Monocarboxynonyl Phthalate Research Articles

Construction of the cancer patients' database based on the US National Health and Nutrition Examination Survey (NHANES) datasets for cancer epidemiology research.

The US National Health and Nutrition Examination Survey (NHANES) dataset does not include a specific question or laboratory test to confirm a history of cancer diagnosis. However, if straightforward variables for cancer history are introduced, US NHANES could be effectively utilized in future cancer epidemiology studies. To address this gap, the authors developed a cancer patient database from the US NHANES datasets by employing multiple R programming codes. To illustrate the practical application of this methodology to a real-world problem, the authors extracted the R codes applied in an academic paper published in another journal on January 30th, 2024 ( https://doi.org/10.1016/j.heliyon.2024.e24337 ). This paper will focus on the construction of the database and analysis using R codes. Entire. In the first example, the urine concentration of monocarboxynonyl phthalate, monocarboxyoctyl phthalate, mono-2-ethyl-5-carboxypentyl phthalate, and mono-2-hydroxy-iso-butyl phthalate (all ng/mL) were used as the independent variable, instead of the serum concentration of perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), perfluorohexane sulfonic acid (PFHxS), and perfluorononanoic acid (PFNA), respectively. In the second example, the serum concentration of 2,3,3',4,4'-Pentachlorobiphenyl (PCB105), 2,3,4,4´,5-Pentachlorobiphenyl (PCB114), 2,3',4,4',5-Pentachlorobiphenyl (PCB118), and 2,2',3,4,4',5'- and 2,3,3',4,4',6-Hexachlorobiphenyl (PCB138) were used as the independent variable, instead of the serum concentration of PFOA, PFOS, PFHxS, and PFNA, respectively. This research offers a comprehensive set of R codes aimed at creating a single, user-friendly variable that encapsulates the history of each type of cancer while also considering the age at which the diagnosis was made. The US NHANES provides a wealth of critical data on environmental toxicant exposures. By employing these R codes, researchers can potentially discover numerous new associations between environmental toxicant exposures and cancer diagnoses. Ultimately, these codes could significantly advance the field of cancer epidemiology in relation to environmental toxicant exposure.

Urinary phthalate metabolites associated with increased prevalence of gallstone disease in U.S. adults: data from the NHANES study

BackgroundPhthalate exposure has been hypothesized to influence cholesterol metabolism and gallstone pathogenesis, but previous studies are limited. We aimed to examine the associations between urinary phthalate metabolites and prevalence of gallstone disease in a nationally representative sample.MethodsWe analyzed data on 1,696 adults aged ≥ 30 years from the National Health and Nutrition Examination Survey (NHANES) 2017–2018. Gallstone disease was defined based on self-reported physician-diagnosis. Exposure was measured by urinary concentrations of 10 phthalate metabolites. Multivariable logistic regression model was to assess individual exposure-effect associations. Weighted quantile sum (WQS) regression, Quantile g-computation (Qgcomp) analysis and Bayesian kernel machine regression (BKMR) assessed metabolite mixtures in relation to gallstones.ResultsIn the multivariable logistic regression model, compared to the lowest quartile (Q1) of urinary mono (2-ethyl-5-carboxypentyl) phthalate (MECPP), the highest quartile (Q4) was associated with an 82% increased risk of gallstone formation (OR: 1.82, 95% CI: 1.17, 2.85). Similarly, for mono(3-carboxypropyl) phthalate (MCPP), the risk increased by 78% in the Q4 group compared to Q1 (OR: 1.78, 95% CI: 1.02, 3.14). The WQS index exhibited a significant positive association with gallstone prevalence (OR: 1.37, 95%CI: 1.02, 1.84). In the Qgcomp model, four urinary phthalate metabolites, including MECPP, MCPP, mono benzyl phthalate (MBzP) and mono-carboxynonyl phthalate (MCNP), were positively associated with an increased risk of gallstones. BKMR identified exposure-response trends for MECPP, MCPP, and MBzP.ConclusionHigher urinary phthalate metabolite concentrations were associated with increased gallstone risk. These novel findings suggest phthalate exposure may contribute to lithogenic pathogenesis. Future prospective and mechanistic research is warranted.

