Exposure assessment of phthalate esters in Japanese pregnant women by using urinary metabolite analysis

Objectives  Our objectives were (1) to evaluate whether single spot urine is suitable media for longer-term phthalate esters exposure assessment, and (2) to estimate intake level of phthalate esters of Japanese pregnant women using urinary metabolites as an indicator of prenatal exposure level in their offspring. Methods  We analyzed nine metabolites (MMP, MEP, MnBP, MBzP, MEHP, MEOHP, MEHHP, MINP, MnOP) of seven phthalate esters in spot urine samples from 50 pregnant women by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Using four urine samples collected from each of 12 subjects from 50 pregnant women within 5–12 weeks, we compared intra- and interindividual variation in urinary metabolites by calculation of intraclass correlation coefficient (ICC). We estimated daily intakes of 50 pregnant women from their urinary metabolite concentrations. Results  ICCs for seven phthalate metabolite concentrations in single spot urine samples were: MMP (0.57), MEP (0.47), MnBP (0.69), MBzP (0.28), MEHP (0.51), MEHHP (0.43), and MEOHP (0.41) in 12 pregnant women. Phthalate ester metabolites had high detection rates in 50 subjects. The mean daily intake ranged from 0.01 to 2 μg/kg per day. The daily intake levels in all subjects were lower than corresponding tolerable daily intake (TDI) set by the European Food Safety Authority (EFSA), though maximum value for DnBP of 6.91 μg/kg per day accounted for 70% of TDI value. Conclusions  Higher ICCs indicated that phthalate metabolite levels in single spot urine could reflect longer-term exposure to the corresponding diesters of subjects. Although the current exposure level was less than TDIs, further studies and exposure monitoring are needed to reveal the toxicity of phthalate esters to sensitive subpopulation.     

孕早期邻苯二甲酸酯暴露与孕晚期空腹血糖水平关联的队列研究

目的 分析孕妇孕早期邻苯二甲酸酯（PAE）暴露与孕晚期FPG水平的关联及患妊娠糖尿病（GDM）的风险。方法 选取2013年5月至2014年9月在马鞍山市妇幼保健院产前检查的3 474名孕妇为研究对象,于孕早、中、晚期分别随访,采用问卷调查收集研究对象的社会人口学资料,记录临床相关信息;收集孕妇晨尿样本,运用固相萃取-高效液相色谱-串联质谱法（SPE-HPLC-MS/MS）检测尿液样本中7种PAE代谢物浓度;在孕早、晚期测定FPG,在孕中期进行75 g口服糖耐量试验（OGTT）。运用线性回归模型分析尿PAE代谢物与孕晚期FPG间的关联性,运用logistic模型分析孕早期PAE暴露水平与孕晚期患GDM的风险。结果 GDM检出率为12.8%;孕早期邻苯二甲酸单甲酯（MMP）、邻苯二甲酸单乙酯（MEP）、邻苯二甲酸单丁酯（MBP）、邻苯二甲酸单苄酯（MBzP）、邻苯二甲酸单（2-乙基-5-羟基己基）酯（MEHHP）暴露水平与孕晚期FPG呈正相关（P<0.05）,邻苯二甲酸单（2-乙基己基）酯（MEHP）、邻苯二甲酸单（2-乙基-5-酮基己基）酯（MEOHP）暴露水平与孕晚期空腹血糖水平呈负相关（P<0.05）。孕早期MEHHP暴露增加正常组和GDM组FPG水平,MMP、MEP、MBP、MBzP、MEHP和MEOHP暴露只影响正常组的FPG水平,对GDM组的FPG水平无影响。孕早期MMP和MBP暴露增加孕晚期患GDM的风险,MEOHP暴露降低孕晚期患GDM的风险。结论 孕早期PAE暴露与孕晚期FPG水平存在关联,不同种类PAE代谢物与孕晚期FPG水平关联性存在差异,PAE代谢物对正常孕妇FPG水平的影响较GDM孕妇更为显著。不同种类PAE代谢物可能增高或降低孕妇孕晚期患GDM的风险性。     

Personal care product use predicts urinary concentrations of some phthalate monoesters

