Mono-(2-ethyl-5-carboxypentyl) Phthalate Research Articles

Developing an intervention strategy to reduce phthalate exposure in Taiwanese girls

Children in Taiwan seem to be exposed to higher concentrations of phthalates than do children in Western countries. We developed intervention strategies to reduce the exposure of phthalates in Taiwanese girls. Thirty girls 4–13years old who had been exposed to high levels of phthalates were selected from prior studies. To reduce their phthalate-exposure sources, we developed seven intervention strategies: handwashing, not using plastic containers, not eating food with a plastic bag/plastic-wrap cover, not microwaving food, not taking nutrition supplements, and reducing use of cosmetics/personal care products. Pre- and post-intervention urine samples were collected during a one-week study. HPLC-MS/MS was used to analyze urinary phthalate metabolites. The dominant urinary phthalate metabolite was mono-n-butyl phthalate (MBP), followed by mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), and mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP). Post-intervention concentrations of eight urinary phthalate metabolites were significantly lower. Girls in the high-frequency handwashing group had significantly lower urinary MBP (p=0.009) and mono-methyl phthalate (MMP) (p=0.07) than did girls in the low-frequency handwashing group. Girls who drank fewer beverages from plastic cups had significantly lower urinary MBP (p=0.016), MEHHP (p=0.038), and MECPP (p=0.012). Girls who used less shampoo and shower gel also had marginally significantly lower urinary MBP (p=0.06) and mono-ethyl phthalate (MEP) (p=0.06). The intervention strategies that we set up in this study were effective for reducing exposure to phthalates in children. Handwashing and drinking fewer beverages from plastic cups were the most effective strategies for reducing phthalate metabolites in urine, especially MBP and di(2-ethylhexyl) phthalate (DEHP) metabolites. Education and voluntary self-restraint were useful for reducing the body burden of phthalates.

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.

PO-0075 Head Circumference In The First Year After Birth – The Effect Of Prenatal Exposure To Organochlorines And Phthalates

Background Children with autism may experience increased head growth during the first year of life. Furthermore, early life exposure to endocrine disrupting chemicals (EDCs) may be associated with an increased risk of autism. Exposure to EDCs has been associated with fetal head circumference (HC), however research on long-term effects is scarce. Objective To assess the association between prenatal exposure to various EDCs and HC in the first year of life. Methods Cord plasma or breast milk was used to determine exposure to amongst others dichlorodiphenyldichloroethylene (DDE), mono (2-ethyl-5-hydroxyhexyl)phthalate (MEHHP), and mono (2-ethyl-5-carboxypentyl)phthalate (MECPP). Data on HC until 11 months after birth was obtained. Mixed models were composed for each compound. Exposure quartiles, time, and gender were added to the models as fixed effects. Subject was added as a random effect. Results Boys with high MECPP exposure had a consistently higher HC than lower exposed boys (p = 0.047). This was also observed for girls in Q2 for both MEHHP (p = 0.018) and DDE (p Conclusion For MECPP, MEHHP, and DDE exposure over time, a higher HC was observed in low exposed children in a gender-specific way. Follow-up is warranted to see if associations persist into later childhood and are related to autism spectrum disorders.

PS-357 First Year Growth In Relation To Prenatal Exposure To Endocrine Disruptors – A Dutch Prospective Cohort Study

Background Growth in the first year of life may already be predictive of growth and obesity later in childhood. Early life exposure to endocrine disrupting chemicals (EDCs) has been associated with obesity in children and older populations. Objective To assess the association between prenatal exposure to various EDCs and child growth in the first year of life. Methods Cord plasma or breast milk was used to determine exposure to amongst others dichlorodiphenyldichloroethylene (DDE), mono (2-ethyl-5-oxohexyl) phthalate (MEOHP), and mono (2-ethyl-5-carboxypentyl) phthalate (MECPP). Data on weight and length until 11 months after birth was obtained. Mixed models were composed for each compound and health outcome. Exposure quartiles, time, and gender were added to the models as fixed effects. Subject was added as a random effect. Results For MEOHP, boys in Q1 had a consistently higher BMI than higher exposed boys (p = 0.029). MECPP exposure was related to increased BMI over time in both boys and girls in Q1, though the association was not significant (p = 0.117). The effect of MECPP exposure on BMI was mainly due to weight, which was higher in the low exposed groups. For DDE interaction between time and exposure was significant (p = 0.078). For boys in particular, those with relatively low exposures had higher BMI curves during the first year. Conclusion Low exposure to phthalates and DDE was associated with BMI during the first year after birth. Results were gender specific, and associations were mostly non-monotonic. Follow-up is warranted to see if these effects are persistent during childhood.

