Electronic nicotine delivery systems (ENDS) - which include electronic cigarettes or e-cigarettes, or simply e-cigs, and marijuana vaping have become increasingly popular. ENDS devices have been established as one of the tobacco quit methods and promoted to be safer compared to traditional tobacco cigarettes. Emerging evidence demonstrates that e-cigarette and marijuana vape use can be harmful, with potential associations with cancer. Herein, we summarize the level of evidence to date for altered immune response, with a focus on cancer risks in the offspring after maternal use of, or aerosol exposures from, ENDS or marijuana vape during pregnancy. From 27 published articles retrieved from PubMed, we sought to find out identified carcinogens in ENDS aerosols and marijuana vapor, which cross the placental barrier and can increase cancer risk in the offspring. Carcinogens in vaping aerosols include aldehydes, metals, tobacco-specific nitrosamines, tobacco alkaloids, polycyclic aromatic hydrocarbons, and volatile organic compounds. Additionally, there was only one passive vaping exposure case study on a human fetus, which noted that glycerol, aluminum, chromium, nickel, copper, zinc, selenium, and lead crossed from the mother to the offspring’s cord blood. The carcinogens (metals) in that study were at lower concentrations compared to the mother’s biological matrices. Lastly, we observed that in utero exposures to ENDS-associated chemicals can occur in vital organs such as the lungs, kidneys, brain, bladder, and heart. Any resulting DNA damage increases the risk of tumorigenesis. Future epidemiological studies are needed to examine the effects of passive aerosol exposures from existing and emerging electronic nicotine and marijuana products on developing offspring to cancer.

The emerging concern about chemicals in electronic cigarettes, even those without nicotine, demands the development of advanced criteria for their exposure and risk assessment. This study aims to highlight the sensitivity of lung nuclear receptors (NRs) to electronic cigarette e-liquids, independent of nicotine presence, and the influence of the sex variable on these effects. Adult male and female C57BL/6J mice were exposed to electronic cigarettes with 0%, 3%, and 6% nicotine daily (70 mL, 3.3 s, 1 puff per min/30 min) for 14 days, using the inExpose full body chamber (SCIREQ). Following exposure, lung tissues were harvested, and RNA extracted. The expression of 84 NRs was determined using the RT2 profiler mRNA array (Qiagen). Results exhibit a high sensitivity to e-liquid exposure irrespective of the presence of nicotine, with differential expression of NRs, including one (females) and twenty-four (males) in 0% nicotine groups compared to non-exposed control mice. However, nicotine-dependent results were also significant with seven NRs (females), fifty-three NRs (males) in 3% and twenty-three NRs (female) twenty-nine NRs (male) in 6% nicotine groups, compared to 0% nicotine mice. Sex-specific changes were significant, but sex-related differences were not observed. The study provides a strong rationale for further investigation.

