Monocarboxynonyl Phthalate Research Articles

In Utero Exposure to Select Phenols and Phthalates and Respiratory Health in Five-Year-Old Boys: A Prospective Study.

Background:Phenols and phthalates may have immunomodulatory and proinflammatory effects and thereby adversely affect respiratory health.Objective:We estimated the associations between gestational exposure to select phthalates and phenols and respiratory health in boys.Methods:Among 587 pregnant women from the EDEN (Etude des Déterminants pré et post natals du développement et de la santé de l’Enfant) cohort who delivered a boy, 9 phenols and 11 phthalates metabolites were quantified in spot pregnancy urine samples. Respiratory outcomes were followed up by questionnaires until age 5, when forced expiratory volume in 1 s () was measured by spirometry. Adjusted associations of urinary metabolites log–transformed concentrations with respiratory outcomes and in percent predicted () were estimated by survival and linear regression models, respectively.Results:No phenol or phthalate metabolite exhibited clear deleterious associations simultaneously with several respiratory outcomes. Ethyl-paraben was associated with increased asthma rate [; 95% confidence interval (CI): 1.00, 1.21] and tended to be negatively associated with (; 95% CI: , 0.05); bisphenol A tended to be associated with increased rates of asthma diagnosis (; 95% CI: 0.97, 1.55) and bronchiolitis/bronchitis (; 95% CI: 0.99, 1.30). Isolated trends for deleterious associations were also observed between 2,5-dichlorophenol and wheezing, and between monocarboxynonyl phthalate, a metabolite of di-isodecyl phthalate (DIDP), and wheezing.Conclusion:Ethyl-paraben, bisphenol A, 2,5-dichlorophenol, and DIDP tended to be associated with altered respiratory health, with ethyl-paraben and bisphenol A exhibiting some consistency across respiratory outcomes. The trends between bisphenol A pregnancy level and increased asthma and bronchiolitis/bronchitis rates in childhood were consistent with a previous cohort study. https://doi.org/10.1289/EHP1015

Early Prenatal Phthalate Exposure, Sex Steroid Hormones, and Birth Outcomes.

Adequate sex steroid hormone concentrations are essential for normal fetal genital development in early pregnancy. Our previous study demonstrated an inverse relationship between third-trimester di-2-ethyl hexyl phthalate exposure and total testosterone (TT) concentrations. Here, we examine early-pregnancy phthalates, sex steroid hormone concentrations, and newborn reproductive outcomes. We examined associations between urinary phthalate metabolite concentrations in early pregnancy and serum free testosterone (FT), TT, estrone (E1), and estradiol (E2) in 591 woman/infant dyads in The Infant Development and Environment Study; we also examined relationships between hormones and newborn genital outcomes using multiple regression models with covariate adjustment. E1 and E2 concentrations were 15% to 30% higher in relation to 1-unit increases in log monoisobutyl phthalate (MiBP), mono-2-ethyl hexyl phthalate, and mono-2-ethyl-5-oxy-hexyl phthalate concentrations, and E2 was 15% higher in relation to increased log monobenzyl phthalate (MBzP). FT concentrations were 12% lower in relation to 1-unit increases in log mono(carboxynonyl) phthalate (MCNP) and mono-2-ethyl-5-carboxypentyl phthalate concentrations. Higher maternal FT was associated with a 25% lower prevalence of having a male genital abnormality at birth. The positive relationships between MiBP, MBzP, and DEHP metabolites and E1/E2 are unique and suggest a positive estrogenic effect in early pregnancy. The inverse relationship between MCNP and DEHP metabolites and serum FT supports previous work examining phthalate/testosterone relationships later in pregnancy. Higher FT in relation to a 25% lower prevalence of male genital abnormalities confirms the importance of testosterone in early fetal development.

Urinary concentrations of 25 phthalate metabolites in Brazilian children and their association with oxidative DNA damage

