Age and sex differences in childhood and adulthood obesity association with phthalates: Analyses of NHANES 2007–2010

Background

Exposure to environmental chemicals may play a role in the development of obesity. Evidence suggests phthalate exposure may be associated with obesity in children and adults.

Objective

To examine the association of ten urinary phthalate metabolites mono-n-butyl phthalate (MnBP), mono-ethyl phthalate (MEP), mono-isobutyl phthalate (MiBP), mono-2-ethyl-5-carboxypentyl phthalate (MECPP), mono-2-ethyl-5-hydroxyhexyl phthalate (MEHHP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), mono-2-ethylhexyl phthalate (MEHP), mono-benzyl phthalate (MBzP), mono-(carboxylnonyl) phthalate (MCNP), and mono-(carboxyoctyl) phthalate (MCOP) grouped by molecular weight of their parent compounds with body weight outcomes in children, adolescent and adult participants in the National Health and Nutrition Examination Survey (NHANES) 2007–2010.

Methods

We performed multinomial logistic regression to analyze the association between obesity and urinary phthalate metabolite concentrations in children and adolescents and adults.

Results

Low molecular weight (LMW) phthalate metabolites (MnBP, MEP and MiBP) are significantly (p < 0.05) associated with higher odds for obesity in male children and adolescents. High molecular weight (HMW) phthalate metabolites (MECPP, MEHHP, MEOHP, MEHP, MBzP, MCNP, and MCOP) and di-2-ethylhexyl phthalate (DEHP) metabolites (MEHHP, MEOHP, MEHP and MECPP) are significantly (p < 0.05) associated with higher OR for obesity in all adults. Additionally, DEHP metabolites are significantly associated with obesity in all female adults; whereas DEHP and HMW metabolites are significantly associated with OR for obesity in males 60 years and older.

Conclusions

We found age and sex differences in the association between urinary phthalate metabolite concentrations and body weight outcomes. Reverse causation cannot be excluded since overweight and obese people will have more fat mass, they may store more phthalates, thus leading to higher excretion concentrations.     

Variability and predictors of urinary phthalate metabolites in Spanish pregnant women

Developmental exposure to phthalates may be associated with adverse health outcomes but information on the variability and predictors of urinary phthalate metabolite concentrations during pregnancy is limited. We evaluated in Spanish pregnant women (n = 391) the reproducibility of urinary phthalate metabolite concentrations and predictors of exposure. We measured mono-(4-methyl-7-hydroxyoctyl) phthalate (7-OHMMeOP), mono-(2-ethylhexyl) phthalate (MEHP), mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP), mono-(2-carboxyhexyl) phthalate (MCMHP), mono-benzyl phthalate (MBzP), mono-ethyl phthalate (MEP), mono-iso-butyl phthalate (MiBP) and mono-n-butyl phthalate (MnBP) in two spot urine samples collected in the first and third pregnancy trimesters. Questionnaires on predictors and food-frequency questionnaires were administered in the first and/or third pregnancy trimesters. Using creatinine-adjusted phthalate metabolite concentrations (log₁₀-trasformed) we calculated intraclass correlation coefficients (ICCs). Linear mixed and regression models assessed the associations between predictors and phthalate metabolites. The ICCs ranged from 0.24 to 0.07 and were higher for MBzP, MEP, MiBP, and lower for MEOHP and MEHHP. Overweight, lower education and social class, and less frequent consumption of organic food were associated with higher levels of some phthalate metabolites. The use of household cleaning products (bleach, ammonia, glass cleaners, oven cleaning sprays and degreasing products) at least once per week during pregnancy was associated with 10–44% higher urinary phthalate metabolites. Bottled-water consumption, consumption of food groups usually stored in plastic containers or cans, use of plastic containers for heating food and cosmetic use were not associated with increased concentrations of phthalate metabolites. This large study with repeated phthalate measurements suggests that, in this Spanish setting, sociodemographic and lifestyle factors and household cleaning product use are better predictors of phthalate exposure levels in pregnant women than average water and food consumption and use of plastic containers and cosmetics.     