First year growth in relation to prenatal exposure to endocrine disruptors - a Dutch prospective cohort study.

Growth in the first year of life may already be predictive of obesity later in childhood. The objective was to assess the association between prenatal exposure to various endocrine disrupting chemicals (EDCs) and child growth during the first year. Dichloro-diphenyldichloroethylene (DDE), mono(2-ethyl-5-carboxypentyl)phthalate (MECPP), mono(2-ethyl-5-hydroxyhexyl)phthalate (MEHHP), mono(2-ethyl-5-oxohexyl)phthalate (MEOHP), polychlorinated biphenyl-153, perfluorooctanesulfonic acid, and perfluoro-octanoic acid were measured in cord plasma or breast milk. Data on weight, length, and head circumference (HC) until 11 months after birth was obtained from 89 mother-child pairs. Mixed models were composed for each health outcome and exposure in quartiles. For MEOHP, boys in quartile 1 had a higher BMI than higher exposed boys (p = 0.029). High DDE exposure was associated with low BMI over time in boys (0.8 kg/m2 difference at 11 m). Boys with high MECPP exposure had a greater HC (1.0 cm difference at 11 m) than other boys (p = 0.047), as did girls in the second quartile of MEHHP (p = 0.018) and DDE (p < 0.001) exposure. In conclusion, exposure to phthalates and DDE was associated with BMI as well as with HC during the first year after birth. These results should be interpreted with caution though, due to the limited sample size.

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

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

Environmental Phthalate Exposure and Preterm Birth

Preterm birth is a leading cause of neonatal mortality, with a variety of contributing causes and risk factors. Environmental exposures represent a group of understudied, but potentially important, factors. Phthalate diesters are used extensively in a variety of consumer products worldwide. Consequently, exposure in pregnant women is highly prevalent. To assess the relationship between phthalate exposure during pregnancy and preterm birth. This nested case-control study was conducted at Brigham and Women's Hospital, Boston, Massachusetts. Women were recruited for a prospective observational cohort study from 2006-2008. Each provided demographic data, biological samples, and information about birth outcomes. From within this group, we selected 130 cases of preterm birth and 352 randomly assigned control participants, and we analyzed urine samples from up to 3 time points during pregnancy for levels of phthalate metabolites. Phthalate exposure during pregnancy. We examined associations between average levels of phthalate exposure during pregnancy and preterm birth, defined as fewer than 37 weeks of completed gestation, as well as spontaneous preterm birth, defined as preterm preceded by spontaneous preterm labor or preterm premature rupture of the membranes (n = 57). Geometric means of the di-2-ethylhexyl phthalate (DEHP) metabolites mono-(2-ethyl)-hexyl phthalate (MEHP) and mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP), as well as mono-n-butyl phthalate (MBP), were significantly higher in cases compared with control participants. In adjusted models, MEHP, MECPP, and Σ DEHP metabolites were associated with significantly increased odds of preterm birth. When spontaneous preterm births were examined alone, MEHP, mono-(2-ethyl-5-oxohexyl) phthalate, MECPP, Σ DEHP, MBP, and mono-(3-carboxypropyl) phthalate metabolite levels were all associated with significantly elevated odds of prematurity. Women exposed to phthalates during pregnancy have significantly increased odds of delivering preterm. Steps should be taken to decrease maternal exposure to phthalates during pregnancy.

Environmental phthalate exposure is associated with increased odds of preterm birth

Background: Preterm birth is a leading cause of neonatal mortality with a variety of associated risk factors. Environmental exposures represent an important but understudied set of potential contributors. Phthalate diesters are used extensively in a variety of consumer products worldwide. Consequently, exposure in pregnant women is highly prevalent. In this study we investigate the relationship between phthalate exposure during pregnancy and preterm birth. Methods: From 2006-2008 women planning to deliver at the Brigham and Women’s Hospital in Boston were prospectively enrolled in an observational cohort study. Each provided demographic data, samples, and information about birth outcomes. Within this group we selected 132 cases of preterm birth and 350 randomly assigned controls, and analyzed urine samples from three time points during pregnancy for levels of phthalate metabolites. We hypothesized there is a relationship between phthalate exposure and preterm birth. Results: Geometric means of the di-2-ethylhexyl phthalate (DEHP) metabolites mono-(2-ethyl)-hexyl phthalate (MEHP) and mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP), as well as mono-n-butyl phthalate (MBP) and mono-(3-carboxypropyl) phthalate (MCPP) were significantly higher in cases compared to controls. In adjusted models, MEHP, MECPP, and ?DEHP metabolites were associated with significantly increased odds of preterm birth. When spontaneous preterm births were examined alone, MEHP, mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), MECPP, ?DEHP, MBP, and MCPP metabolite levels were all associated with significantly elevated odds of delivery. Conclusions: These results are consistent with evidence from toxicological and exploratory human studies and support a relationship between phthalate exposure and increased risk of preterm birth. As phthalate exposure can be avoided, steps should be taken to decrease maternal exposure to phthalates during pregnancy.