Combined effects and potential mechanisms of phthalate metabolites on serum sex hormones among reproductive-aged women: An integrated epidemiology and computational toxicology study

The reproductive age is a crucial stage for women to bear offspring. However, reproductive-aged women are simultaneously exposed to various phthalates, which may pose a threat to their reproductive health. This study employed generalized linear regression and weighted quantile sum (WQS) regression to explore the associations between monoesters of phthalates (MPAEs) and sex hormones in 913 reproductive-aged women in the National Health and Nutrition Examination Survey. Key risk factors driving hormone disruption were identified based on the weights of the WQS models. Interaction models were used to unravel the synergistic or antagonistic effects between MPAEs. The potential toxicological targets of MPAEs interfering with sex hormone-binding globulin (SHBG) levels were revealed based on prior knowledge and molecular docking of hepatocyte nuclear factor 4α (HNF4α). Compared with the first quartile, mono-benzyl phthalate (MBZP) in the second quartile exhibited a decrease in total testosterone (TT) and TT/E2 (estradiol) ratio. Mono-2-ethyl-5-carboxypentyl phthalate (MECPP) in the fourth quartile showed a decrease in SHBG and TT/E2. Additionally, mono-(carboxyoctyl) phthalate and mono-(carboxynonyl) phthalate (MCNP) were negatively associated with SHBG. Each unit increase in the WQS index of MPAE mixtures was associated with 6.73 % lower SHBG levels (95 %CI: −12.80 %, −0.24 %) with mono-(3-carboxypropyl) phthalate, MCNP, MBZP, and MECPP identified as major risk factors. Interaction analyses revealed that the effects of high-risk MPAEs on SHBG were predominantly antagonistic. Molecular docking suggested that MPAEs might compete to bind tryptophan residues of HNF4α. This study provides key information to help develop the most effective phthalate interventions and improve the reproductive health of reproductive-aged women.

Associations Between Urinary Phthalate Metabolites and Decreased Serum α-Klotho Level: A Cross-Sectional Study Among US Adults in Middle and Old Age.

Phthalates are widely used chemicals with ubiquitous human exposure. Evidence indicated that phthalate exposure was associated with an increased risk of aging-related diseases. Klotho is a transmembrane protein with anti-aging functions, and its association with phthalates remains unknown. To find the association between phthalate exposure and serum α-Klotho, a cross-sectional study was performed in 4482 adults (40-79 years old) who completed the National Health and Nutrition Examination Survey (NHANES) (2007-2016). As shown in the results of multivariable linear regression analyses, mono(carboxynonyl) phthalate (MCNP) and mono-n-butyl phthalate (MBP) were inversely associated with α-Klotho, and the regression coefficients of MCNP and MBP were -1.14 (95% confidence interval (CI): -2.00, -0.27) and -0.08 (95% CI: -0.14, -0.02). Subgroup analyses based on the quartiles of each phthalate metabolite showed that both MCNP and MBP were only inversely associated with α-Klotho in the subgroups of the highest levels. For mono-isobutyl phthalate (MIBP), the inverse association with α-Klotho was only statistically significant in the subgroup of the lowest level, and the regression coefficient was -26.87 (95% CI: -52.53, -1.21). Our findings suggest that α-Klotho might be involved in the association of phthalate exposure with aging-related diseases. Future research investigating the causality between phthalates and α-Klotho and its underlying mechanisms is encouraged.

Association between urinary phthalate metabolites and Anemia in US adults

Initial research indicates a possible connection between exposure to phthalates and the development of anemia. To fill the gap in epidemiological data, our study utilized data from across the United States, representative on a national scale, to evaluate the association between the concentration of phthalate metabolites in urine and both anemia and iron levels. We gathered data on 11,406 individuals from the National Health and Nutrition Examination Survey (NHANES) database, spanning 2003–2018. We conducted logistic and linear regression analyses, adjusted for potential confounding factors, to evaluate the correlations between different phthalate metabolites and anemia, as well as serum iron levels, including gender-stratified analysis. Most urinary phthalate metabolites were positively correlated with an increased risk of anemia, and the majority were negatively correlated with serum iron levels. The study revealed that for every unit increase in ln-transformed metabolite concentrations, the odds ratios (ORs) for anemia increased to varying degrees, depending on the phthalate: Monobutyl phthalate (MBP) at 1.08 (95% CI 1.01–1.17, P = 0.0314), mono(3-carboxypropyl) phthalate (MCPP) at 1.17 (95% CI 1.10–1.24, P < 0.0001), mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) at 1.08 (95% CI 1.02–1.15, P = 0.0153), mono(2-ethyl-5-oxohexyl) phthalate (MEOHP) at 1.14 (95% CI 1.07–1.21, P < 0.0001), mono(2-ethyl-5-carboxypentyl) phthalate (MECPP) at 1.11 (95% CI 1.03–1.18, P = 0.0030), monocarboxynonyl phthalate (MCNP) at 1.11 (95% CI 1.03–1.19, p = 0.0050), and monocarboxyoctyl phthalate (MCOP) at 1.13 (95% CI 1.07–1.19, P < 0.0001). Increased levels of MBP, MEHP, MBzP, MCPP, MEHHP, MEOHP, MIBP, MECPP, MCNP, and MCOP were linked with changes in serum iron levels, ranging from − 0.99 µg/dL (95% CI − 1.69 to − 0.29) to − 3.72 µg/dL (95% CI − 4.32 to − 3.11). Mixed-exposure analysis shows consistency with single-exposure model. Further mediation analysis showed that the association between single urinary phthalates and the risk of anemia was mediated by serum iron with a mediation ratio of 24.34–95.48% (P < 0.05). The presence of phthalate metabolites in urine shows a positive correlation with the prevalence of anemia, which was possibly and partly mediated by iron metabolism. Nonetheless, to confirm a definitive causal link and comprehend the underlying mechanisms of how phthalate exposure influences anemia, additional longitudinal and experimental research is required.