Phthalates are multifunctional chemicals used in a variety of applications, including personal care products. The present study explored the relationship between patterns of personal care product use and urinary levels of several phthalate metabolites. Subjects include 406 men who participated in an ongoing semen quality study at the Massachusetts General Hospital Andrology Laboratory between January 2000 and February 2003. A nurse-administered questionnaire was used to determine use of personal care products, including cologne, aftershave, lotions, hair products, and deodorants. Phthalate monoester concentrations were measured in a single spot urine sample by isotope dilution-high-performance liquid chromatography coupled to tandem mass spectrometry. Men who used cologne or aftershave within 48 hr before urine collection had higher median levels of monoethyl phthalate (MEP) (265 and 266 ng/mL, respectively) than those who did not use cologne or aftershave (108 and 133 ng/mL, respectively). For each additional type of product used, MEP increased 33% (95% confidence interval, 14-53%). The use of lotion was associated with lower urinary levels of monobutyl phthalate (MBP) (14.9 ng/mL), monobenzyl phthalate (MBzP) (6.1 ng/mL), and mono(2-ethylhexyl) phthalate (MEHP) (4.4 ng/mL) compared with men who did not use lotion (MBP, 16.8 ng/mL; MBzP, 8.6 ng/mL; MEHP, 7.2 ng/mL). The identification of personal care products as contributors to phthalate body burden is an important step in exposure characterization. Further work in this area is needed to identify other predictors of phthalate exposure.     

Urinary levels of seven phthalate metabolites in the U.S. population from the National Health and Nutrition Examination Survey (NHANES) 1999-2000

We measured the urinary monoester metabolites of seven commonly used phthalates in approximately 2,540 samples collected from participants of the National Health and Nutrition Examination Survey (NHANES), 1999-2000, who were greater than or equal to 6 years of age. We found detectable levels of metabolites monoethyl phthalate (MEP), monobutyl phthalate (MBP), monobenzyl phthalate (MBzP), and mono-(2-ethylhexyl) phthalate (MEHP) in > 75% of the samples, suggesting widespread exposure in the United States to diethyl phthalate, dibutyl phthalate or diisobutylphthalate, benzylbutyl phthalate, and di-(2-ethylhexyl) phthalate, respectively. We infrequently detected monoisononyl phthalate, mono-cyclohexyl phthalate, and mono-n-octyl phthalate, suggesting that human exposures to di-isononyl phthalate, dioctylphthalate, and dicyclohexyl phthalate, respectively, are lower than those listed above, or the pathways, routes of exposure, or pharmacokinetic factors such as absorption, distribution, metabolism, and elimination are different. Non-Hispanic blacks had significantly higher concentrations of MEP than did Mexican Americans and non-Hispanic whites. Compared with adolescents and adults, children had significantly higher levels of MBP, MBzP, and MEHP but had significantly lower concentrations of MEP. Females had significantly higher concentrations of MEP and MBzP than did males, but similar MEHP levels. Of particular interest, females of all ages had significantly higher concentrations of the reproductive toxicant MBP than did males of all ages; however, women of reproductive age (i.e., 20-39 years of age) had concentrations similar to adolescent girls and women 40 years of age. These population data on exposure to phthalates will serve an important role in public health by helping to set research priorities and by establishing a nationally representative baseline of exposure with which population levels can be compared.     

Determination of Phthalates in Diet and Bedding for Experimental Animals Using Gas Chromatography-Mass Spectrometry

We have developed a gas chromatography–mass spectrometry method to measure five phthalates (dibutyl phthalate, butylbenzyl phthalate, di-2-ethylhexyl phthalate, diisooctyl phthalate, and diisononyl phthalate) in diets and beddings for experimental animals. The recoveries from diets and beddings spiked with five phthalates were 98.8%–148% with coefficients of variation of 0.4%–7.8% for diets and 94.7%–146% with coefficients of variation of 1.0%–5.0% for beddings. We analyzed commercial animal diets and beddings, and found that the levels of phthalates varied from sample to sample; the concentrations of five phthalates were 141–1,410 ng/g for diets and 20.5–7,560 ng/g for beddings.     

Concentrations of Polybrominated Diphenyl Ethers in Sediments from Jukskei River,Gauteng, South Africa

This study determined concentration levels of polybrominated diphenyl ethers (PBDEs) in sediment samples collected from Jukskei River in South Africa. Final extracts, after concentration and dilution to 200 μL were analyzed by injecting 1 μL in the GC–ECD and GC–MS. Results obtained showed good recoveries (73%–114%, with RSD < 17%). The concentrations of ∑PBDEs in sediment for the seven sampling sites ranged from 0.92 to 6.76 ng g⁻¹ dry weight and total PBDEs with a total BDE sum of 23.85 ng g⁻¹ dry weights. Concentrations of PBDEs obtained in the present study are significantly lower than the values reported from developed countries.     