Long-standing research shows that cigarette smoking is known to impact DNA methylation and promote severe lung disease - however, research on electronic nicotine delivery systems (ENDS) or e-cigarettes and their effect on methylation and expression of oxidative stress genes is limited. Furthermore, the component of sex as a variable for susceptibility to methylation changes and lung damage - specifically for females - is not well understood. Given the strikingly increased use of ENDS - especially among youth and young adults - it is critical that its mechanism and impacts become well-understood. This study analyzes the sex-specific associations that exist in DNA methylation and expression of specific genes using a mouse model of ENDS exposure. We hypothesize that e-cigarette exposure will result in a differential and sex-specific gene expression activation in lung tissue. Our experiment focused on six different genes - glutathione peroxidase 1 ( GPX1) & G protein coupled receptor 132 ( GPR132) (both previously shown to display sex-specific methylation patterns in DNA samples from smokers), Interleukin-5 ( IL-5), Interleukin-6 ( IL-6), & Interleukin-7 ( IL-7) (due to their significant role in inflammation), as well as Chemokine (C-X-C motif) ligand 1 ( CXCL1) (with its crucial role in recruiting immune cells at various tissues, including the lungs). Our experiment used adult (8-10 weeks old) male and female C57BL/6J mice. These were divided in four groups (n=6/group; 3 males and 3 females) and treated for 14 days, as follows; group I: no treatment (control), group II: 0% nicotine e-liquid [50% propylene glycol (PG) and 50% vegetable glycerin (VG)], group III: 3% nicotine & group IV: 6% nicotine in PG/VG using an inExpose full body chamber (SCIREQ); e-cigarette puff (70 ml, 3.3s, 1 or 2 puffs per min/30 min/day). Following exposure, lungs were harvested and DNA was extracted for future analysis with the EZ DNA Methylation Sample Direct Kit. Total RNA was also extracted with the Direct-zol kit (Zymo) and retro-transcribed with the High Capacity cDNA kit (Thermo). The expression of all genes was determined with a Taqman gene expression assay (Thermo) using a QuantStudio 5 Real-Time PCR system. Ct values were analyzed with the deltadeltaCt method, and statistical analyses were conducted in Prism. Our preliminary results indicate that e-cigarette exposure resulted in an increased, although not statistically significant, expression of GPR132 in males, but not females. However, a significant interaction of sex and exposure was found for GPR132 expression (two-way ANOVA, p<0.05), with control (group I) females displaying higher GPR132 lung tissue expression than males, and female mice exposed to 3% nicotine displaying lower GPR132 expression than males. No differences in GPX1 expression were found for either sex or treatment exposure. The expression of IL-5 in control (group 1) and 0% nicotine (group 2) varied by sex - expression was relatively high in control (group 1) females, but lower in 0% nicotine (group 2) females. By contrast, expression was relatively low in control (group 1) males, but greater in 0% nicotine (group 2) males. The expression of IL-6 in control (group 1) mice greatly varied by sex - expression in 0% nicotine (group 2) females was relatively higher compared to the expression in 0% nicotine (group 2) males. In females, expression was much lower in 0% (group 1), 3% (group 2), and 6% (group 3) mice. In males, however, the expression amongst all groups was not significantly different. The expression of IL-7 in 0% nicotine (group 2) mice varied by sex - expression, in 0% nicotine (group 2) females was relatively high (compared to the control (group 1) females), while expression, in 0% nicotine (group 2) males was relatively lower (against 0% nicotine (group 2) females). (and not significantly different when compared to control (group 1) males). In both females and males, an increase in CXCL1 Gene expression was found with 0% Nicotine (group 2) compared to the control (group 1) - with increased nicotine concentrations of 3% and 6% (groups 3 and 4, respectively), however, CXCL1 gene expression decreased. We conclude that e-cigarette exposure results in a differential and sex-specific gene expression activation in lung tissue. In looking to the future, several, closely-related matters are of paramount importance to investigate. First and foremost, our ongoing measurement and analysis of DNA methylation patterns in mice will help us to identify the effects of ENDS exposure in the male and female lung. Additionally, the relatively limited (and often conflicting) data on “flavored” e-cigarettes - which are marketed towards younger individuals - necessitates the need to study their effects on gene expression. Finally, beyond gene expression, a future, in-depth analysis on the mechanisms giving rise to the changes observed in gene expression - based on sex, exposure, or an interaction of sex and exposure - will be instrumental in bettering our (thus far) limited knowledge of e-cigarette exposure. We acknowledge the support from School of Public Health, Indiana University, Bloomington, Indiana, USA. This work was partially funded by the Offce of the Vice Provost of Research at Indiana University - Bloomington through the research Equipment Fund. Equipment used in this study was supported, in part, with funding from the Indiana Clinical and Translational Sciences Institute, funded in part by grant number UL1 TR002529 from the National Institutes of Health, National Center for Advancing Translational Sciences, Clinical and Translational Sciences Award. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Background/Objective Phthalates and phthalate replacements are used in multiple everyday products, making many of them bioavailable to children. Experimental studies suggest that phthalates and their replacements may be obesogenic, however, epidemiologic studies remain inconsistent. Therefore, our objective was to examine the association between phthalates, phthalate replacements and childhood adiposity/obesity markers in children.Subjects/Methods A cross-sectional study was conducted in 630 racial/ethnically diverse children ages 4-8 years. Urinary oxidative metabolites of DINCH and DEHTP, three low molecular weight (LMW) phthalates, and eleven high molecular weight (HMW) phthalates were measured. Weight, height, waist circumference and % body fat were measured. Composite molar sum groups (nmol/ml) were natural log-transformed. Linear regression models adjusted for urine specific gravity, sex, age, race-ethnicity, birthweight, breastfeeding, reported activity level, mother's education and pre-pregnancy BMI.Results All children had LMW and HMW phthalate metabolites and 88% had DINCH levels above the limit of detection. One unit higher in the log of DINCH was associated with 0.106 units lower BMI z-score [beta = -0.106 (95% CI: -0.181, -0.031)], 0.119 units lower waist circumference z-score [beta = -0.119 (95% CI: -0.189, -0.050)], and 0.012 units lower percent body fat [beta = -0.012 (95% CI: -0.019, -0.005)]. LMW and HMW group values were not associated with adiposity/obesity.Conclusions We report an inverse association between child urinary DINCH levels, a non-phthalate plasticizer that has replaced DEHP in several applications, and BMI z-score, waist circumference z-score and % body fat in children. Few prior studies of phthalates and their replacements in children have been conducted in diverse populations. Moreover, DINCH has not received a great deal of attention or regulation, but it is a common exposure. In summary, understanding the ubiquitous nature of these chemical exposures and ultimately their sources will contribute to our understanding of their relationship with obesity.