Impact of phthalate metabolites on vitamin D levels and subclinical inflammation: national health and nutrition examination survey, 2013–2018

ABSTRACT This study explores the association between phthalates and total vitamin D levels and the link between phthalates exposure and subclinical inflammation using monocyte percentage to high-density lipoprotein cholesterol ratio (MHR), utilizing three National Health and Nutrition Examination Survey (NHANES) survey cycles 2013-2018. This study is cross-sectional, utilizing one-time urine samples from randomly selected NHANES participants to assess phthalate metabolites. An inverse association between vitamin D and all Di(2-ethylhexyl) phthalate (DEHP) metabolites was found. The molar sum of DEHP metabolites was inversely associated with vitamin D (β −2.329; 95% CI −3.937,−0.720). An inverse association was observed between monocarboxynonyl phthalate and vitamin D (β −0.0278; 95% CI −0.0527,−0.00298). A similar relationship was found between monocarboxyoctyl phthalate and vitamin D (β −0.0160; 95% CI −0.0242,−0.00775). There was no association between phthalate metabolites and MHR. Stratified analysis showed that the association between phthalate metabolites and MHR may vary according to vitamin D status.

Association between urinary phthalate metabolites and chronic obstructive pulmonary disease incidence in US adults: results from NHANES 2007-2018.

Despite associations between urinary phthalates and respiratory symptoms and disorders have been investigated, knowledge about their impact on COPD incidence remains limited. Using data of 8242 adults (aged 20-80years) from the 2007-2018 National Health and Nutrition Examination Survey (NHANES), the association of mixed urinary phthalate metabolites with COPD incidence was evaluated. Among them, 789 were COPD patients, and the rest were non-COPD participants. In the single-pollutant models, a variety of phthalate metabolites were identified as independent positive factors for COPD incidence, including mono-(carboxynonyl) phthalate (MCNP), mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP), mono-n-butyl phthalate (MnBP), mono-(3-carboxylpropyl) phthalate (MCPP), mono-ethyl phthalate (MEP), mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), and mono-benzyl phthalate (MBzP). Multi-pollutant models, including weighted quantile sum (WQS) regression, quantile-based g computation (qgcomp), and Bayesian kernel machine regression (BKMR) approaches consistently revealed the positive association between phthalates co-exposure and COPD incidence, and MCPP was recognized as the dominant positive driver. The positive association was more evident in the youth group and the male group. The interactions between certain phthalate metabolites in COPD were also observed. Given the limitations of the cross-sectional design of NHANES study, well-designed longitudinal studies are needed to verify or disprove these findings.

Association of urinary phthalate metabolites with all-cause and cardiovascular disease mortality among adults with diabetes mellitus: National Health and Nutrition Examination Survey 2005-2014.

The study regarding phthalate metabolites and mortality among diabetes mellitus (DM) is limited. We aimed to examine the association of urinary phthalate metabolites with all-cause and cardiovascular disease (CVD) mortality among adults with DM. This study included 8,931 adults from the National Health and Nutrition Examination Survey (NHANES) from 2005-2006 to 2013-2014. Mortality data were linked to National Death Index public access files through December 31, 2015. Cox proportional hazard models were used to estimate hazard ratios (HR) and 95% confidences (CIs) for mortality. We identified 1,603 adults with DM [mean ± SE age, 47.08 ± 0.30 years; 50.5% (833) were men]. Mono-(carboxynonyl) phthalate (MCNP), mono-2-ethyl-5-carboxypentyl phthalate (MECPP), and the sum of Di (2-ethylhexyl) phthalate (DEHP) metabolites (∑DEHP) were positively associated with DM (MCNP: OR = 1.53, 95%CI = 1.16-2.01; MECPP: OR = 1.17, 95% CI = 1.03-1.32; ∑DEHP: OR = 1.14, 95% CI = 1.00-1.29). Among DM patients, mono-(3-carboxypropyl) phthalate (MCPP) was associated with a 34% (HR 1.34, 95% CI 1.12-1.61) increased risk of all-cause mortality while the HRs (95%CI) of CVD mortality were 2.02 (1.13-3.64) for MCPP, 2.17 (1.26-3.75) for mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), 2.47 (1.43-4.28) for mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), 2.65 (1.51-4.63) for MECPP, and 2.56 (1.46-4.46) for ∑DEHP, respectively. This study is an academic exploration of the association between urinary phthalate metabolites and mortality among adults with DM, suggesting that exposure to phthalates might be associated with an increased risk of all-cause and CVD mortality in DM. These findings suggest that patients with DM should carefully use plastics products.