Variability of urinary phthalate metabolite and bisphenol A concentrations before and during pregnancy

Background: Gestational phthalate and bisphenol A (BPA) exposure may increase the risk of adverse maternal/child health outcomes, but there are few data on the variability of urinary biomarkers before and during pregnancy.Objective: We characterized the variability of urinary phthalate metabolite and BPA concentrations before and during pregnancy and the ability of a single spot urine sample to classify average gestational exposure.Methods: We collected 1,001 urine samples before and during pregnancy from 137 women who were partners in couples attending a Boston fertility clinic and who had a live birth. Women provided spot urine samples before (n ≥ 2) and during (n ≥ 2) pregnancy. We measured urinary concentrations of monoethyl phthalate (MEP), mono-n-butyl phthalate (MBP), mono-iso-butyl phthalate, monobenzyl phthalate (MBzP), four metabolites of di-(2-ethylhexyl) phthalate (DEHP), and BPA. After adjusting for specific gravity, we characterized biomarker variability using intraclass correlation coefficients (ICCs) and conducted several surrogate category analyses to determine whether a single spot urine sample could adequately classify average gestational exposure.Results: Absolute concentrations of phthalate metabolites and BPA were similar before and during pregnancy. Variability was higher during pregnancy than before pregnancy for BPA and MBzP, but similar during and before pregnancy for MBP, MEP, and ΣDEHP. During pregnancy, MEP (ICC = 0.50) and MBP (ICC = 0.45) were less variable than BPA (ICC = 0.12), MBzP (ICC = 0.25), and ΣDEHP metabolites (ICC = 0.08). Surrogate analyses suggested that a single spot urine sample may reasonably classify MEP and MBP concentrations during pregnancy, but more than one sample may be necessary for MBzP, DEHP, and BPA.Conclusions: Urinary phthalate metabolites and BPA concentrations were variable before and during pregnancy, but the magnitude of variability was biomarker specific. A single spot urine sample adequately classified MBP and MEP concentrations during pregnancy. The present results may be related to unique features of the women studied, and replication in other pregnancy cohorts is recommended.     

Biomonitoring of phthalate metabolites in the Canadian population through the Canadian Health Measures Survey (2007–2009)

Human exposure to phthalates occurs through multiple sources and pathways. In the Canadian Health Measures Survey 2007–2009, 11 phthalate metabolites, namely, MMP, MEP, MnBP, MBzP, MCHP, MCPP, MEHP, MEOHP, MEHHP, MnOP, and MiNP were measured in urine samples of 6–49 year old survey respondents (n = 3236). The phthalate metabolites biomonitoring data from this nationally-representative Canadian survey are presented here. The metabolites MEP, MnBP, MBzP, MCPP, MEHP, MEOHP and MEHHP were detected in >90% of Canadians while MMP, MCHP, MnOP and MiNP were detected in <20% of the Canadian population. Step-wise regression analyses were carried out to identify important predictors of volumetric concentrations (μg/L) of the metabolites in the general population. Individual multiple regression models with covariates age, sex, creatinine, fasting status, and the interaction terms age × creatinine, age × sex and fasting status × creatinine were constructed for MEP, MnBP, MBzP, MCPP, MEHP, MEOHP and MEHHP. The least square geometric mean (LSGM) estimates for volumetric concentration (μg/L) of the metabolites derived from respective regression models were used to assess the patterns in the metabolite concentrations among population sub-groups. The results indicate that children had significantly higher urinary concentrations of MnBP, MBzP, MEHP, MEHHP, MEOHP and MCPP than adolescents and adults. Moreover, MEP, MBzP, MnBP and MEOHP concentrations in females were significantly higher than in males. We observed that fasting status significantly affects the concentrations of MEHP, MEHHP, MEOHP, and MCPP metabolites analyzed in this study. Moreover, our results indicate that the sampling time could affect the DEHP metabolite concentrations in the general Canadian population.     

