortisol secretion from H295R cells, the effects of these chems. on various steroidogenic enzymes, such as C20,22-lyase (CYP11A), 3?-hydroxysteroid dehydrogenase type II (3?-HSDII), 17?-hydroxylase/C17,20-lyase (CYP17), 21-hydroxylase (CYP21B) and 11?-hydroxylase (CYP11B1), were investigated. DCHP significantly inhibited CYP21B activity at 25 ?M. 4-t-OP strongly inhibited CYP11A activity at 12.5 and 25 ?M, and inhibited CYP17 and CYP21B at 25 ?M. Similarly, 4-NP inhibited CYP11A at 25 ?M and strongly inhibited CYP17 and CYP21B at 12.5 and 25 ?M. Neither DCHP nor any of the alkylphenols tested altered 3?-HSDII activity.

Abstract  A method was established for the simultaneous determination of some phthalic acid esters, namely, dimethyl phthalate (DMP), diethyl phthalate (DEP), dipropyl phthalate (DPrP), dibutyl phthalate (DBP), diamyl phthalate (DAP), dihexyl phthalate (DHP), benzyln-butyl phthalate (BBP), di-(2-ethylhexyl) phthalate (DEHP), dicyclohexyl phthalate (DCHP), di-n-octyl phthalate (DNOP), diisononyl phthalate (DINP) and diisodecyl phthalate (DIDP) in textiles by solid phase extraction (SPE) coupled with gas chromatography (GC). The phthalic acid esters in textiles were extracted by Soxhlet extraction with hexane, the extracts were then cleaned up and enriched by a strong anion exchange (SAX) SPE cartridge. The parameters affecting the purification efficiency of SPE cartridge, such as solvent conditioning, rinsing, and elution, were studied. Conditioning with 5 mL hexane and rinsing with 3 mL isooctane were proved to be the optimal conditions. Of the several solvent ratios (ethylacetate in hexane) used for selective elution of phthalic acid esters from the SAX SPE cartridge, the 15% (v/v) content for ethylacetate in hexane gave the best result. Under the optimized conditions, the recoveries of phthalic acid esters for spiked standards (n=7) were 86.3%-102.7%, and the relative standard deviations (RSDs) were less than 5%. In this method the detection limits for DMP, DEP, DPrP, DBP, DAP, BBP, DCHP, DEHP, DNOP were all below 1 mg/kg, and the detection limits for DINP and DIDP were 1.74 mg/kg and 1.55 mg/kg respectively. This SPE-GC method is sensitive, accurate and suitable for the analysis of phthalate environmental hormones in textiles.

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  15 hazardous industrial waste samples were evaluated for mutagenicity in the Salmonella plate-incorporation assay using strains TA98 and TA100 in the presence and absence of Aroclor 1254-induced rat liver S9. Dichloromethane/methanol extracts of the crude wastes were also evaluated. 7 of the crude wastes were mutagenic, but only 2 of the extracts of these 7 wastes were mutagenic; extracts of 2 additional wastes also were mutagenic. In addition, 10 of the crude wastes were administered by gavage to F-344 rats, and 24-h urine samples were collected. Of the 10 raw urines evaluated, 3 were mutagenic in strain TA98 in the presence of S9 and β-glucuronidase. The 3 crude wastes that produced these 3 mutagenic urines were, themselves, mutagenic. Adequate volumes of 6 of the 10 raw urines were available for extraction/concentration. These 6 urines were incubated with β-glucuronidase and eluted through Sep-Pak® C18 columns; the methanol eluates of 3 of the urines were mutagenic, and these were the same 3 whose raw urines also were mutagenic. In general, the C18/methanol extraction procedure reduced the cytotoxicity and increased the mutagenic potency of the urines. To our knowledge, this is the first report of the mutagenicity of urine from rodents exposed to hazardous wastes. Based on the present results, the use of only strain TA98 in the presence of S9 might be adequate for general screening of hazardous wastes or waste extracts for genotoxicity. The urinary mutagenesis assay does not appear to be a useful adjunct to the Salmonella assay for screening hazardous wastes. The problems associated with chemically fractionating diverse types of hazardous wastes for bioassay are also discussed.

Abstract  The toxicity of 76 priority pollutants to lettuce (Lactuca sativa) was determined in soil and in nutrient solution. In the first case a static and in the latter a semistatic exposure was established Volatile and easily degradable compounds had high EC50 values in soil (> 1,000 μg/g). In nutrient solution, however, several of these compounds were rather toxic. Quantitative structure‐activity relationships (QSARs) relating EC50 values to log Kow could be described for the toxicity in nutrient solution. Generally, the toxicity of the compounds increased with increasing lipophilicity. Deviations were (partly) caused by reactivity (N‐containing compounds, double bonds in compounds), low lipophilicity (log Kow values < 1), and EC50 values close to solubility. To relate toxicity in soil and nutrient solution, soil EC50 values were recalculated to values in the soil pore water using calculated adsorption coefficients. Estimated pore‐water EC50 values showed a good correlation with values determined in nutrient solution but were not equal to these values. The differences can be attributed to differences in exposure (static vs. semistatic).