Prenatal exposure to bisphenol A and phthalates and behavioral problems in children at preschool age: the Hokkaido Study on Environment and Children’s Health

Background

Studies reported adverse behavioral development including internalizing and externalizing problems in association with prenatal exposure to bisphenol A (BPA) and phthalates; however, findings were not sufficient due to using different assessment tools and child ages among studies. This study aimed to examine associations between maternal serum levels of BPA and phthalate metabolites and behavioral problems at preschool age.

Methods

The Strengths and Difficulties Questionnaire (SDQ) was used to assess behavioral problems at 5 years of age. BPA and phthalate metabolite levels in the first trimester maternal serum was determined by LC-MS/MS for 458 children. Variables used for adjustment were parental ages, maternal cotinine levels, family income during pregnancy, child sex, birth order, and age at SDQ completed.

Results

The median concentrations of BPA, MnBP, MiBP, MEHP, and MECPP, primary and secondary metabolites of phthalates, were 0.062, 26.0, 7.0, 1.40, and 0.20 ng/ml, respectively. MECPP level was associated with increase conduct problem risk (OR?=?2.78, 95% CI 1.36–5.68) overall and the association remained after child sex stratification, and odds ratios were increased with wider confidence interval (OR?=?2.85, 95% CI 1.07–7.57 for boys, OR?=?4.04, 95% CI 1.31–12.5 for girls, respectively). BPA, ∑DBP_m (MnBP + MiBP), and ∑DEHP_m (MEHP+MECPP) levels were not associated with any of the child behavioral problems.

Conclusions

Our analyses found no significant association between BPA or summation of phthalate metabolite levels and any of the behavioral problems at 5 years of age but suggested possible association between MECPP levels and increased risk of conduct problems.

     

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.     

Exposure sources and their relative contributions to urinary phthalate metabolites among children in Taiwan

Phthalate exposure is omnipresent and known to have developmental and reproductive effects in children. The aim of this study was to determine the phthalate exposure sources and their relative contributions among children in Taiwan. During the first wave of the Risk Assessment of Phthalate Incident in Taiwan (RAPIT), in 2012, we measured 8 urinary phthalate metabolites in 226 children aged 1–11 years old and in 181 children from the same cohort for the wave 2 study in 2014. A two-stage statistical analysis approach was adopted. First, a stepwise regression model was used to screen 80 questions that explored the exposure frequency and lifestyle for potential associations. Second, the remaining questions with positive regression coefficients were grouped into the following 6 exposure categories: plastic container/packaging, food, indoor environment, personal care products, toys, and eating out. A mixed model was then applied to assess the relative contributions of these categories for each metabolite. The use of plastic container or food packaging were dominant exposure sources for mono-2-ethylhexyl phthalate (MEHP), mono-2-ethyl-5-hydroxyhexyl phthalate (MEHHP), mono-2-ethyl-5-oxohexyl phthalate (MEOHP), and mono-n-butyl phthalate (MnBP). The indoor environment was a major exposure source of mono-methyl phthalate (MMP), mono-benzyl phthalate (MBzP), and mono-isobutyl phthalate (MiBP). The consumption of seafood showed a significant correlation with MEHP. The children's modified dietary behavior and improved living environment in the second study wave were associated with lower phthalate metabolite levels, showing that phthalate exposures can be effectively reduced.     

Phthalate-induced oxidative stress and association with asthma-related airway inflammation in adolescents

Background

In Belgium, around 8.5% of the children have asthmatic symptoms. Increased asthma risk in children has been reported in relation to exposure to phthalate plasticizers but the underlying mechanisms are largely unknown.