Dissipation of Diethyl Aminoethyl Hexanoate (DA-6) Residues in Pakchoi,Cotton Crops and Soil

QuEChERS procedure and acetonitrile extraction, oscillation and ultrasonic procedure followed by GC–MS and LC–MS/MS (QqQ) detections were established for determination of diethyl aminoethyl hexanoate (DA-6) residues in pakchoi, cotton leaf, cotton seed and soil. At concentration levels of 0.005–1 mg kg⁻¹, recoveries were in the range of 80.5%–103.3%, with a RSD less than 14.2%. The LOQs of methods were 0.005, 0.003, 0.005 and 0.001 mg kg⁻¹ for the pakchoi, cotton leaf, soil and cotton seed samples, respectively. DA-6 was applied in supervised field trials at GAP conditions to pakchoi and cotton. It was found that the dissipation half-lives of DA-6 were 5.4–8.2 days and 1.1–2.2 days and 1.5–1.9 days in cotton crop, pakchoi and soil respectively. At harvest, no detectable residues (<LOD) were found in cotton samples. However, residues was detected in pakchoi (0.007–0.013 mg/kg) in Beijing and soil (0.008–0.014 mg/kg) in Changsha in 2008.     

High Performance Liquid Chromatography Method for Residues Analysis of Thidiazuron in Apple and Soil

A rapid, sensitive and reliable analytical method for thidiazuron residues in apple and soil was established. The residual levels of the pesticide in apple and soil were determined by high performance liquid chromatography (HPLC) with UV detector. Samples of apple and soil were extracted with acetonitrile–water solutions, and then cleaned up by Florisil or C₁₈ cartridges. The results showed good linearity (r ²  = 1.000) over the concentration range of 0.01–5.0 mg/L. Limits of quantification (LOQ) of the method were 0.01 mg/kg for both soil and apple. Recovery from the apple and soil samples were 83.36%–84.08% and 85.27%–89.83%, respectively, and the corresponding relative standard deviations (RSDs) of the recovery data were 0.155%–0.524% and 0.475%–4.79% for the three fortified levels (0.01, 0.1, 0.5 mg/kg). The analyte in the samples were further confirmed by electrospray ionization tandem mass spectrometry (ESI–MS/MS). It was demonstrated that the proposed method was simple and efficient, and particularly suitable for detecting thidiazuron residues in apple and soil.     

Decreased serum free testosterone in workers exposed to high levels of di-n-butyl phthalate (DBP) and di-2-ethylhexyl phthalate (DEHP): a cross-sectional study in China

BACKGROUND: Observations of adverse developmental and reproductive effects in laboratory animals and wildlife have fueled increasing public concern regarding the potential for various chemicals to impair human fertility. OBJECTIVE: Our objective in this study was to assess the effect of occupational exposure to high levels of phthalate esters on the balance of gonadotropin and gonadal hormones including luteinizing hormone, follicle-stimulating hormone, free testosterone (fT), and estradiol. METHODS: We examined urine and blood samples of 74 male workers at a factory producing unfoamed polyvinyl chloride flooring exposed to di-n-butyl phthalate (DBP) and di-2-ethylhexyl phthalate (DEHP) and compared them with samples from 63 male workers from a construction company, group matched for age and smoking status. RESULTS: Compared to the unexposed workers, the exposed workers had substantially and significantly elevated concentrations of mono-n-butyl phthalate (MBP; 644.3 vs. 129.6 microg/g creatinine, p < 0.001) and mono-2-ethylhexyl phthalate (MEHP; 565.7 vs. 5.7 microg/g creatinine, p < 0.001). fT was significantly lower (8.4 vs. 9.7 microg/g creatinine, p = 0.019) in exposed workers than in unexposed workers. fT was negatively correlated to MBP (r = -0.25, p = 0.03) and MEHP (r = -0.19, p = 0.095) in the exposed worker group. Regression analyses revealed that fT decreases significantly with increasing total phthalate ester score (the sum of quartiles of MBP and MEHP; r = -0.26, p = 0.002). CONCLUSION: We observed a modest and significant reduction of serum fT in workers with higher levels of urinary MBP and MEHP compared with unexposed workers.     