The mechanisms underlying the differential allergic inflammation phenotype observed in males and females remain unknown, however, both sex hormones and sex-specific genes have been suggested to play a role. This study aimed to identify differentially expressed genes, associated cellular functions, and regulatory pathways in lung tissue from the combination of the Four Core Genotype (FCG) model with a mouse model of allergic inflammation triggered by HDM.For this, FCG adult mice (10 weeks old) of all genotypes (XXM, XXF, XYM, XYF) were challenged intranasally by administering 50 μl of HDM solution (25 μg of HDM extract from two species, Dermatophagoides pteronyssinus, and Dermatophagoides farinae) or vehicle (phosphate-buffered saline, PBS) five times in a week for 5 weeks. At 72hrs after the last exposure, airway hyperreactivity (AHR) was assessed through methacholine challenge (MCh) using the Flexivent rodent ventilator system (SCIREQ), and lung inflammation was determined via Bronchoalveolar Lavage Fluid (BALF) cytospin analysis and histological assessment of fixed lung tissue. Lung tissue was harvested, and RNA was extracted using the Direct-zol kit (Zymo). Samples (n=3/group) underwent RNA-Seq analysis. Differential expression of replicated count data was examined using the edgeR package on the R software and gene enrichment analysis was done using the Ingenuity Pathway Analysis (IPA) system with a threshold of ‑Log (P‑value)>2.Increased AHR and neutrophilic inflammation were observed in groups, XYF and XXF mice challenged with HDM (vs Control). RNA-Seq analysis showed 3154 differentially expressed genes in the FCG mice challenged with HDM among which are 38 downregulated and 151 upregulated genes in the XXF group, 87 downregulated and 1 upregulated gene in the XXM group, 35 downregulated and 279 upregulated genes in the XYF group, and 150 upregulated genes in the XYM group using the threshold of fold changes ≥1.2 and P<0.05. KRT4 gene was highly upregulated in XYF and XXF. IPA revealed the most activated upstream regulators in XXM, XXF, XYM, and XYF are EBI3, TGFB1, IL11RA, and STAT3 respectively. Canonical pathways that are found to be enriched in groups with female gonads only (XXF and XYF) was nicotine degradation III while PXR-RXR activation was found in XXF, XYF, and XYM. Interestingly, the pathways activated in groups XYF and XXF were associated with inflammatory response, organismal injury and abnormality, and respiratory disease while activated pathways in XYM and XXM were associated with cellular development, growth, proliferation and movement, and immune cell trafficking.These findings showed a fundamental difference in the gene expression profiles of FCG mice challenged with HDM. In addition, this study identified different pathways that are involved in the sex disparities in allergic airway inflammation model of asthma which may serve as targets for the development of sex-specific therapeutic prevention and treatment of asthma. Public grant: NIH R01HL159764 and R03HL141618 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

miRNAs play important roles in regulating gene and environmental interactions. However, their role in mediating sex differences in allergic responses and lung diseases has not been elucidated. Our study used a targeted omics approach to characterize the contributions of gonadal hormones and chromosomal components to lung responses to an allergen challenge. Our results point to the influence of sex hormones in miRNA expression and proinflammatory markers in allergic airway inflammation.