Austrian reference values for phthalate metabolite exposure in children/adolescents and adults

Reference values (RV₉₅) are statistically derived values comprising the rounded 95th percentiles within the 95% confidence interval and indicate the upper margin of background exposure to chemical substances in a population at a given time period. Based on representative national human biomonitoring data on several urinary phthalate metabolites in children, adolescents and adults from 2010 to 2011, RV₉₅ were derived for the Austrian population based on a IUPAC guideline and the recommendation of the German Human Biomonitoring Commission. The RV₉₅ (rounded values) for phthalate metabolites in children and adolescents aged 6–15 years are 110?μg/l (confidence interval of 95th population percentile: 83.7–163) for mono-ethyl phthalate (MEP), 45?μg/l (40.9–60.6) for mono-n-butyl phthalate (MnBP), 130?μg/l (126–161) for mono-isobutyl phthalate (MiBP), 25?μg/l (17.8–33.6) for mono-benzyl phthalate (MBzP), 100?μg/l (94.0–126) for the sum of the di(2-ethylhexyl) phthalate (DEHP) metabolites including mono(2-ethylhexyl) phthalate (MEHP), mono(2-ethyl-5-hydroxyhexyl) phthalate (5OH-MEHP), mono(2-ethyl-5-oxohexyl) phthalate (5oxo-MEHP) and mono(2-ethyl-5-carboxypentyl) phthalate (5cx-MEPP), and 1.5?μg/l (0.64–1.6) for mono-cyclohexyl phthalate (MCHP). In adults aged 18–81 years, RV₉₅ are 440?μg/l (353–636) for MEP, 40?μg/l (33.1–52.1) for MnBP, 110?μg/l (87.3–118) for MiBP, 10?μg/l (7.2–11.8) for MBzP, 50?μg/l (44.6–68.3) for the sum of MEHP, 5OH-MEHP, 5oxo-MEHP and 5cx-MEPP, and 1.5?μg/l (0.95–1.8) for MCHP. For almost all investigated metabolites, children and adolescents exhibit higher RV₉₅ than adults, with the exceptions being MEP and MCHP. Compared to available RV₉₅ for Germany and Canada, Austrian values are lower for all investigated population groups.     

Mono(2-ethyl-5-hydroxyhexyl) phthalate and mono-(2-ethyl-5-oxohexyl) phthalate as biomarkers for human exposure assessment to di-(2-ethylhexyl) phthalate

Exposure to di-(2-ethylhexyl) phthalate (DEHP) is prevalent based on the measurement of its hydrolytic metabolite mono-(2-ethylhexyl) phthalate (MEHP) in the urine of 78% of the general U.S. population studied in the 1999-2000 National Health and Nutrition Examination Survey (NHANES). However, despite the high level of production and use of DEHP, the urinary MEHP levels in the NHANES samples were lower than the monoester metabolites of phthalates less commonly used than DEHP, suggesting metabolic differences between phthalates. We measured MEHP and two oxidative DEHP metabolites, mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP) and mono (2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) to verify whether these other metabolites account for a greater proportion of DEHP metabolic products in 127 paired human urine and serum samples. We found that the urinary levels of MEHHP and MEOHP were 10-fold higher than levels of MEHP; concentrations of urinary MEOHP and MEHHP were strongly correlated (r = 0.928). We also found that the serum levels of MEOHP and MEHHP were comparatively lower than those in urine. Furthermore, the glucuronide-bound conjugates of the oxidative metabolites were the predominant form in both urine and serum. MEOHP and MEHHP cannot be formed by serum enzymes from the hydrolysis of any contamination from DEHP potentially introduced during blood collection and storage. Therefore, concentrations of MEHHP and MEOHP in serum may be a more selective measure of DEHP exposure than is MEHP. However, additional data on the absorption, distribution, metabolism, and elimination of these oxidative metabolites are needed to completely understand the extent of DEHP exposure from the serum concentrations of oxidative DEHP metabolites.     

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.     

Assessing human exposure to phthalates using monoesters and their oxidized metabolites as biomarkers