Determination of DDT and Metabolites in Surface Water and Sediment Using LLE, SPE, ACE and SE

Surface water and sediment samples collected from Jukskei River in South Africa, were subjected to different extraction techniques, liquid–liquid (LLE), solid-phase extraction (SPE), activated carbon extraction (ACE) and soxhlet extraction (SE) for sediment. The samples were extracted with dichloromethane, cleaned in a silica gel column and the extracts quantified using a Varian 3800 GC-ECD. The percentage recovery test for 2,4′DDT, DDE and DDD and 4,4′DDT, DDE and DDD in water ranged from 80%–96% and 76%–95% (LLE); 56%–76% and 56%–70% (SPE) and 75%–84% (ACE), respectively; while that recoveries for sediment samples varied from 65%–95% for 2,4′DDT, DDE and DDD and 80%–91% for 4,4′DDT, DDE and DDD. The high recoveries exhibited by ACE compared very well with LLE and SE. This was not the case with SPE which exhibited the lowest value of recoveries for both 2,4 and 4,4′DDD, DDE and DDT standard samples. The mean concentrations of DDT and metabolites ranged from nd-1.10 μg/L, nd-0.80 μg/L, nd-1.21 μg/L and 1.92 μg/L for LLE, SPE, ACE and SE, respectively. The total DDT (2,4′ and 4,4′-DDT) in water and sediment samples ranged from 1.20–3.25 μg/L and 1.82–5.24 μg/L, respectively. The low concentrations of the DDT metabolites obtained in the present study may suggest a recent contamination of the river by DDT.     

Evaluation of the effect of governmental control of human exposure to two phthalates in Japan using a urinary biomarker approach

In Japan, the use of certain phthalates has been regulated. We analyzed the effectiveness of these measures using an analytical biomarker approach. We measured two phthalate metabolites, mono-n-butyl phthalate (MBP) and mono-2-ethylhexyl phthalate (MEHP) in urine samples from 36 participants using enzymatic deconjugation, offline solid phase extraction, and HPLC-ESI-MS/MS. From the levels measured and individual values of creatinine excretion rate the daily intake was determined and compared to each corresponding tolerable daily intake (TDI). The levels of urinary MBP and MEHP were < 1.8-280 and 0.76-25 microg/l, respectively. The ranges of the estimated daily intake of di-n-butyl phthalate (DBP) and di-2-ethylhexyl phthalate (DEHP) from 35 adult urine samples were 0.22-4.5 and 0.37-7.3 microg/kg/ day, respectively. These values were lower than the corresponding TDIs. After comparing these values to previous exposure assessment data on DEHP in Japan, it could be seen that the DEHP intake dropped over the period from 1998 to 2001. Children were not covered in the present study, so the results may only be applicable to adults, not to the Japanese population at large. Even so, the small number of people in one specific geographic area cannot be considered representative of the adult Japanese population. In addition to MEHP, the secondary metabolites of DEHP, which are more suitable biomarkers should be measured in the future.     

Association of Exposure to Phthalates with Endometriosis and Uterine Leiomyomata: Findings from NHANES, 1999–2004

Background

Phthalates are ubiquitous chemicals used in consumer products. Some phthalates are reproductive toxicants in experimental animals, but human data are limited.

Objective

We conducted a cross-sectional study of urinary phthalate metabolite concentrations in relation to self-reported history of endometriosis and uterine leiomyomata among 1,227 women 20–54 years of age from three cycles of the National Health and Nutrition Examination Survey (NHANES), 1999–2004.

Methods

We examined four phthalate metabolites: mono(2-ethylhexyl) phthalate (MEHP), monobutyl phthalate (MBP), monoethyl phthalate (MEP), and monobenzyl phthalate (MBzP). From the last two NHANES cycles, we also examined mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) and mono(2-ethyl-5-oxohexyl) phthalate (MEOHP). We used logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs), adjusting for potential confounders.

Results

Eighty-seven (7%) and 151 (12%) women reported diagnoses of endometriosis and leiomyomata, respectively. The ORs comparing the highest versus lowest three quartiles of urinary MBP were 1.36 (95% CI, 0.77–2.41) for endometriosis, 1.56 (95% CI, 0.93–2.61) for leiomyomata, and 1.71 (95% CI, 1.07–2.75) for both conditions combined. The corresponding ORs for MEHP were 0.44 (95% CI, 0.19–1.02) for endometriosis, 0.63 (95% CI, 0.35–1.12) for leiomyomata, and 0.59 (95% CI, 0.37–0.95) for both conditions combined. Findings for MEHHP and MEOHP agreed with findings for MEHP with respect to endometriosis only. We observed null associations for MEP and MBzP. Associations were similar when we excluded women diagnosed > 7 years before their NHANES evaluation.

Conclusion

The positive associations for MBP and inverse associations for MEHP in relation to endometriosis and leiomyomata warrant investigation in prospective studies.     