Gene expression profiling helps to provide deep insight into the global view of disease-related mechanisms and responses to therapy. Using the Four-Core Genotype mouse model, our findings revealed the influence of sex hormones and sex chromosomes in the gene expression of lungs exposed to an aeroallergen (House Dust Mite) and identified sex-specific pathways to better understand sex disparities associated with allergic airway inflammation.

Thirdhand smoke (THS) is the accumulation of secondhand smoke on surfaces that ages with time. THS exposure is a potential health threat to children, partners of smokers, and workers in environments with current or past smoking, and needs further investigation. In this study, we hypothesized that thirdhand Electronic Nicotine Delivery Systems (ENDS) exposures elicit lung and systemic inflammation due to resuspended particulate matter (PM) and inorganic compounds that remain after active vaping has ceased. To test our hypothesis, we exposed C57BL/6J mice to cotton towels contaminated with ENDS aerosols from unflavored vape fluid (6 mg nicotine in 50/50 propylene glycol/vegetable glycerin) for 1h/day, five days/week, for three weeks. We assessed protein levels in serum and bronchoalveolar lavage fluid (BALF) using a multiplex protein assay. The mean ± sd for PM10 and PM2.5 measurements in exposed mouse cages were 8.3 ± 14.0 and 4.6 ± 7.5 µg/m3, compared to 6.1 ± 11.2 and 3.7 ± 6.6 µg/m3 in control cages respectively. Two compounds, 4-methyl-1, 2-dioxolane and 4-methyl-cyclohexanol, were detected in vape fluid and on ENDS-contaminated towels, but not on control towels. Mice exposed to ENDS-contaminated towels had lower levels of serum Il-7 (P = 0.022, n = 7), and higher levels of Il-13 in the BALF (P = 0.006, n = 7) than those exposed to control towels (n = 6). After adjusting for sex and age, Il-7 and Il-13 levels were still associated with thirdhand vaping exposure (P = 0.010 and P = 0.017, respectively). This study provides further evidence that thirdhand ENDS aerosols can contaminate surfaces, and subsequently influence lung and systemic health upon exposure.

Air pollution health disparities can be reduced. The 'triple jeopardy' of air pollution exposures, health disparities and the COVID-19 pandemic presents a unique situation from which lessons we can learn. During the surge of the pandemic, there was evidence of reductions in ambient air pollutant concentrations during forced lockdowns, reductions in asthma hospitalizations and medication prescriptions, as well as expansion of telemedicine. It is time to use the accumulated knowledge to prepare for imminent COVID variants and future pandemics and implement informed changes to reduce air pollution health disparities. The lessons we have learned, when revisited and implemented, can be beneficial to all, particularly the most vulnerable among us. Such lessons are important starting points that can inform sustainable intervention strategies to reduce current air pollution and health disparities.

Perfluoroalkyl substances (PFAS) are widely distributed suspected obesogens that cross the placenta. However, few data are available to assess potential fetal effects of PFAS exposure on children's adiposity in diverse populations. To address the data gap, we estimated associations between gestational PFAS concentrations and childhood adiposity in a diverse mother-child cohort. We considered 6 PFAS in first trimester blood plasma, measured using ultra-high-performance liquid chromatography with tandem mass spectrometry, collected from non-smoking women with low-risk singleton pregnancies (n = 803). Body mass index (BMI), waist circumference (WC), fat mass, fat-free mass, and % body fat were ascertained in 4-8 year old children as measures of adiposity. We estimated associations of individual gestational PFAS with children's adiposity and overweight/obesity, adjusted for confounders. There were more non-Hispanic Black (31.7 %) and Hispanic (42.6 %) children with overweight/obesity, than non-Hispanic white (18.2 %) and Asian/Pacific Islander (16.4 %) children (p < 0.0001). Perfluorooctane sulfonate (PFOS; 5.3 ng/mL) and perfluorooctanoic acid (2.0 ng/mL) had the highest median concentrations in maternal blood. Among women without obesity (n = 667), greater perfluoroundecanoic acid (PFUnDA) was associated with their children having higher WC z-score (beta = 0.08, 95%CI: 0.01, 0.14; p = 0.02), fat mass (beta = 0.55 kg, 95%CI: 0.21, 0.90; p = 0.002), and % body fat (beta = 0.01 %; 95%CI: 0.003, 0.01; p = 0.004), although the association of PFUnDA with fat mass attenuated at the highest concentrations. Among women without obesity, the associations of PFAS and their children's adiposity varied significantly by self-reported race-ethnicity, although the direction of the associations was inconsistent. In contrast, among the children of women with obesity, greater, PFOS, perfluorononanoic acid, and perfluorodecanoic acid concentrations were associated with less adiposity (n = 136). Our results suggest that specific PFAS may be developmental obesogens, and that maternal race-ethnicity may be an important modifier of the associations among women without obesity.