Exposure of humans to phthalates has received considerable attention due to the ubiquitous occurrence and potential adverse health effects of these chemicals. Nevertheless, little is known about the exposure of the Brazilian population to phthalates. In this study, concentrations of 25 phthalate metabolites were determined in urine samples collected from 300 Brazilian children (6-14years old). Further, the association between urinary phthalate concentrations and a biomarker of oxidative stress, 8-hydroxy-2'-deoxyguanosine (8OHDG), was examined. Overall, eleven phthalate metabolites were found in at least 95% of the samples analyzed. The highest median concentrations were found for monoethyl phthalate (mEP; 57.3ngmL-1), mono-(2-ethyl-5-carboxypentyl) phthalate (mECPP; 52.8ngmL-1), mono-isobutyl phthalate (mIBP; 43.8ngmL-1), and mono-n-butyl phthalate (mBP; 42.4ngmL-1). The secondary metabolites of di(2-ethylhexyl) phthalate (DEHP), and mEP, mIBP, and mBP were the most abundant compounds, accounting for >90% of the total concentrations. On the basis of the measured concentrations of urinary phthalate metabolites, we estimated daily intakes of the parent phthalates, which were 0.3, 1.7, 1.8, 2.1, and 7.2μg/kg-bw/day for dimethyl phthalate, di-n-butyl phthalate, diisobutyl phthalate, diethyl phthalate, and DEHP, respectively. Approximately one-quarter of the Brazilian children had a hazard index of >1 for phthalate exposures. Statistically significant positive associations were found between 8OHDG and the concentration of the sum of phthalate metabolites, sum of DEHP metabolites, mEP, mIBP, mBP, monomethyl phthalate, mono(3-carboxypropyl) phthalate, monobenzyl phthalate, monocarboxyoctyl phthalate, monocarboxynonyl phthalate, monoisopentyl phthalate, and mono-n-propyl phthalate. To the best of our knowledge, this is the first study to report the exposure of a Brazilian population to phthalates.

Urinary phthalate metabolites and depression in an elderly population: National Health and Nutrition Examination Survey 2005–2012

Previous animal studies have demonstrated that phthalate exposure is associated with depression-like behaviors. However, no human study has explored this relationship. We explored the association between urinary phthalate metabolite concentrations and depression in a nationally representative sample of the U.S. elderly population. We analyzed 2030 participants aged 60 years or older with available data on phthalates and depression from the 2005 to 2012 National Health and Nutrition Examination Survey (NHANES). We selected 10 urinary phthalate metabolites with a weighted detection rate >60%. Depression was defined as a 9-item Patient Health Questionnaire score ≥10. The models were adjusted for age, sex, race/ethnicity, education level, income-to-poverty ratio, health insurance coverage, marital status, smoking status, alcohol consumption, moderate physical activity, body mass index, comorbidity status, NHANEs cycle, and urinary creatinine levels. One-unit increases in log-transformed mono-(3-carboxypropyl) phthalate (MCPP) (odds ratio [OR]=1.24, 95% confidence interval [CI]=1.02–1.52) and mono(carboxynonyl) phthalate (MCNP) (OR=1.42, 95% CI=1.15–1.75) were positively associated with depression. When we stratified the urinary phthalate metabolites into quartiles, the highest quartiles (Q4) of MCNP (OR=2.57, 95% CI=1.25–5.27) and mono-n-butyl phthalate (MBP) (OR=2.40, 95% CI=1.10–5.22) were associated with depression compared with the lowest quartiles (Q1). Concentrations of urinary phthalate metabolites MCPP, MCNP, and MBP were positively associated with the risk of depression in a representative sample of the U.S. elderly population. However, the present cross-sectional study is hypothesis generating and the associations need to be investigated through further longitudinal studies.

Temporal Trends in Phthalate Exposures: Findings from the National Health and Nutrition Examination Survey, 2001–2010

Background: Phthalates are ubiquitous environmental contaminants. Because of potential adverse effects on human health, butylbenzyl phthalate [BBzP; metabolite, monobenzyl phthalate (MBzP)], di-n-butyl phthalate [DnBP; metabolite, mono-n-butyl phthalate (MnBP)], and di(2-ethylhexyl) phthalate (DEHP) are being replaced by substitutes including other phthalates; however, little is known about consequent trends in population-level exposures.Objective: We examined temporal trends in urinary concentrations of phthalate metabolites in the general U.S. population and whether trends vary by sociodemographic characteristics.Methods: We combined data on 11 phthalate metabolites for 11,071 participants from five cycles of the National Health and Nutrition Examination Survey (2001–2010). Percent changes and least square geometric means (LSGMs) were calculated from multivariate regression models.Results: LSGM concentrations of monoethyl phthalate, MnBP, MBzP, and ΣDEHP metabolites decreased between 2001–2002 and 2009–2010 [percent change (95% CI): –42% (–49, –34); –17% (–23, –9); –32% (–39, –23) and –37% (–46, –26), respectively]. In contrast, LSGM concentrations of monoisobutyl phthalate, mono(3-carboxypropyl) phthalate (MCPP), monocarboxyoctyl phthalate, and monocarboxynonyl phthalate (MCNP) increased over the study period [percent change (95% CI): 206% (178, 236); 25% (8, 45); 149% (102, 207); and 15% (1, 30), respectively]. Trends varied by subpopulations for certain phthalates. For example, LSGM concentrations of ΣDEHP metabolites, MCPP, and MCNP were higher in children than adults, but the gap between groups narrowed over time (pinteraction < 0.01).Conclusions: Exposure of the U.S. population to phthalates has changed in the last decade. Data gaps make it difficult to explain trends, but legislative activity and advocacy campaigns by nongovernmental organizations may play a role in changing trends.Citation: Zota AZ, Calafat AM, Woodruff TJ. 2014. Temporal trends in phthalate exposures: findings from the National Health and Nutrition Examination Survey, 2001–2010. Environ Health Perspect 122:235–241; http://dx.doi.org/10.1289/ehp.1306681