Estimation of intake level of di (2-ethyhexyl) phthalate (DEHP) in Japanese pregnant women based on measurement of concentrations of three urinary metabolites

OBJECTIVES: [corrected] The daily intake level of di (2-ethyhexyl) phthalate (DEHP) of Japanese pregnant women was estimated on the basis of the measurement of the urinary concentrations of three DEHP metabolites. METHODS: Spot urine samples were collected from 42 pregnant women who visited the gynecology division of a hospital for routine health check between June and October, 2003. The urinary concentrations of three DEHP metabolites, namely, mono (2-ethyhexyl) phthalate (MEHP), mono (2-ethy-5-hydroxyhexyl) phthalate (MEHHP), and mono (2-ethyl-5-oxohexyl) phthalate (MEOHP) were measured by HPLC/MS/MS. RESULTS: The concentrations of urinary MEHP, MEOHP and MEHHP (n=40) were 3.27-39.5 (median 9.83), 1.51-41.0 (median 10.4) and 4.6-26.6 (median 10.9) microg/g cre, respectively. The ranges of the estimated daily intake of DEHP per body weight based on the MEHP, MEOHP and MEHHP concentrations (n=40) were 3.45-41.6 (median 10.4), 0.66-17.9 (median 4.55) and 1.47-8.57 (median 3.51) microg/kg/day, respectively. The maximum estimated intake level per body weight (41.6 microg/kg/day) reached the Tolerable Daily Intake (TDI) level of 40-140 microg/kg/day set by the Ministry of Health and Welfare (now the Ministry of Health, Labour and Welfare). CONCLUSIONS: The health risk of DEHP exposure of our study subjects was found to be minimum from the viewpoint of the current knowledge of its risk level, although the human health effects of low-level DEHP exposure have to be studied further.     

Urinary excretion of phthalate metabolites in 129 healthy Danish children and adolescents: estimation of daily phthalate intake

Background

Phthalates are a group of chemicals with widespread use in the industrial production of numerous consumer products. They are suspected to be involved in male reproductive health problems and have also been associated with several other health problems in children including obesity and asthma.

Objectives

To study the urinary excretion of phthalate metabolites in Danish children recruited from the general population, and to estimate the daily intake of phthalates in this segment of the population.

Method

One 24 h urine sample and to consecutive first morning urine samples were collected from 129 healthy Danish children and adolescents (range 6–21 yrs). The concentrations of 11 phthalate metabolites of 5 different phthalate diesters were analyzed by liquid chromatography–tandem mass spectrometry.

Results

The analyzed metabolites were detectable in almost all 24 h urine samples. The median concentrations of monoethyl phthalate (MEP), monobenzyl phthalate (MBzP) and the sums of the two monobutyl phthalate isoforms (∑MBP(i+n)), metabolites of di-(2-ethylhexyl) phthalate (∑DEHPm) and of di-iso-nonyl phthalate (∑DiNPm) were 29, 17, 111, 107 and 31 ng/mL, respectively. The youngest children were generally more exposed to phthalates than older children and adolescents (except diethyl phthalate (DEP)). Boys were more exposed than girls. The median estimated daily intake of phthalate diesters was: 4.29 (dibutyl phthalate isoforms (DBP(i+n))), 4.04 (DEHP), 1.70 (DiNP), 1.09 (DEP) and 0.62 (butylbenzyl phthalate (BBzP)), all calculated as μg/kg body weight/24 h. Between 40% and 48% of the absolute amount of phthalate metabolites excreted over 24 h were excreted in first morning urine voids.

Conclusion

Danish children are exposed simultaneously to multiple phthalates. The highest exposure levels were found for DBP(i+n) and DEHP, which in animal models are the known most potent anti-androgenic phthalates. The combined exposure to the two isoforms of DBP, which have similar endocrine-disrupting potencies in animal models, exceeded the TDI for di-n-butyl phthalate (DnBP) in several of the younger children.     