Phthalates are a group of industrial chemicals with many commercial uses, such as solvents, additives, and plasticizers. For example, di-(2-ethylhexyl) phthalate (DEHP) is added in varying amounts to certain plastics, such as polyvinyl chloride, to increase their flexibility. In humans, phthalates are metabolized to their respective monoesters, conjugated, and eliminated. However, despite the high production and use of DEHP, we have recently found that the urinary levels of the DEHP metabolite mono-(2-ethylhexyl) phthalate (MEHP) in 2,541 persons in the United States were lower than we anticipated, especially when compared with urinary metabolite levels of other commonly used phthalates. This finding raised questions about the sensitivity of this biomarker for assessing DEHP exposure. We explored the utility of two other DEHP metabolites, mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP) and mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), as additional DEHP biomarkers. These metabolites are formed by oxidative metabolism of MEHP. In urine from 62 people, both the range and the mean urinary levels of MEOHP and MEHHP were on average 4-fold higher than those of MEHP; the mean of the individual ratios of MEHHP/MEOHP, MEHHP/MEHP, and MEOHP/MEHP were 1.4, 8.2, and 5.9, respectively. These data suggest that MEOHP and MEHHP are more sensitive biomarkers of exposure to DEHP than is MEHP. These findings also suggest a predominant human metabolic route for DEHP hydrolysis to MEHP followed by oxidation of MEHP; they also imply that a similar mechanism may be relevant for other high-molecular-weight phthalates, such as di-n-octyl, di-isononyl, and di-isodecyl phthalates.     

Occurrence and daily variation of phthalate metabolites in the urine of an adult population

Phthalates like di-(2-ethylhexyl) phthalate (DEHP) are commonly used as plasticizers and their metabolites are suspect of especially reproductive toxicity. The aim of our study was to assess phthalate exposure in adults by measuring urinary phthalate metabolite levels and to explore individual temporal variability. Urine samples were collected by 27 women and 23 men aged 14-60 years during 8 consecutive days. We quantified four monoesters, four oxidative DEHP metabolites, and two secondary metabolites of di-isononyl phthalate (DiNP) by a LC/LC-MS/MS method. If we analyzed all 399 available samples independent of classification, the highest median values of primary metabolites in this study were found for mono-n-butyl phthalate (MnBP: 49.6 microg/l), followed by mono-isobutyl phthalate (MiBP: 44.9 microg/l), mono-benzyl phthalate (MBzP: 7.2 microg/l), and mono-2-ethylhexyl phthalate (MEHP: 4.9 microg/l). The median concentrations of the oxidized metabolites of DEHP were 8.3 microg/l for mono-(2-carboxymethylhexyl) phthalate (2cx-MMHP), 19.2 microg/l for mono-(2-ethyl-5-hydroxyhexyl) phthalate (5OH-MEHP), 14.7 microg/l for mono-(2-ethyl-5-oxohexyl) phthalate (5oxo-MEHP), and 26.2 microg/l for mono-(2-ethyl-5-carboxypentyl) phthalate (5cx-MEPP). The concentrations of the two DiNP secondary metabolites mono (oxoisononyl) phthalate (oxo-MiNP) and mono(hydroxyisononyl) phthalate (OH-MiNP) ranged from 相似文献   

Urinary metabolites of di(2-ethylhexyl) phthalate relation to sperm motility,reactive oxygen species generation,and apoptosis in polyvinyl chloride workers

Purpose

To measure the concentrations of urinary di(2-ethylhexyl) phthalate (DEHP) metabolites in polyvinyl chloride (PVC) workers and a control group for determining the relationship of DEHP exposure to semen quality, sperm reactive oxygen species (ROS) generation, and sperm apoptosis.

Methods

We assessed the metabolites of DEHP, namely urinary mono-(2-ethylhexyl) phthalate (MEHP), mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), and mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), and semen quality, such as sperm concentration, motility, morphology, ROS generation, and DNA damage by using terminal deoxynucleotidyl transferase-mediated nick end labeling assay obtained from 47 workers employed within two PVC pellet plants and 15 graduate students in Taiwan.

Results

Sperm concentration and motility were significantly affected in the high-exposure group. The percentage and intensity of sperm ROS generation were higher in the high-exposure group than those in the control group. After adjustment for age, smoking status, and coffee consumption, the decrease in sperm motility was inversely associated with the concentration of MEHP (β = ?0.549, p = 0.0085), MEHHP (β = ?0.155, p = 0.0074), and MEOHP (β = ?0.201, p = 0.0041). Moreover, sperm apoptosis and ROS generation were positively associated with MEHHP and MEOHP concentration, respectively.