Associations of urinary metabolite concentrations of phthalates and phthalate replacements with body composition from mid-childhood to early adolescence

BackgroundPhthalates may adversely influence body composition by lowering anabolic hormones and activating peroxisome-proliferator activated receptor gamma. However, data are limited in adolescence when body mass distributions rapidly change and bone accrual peaks. Also, potential health effects of certain phthalate/replacements [e.g., di-2-ethylhexyl terephthalate (DEHTP)] have not been well studied. MethodsAmong 579 children in the Project Viva cohort, we used linear regression to evaluate associations of urinary concentrations of 19 phthalate/replacement metabolites from mid-childhood (median: 7.6 years; 2007–2010) with annualized change in areal bone mineral density (aBMD) and lean, total fat, and truncal fat mass as measured by dual-energy X-ray absorptiometry between mid-childhood and early adolescence (median: 12.8 years). We used quantile g-computation to assess associations of the overall chemical mixture with body composition. We adjusted for sociodemographics and tested for sex-specific associations. ResultsUrinary concentrations were highest for mono-2-ethyl-5-carboxypentyl phthalate [median (IQR): 46.7 (69.1) ng/mL]. We detected metabolites of most replacement phthalates in a relatively small number of participants [e.g., 28% for mono-2-ethyl-5-hydrohexyl terephthalate (MEHHTP; metabolite of DEHTP)]. Detectable (vs. non-detectable) MEHHTP was associated with less bone and greater fat accrual in males and greater bone and lean mass accrual in females [e.g., change in aBMD Z-score/year (95% CI): −0.049 (−0.085, −0.013) in males versus 0.042 (0.007, 0.076) in females; pinteraction<0.01]. Children with higher concentrations of mono-oxo-isononyl phthalate and mono-3-carboxypropyl phthalate (MCPP) had greater bone accrual. Males with higher concentrations of MCPP and mono-carboxynonyl phthalate had greater accrual of lean mass. Other phthalate/replacement biomarkers, and their mixtures, were not associated with longitudinal changes in body composition. ConclusionsConcentrations of select phthalate/replacement metabolites in mid-childhood were associated with changes in body composition through early adolescence. As use of phthalate replacements such as DEHTP may be increasing, further investigation can help better understand the potential effects of early-life exposures.

Phthalate exposure enhances incidence of urinary incontinence: US NHANES, 2003-2004 and 2005-2006.

The aim of this study is to investigate the associations between phthalate exposure and UI in a nationally representative sample of US adults. Cross-sectional data from the National Health and Nutrition Examination Survey (NHANES) database was used for analysis. In total, 2,818 participants with measurements for phthalate metabolites and complete UI questionnaire data were enrolled in our study. Furthermore, seven phthalate metabolites were measured, which were obtained from urine samples and creatinine-standardized in the subsequent analyses. After dividing these phthalate metabolites into three groups, multivariable regression models were performed to evaluate the association between phthalate metabolites and UI rates. Moreover, interaction analyses and subgroup analyses stratified by gender were performed. In these seven phthalate metabolites, high level of mono-carboxynonyl phthalate (MCNP), mono-carboxyoctyl phthalate (MCOP), mono-isobutyl phthalate (MiBP), mono-n-butyl phthalate (MBP), and mono-3-carboxypropyl phthalate (MCPP) showed increased risk of UI (odds ratio (OR) = 1.52, 1.42, 1.43, 1.50, 1.51, respectively, all p value < 0.05). Trend test showed that incidence of UI increased significantly with concentration. A higher incidence of UI among participants was observed in the maximal tertile of phthalate when comparing with the lowest tertile. Subgroup analysis found that different phthalates have varying influence for different types of UI. Moreover, the analyses stratified for sex indicated that the high concentrations of MCNP and median concentrations of MCCP were associated with increase of the odds of UI in women and in men, respectively. Overall, the exposure to phthalates was positively associated with UI among US adults. Notably, different phthalates have varying influence for different types of UI, and male and female exposure to phthalate could result in the different prevalence of UI.

Association between environmental exposure to phthalates and allergic disorders in Korean children: Korean National Environmental Health Survey (KoNEHS) 2015-2017.