Abstract  Ten surficial sediment samples were collected adjacent to each of four combined sewer overflow (CSO) outfalls along the lower Passaic River in New Jersey and analyzed for priority pollutant organic and inorganic chemicals. The objectives of this investigation were to (t) characterize chemical contamination in sediments impacted by these CSOs, (2) evaluate the spatial distribution of contaminants. and (3) evaluate the possible sources of contaminants within the respective CSO districts. The results indicate that sediments proximate to the CSO outfalls are contaminated with a range of chemicals including toxic metals, polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs), pesticides, and other organic chemicals. The spatial distribution of these contaminants strongly suggest that the CSOs are the primary source of contamination in sediments near these outtalls. While the contribution of residential waste and stormwater may be substantial, evaluation of the industries operating with the CSO districts provides a link between the facilities that discharge wastes to the combined sewer system and chemical contaminants found in the sediments. Until adequate controls are implemented, CSOs will continue to be on-going sources of contamination affecting the water and sediment quality of the Passaic River.

Abstract  The content of wastewater resulting from the manufacture of rubber antioxidants and accelerators by a factory situated in the Ebro basin (Spain) has been determined using gas chromatography-mass spectrometry (GC-MS) and gas chromatography-flame ionization detection (GC-FID). The change in the pollutants was studied in the riverbed via two modules which continuously gathered pollutants on various solid supports (activated carbon and XAD-2 resins). These modules were located in Bocal Station, lying a further 100 km downstream from the factory, and from the Zaragoza water supply. Forty-six different compounds were identified at Bocal Station, the majority resulting from the production of rubber additives. Due to the immunity of different waste substances, and to the toxic nature of some, we studied their reaction when subjected to techniques of chemical oxidation using ozone.

Abstract  These studies compared the reproductive toxicity of four phthalates by a continuous breeding protocol. Mice were given diets with diethyl phthalate (DEP) (0.0, 0.25, 1.25, or 2.5%), di-n-butyl phthalate (DBP) (0.0, 0.03, 0.3, or 1.0%), di-n-hexyl phthalate (DHP) (0.0, 0.3, 0.6, or 1.2%), or di(2-ethylhexyl) phthalate (DEHP) (0.0, 0.01, or 0.3%). Both male and female CD-1 mice were dosed for 7 days prior to and during a 98-day cohabitation period. Reproductive function was evaluated during the cohabitation period by measuring the numbers of litters per pair and of live pups per litter, pup weight, and offspring survival. There was no apparent effect on reproductive function in the animals exposed to DEP, despite significant effects on body weight gain and liver weight. DBP exposure resulted in a reduction in the numbers of litters per pair and of live pups per litter and in the proportion of pups born alive at the 1.0% amount, but not at lower dose levels. A crossover mating trial demonstrated that female mice, but not males, were affected by DBP, as shown by significant decreases in the percentage of fertile pairs, the number of live pups per litter, the proportion of pups born alive, and live pup weight. DHP in the diet resulted in dose-related adverse effects on the numbers of litters per pair and of live pups per litter and proportion of pups born alive at 0.3, 0.6, and 1.2% DHP in the diet. A crossover mating study demonstrated that both sexes were affected. DEHP (at 0.1 and 0.3%) caused dose-dependent decreases in fertility and in the number and the proportion of pups born alive. A crossover mating trial showed that both sexes were affected by exposure to DEHP. These data demonstrate the ability of the continuous breeding protocol to discriminate the qualitative and quantitative reproductive effects of the more and less active congeners as well as the large differences in reproductive toxicity attributable to subtle changes in the alkyl substitution of phthalate esters.

Abstract  Di(2-ethylhexyl)phthalate and 33 other phthalates, ethylhexanol derivatives, and related chemicals were tested for mutagenicity in Salmonella typhimurium strains TA98, TA100, TA1535, and TA1537 without metabolic activation and in the presence of rat and hamster liver S-9 metabolic activation systems. No mutagenic activity was seen with any of the chemicals tested.

Abstract  Neurotoxicity has been described in workers exposed to solvents, PCBs, certain metals, and polyaromatic hydrocarbons but not often in residents near refineries or factories. We compared the neurobehavioral performance of residents near a plant that reprocessed used motor oil and chemical waste from 1966?1983 to referents from beyond the plant's modeled air dispersal and water drainage zones. Neurophysiological and psychological tests, a Profile of Mood States (POMS) and a symptom questionnaire were administered to 131 subjects exposed at the site who were matched for age, sex, and ethnicity 2:1 with 66 unexposed subjects from 35 km away. Test scores were adjusted for a 1.4-year difference in educational attainment by coefficients from regression equations but not for income as the latter coefficients were not significant. Exposed subjects were significantly impaired for body balance (sway speed) and simple and two choice visual reaction time as compared to referents. Blink reflex latency (R-1) and eye closure speed were normal in both groups. Cognitive function in the exposed was impaired as measured by Culture Fair and by block design from the WAIS. Placing pegs in a grooved board and making of trails (A and B) were also impaired. Group differences in recall and memory were not significant. The exposed group's symptom frequencies and POMS scores for depression, anger, confusion, tension, and fatigue were elevated indicating depression. Confounding from medical and neurological disorders or occupational exposures was minimal. Subjects exposed residentially for up to 17 years to chemicals dispersed from a waste oil reprocessing plant showed neurophysiological and neuropsychological impairment.