Predictors of urinary bisphenol A and phthalate metabolite concentrations in Mexican children

Exposure to endocrine disrupting chemicals such as bisphenol A (BPA) and phthalates is prevalent among children and adolescents, but little is known regarding important sources of exposure at these sensitive life stages. In this study, we measured urinary concentrations of BPA and nine phthalate metabolites in 108 Mexican children aged 8–13years. Associations of age, time of day, and questionnaire items on external environment, water use, and food container use with specific gravity-corrected urinary concentrations were assessed, as were questionnaire items concerning the use of 17 personal care products in the past 48-h. As a secondary aim, third trimester urinary concentrations were measured in 99 mothers of these children, and the relationship between specific gravity-corrected urinary concentrations at these two time points was explored. After adjusting for potential confounding by other personal care product use in the past 48-h, there were statistically significant (p<0.05) positive associations in boys for cologne/perfume use and monoethyl phthalate (MEP), mono(3-carboxypropyl) phthalate (MCPP), mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), and mono(2-ethyl-5-oxohexyl) phthalate (MEOHP), and in girls for colored cosmetics use and mono-n-butyl phthalate (MBP), mono(2-ethylhexyl) phthalate (MEHP), MEHHP, MEOHP, and mono(2-ethyl-5-carboxypentyl) phthalate (MECPP), conditioner use and MEP, deodorant use and MEP, and other hair products use and MBP. There was a statistically significant positive trend for the number of personal care products used in the past 48-h and log-MEP in girls. However, there were no statistically significant associations between the analytes and the other questionnaire items and there were no strong correlations between the analytes measured during the third trimester and at 8–13years of age. We demonstrated that personal care product use is associated with exposure to multiple phthalates in children. Due to rapid development, children may be susceptible to impacts from exposure to endocrine disrupting chemicals; thus, reduced or delayed use of certain personal care products among children may be warranted.

Prenatal urinary phthalate metabolites levels and neurodevelopment in children at two and three years of age

BackgroundPrevious studies suggest that prenatal phthalate exposure affects neurodevelopment and behavior during the first years of life. ObjectivesTo evaluate the effect of maternal urinary concentrations of phthalate metabolites during pregnancy on mental and psychomotor development in children 24–36months of age. MethodsThis analysis was conducted on the first three years of life among a subsample of 136 mother–child pairs from the ELEMENT cohort studies conducted in Mexico City. Maternal urine samples collected during the third trimester of pregnancy were analyzed for 9 phthalate metabolites: Mono-ethyl phthalate (MEP), Mono-n-butyl phthalate (MnBP), mono-isobutyl phthalate (MiBP), mono-benzyl phthalate (MBzP), Mono-3-carboxypropyl phthalate (MCPP), and four di-2-ethylhexyl phthalate (DEHP) metabolites [mono-2-ethylhexyl-phthalate (MEHP), mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), and mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP)]. Among the 136 children, 135 (99.3%) completed the study period. Child neurodevelopment was assessed using mental and psychomotor development indexes (MDI and PDI) from a Bayley (BSID II) test at 24, 30, and 36months of age. The effect of prenatal phthalate exposure on neurodevelopment was estimated using linear regression models for longitudinal data clustered at the individual level. ResultsNo significant associations were observed among all children combined, but differential effects by gender were found. Among girls, there was a negative association between MDI and DEHP metabolites MEHP (β=−2.11 [95% CI: −3.73, −0.49]), MEHHP (β=−1.89 [95% CI: −3.64, −0.15]), MEOHP (β=−1.80 [95% CI: −3.58, −0.03]) MECPP (β=−2.52 [95% CI: −4.44, −0.61]), and ΣDEHP (β=−3.41 [95% CI: −5.26, −1.55]); there was no significant effect among boys. Male PDI was positively related to MBzP (β=1.79 [95% CI: 0.14, 3.45]) and MCPP (β=1.64 [95% CI: 0.15, 3.12]); there was no significant effect on PDI among girls. ConclusionThis study demonstrates that sex plays a role of an effect modifier in the association between prenatal phthalate exposure and neurodevelopment.