Phthalates are common industrial chemicals that are used as plasticizers in plastics, personal care products, and building materials. Although these chemicals have been suspected as risk factors for allergic outcomes among children, inconsistent associations between environmental exposure to phthalates and allergic disorders have been found across different populations. Therefore, this study aimed to assess whether environmental phthalate exposure was associated with parent-reported current allergic symptoms (atopic dermatitis, AD; asthma; and allergic rhinitis, AR) and the index of allergic response (levels of serum total immunoglobulin E, IgE) in a nationally representative sample of children. In this study, children aged 3-17 years (n=2208) were recruited from the Korean National Environmental Health Survey (KoNEHS) 2015-2017 to conduct an analysis of their current allergic symptoms. Among this number of children, the total IgE analysis included 806 participants because total IgE levels were only measured in children aged 12-17 years. After adjusting for all covariates, mono-benzyl phthalate (MBzP) [OR (95% CI)=1.15 (1.01, 1.30)], mono-(carboxyoctyl) phthalate (MCOP) [OR (95% CI)=1.35 (1.02, 1.78)], and the sum of di-(2-ethylhexyl) phthalate metabolites (∑DEHP) [OR (95% CI)=1.39 (1.09, 1.79)] were associated with increased odds of current AD. MCOP [OR (95% CI)=1.19 (1.01, 1.40)], mono-(carboxynonyl) phthalate (MCNP) [OR (95% CI)=1.24 (1.05, 1.45)], and ∑DEHP [OR (95% CI)=1.22 (1.02, 1.44)] were also associated with increased odds of current AR. Individual DEHP metabolites showed similar associations with current AD and AR. In addition, MCNP was positively related to IgE levels [β (95% CI)=0.26 (0.12, 0.40)]. MBzP [OR (95% CI)=1.17 (1.01, 1.35)], MCOP [OR (95% CI)=1.62 (1.12, 2.32)], and mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP) [OR (95% CI)=1.36 (1.06, 1.76)] showed positive relationships with allergic multimorbidity. Moreover, higher concentrations of MCNP were related to increased odds of experiencing both current AR and total IgE levels [OR (95% CI)=1.98 (1.29, 3.04)], and children with elevated IgE levels (>100IU/mL) were more likely to have current AR associated with MCNP than those without elevated IgE levels (p=0.007). Specifically, the relationship between MCNP and current AR was significantly mediated through alterations in IgE levels (14.7%), and MCNP also showed the positive association with current AR, independent of IgE (85.3%). These results suggest that environmental exposure to phthalates may affect the immune system and increase the occurrence of allergic symptoms in children.

Association between urinary concentration of phthalate metabolites and allergic disorders in Korean children: Korean National Environmental Health Survey (KoNEHS) 2015-2017

BACKGROUND AND AIM: Phthalates are common industrial chemicals used primarily as plasticizers that make plastic flexible. Children are more prone to these chemicals through various routes of exposure including dermal absorption, inhalation, and ingestion (such as food, water, and dust) than adults and several studies have reported that phthalate exposure may increase the risk of allergic diseases. Therefore, we aimed to examine the association between urinary concentration of phthalate metabolites and allergic disorders in a nationally representative sample of Korean children. METHODS: In this study, we used data on urinary phthalate metabolites, allergic symptoms such as atopic dermatitis (AD), asthma, and allergic rhinitis (AR), and serum total immunoglobin E (IgE) levels from participants aged 3–17 in the Korean National Environmental Health Survey 2015–2017. After adjusted for all covariates, Odds ratio (OR) and their 95% confidence intervals (95% CI) per one ln–unit increase change in the concentration of phthalate metabolites were estimated using logistic regression. RESULTS:Urinary high–molecular–weight phthalate metabolites (HMW) were positively associated with current AD and AR. A significant increase of the OR for high group of IgE levels with increase of urinary mono-(carboxynonyl) phthalate (MCNP) concentrations was found [OR=1.43 (1.06, 1.91)]. Mono–benzyl phthalate, mono–(carboxyoctyl) phthalate, and mono–(2–ethyl–5–oxohexyl) phthalate were positively associated with allergic multimorbidity which means co–occurrence of at least two allergic diseases in one individual. Children with high IgE were more likely to have an AR associated MCNP than those with low IgE or high IgE only (p = 0.007). Specifically, we estimated that 14.7% of total effect of MCNP on AR was mediated by IgE. However, no phthalate metabolites were significantly associated with current asthma. CONCLUSIONS:Our observations revealed that some HMW phthalate metabolites were positively associated with current allergic symptoms and high total IgE levels in children. These results suggested that environmental exposure to phthalates could enhance allergic response in children. KEYWORDS: Atopic dermatitis, Asthma, Allergic rhinitis, Allergic multimorbidity, Total immunogliblin E, Phthalate metabolites

Urinary phthalate metabolite concentrations and adolescent sleep duration.