Phthalates and Childhood Asthma: Revealing an Association through Urinary Biomarkers

Exposure to phthalates, substances used as plasticizers in a large number of consumer goods, can occur by ingestion, inhalation, or skin contact. Children––who are uniquely vulnerable to adverse health effects of environmental exposures because of their still-developing neuro-logical, immunological, and respiratory systems—can receive particularly high exposures due to more frequent contact with phthalate-rich surfaces such as plastic toys and polyvinyl chloride (PVC) flooring, as well as house dust, which collects phthalates (and other chemicals). Researchers now report an association between phthalate exposure and asthma and allergic disease in a cohort of 10-year-old Norwegian children [EHP 121(2):251–256; Bertelsen et al.]. The research team conducted a cross-sectional analysis of urine sample data from 623 children participating in the 10-year followup to the prospective Environment and Childhood Asthma study in Oslo. The followup included structured interviews with parents and blood tests, lung function tests, clinical examinations, and skin prick tests for allergic sensitization for children. Samples of first-morning urine were collected and assessed for three metabolites of low-molecular-weight phthalates (commonly used in personal care products) and eight metabolites of high-molecular-weight phthalates (commonly used in PVC applications such as flooring, electrical cords, car interiors, and toys). The investigators used logistic regression modeling to estimate associations between current asthma and phthalate metabolite concentrations. Hand-to-mouth activity combined with phthalate-rich surfaces such as PVC toys and dusty floors can mean particularly high phthalate exposures for children. Previous animal studies have shown an association between high-molecular-weight phthalates and allergic disease development, while epidemiological studies have shown exposure to house dust containing several of these chemicals to be associated with asthma and allergic disease. The current analysis revealed an association between asthma in children and the highest quartiles of exposure to the metabolites mono-carboxyoctyl phthalate and mono-carboxynonyl phthalate. The parent compounds of these metabolites are high-molecular-weight phthalates used primarily as plasticizers in PVC items. No association was observed between asthma and the nine other metabolites, nor was any association detected between any metabolites and allergic sensitization. Limitations of the study include the cross-sectional design and measurements based on single urine samples, which do not reflect phthalate exposures over time. However, the findings do support the growing body of evidence showing an association between asthma and exposure to high-molecular-weight phthalates.

Urinary Biomarkers for Phthalates Associated with Asthma in Norwegian Children

Background: High-molecular-weight phthalates in indoor dust have been associated with asthma in children, but few studies have evaluated phthalate biomarkers in association with respiratory outcomes.Objectives: We explored the association between urinary concentrations of phthalate metabolites and current asthma.Methods: In a cross-sectional analysis, 11 metabolites of 8 phthalates [including four metabolites of di(2-ethylhexyl) phthalate] were measured in one first morning void collected from 2001 through 2004 from 623 10-year-old Norwegian children. Logistic regression models controlling for urine specific gravity, sex, parental asthma, and income were used to estimate associations between current asthma and phthalate metabolite concentrations by quartiles or as log10-transformed variables.Results: Current asthma was associated with both mono(carboxyoctyl) phthalate (MCOP) and mono(carboxynonyl) phthalate (MCNP), although the association was limited to those in the highest quartile of these chemicals. The adjusted odds ratio (aOR) for current asthma was 1.9 (95% CI: 1.0, 3.3) for the highest MCOP quartile compared with the lowest quartile, and 1.3 (95% CI: 0.98, 1.7) for an interquartile-range increase. The aOR for current asthma was 2.2 (95% CI: 1.2, 4.0) for the highest MCNP quartile and 1.3 (95% CI: 1.0, 1.7) for an interquartile-range increase. The other phthalate metabolites were not associated with current asthma.Conclusions: Current asthma was associated with the highest quartiles of MCOP and MCNP, metabolites of two high molecular weight phthalates, diisononyl phthalate and diisodecyl phthalate, respectively. Given the short biological half-life of the phthalates and the cross-sectional design, our findings should be interpreted cautiously.

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.