Abstract  Method was developed for the simultaneous determination of 17 classified and suspected endocrine-disrupting compounds (EDCs). Phenol, 2-nitrophenol, 4-nitrophenol, 4-dinitrophenol, 4-chlorophenol, 2,4-dimethylphenol, 2: methyl 4,6-dinitro-phenol, 2-chlorophenol, 2,4-dichlorophenol, 4-chloro-3-methylphenol, pentachlorophenol, dimethyl phthalate, diethyl phthalate, benzylbutyl phthalate, dioctyl phthalate, diethylhexylphthalate and dibutyl phthalate. Qualitative and quantitative analyses were performed by gas chromatography mass spectrometry (GC-MS) using)B-5MS column. These compounds were evaluated using solid-phase extraction for raw and treated wastewater from a municipal treatment plant. Phenols were derivatized with N-(t-butyldimethylsilyl)-N-methyl-trifluoroacetamide (MTBSTFA) to form their respective t-butyldimethylsilyl derivatives. The extraction recovery range from 73.21 to 01.32% for 2,4,6-TCP and DEHP respectively. The occurrence pattern of phenol is in the order of PCP > 2CP > POH > 2NP > 2M- 4,6 DNP (old plant) and PCP > 2M- 4,6 DNP > POH 2CP 2NP for old and new plants respectively. Phthalates ranked as DEP > DBP > DEHP with corresponding values of 2473 991; 2000 : 236; and 192 = 127 mu gL(-1) in the new plant. The average percent removal of analytes range from 54.77 to 89.34% in the two plants investigated.

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  Human phthalate exposure occurs as mixtures of diesters with varying activity towards testosterone-dependent development. Dibutyl (DBP), diethylhexyl (DEHP) and butylbenzyl (BBP) phthalate disrupt sexual development in the fetal rat. Dimethyl (DMP) and diethyl (DEP) phthalate do not. These differences in potency may result from differential delivery of the monophthalates to the testes or from variation in the abilities of the compounds to alter steroidogenesis. We tested five phthalates in pregnant rats (500mg/kg-d, GD12-19) and analyzed the fetal testes for corresponding monoesters (MMP, MEP, MBP, MEHP, MBeP). Testes MMP and MEP levels were 2-40-fold higher than the active monoesters, MBP and MEHP. BBP exposure led to low concentrations of MBeP, but similar MBP levels to DBP. An in vitro MA-10 cell assay measured the direct effect of monophthalates on testosterone production. MEHP inhibited LH-stimulated testosterone production at 1microM. RT-PCR confirmed down-regulation of genes associated with cholesterol transport and steroid synthesis and metabolism by MEHP. Five additional phthalates were tested for testosterone inhibition. MBP and mono-n-octyl phthalate were similar to MEHP; MMP, MEP and MBeP were poor inhibitors of testosterone production. Based on these results, differences in the phthalates' ability to interfere with sexual development in vivo appears to be more associated with differential potency for testosterone inhibition than differences in tissue doses.

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 assess maternal-fetal exposure to phthalates and investigate whether in utero phthalate exposure is associated with low birth weight (LBW). STUDY DESIGN: A total of 201 newborn-mother pairs (88 LBW cases and 113 controls) residing in Shanghai were enrolled in this nested case-control study during 2005-2006. Maternal blood, cord blood, and meconium specimens were collected and analyzed for phthalates by high-performance liquid chromatography-mass spectrometry. Nonparametric tests were used to compare demographic characteristics in cases and controls. Conditional logistic regression and Spearman correlation were used to analyze the association between phthalate exposure and LBW. RESULTS: No significant differences in gestational age, prepregnancy body mass index, prenatal care, vitamin supplementation, or socioeconomic levels were found between the LBW and control infants. More than 70% of the biosamples had quantifiable levels of phthalates, with higher levels in the LBW infants compared with the controls. Prenatal di-n-butyl phthalate (DBP) exposure was associated with LBW, and di-2-ethylhexyl phthalate (DEHP) was negatively associated with birth length. After adjusting for the potential confounders, DBP concentrations in the highest quartile were associated with an increased risk of LBW. CONCLUSIONS: Newborns in China are ubiquitously exposed to phthalates; significantly higher phthalate levels were detected in LBW cases compared with controls. In utero DBP and DEHP exposures were associated with LBW in a dose-dependent manner. Prenatal phthalate exposure may be a risk factor for LBW.

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.