Background:Some environmental chemicals, such as phthalates, are capable of disrupting endocrine function related to the development and regulation of sleep patterns. However, the contribution of phthalate exposure to inadequate sleep during adolescence is unknown. We aim to evaluate the association between phthalate exposure and short sleep duration during adolescence.Methods:We used data from participants 16–17 years of age in the 2005–2010 cycles of the National Health and Nutrition Examination Survey. Participants reported typical sleep duration during weekdays, which we categorized into short sleep duration (less than 8 hours per night) and adequate sleep duration (8 or more hours) based on consensus guidelines. We used weighted logistic regression to evaluate the association between log10-transformed urinary phthalate metabolite concentrations and odds of short sleep duration.Results:An interquartile range increase in di(2-ethylhexyl) phthalate metabolites, monocarboxynonyl phthalate, monocarboxyoctyl phthalate, and mono-isobutyl phthalate was associated with 1.48 (95% confidence interval [95% CI] = 1.02, 2.16), 1.64 (95% CI = 1.17, 2.32), 1.46 (95% CI = 0.99, 2.16), and 1.92 (95% CI = 1.08, 3.43) times the odds of short sleep duration, respectively. Furthermore, we observed monotonic dose-response relations between some phthalate metabolites and odds of short sleep duration.Conclusions:Our results suggest that higher urinary concentrations of several phthalate metabolites are associated with short sleep duration during adolescence. Understanding the contribution of modifiable environmental factors to inadequate sleep duration is of great public health importance because inadequate sleep can have substantial health implications.

Biomarkers of phthalates and inflammation: Findings from a subgroup of Women's Health Initiative participants.

Recent experimental work has shown that phthalates may increase inflammation. Prior research has not examined the role of exposure to phthalates in relation to inflammatory status among postmenopausal women who are at higher risk of developing inflammation-related chronic disorders. We aimed to examine the associations of urinary phthalate biomarker concentrations with circulating levels of c-reactive protein [CRP] and interleukin-6 [IL-6] among 443 postmenopausal women selected into a breast cancer case-control study nested within the Women's Health Initiative (WHI). A total of 13 phthalate metabolites were measured in urine samples provided at WHI enrollment from 1993 to 1998. We also measured baseline levels of CRP and IL-6 in these women's serum or plasma samples. Multivariable linear models were used to investigate the role of each phthalate biomarker in relation to CRP and IL-6, adjusting for potential confounding factors and specifically evaluating the role of BMI. In adjusted models we observed positive associations of monocarboxynonyl phthalate (MCNP) with CRP (β=0.092; 95% CI 0.026, 0.158) and IL-6 (β=0.108; 95% CI 0.013, 0.204). These positive associations were attenuated and non-significant, however, after further adjustment for body mass index (BMI). In contrast, we observed inverse associations of monoethyl phthalate (MEP) (β=-0.019; 95% CI -0.036, -0.001) and monobenzyl phthalate (MBzP) (β=-0.034; 95% CI -0.058, -0.010) with CRP levels only after adjustment for BMI. Other phthalate biomarkers examined were not significantly associated with either CRP or IL-6 levels. Overall, these results do not suggest an important role for phthalates in promoting an inflammatory response. Future prospective studies are warranted to improve understanding of these associations, particularly in clarifying the role of BMI.

Gestational and childhood exposure to phthalates and child behavior

BackgroundEarly-life phthalate exposures may adversely influence neurodevelopment by disrupting thyroid hormone homeostasis, altering brain lipid metabolism, or reducing gonadal hormone concentrations. Previous literature examining gestational phthalate exposure and child behavior were inconclusive and few prospective studies have examined childhood phthalate exposure, particularly phthalate mixtures. We investigated whether gestational and childhood phthalate exposures were associated with child behavior. MethodsWe used data from 314 mother–child pairs in the HOME Study, a longitudinal pregnancy and birth cohort that enrolled pregnant women from Cincinnati, Ohio. We quantified urinary concentrations of 11 phthalate metabolites in samples collected twice during gestation from women and six times from their children when they were ages 1, 2, 3, 4, 5, and 8 years. We assessed children’s behavior at ages 2, 3, 4, 5, and 8 years using the Behavioral Assessment System for Children-2. Using linear mixed models, we estimated covariate-adjusted associations of measurement-error-corrected gestational and childhood phthalate metabolite concentrations (per interquartile range increase) with repeated child behavior assessments. We used Weighted Quantile Sum (WQS) regression to estimate the association of phthalate mixtures with child behavior. ResultsGestational mono(3-carboxypropyl) phthalate (MCPP) concentrations were associated with more problem behaviors (internalizing: β = 0.9, 95% confidence interval [CI] = -0.1, 1.9; externalizing: β = 1.0, 95%CI = -0.1, 2.0; behavioral symptoms index [BSI]: β = 1.1, 95%CI = 0.1, 2.1). Higher childhood monobenzyl phthalate (MBzP) (β = 1.4; 95%CI = 0.0, 2.7), monocarboxynonyl phthalate (MCNP) (β = 3.2; 95%CI = 1.6, 4.8), monocarboxyoctyl phthalate (MCOP) (β = 0.9; 95%CI = 0.0, 1.7), MCPP (β = 1.8; 95%CI = 0.2, 3.5), and monoethyl phthalate (MEP) (β = 1.6; 95%CI = 0.1, 3.1) concentrations were associated with higher BSI composite scores. Consistent with this, the weighted childhood phthalate index was associated with more problem behaviors (internalizing: β = 1.5, 95%CI = −0.2, 3.1; externalizing: β = 1.7, 95%CI = 0.1, 3.5; BSI: β = 1.7, 95%CI = 0.2, 3.2); MBzP, MCNP, and MEP largely contributed to these associations. ConclusionOur findings suggest that childhood exposure to phthalate mixtures may be associated with children’s problem behaviors.