Abstract 35: Within-person reproducibility of urinary bisphenol A and phthalate metabolites among women in the Nurses' Health Studies.

Abstract The purpose of our study was to examine the long-term within-person reproducibility of bisphenol A (BPA) and 8 phthalate metabolites. Associations of BPA and phthalates with health are increasingly being investigated in epidemiologic studies, although existing studies are largely cross-sectional. Most previous studies of within-person variability in urinary BPA and phthalate metabolite concentrations have focused on stability over 3 months or less. Long-term reproducibility data are needed to assess the potential usefulness of these biomarkers for predicting risk of disease onset in prospective studies. We measured BPA and 8 phthalate metabolites in spot urine samples donated 1 to 3 years apart by women in the Nurses' Health Study and Nurses' Health Study II (n=80 for analyses of BPA; n=40 for phthalate metabolites); 86% of samples were first-morning urines. Specific phthalate metabolites were mono-ethyl phthalate (MEP), mono-isobutyl phthalate (MiBP), mono-n-butyl phthalate (MnBP), mono-benzyl phthalate (MBzP), mono-(2-ethylhexyl) phthalate (MEHP), mono-(2-ethyl-5-hydrohexyl) phthalate (MEHHP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), and mono-(2-ethyl-5carboxypentyl) phthalate (MECPP). To measure within-person reproducibility, we calculated Spearman rank correlation coefficients and intraclass correlations (ICCs) for creatinine-adjusted BPA and phthalate metabolite concentrations; ICCs were estimated using natural log-transformed values. Additional analyses were restricted to first-morning urine samples. Distributions (medians [5th to 95th percentiles]) of creatinine-adjusted analyte concentrations (ng/mg creatinine) were: 3 (1-6) for BPA, 141 (21-895) for MEP, 4 (1-12) for MiBP, 37 (10-177) for MnBP, 14 (4-97) for MBzP, 5 (2-26) for MEHP, 32 (9-163) for MEHHP, 26 (7-136) for MEOHP, and 43 (16-215) for MECPP. Over 1 to 3 years, within-person variability of BPA was high relative to total variability (ICC=0.14) and rankings of BPA levels between time-points were weakly correlated (Spearman correlation=0.19). All phthalate metabolites, except MEHP, demonstrated moderate within-person stability over time (Spearman correlation or ICC=0.39-0.55). Restricting analyses to first-morning urine samples did not alter results. Overall, we found that single measurements of BPA in spot urine samples were highly variable within women over 1 to 3 years. However, the majority of urinary phthalate metabolites appeared moderately reproducible within women over time. Our results suggest that investigation of associations between a single urinary BPA measurement and disease risk likely will be challenging in epidemiologic studies, while single measurements of urinary phthalate metabolites are reasonable measures of long-term exposure. Further, reproducibility data could be used to correct for within-person variability that results in the attenuation of estimates of relative risk. Citation Format: Mary Townsend, Adrian Franke, Xingnan Li, Frank Hu, A. Heather Eliassen. Within-person reproducibility of urinary bisphenol A and phthalate metabolites among women in the Nurses' Health Studies. [abstract]. In: Proceedings of the AACR Special Conference on Post-GWAS Horizons in Molecular Epidemiology: Digging Deeper into the Environment; 2012 Nov 11-14; Hollywood, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2012;21(11 Suppl):Abstract nr 35.

RELATIONSHIPS BETWEEN URINARY PHTHALATE METABOLITES AND POTENTIAL BIOMARKERS OF INFLAMMATION AND OXIDATIVE STRESS FROM NHANES 1999-2006