Conclusions

This was the first study to explore the associations between levels of DEHP exposure, sperm motility, ROS generation, and apoptosis. The results suggested that urinary MEHHP and MEOHP were sensitive biomarkers for reflecting the relationship between DEHP exposure and semen quality.     

Urinary Phthalate Metabolite Concentrations and Diabetes among Women in the National Health and Nutrition Examination Survey (NHANES) 2001-2008

Background: Previous studies have shown that women have higher urinary concentrations of several phthalate metabolites than do men, possibly because of a higher use of personal care products. Few studies have evaluated the association between phthalate metabolites, diabetes, and diabetes-related risk factors among women.Objective: We explored the association between urinary phthalate metabolite concentrations and diabetes among women who participated in a cross-sectional study.Methods: We used urinary concentrations of phthalate metabolites, analyzed by the Centers for Disease Control and Prevention, and self-reported diabetes of 2,350 women between 20 and 79 years of age who participated in the NHANES (2001-2008). We used multiple logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) and adjusted for urinary creatinine, sociodemographic characteristics, dietary factors, and body size. A secondary analysis was conducted for women who did not have diabetes to evaluate the association between phthalate metabolite concentrations and fasting blood glucose (FBG), homeostasis model assessment-estimated insulin resistance, and glycosylated hemoglobin A1c.Results: After adjusting for potential confounders, women with higher levels of mono-n-butyl phthalate (MnBP), mono-isobutyl phthalate (MiBP), monobenzyl phthalate (MBzP), mono-(3-carboxypropyl) phthalate (MCPP), and three di-(2-ethylhexyl) phthalate metabolites (ΣDEHP) had an increased odds of diabetes compared with women with the lowest levels of these phthalates. Women in the highest quartile for MBzP and MiBP had almost twice the odds of diabetes [OR = 1.96 (95% CI: 1.11, 3.47) and OR = 1.95 (95% CI: 0.99, 3.85), respectively] compared with women in the lowest quartile. Nonmonotonic, positive associations were found for MnBP and ΣDEHP, whereas MCPP appeared to have a threshold effect. Certain phthalate metabolites were positively associated with FBG and insulin resistance.Discussion: Urinary levels of several phthalates were associated with prevalent diabetes. Future prospective studies are needed to further explore these associations to determine whether phthalate exposure can alter glucose metabolism and increase the risk of insulin resistance and diabetes.     

Metabolites of the plasticizer di (2-ethylhexyl) phthalate in urine samples of workers in polyvinylchloride processing industries

Summary Little is known about occupational exposure to the plasticizer di(2-ethylhexyl)phthalate (CAS number 117-81-7), a compound widely used in polyvinylchloride (PVC) plastics. We have studied the uptake of DEHP in workers by determining the concentrations of four metabolites of DEHP in urine samples, i.e., mono(2-ethylhexyl)phthalate (MEHP), mono (5-carboxy-2-ethylpentyl)phthalate, mono(2-ethyl-5-oxohexyl)phthalate, and mono(2-ethyl-5-hydroxyhexyl)phthalate. In addition DEHP concentrations in the air were determined by personal air sampling. Nine workers in a PVC boot factory exposed to a maximum of 1.2 mg/m³ DEHP showed an increase in the urinary concentrations of all four metabolites over the workshift. These results were obtained on both the first and the last day of the workweek. With the exception of MEHP, the increases in the concentrations of the metabolites during a workday were statistically significant. Six workers from a PVC cable factory exposed to a maximum of 1.2 mg/m³ DEHP showed a one-to fourfold increase in the concentrations of the four metabolites over the workshift, but these increases were not statistically significant. These results indicate that measurement of DEHP metabolites in urine samples may be of use for monitoring the occupational exposure to DEHP.     