SummaryBackgroundThe prevalence of obesity in US children has more than tripled in the past 40 years; hence, it is critical to identify potentially modifiable factors that may mitigate the risk.ObjectivesTo examine the association between maternal pre‐pregnancy body mass index (BMI), gestational weight gain (GWG) and child adiposity as measured by BMI, waist circumference and percent body fat in a racial‐ethnically diverse cohort.MethodsIn a prospective cohort study of healthy women without chronic disease, we examined the association between pre‐pregnancy BMI, GWG and child adiposity. Children ages 4–8 years (n = 816) in the Environmental Influences on Child Health Outcomes‐NICHD Fetal Growth Studies were assessed. Trained study staff ascertained maternal pre‐pregnancy BMI, GWG and child adiposity.ResultsThe odds of child obesity (≥95th BMI percentile) increased independently for each unit increase in maternal pre‐pregnancy BMI [OR = 1.12 (95% CI: 1.08, 1.17)] and for each 5‐kg increase in GWG [OR = 1.25 (95% CI: 1.07, 1.47)]. The odds of child waist circumference (≥85th percentile) also increased independently for pre‐pregnancy BMI [OR = 1.09 (95% CI: 1.05, 1.12)] and GWG [OR = 1.18 (95% CI: 1.04, 1.34)].ConclusionsMaternal pre‐pregnancy BMI and GWG were each independently and positively associated with child obesity and high child waist circumference.

In the preceding paper it was shown that an isoform of serum albumin (ASA: active serum albumin) causes a rapid retraction of neurites and increases intracellular content of Ins1,4,5P3 in PC12 cells. Here we examined whether ASA's effects in nerve growth factor-differentiated PC12 cells were mediated through the Ins1,4,5P3/Ca2+ second messenger pathway by monitoring intracellular Ca2+ (Ca2+i) with Fura2. It was found that ASA caused a dose-dependent increase in Ca2+i. In Ca2+-free medium, the increase in Ca2+i elicited by ASA was smaller, but the rise in Ins1,4,5P3 content was not appreciably changed. The small Ca2+i increase seen in Ca2+-free medium was probably due to the release of Ca2+ from Ins1,4,5P3-sensitive intracellular stores. In Ca2+-containing medium the Ca2+ transient induced by ASA was not affected by organic Ca2+ channel blockers, but decreased when Co2+, Mn2+ or Zn2+ were present in the extracellular medium. The effect of other ligands, such as carbachol and bradykinin, whose receptors are coupled to the phosphoinositide system was also investigated. Carbachol at concentrations from 2 to 200 μM, and bradykinin at a concentration of 2 μM did not cause neurite retraction, whereas 200 μM bradykinin caused an approximately 40% decrease in neurite length. Thapsigargin, a Ca2+-ATPase inhibitor, caused a sustained elevation of Ca2+i and retraction of neurites, whereas depolarization of the cells by high K+ gave only a transient elevation of Ca2+i, and no neurite retraction. Therefore, a sustained elevation in Ca2+i might be a sufficient trigger to induce neurite retraction in differentiated PC12 cells. Since ASA induces only a transient rise in Ca2+i in most cells, the Ca2+i transient evoked by ASA alone may not be sufficient to cause neurite retraction in PC12 cells.