Background and Aims: Phthalate exposure has been associated with a wide range of adverse health outcomes in epidemiologic studies, and one hypothesized mechanism is potentially through induction of inflammation and oxidative stress. We recently reported associations between urinary phthalate metabolites and levels of serum gamma glutamyltransferase (GGT), an indicator of oxidative stress, and C-reactive protein (CRP), a marker of inflammation. In this study we expanded our analysis to investigate associations with other potential markers of oxidative stress (bilirubin) and inflammation (alkaline phosphatase, absolute neutrophil count [ANC], ferritin, and fibrinogen). We hypothesized that higher phthalate metabolite concentrations would be associated with elevations in the inflammation markers and decreases in bilirubin, an indication of increased oxidative stress. Methods: In this exploratory analysis, we combined data from the National Health and Nutrition Examination Survey (NHANES) collected between 1999 and 2006 and performed multivariable regression analyses. Results: After adjustment for covariates we found ANC to be significantly and positively associated with the metabolites mono-butyl phthalate (MnBP), mono-benzyl phthalate (MBzP), mono-(3-carboxypropyl) phthalate (MCPP), mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono-2-ethyl-5-carboxypentyl phthalate (MECPP), and a combined measure of the dibutyl phthalate metabolites (p &lt; 0.05). We also observed significant positive associations between alkaline phosphatase levels and the metabolites MnBP, MBzP, MCPP, MEHHP, mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), mono-isobutyl phthalate (MiBP), mono-(carboxynonyl) phthalate (MCNP), and the aforementioned combination measure (p &lt; 0.05). Lastly, bilirubin was significantly and inversely associated with the metabolites MnBP, mono-(2-ethyl)-hexyl phthalate (MEHP), MBzP, MCPP, MEHHP, MEOHP, MiBP, MECPP, and the combined DBP metabolites (p &lt; 0.0001). Conclusions: Concentrations of some urinary phthalate metabolites are associated with increases in ANC and alkaline phosphatase levels, as well as decreased bilirubin levels, which may be indicative of increased inflammation and oxidative stress. These markers may be useful in other studies of low-dose exposure to environmental contaminants in NHANES and other datasets.

Phthalate exposure associated with self-reported diabetes among Mexican women

Background Phthalates are ubiquitous industrial chemicals used as plasticizers in plastics made of polyvinyl chloride (PVC) to confer flexibility and durability. They are also present in products used for personal-care, industry and in medical devices. Phthalates have been associated with several adverse health effects, and recently it has been proposed that exposure to phthalates, could have an effect on metabolic homeostasis. This exploratory cross-sectional study evaluated the possible association between phthalate exposure and self-reported diabetes among adult Mexican women. Methods As part of an on-going case-control study for breast cancer, only controls were selected, which constituted 221 healthy women matched by age (±5 years) and place of residence with the cases. Women with diabetes were identified by self-report. Urinary concentrations of nine phthalate metabolites were measured by online solid phase extraction coupled to high performance liquid chromatography-isotope-dilution tandem mass spectrometry. Results Participants with diabetes had significantly higher concentrations of di(2-ethylhexyl) pththalate (DEHP) metabolites: mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono(2-ethyl-5-oxohexyl) phthalate (MEOHP) and mono(2-ethyl-5-carboxypentyl) phthalate (MECPP) but lower levels of monobenzyl phthalate (MBzP) a metabolite of benzylbutyl phthalate, compared to participants without diabetes. A marginally significant positive associations with diabetes status were observed over tertiles with MEHHP (OR T3 vs. T1=2.66; 95% CI: 0.97–7.33; p for trend=0.063) and MEOHP (OR T3 vs. T1=2.27; 95% CI; 0.90–5.75; P for trend=0.079) even after adjusting for important confounders. Conclusions The results suggest that levels of some phthalates may play a role in the genesis of diabetes.

Personal care product use and urinary levels of phthalate metabolites in Mexican women

Sources of phthalates other than Polyvinyl chloride (PVC) related products are scarcely documented in Mexico. The objective of our study was to explore the association between urinary levels of nine phthalate metabolites and the use of personal care products.Subjects included 108 women who participated as controls in an ongoing population-based case-control study of environmental factors and genetic susceptibility to breast cancer in northern Mexico. Direct interviews were performed to inquire about sociodemographic characteristics, reproductive history, use of personal care products, and diet. Phthalate metabolites measured in urine by high performance liquid chromatography–isotope dilution tandem mass spectrometry were monoethyl phthalate (MEP), monobenzyl phthalate (MBzP), mono-n-butyl phthalate (MBP), mono-isobutyl phthalate (MiBP), mono-3-carboxypropyl phthalate (MCPP) as well as mono-2-ethylhexyl phthalate (MEHP), mono-2-ethyl-5-oxohexyl phthalate (MEOHP), mono-2-ethyl-5-hydroxyhexyl phthalate (MEHHP), mono-2-ethyl-5-carboxypentyl phthalate (MECPP) that are metabolites of di-ethylhexyl phthalate (DEHP). Detectable urinary concentrations of phthalate metabolites varied from 75% (MEHP) to 100% (MEP, MBP, MEOHP, MEHHP and MECPP).Medians of urinary concentrations of some phthalate metabolites were significantly higher among users of the following personal care products compared to nonusers: body lotion (MEHHP, MECPP and sum of DEHP metabolites (ΣDEHP)), deodorant (MEHP and ΣDEHP), perfume (MiBP), anti-aging facial cream (MEP, MBP and MCPP) and bottled water (MCPP, MEHHP and MEOHP). Urinary concentrations of MEP showed a positive relationship with the number of personal care products used.Our results suggest that the use of some personal care products contributes to phthalate body burden that deserves attention due to its potential health impact.