Association between dietary contribution of ultra-processed foods and urinary concentrations of phthalates and bisphenol in a nationally representative sample of the US population aged 6 years and older.

Ultra-processed food consumption has been associated with several health outcomes such as obesity, hypertension, cardiovascular disease and cancer. The deleterious nutrient profile of these products, and the presence of food additives, neoformed contaminants and contact materials such as phthalates and bisphenol may be some of the potential pathways through which ultra-processed food influences disease outcomes. The aim of this study was to examine the association between dietary contribution of ultra-processed foods and urinary biomarker concentrations of parent compounds or their metabolites including Di(2-ethylhexyl) phthalate (ΣDEHP), Di-isononyl phthalate (ΣDiNP), Monocarboxynonyl phthalate (mCNP), Mono (3-carboxypropyl) phthalate (mCPP), Monobenzyl phthalate (mBzP), Bisphenol A (BPA), Bisphenol F (BPF) and Bisphenol S (BPS), in the US. Participants from the cross-sectional 2009-2016 National Health and Nutrition Examination Survey, aged 6+ years, with urinary measures and with one 24-hour dietary recall were included in the study. Ultra-processed foods were identified based on the NOVA classification system, a four-group food classification based on the extent and purpose of industrial food processing. Linear regression was used to compare average urinary creatinine-standardized concentrations across quintiles of energy contribution of ultra-processed foods. Models incorporated survey sample weights and were adjusted for different sociodemographic and life-style variables. Adjusted geometric means of ΣDiNP, mCNP, mCPP, mBzP and BPF increased monotonically from the lowest to the highest quintile of ultra-processed food consumption. As both phthalates/bisphenol and ultra-processed foods have been previously associated with insulin resistance, diabetes, general/abdominal obesity and hypertension, our results suggest the possibility of contact materials in ultra-processed foods as one link between ultra-processed food and these health outcomes. Future studies could confirm findings and further explore these mechanisms of action.

Association between phthalate exposure and asthma risk: A meta-analysis of observational studies.

Phthalates are ubiquitously found in numerous environments and have been related to a variety of adverse health effects. Previous studies have suggested that phthalate exposure is associated with asthma risk in humans; however, such findings are inconsistent. The aim of the present meta-analysis was to clarify the association between phthalate exposure and asthma risk. A literature search was conducted using PubMed, EMBASE and Web of Science for relevant studies published up to January 5, 2020. Fixed-effects or random-effects models were applied to combine the results, and several subgroup analyses were used to explore the sources of heterogeneity. A total of 14 studies containing more than 14,000 participants were included in the present study. A positive, significant association between mono-benzyl phthalate (MBzP) levels and asthma risk was found, and the overall odds ratio (OR) was 1.17 (95% confidence interval [CI]: 1.06-1.28, P-value for overall effect [Pz]=0.001), with a low heterogeneity (P-value for heterogeneity [Phet]=0.193, I2=23.6%). The pooled ORs for mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) and mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP) concentrations were 1.13 (95% CI: 1.03-1.24, Pz=0.011) and 1.20 (95% CI: 1.00-1.42, Pz=0.045), respectively. Children with high levels of MBzP or mono-(carboxynonyl) phthalate (MCNP) were suggested to have increased odds of asthma compared to older populations. In the subgroup analysis by study location, an increased risk for asthma in relation to levels of the sum of di-2-ethylhexyl phthalate (ΣDEHP) was observed in European studies (OR=1.16, 95% CI: 1.00-1.34, Pz=0.048) compared to Asia and North America. Urinary levels of MBzP, MEHHP, MECPP, MCNP, and DEHP were positively related to asthma risk. No significant association was observed for the other phthalate metabolites in relation to asthma risk. Further research is needed to verify these findings and shed light on the molecular mechanism by which phthalates are associated with asthma.

Lowering Urinary Phthalate Metabolite Concentrations among Children by Reducing Contaminated Dust in Housing Units: A Randomized Controlled Trial and Observational Study.