Exposure to phthalates in neonatal intensive care unit infants: urinary concentrations of monoesters and oxidative metabolites

OBJECTIVE: We previously demonstrated that among 54 infants in neonatal intensive care units, exposure to polyvinyl chloride plastic medical devices containing the plasticizer di(2-ethylhexyl) phthalate (DEHP) is associated with urinary concentrations of mono(2-ethylhexyl) phthalate (MEHP) , a DEHP metabolite. In this follow-up report, we studied the neonates' exposure to DEHP-containing devices in relation to urinary concentrations of two other DEHP metabolites, and to urinary concentrations of metabolites of dibutyl phthalate (DBP) and benzylbutyl phthalate (BzBP) , phthalates found in construction materials and personal care products. MEASUREMENTS: A priori, we classified the intensiveness of these 54 infants' exposure to DEHP-containing medical products. We measured three metabolites of DEHP in infants' urine: MEHP and two of its oxidative metabolites, mono(2-ethyl-5-hydroxylhexyl) phthalate (MEHHP) and mono(2-ethyl-5-oxohexyl) phthalate (MEOHP) . We also measured monobutyl phthalate (MBP) , a metabolite of DBP, and monobenzyl phthalate (MBzP), a metabolite of BzBP. RESULTS: Intensiveness of DEHP-containing product use was monotonically associated with all three DEHP metabolites. Urinary concentrations of MEHHP and MEOHP among infants in the high-DEHP-intensiveness group were 13-14 times the concentrations among infants in the low-intensiveness group (p相似文献   

Trends of the internal phthalate exposure of young adults in Germany--follow-up of a retrospective human biomonitoring study

The exposure of the general population to phthalates is of increasing public health concern. Variations in the internal exposure of the population are likely, because the amounts, distribution and application characters of the phthalate use change over time. Estimating the chronological sequences of the phthalate exposure, we performed a retrospective human biomonitoring study by investigating the metabolites of the five most prominent phthalates in urine. Therefore, 24 h-urine samples from the German Environmental Specimen Bank (ESB) collected from 240 subjects (predominantly students, age range 19–29 years, 120 females, 120 males) in the years 2002, 2004, 2006 and 2008 (60 individuals each), were analysed for the concentrations of mono-n-butyl phthalate (MnBP) as metabolite of di-n-butyl phthalate (DnBP), mono-iso-butyl phthalate (MiBP) as metabolite of di-iso-butyl phthalate (DiBP), mono-benzyl phthalate (MBzP) as metabolite of butylbenzyl phthalate (BBzP), mono-(2-ethylhexyl) phthalate (MEHP), mono-(2-ethyl-5-hydroxyhexyl) phthalate (5OH-MEHP), mono-(2-ethyl-5-oxohexyl) phthalate (5oxo-MEHP), mono-(2-ethyl-5-carboxypentyl) phthalate (5cx-MEPP) and mono-(2-carboxymethyl hexyl) phthalate (2cx-MMHxP) as metabolites of di(2-ethylhexyl) phthalate (DEHP), monohydroxylated (OH-MiNP), monooxidated (oxo-MiNP) and monocarboxylated (cx-MiNP) mono-iso-nonylphthalates as metabolites of di-iso-nonyl phthalates (DiNP). Based on the urinary metabolite excretion, together with results of a previous study, which covered the years 1988–2003, we investigated the chronological sequences of the phthalate exposure over two decades. In more than 98% of the urine samples metabolites of all five phthalates were detectable indicating a ubiquitous exposure of people living in Germany to all five phthalates throughout the period investigated. The medians in samples from the different years investigated are 65.4 (2002), 38.5 (2004), 29.3 (2006) and 19.6 μg/l (2008) for MnBP, 31.4 (2002), 25.4 (2004), 31.8 (2006) and 25.5 μg/l (2008) for MiBP, 7.8 (2002), 6.3 (2004), 3.6 (2006) and 3.8 μg/l (2008) for MBzP, 7.0 (2002), 5.6 (2004), 4.1 (2006) and 3.3 μg/l (2008) for MEHP, 19.6 (2002), 16.2 (2004), 13.2 (2006) and 9.6 μg/l (2008) for 5OH-MEHP, 13.9 (2002), 11.8 (2004), 8.3 (2006) and 6.4 μg/l (2008) for 5oxo-MEHP, 18.7 (2002), 16.5 (2004), 13.8 (2006) and 10.2 μg/l (2008) for 5cx-MEPP, 7.2 (2002), 6.5 (2004), 5.1 (2006) and 4.6 μg/l (2008) for 2cx-MMHxP, 3.3 (2002), 2.8 (2004), 3.5 (2006) and 3.6 μg/l (2008) for OH-MiNP, 2.1 (2002), 2.1 (2004), 2.2 (2006) and 2.3 μg/l (2008) for oxo-MiNP and 4.1 (2002), 3.2 (2004), 4.1 (2006) and 3.6 μg/l (2008) for cx-MiNP. The investigation of the time series 1988–2008 indicates a decrease of the internal exposure to DnBP by the factor of 7–8 and to DEHP and BzBP by the factor of 2–3. In contrast, an increase of the internal exposure by the factor of 4 was observed for DiNP over the study period. The exposure to DiBP was found to be stable. In summary, we found decreases of the internal human exposure for legally restricted phthalates whereas the exposure to their substitutes increased. Future investigations should verify these trends. This is of increasing importance since the European Commission decided to require ban or authorization from 1.1.2015 for DEHP, DnBP, DiBP and BzBP according to REACh Annex XIV.     