Associations Between Maternal Prenatal Phthalate Urinary Metabolite Concentrations and Child Mental and Motor Development at Age 3 Years

O-30C7-1 Background/Aims: Recent epidemiologic research has shown inverse associations between prenatal and postnatal phthalate urinary metabolite concentrations and child IQ and executive function. Methods: We have evaluated relationships between maternal prenatal urinary metabolite concentrations and child age 3 Mental Development Index (MDI) and Psychomotor Development Index (PDI) on the Bayley Scales of Infant Development II among 315 mothers and children in New York City. Metabolites were mono-n-butyl phthalate (MnBP), mono-benzyl phthalate, monoisobutyl phthalate (MiBP), and 4 di-2-ethylhexyl phthalate (DEHP) metabolites: mono-2-ethylhexyl phthalate (MEHP), mono-2-ethyl-5-hydroxyhexyl phthalate, mono-2-ethyl-5-oxohexyl phthalate, and mono-2-ethyl-5-carboxypentyl phthalate (MECPP). Concentrations were adjusted for specific gravity and log-transformed. Models controlled for race/ethnicity, child gender, gestational age, maternal education, material hardship, prenatal environmental tobacco smoke, and quality of the home environment. Chlorpyrifos levels were low with little variability. Prenatal polycyclic aromatic hydrocarbons did not improve model fit. Thus, neither was included in the models. Results: None of the metabolites were significantly associated with child MDI. However, MEHP/sum of the 4 DEHP metabolites × 100 (%MEHP, thought to be a biomarker of susceptibility) was inversely associated with MDI (B = −0.22; 95% CI: 01, −0.46; P = 0.06). Child PDI scores decreased with increasing concentrations of (ln)MnBP (B = −2.4; 95% CI: −0.7, −4.1; P = 0.007) and (ln)MiBP (B = −2.0; 95% CI: −0.4, −3.6; P = 0.01) and the odds ratio for risk of motor delay increased significantly (1.5; 95% CI: 1.0, 2.2; P = 0.04 and 1.8; 95% CI: 1.2, 2.6; P = 0.004 for (ln)MnBP and (ln)MiBP). In contrast (ln) MECPP was positively associated with child PDI scores (B = 1.9; 95% CI: 0.4, 3.5; P = 0.01) but did not modulate risk of motor delay (P = 0.5). Conclusion: Prenatal exposure to some phthalates may modulate child development. However, these are among the first reports of effects on mental and motor development and should be interpreted with caution. Additional research is warranted to explore these hypotheses.

Correlations Between Phthalate Metabolites in Urine, Serum, and Seminal Plasma from Young Danish Men Determined by Isotope Dilution Liquid Chromatography Tandem Mass Spectrometry

Phthalates are suspected of endocrine disrupting effects. We aimed to develop an analytical method for simultaneous determination of several phthalate metabolites in human urine, serum, and seminal plasma and to study correlations between levels of metabolites in these matrices. Thirteen metabolites were determined in samples from 60 young Danish men. Metabolites of common di-ester phthalates were detected in most urine samples. Summed di-(2-ethylhexyl) phthalate (DEHP) metabolites were excreted in urine in the highest amount (median = 91.1 ng/mL), followed by monoethyl phthalate (MEP), mono-iso-butyl phthalate (MiBP), mono-n-butyl phthalate (MnBP), mono-benzyl phthalate (MBzP), and finally summed di-isononyl phthalate (DiNP) metabolites. All these metabolite levels correlated significantly, indicating that when a participant was highly exposed to one phthalate he was also highly exposed to other phthalates. Several metabolites were also detectable in serum and in seminal plasma, although in much lower levels. Significant correlations between MEP and MiBP levels in serum and urine were observed, showing that serum levels could be used as biomarkers of human exposure. For DEHP and DiNP metabolites, correlations between urine and serum levels were only observed for mono(2-ethyl-5-carboxypentyl) phthalate (MECPP) and mono-(4-methyl-7-carboxyheptyl) phthalate (MCiOP), indicating that these secondary carboxylated metabolites were better serum markers than primary metabolites [mono(2-ethylhexyl) phthalate (MEHP) and mono-iso-nonyl phthalate (MiNP)]. In seminal plasma, only MEP levels correlated significantly to levels in urine and in serum.