Dust in homes can contain phthalates that may adversely affect child development, but whether residential interventions and dust removal can prevent children's exposure to phthalates is unknown. We quantified the influence of a residential lead hazard intervention and dust control on children's urinary phthalate metabolite concentrations. Between 2003 and 2006, The Health Outcomes and Measures of the Environment (HOME) Study randomized 355 pregnant women to receive an intervention to reduce either residential lead or injury hazards before delivery. We quantified eight urinary phthalate metabolites from 288 children at ages 1, 2, or 3 years (680 observations). During yearly home visits, we assessed dust accumulation in housing units. Children in the lead intervention group had 11-12% lower concentrations of the sum of di(2-ethylhexyl) phthalate metabolites, monocarboxyoctyl phthalate, and monocarboxynonyl phthalate compared to the injury intervention group. Monoethyl phthalate concentrations did not differ by group. In observational analyses, children living in housing units that appeared clean had 12-17% lower concentrations of these phthalate metabolites and monobenzyl phthalate, compared to children living in housing units with more dust accumulation. Features of this lead hazard intervention and measures to control dust may reduce children's exposure to phthalates found in building materials and household furnishings.

Phthalates and asthma in children and adults: US NHANES 2007\u20132012

Environmental exposure to phthalates may contribute to an increased risk of asthma in children and adults. We aimed to assess the direction and strength of the association between urinary phthalates metabolites and current asthma in children and adults that participated in the National Health and Nutrition Examination Survey (NHANES) 2007–2012. Data on ten urinary phthalate metabolites, self-reported questionnaires, spirometry measures, and covariates were obtained from 7765 participants (28.1% were children aged 6–17 years) taking part in the NHANES 2007–2012. Asthma was assessed using self-reported questionnaires for children and adults, and via spirometry measures for adults alone. We used crude and adjusted logistic regression models to estimate the odds ratios (ORs) and 95% confidence interval (CI) per one log10 unit change in the concentration of phthalate metabolites. We further modeled the effect modification by sex. Out of 10 metabolites, only mono-benzyl phthalate (MBzP) was positively associated with the prevalence of self-reported asthma in children, after adjusting for a range of potential confounders (odds ratio 1.54; 95% confidence interval 1.05–2.27). No significant relationship was observed for adults. The association of mono-ethyl phthalate (MEP) was modified by sex, with significantly increased odds of asthma among males [boys (2.00; 1.14–3.51); adult males (1.32; 1.04–1.69)]. While no other phthalates showed a positive relationship with current asthma in males, mono-(carboxynonyl) phthalate (MCNP) and mono-(3-carboxylpropyl) phthalate (MCPP) were inversely associated with spirometrically defined asthma in adult females. A sex-specific relationship in adults was evident when spirometry, but not self-reported measures were used to define asthma. We found no clear association between exposure to phthalates and current asthma, except for a significant relationship between MBzP metabolites and self-reported asthma in children. As a result, exposure to phthalates and asthma development and/or exacerbations remains controversial, suggesting a need for a well-designed longitudinal study.

Phthalates exposure and uterine fibroid burden among women undergoing surgical treatment for fibroids: a preliminary study

To examine the association between phthalate exposure and two measures of uterine fibroid burden: diameter of largest fibroid and uterine volume. Pilot, cross-sectional study. Academic medical center. Fifty-seven premenopausal women undergoing either hysterectomy or myomectomy for fibroids. None. The diameter of the largest fibroid and uterine dimensions were abstracted from medical records. Spot urine samples were analyzed for 14 phthalate biomarkers using mass spectrometry. We estimated associations between fibroid outcomes and individual phthalate metabolites, sum of di(2-ethylhexyl) phthalate metabolites (∑DEHP), and a weighted sum of anti-androgenic phthalate metabolites (∑AA Phthalates) using linear regression, adjusting for age, race/ethnicity, and body mass index. Fibroid outcomes were also examined dichotomously (divided at the median) using logistic regression. Most women were of black ethnicity, overweight or obese, and college educated. In multivariable models, higher levels of mono-hydroxyisobutyl phthalate, monocarboxyoctyl phthalate, monocarboxynonyl phthalate, mono(2-ethylhexyl) phthalate, mono(2-ethyl-5-hydroxyhexyl phthalate) (MEHHP), mono(2-ethyl-5-oxohexyl) phthalate (MEOHP), and mono(2-ethyl-5-carboxypentyl) phthalate (MECPP), ∑DEHP, and ∑AA Phthalates were positively associated with uterine volume. Associations were most pronounced for individual DEHP metabolites (MEHHP, MEOHP, MECPP), ∑DEHP, and ∑AA Phthalates. For example, a doubling in ∑DEHP and ∑AA Phthalates was associated with 33.2% (95% confidence interval 6.6-66.5) and 26.8% (95% confidence interval 2.2-57.4) increase in uterine volume, respectively. There were few associations between phthalate biomarkers and fibroid size. Exposure to some phthalate biomarkers was positively associated with uterine volume, which further supports the hypothesis that phthalate exposures may be associated with fibroid outcomes. Additional studies are needed to confirm these relationships.