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。     

Determination of four metabolites of the plasticizer di (2-ethylhexyl) phthalate in human urine samples

Summary A method for biological monitoring of exposure to the plasticizer di(2-ethylhexyl)phthalate (DEHP) is described. In this method the four main metabolites of DEHP [i.e., mono (2-ethylhexyl) phthalate (MEHP), mono (5-carboxy-2-ethylpentyl)phthalate, mono(2-ethyl-5-oxohexyl)phthalate, and mono(2-ethyl-5-hydroxyhexyl)-phthalate] are determined in urine samples. The procedure includes enzymatic hydrolysis, ether extraction, and derivatization with triethyloxonium tetrafluoroborate. Analysis is performed by gas chromatography electron impact mass spectrometry. The detection limit for all four metabolites is less than 25 g/l urine. The coefficient of variation based on duplicate determinations of urine samples of workers occupationally exposed to DEHP was 16% for MEHP (mean concentration 0.157 mg/l) and 6% -9% for the other three metabolites (mean concentrations 0.130-0.175 mg/1). The method described here was used to study DEHP metabolism in man. Most persons excrete mono(2-ethyl-5-oxohexyl)-phthalate and mono (2-ethyl-5-hydroxyhexyl)phthalate as a (glucuronide) conjugate. Mono (5-carboxy-2-ethyl-pentyl)phthalate is mainly excreted in free form, while for MEHP a large interindividual variation in conjugation status was observed. Of the four metabolites quantified, 52% are products of a ((-l)-hydroxylation reaction of MEHP [i.e., mono (2-ethyl-5-oxohexyl)phthalate and mono (2-ethyl-5-hydroxyhexyl)phthalate], 22% is the product of a -hydroxylation reaction of MEHP [i.e., mono (5-carboxy-2-ethylpentyl)phthalate], and 26% is not oxidized further (i.e., MEHP). A good correlation is obtained when the amount of MEHP -hydroxylation products is compared with the amount of MEHP (-1)hydroxylation products in urine samples. When the internal dose of DEHP has to be established we recommend that the levels of all four metabolites of DEHP be studied in urine samples.     

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.     

Urinary phthalate metabolites and metabolic syndrome in U.S. adolescents: Cross-sectional results from the National Health and Nutrition Examination Survey (2003–2014) data

Objective

There is limited research on the association between phthalates and metabolic syndrome (MetS). Among adolescents, phthalate exposure, which can occur from multiple sources, has been linked to several risk factors for MetS. The objective was to investigate the association between urinary phthalate metabolite concentrations (i.e., mono-ethyl phthalate (MEP), mono-n-butyl phthalate (MnBP), mono-isobutyl phthalate (MiBP), mono-benzyl phthalate (MBzP), mono-(3-carboxylpropyl) phthalate (MCPP), and di(2-ethylhexyl phthalate (DEHP)) and MetS in adolescents aged 12–19 years using the National Health and Nutrition Examination Survey (NHANES) data (2003–2014). A secondary aim was to assess if observed associations varied by a measure of socioeconomic status, economic adversity, which was defined using parental income and educational attainment as well as household food security.