Temporal variability of urinary phthalate metabolite levels in men of reproductive age

Phthalates are a family of multifunctional chemicals widely used in personal care and other consumer products. The ubiquitous use of phthalates results in human exposure through multiple sources and routes, including dietary ingestion, dermal absorption, inhalation, and parenteral exposure from medical devices containing phthalates. We explored the temporal variability over 3 months in urinary phthalate metabolite levels among 11 men who collected up to nine urine samples each during this time period. Eight phthalate metabolites were measured by solid-phase extraction-high-performance liquid chromatography-tandem mass spectrometry. Statistical analyses were performed to determine the between- and within-subject variance apportionment, and the sensitivity and specificity of a single urine sample to classify a subject's 3-month average exposure. Five of the eight phthalates were frequently detected. Monoethyl phthalate (MEP) was detected in 100% of samples; monobutyl phthalate, monobenzyl phthalate, mono-2-ethylhexyl phthalate (MEHP), and monomethyl phthalate were detected in > 90% of samples. Although we found both substantial day-to-day and month-to-month variability in each individual's urinary phthalate metabolite levels, a single urine sample was moderately predictive of each subject's exposure over 3 months. The sensitivities ranged from 0.56 to 0.74. Both the degree of between- and within-subject variance and the predictive ability of a single urine sample differed among phthalate metabolites. In particular, a single urine sample was most predictive for MEP and least predictive for MEHP. These results suggest that the most efficient exposure assessment strategy for a particular study may depend on the phthalates of interest.     

Urinary phthalate metabolites and male reproductive function parameters in Chongqing general population,China

This study was designed to investigate the phthalates exposure levels in general population in Chongqing City of China, and to determine the possible associations between phthalate exposure and male reproductive function parameters. We recruited 232 general men through Chongqing Family Planning Research Institute and Reproductive Center of Chongqing. In a single spot urine sample from each man, phthalate metabolites, including mono-butyl phthalate (MBP), mono-ethyl phthalate (MEP), mono-(2-ethylhexyl) phthalate (MEHP), mono-benzyl phthalate (MBzP), phthalic acid (PA), and total PA were analyzed using solid phase extraction and coupled with high-performance liquid chromatography and detection by tandem mass spectrometry. Semen parameters were dichotomized based on World Health Organization reference values. Sperm DNA damage were analyzed using the alkaline single-cell gel electrophoresis assay. Reproductive hormones were determined in serum by the radioimmunoassay kit. We observed a weak association between urinary MBP concentration and sperm concentration in Chongqing general population. MBP levels above the median were 1.97 times (95% confidence interval [CI] 0.97–4.04) more likely to have sperm concentration below the reference value. There were no other associations between phthalate metabolites and reproductive function parameters after adjusted for potential risk factors. Our study suggested that general population in Chongqing area of China exposure to the environmental level of phthalate have weak or without adverse effects on the reproduction.     

Relationship between Environmental Phthalate Exposure and the Intelligence of School-Age Children

Background

Concern over phthalates has emerged because of their potential toxicity to humans.

Objective

We investigated the relationship between the urinary concentrations of phthalate metabolites and children’s intellectual functioning.

Methods

This study enrolled 667 children at nine elementary schools in five South Korean cities. A cross-sectional examination of urine phthalate concentrations was performed, and scores on neuropsychological tests were obtained from both the children and their mothers.

Results

We measured mono-2-ethylhexyl phthalate (MEHP) and mono(2-ethyl-5-oxohexyl)phthalate (MEOHP), both metabolites of di(2-ethylhexyl)phthalate (DEHP), and mono-n-butyl phthalate (MBP), a metabolite of dibutyl phthalate (DBP), in urine samples. The geometric mean (ln) concentrations of MEHP, MEOHP, and MBP were 21.3 μg/L [geometric SD (GSD) = 2.2 μg/L; range, 0.5–445.4], 18.0 μg/L (GSD = 2.4; range, 0.07–291.1), and 48.9 μg/L (GSD = 2.2; range, 2.1–1645.5), respectively. After adjusting for demographic and developmental covariates, the Full Scale IQ and Verbal IQ scores were negatively associated with DEHP metabolites but not with DBP metabolites. We also found a significant negative relationship between the urine concentrations of the metabolites of DEHP and DBP and children’s vocabulary subscores. After controlling for maternal IQ, a significant inverse relationship between DEHP metabolites and vocabulary subscale score remained. Among boys, we found a negative association between increasing MEHP phthalate concentrations and the sum of DEHP metabolite concentrations and Wechsler Intelligence Scale for Children vocabulary score; however, among girls, we found no significant association between these variables.

Conclusion

Controlling for maternal IQ and other covariates, the results show an inverse relationship between phthalate metabolites and IQ scores; however, given the limitations in cross-sectional epidemiology, prospective studies are needed to fully explore these associations.