Personal Care Productsʼ Use and Its Association with Urine Concentrations of Phthalate Metabolites

ISEE-0235 Background and Objective: Sources of phthalates other than PVC related products are scarcely documented in Mexico. The aim of this study was to explore the association between urinary levels of nine phthalate metabolites and use of personal care products as well as other potential environmental sources. Methods: Subjects included 108 women who participated as controls in an ongoing population based case-control study of environmental factors and genetic susceptibility to Breast Cancer in northern Mexico. Direct interviews were performed to inquire about reproductive history, use of personal care products and diet. The following phthalate metabolites were measured in urine by HPLC-MS/MS at the CDC: monoethyl phthalate (MEP), monobenzyl phthalate (MBzP), mono-n-butyl phthalate (MBP), mono-isobutyl phthalate (MiBP), mono-2-ethylhexyl phthalate (MEHP), mono-2-ethyl-5-oxohexyl phthalate (MEOHP), mono-2-ethyl-5-hydroxyhexyl phthalate (MEHHP), mono-2-ethyl-5-carboxypentyl phthalate (MECPP) and, mono-3-carboxypropyl phthalate (MCPP). Results: Detectable urinary concentrations of phthalate metabolites varied from 75% (MEHP) to 100% (MEP, MBP, MEOHP, MEHHP, MECPP). Setting a cut off point of P < 0.05, linear regression models showed that anti-age creams' use was significantly associated with concentrations of MEP (β = 0.84) and MCPP (β = 0.51), perfume use significantly predicted increasing concentrations of MBP (β = 0.36) and MiBP (β = 0.5). MBzP concentration was related to the use of hair conditioner (β = 0.58) while DEHP metabolites concentrations were significantly associated to deodorant (MEHP β = 0.49) and body cream use (MECPP, MEHHP, β = 0.4 and 0.47). Bottled water consumption was associated to concentrations of MCPP, MEOHP, MEHHP and MECPP (β = 0.39, 0.39, 0.39 and 0.33 respectively). Conclusion: The results of this study suggest that using personal care products contributes to phthalates body burden. Further estimation of dermal and inhalation exposure by specific products is warranted. “The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the Centers for Disease Control and Prevention.”

Correlations of Urinary and Amniotic Fluid Phthalate Metabolite Concentrations and Expression of Imprinted Genes in Human Placenta

ISEE-0110 Background and Objective: Prenatal exposure to phthalates has been associated with reproductive toxicity and neurodevelopmental consequences in offspring. Fetal exposure is typically estimated by prenatal maternal urinary biomarker levels; however, the extent to which fetuses are directly exposed to metabolites in amniotic fluid has not been established. Methods: A pilot study to estimate the correlation between urine and amniotic fluid concentrations of phthalate metabolites, and their relations with placental expression of imprinted genes was performed (n = 11). This study was nested within the Study of Advanced Reproductive Age and Environmental Health (SARAEH), which enrolled 97 women who were undergoing amniocentesis at the Mount Sinai Medical Center as a part of their routine prenatal care. Women were enrolled on the day of their procedure, and a sample of their urine was obtained immediately following the amniocentesis. At delivery, placental biopsies were obtained for RNA collection. Phthalate concentrations were normalized by specific gravity. Results: Women were predominantly white (n = 10), with a mean age of 36 years. Eleven phthalate metabolites were detected in most prenatal urines. Few amniotic fluid samples had measureable phthalate metabolites, with the exception of mono(2-ethyl-5-carboxypentyl) phthalate (MECPP), an oxidative metabolite of di(2-ethylhexyl) phthalate, which was detectable in all samples. Amniotic fluid concentration of MECPP ranged from 0.7–2.1 ug/L (med 1.1, sd = 0.23). Urine concentration of MECPP ranged from 4.2–359 ug/L (med 81.6, sd = 105.8). There was no correlation between amniotic fluid and urinary concentrations of MECPP. Among other associations, placental expression of IGF2 was increased with increasing urinary concentration of high molecular weight metabolites. Conclusion: Direct fetal exposure to phthalate metabolites in amniotic fluid appears to be minimal, and limited to MECPP. Disruption of placentally imprinted genes may be an alternative mechanism linking phthalate exposure to effects in offspring.

Concentrations of Phthalate Metabolites in Milk, Urine, Saliva, and Serum of Lactating North Carolina Women

BackgroundPhthalates are ubiquitous in the environment, but concentrations in multiple media from breast-feeding U.S. women have not been evaluated.ObjectivesThe objective of this study was to accurately measure and compare the concentrations of oxidative monoester phthalate metabolites in milk and surrogate fluids (serum, saliva, and urine) of 33 lactating North Carolina women.MethodsWe analyzed serum, saliva, urine, and milk for the oxidative phthalate metabolites mono(3-carboxypropyl) phthalate, mono(2-ethyl-5-carboxypentyl) phthalate (MECPP), mono(2-ethyl-5-hydroxyhexyl) phthalate, and mono(2-ethyl-5-oxohexyl) phthalate using isotope-dilution high-performance liquid chromatography tandem mass spectroscopy. Because only urine lacks esterases, we analyzed it for the hydrolytic phthalate monoesters.ResultsWe detected phthalate metabolites in few milk (< 10%) and saliva samples. MECPP was detected in > 80% of serum samples, but other metabolites were less common (3–22%). Seven of the 10 urinary metabolites were detectable in ≥ 85% of samples. Monoethyl phthalate had the highest mean concentration in urine. Metabolite concentrations differed by body fluid (urine > serum > milk and saliva). Questionnaire data suggest that frequent nail polish use, immunoglobulin A, and fasting serum glucose and triglyceride levels were increased among women with higher concentrations of urinary and/or serum phthalate metabolites; motor vehicle age was inversely correlated with certain urinary phthalate concentrations.ConclusionsOur data suggest that phthalate metabolites are most frequently detected in urine of lactating women and are less often detected in serum, milk, or saliva. Urinary phthalate concentrations reflect maternal exposure and do not represent the concentrations of oxidative metabolites in other body fluids, especially milk.

Assessing Gestational Exposure to Di(2-Ethylhexyl) Phthalate Using Meconium

P-132 Introduction: Phthalate diesters are multifunctional chemicals used as plasticizers, solvents or additives in a wide spectrum of commercial applications. For example, di(2-ethylhexyl) phthalate (DEHP) is a primary component in polyvinyl chloride plastics used in household products, toys, floor tiles, furniture upholstery, blood storage bags, and medical devices. DEHP and other phthalates are metabolized to their hydrolytic monoesters, which can be further metabolized to other oxidative products. Animal studies suggest that some phthalates, including DEHP, and their metabolites are reproductive and developmental toxicants. Therefore, assessing gestational exposure to phthalates is of interest. Methods: Meconium, which begins to accumulate in the human fetus at approximately week 16 of gestation and is not excreted until after delivery, could be a valid dosimeter of prenatal exposure to phthalates. To explore this hypothesis, we conducted a pilot study and measured mono(2-ethylhexyl) phthalate (MEHP), the hydrolytic monoester of DEHP, and three DEHP oxidative metabolites, mono(2-ethyl-5-carboxypentyl) phthalate (MECPP), mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), and mono(2-ethyl-5-oxohexyl) phthalate (MEOHP), in human meconium samples (0.5 g). Interfering biomolecules were removed from the meconium by centrifugation followed by automated off-line solid phase extraction (SPE) of the supernatant. The phthalate metabolites in the supernatant extract were pre-concentrated by on-line SPE before separation by reversed phase high performance liquid chromatography and detection by isotope-dilution tandem mass spectrometry. Results: The four DEHP metabolites were frequently detected. MEHP was detected in all of the samples analyzed. The concentrations of DEHP oxidative metabolites varied widely; MECPP was the oxidative metabolite found at the highest concentrations. Discussion and Conclusions: Interestingly, the ratios of oxidative metabolite concentrations were quite consistent, suggesting that when MEHP is further metabolized, oxidative metabolites are formed consistently among individuals. Meconium contains enzymes capable of hydrolyzing DEHP to MEHP. Therefore, some of the MEHP present in the meconium may have resulted from the contamination of the meconium with the ubiquitous DEHP during sampling, storage or analysis. The oxidative metabolites cannot be formed by the meconium enzymes. Therefore, concentrations of the DEHP oxidative metabolites in meconium may be a more selective measure of DEHP exposure than the hydrolytic monoester metabolite MEHP. The relevance of the oxidative metabolites of DEHP as useful biomarkers for exposure to phthalates in non-conventional biological matrices will be discussed.