INTRODUCTION:A few studies have identified childhood animal exposure as associated with adiposity, but results are inconsistent and differ in timing.METHODS:We conducted an observational cohort study of children ages 4-8 in the Environmental Influences on Child Health Outcomes [ECHO] study. The main exposure was having a dog in the home and/or regular contact with farm animals during the first year of life. Outcomes of interest were child BMI percentile (adjusted for gender and age) categorized as normal/underweight (<85th percentile), overweight (85th to <95th), and obese (≥95th), and percent fat mass (continuous). Associations were analyzed using multinomial logistic regression and multivariable linear regression, respectively, with and without multiple imputation.RESULTS:First year animal exposure occurred in 245 of 770 (31.8%) children. Children with early animal exposure had 0.53 (95% CI: 0.28, 0.997) times the odds of being in the obese BMI category compared to those exposed to animals after controlling for covariates: maternal pre-pregnancy BMI, race/ethnicity, reported child activity level, receiving food assistance, age child began daycare (<1 year vs 1+), exclusively breastfed x6 months, and NICU admission (n=721). Children with early animal exposure had, on average, 1.5% (95% CI: -3.0, -0.1) less fat mass than exposed children after adjustment for maternal BMI, race/ethnicity, activity, food assistance, breastfeeding, and maternal education (n=548). Multiple imputation did not alter either result.CONCLUSION:These results provide evidence that exposure to dogs or farm animals in the first year of life is associated with lower odds of obesity and lower percent fat mass in childhood.

Background: Exposure to particulate air pollution is one of the greatest environmental risk factors for adverse human health outcomes. However, the constituents that may be responsible for such adverse health effects have not been fully studied. Methods: Total suspended particulates filters collected every 6 days in 2011 from three South Carolina locations were used in this case study. An inductively coupled plasma mass spectrometer interfaced with a laser ablation system (LA-ICP-MS) was used to directly analyze 41 inorganic elemental species on air pollution filters. Then, machine learning and multivariate statistical methods was employed to identify combinatorial patterns in the data and classify sites based on their elemental composition. Results: Forty-one elements were assessed and 33 were used in subsequent analysis. Correlations between United States Environmental Protection Agency (US EPA)’s chemical analysis dataset and data from the current study revealed significant associations between 7/15 elements with enough variation for comparison (r between 0.28 to 0.66, p<0.05). Subsequent multivariate analyses revealed four distinct patterns in the distribution of elements by sample location throughout the year. Conclusion: The different airborne elements may need to be assessed to understand combinations of elements which occur together over space and/or time. Such information can be helpful in planning effective counter measures and strategies to control particulate air pollution.

Asthma in children poses a significant clinical and public health burden. We examined the association between reported neighborhood traffic (a proxy for traffic-related air pollution) and asthma among 855 multi-racial children aged 4–8 years old who participated in the Environmental Influences on Child Health Outcomes (ECHO) cohort. We hypothesized that high neighborhood traffic density would be associated with the prevalence of asthma. Asthma/asthma-like symptoms (defined as current and/or past physician diagnosed asthma, past wheezing, or nighttime cough or wheezing in the past 12 months) was assessed by parental report. The relationship between neighborhood traffic and asthma/asthma-like symptoms was assessed using logistic regression. The prevalence of asthma/asthma-like symptoms among study participants was 23%, and 15% had high neighborhood traffic. Children with significant neighborhood traffic had a higher odds of having asthma/asthma-like symptoms than children without neighborhood traffic [adjusted OR = 2.01 (95% CI: 1.12, 3.62)] after controlling for child’s race-ethnicity, age, sex, maternal education, family history of asthma, play equipment in the home environment, public parks, obesity and prescribed asthma medication. Further characterization of neighborhood traffic is needed since many children live near high traffic zones and significant racial/ethnic disparities exist.

BACKGROUND AND AIM: 1,2-cyclohexane dicarboxylic acid diisononyl ester (DINCH) is a recent plasticizer replacing high molecular weight phthalate diesters in items such as toys, medical devices, and food packaging. Little is known regarding the association of DINCH exposure and adiposity in children. METHODS: Analyses included 629 racial/ethnically diverse children ages 4-8 in the Environmental Influences on Child Health Outcomes (ECHO) study, a follow-up of the NICHD Fetal Growth Studies at 10 US sites. Urinary oxidative metabolites of DINCH (cyclohexane-1,2-dicarboxylic acid mono carboxyisooctyl [MCOCH] and cyclohexane-1,2-dicarboxylic acid mono hydroxyisononyl [MHNCH] esters) were determined using liquid chromatography tandem-mass spectrometry (UPLC-ESI-MS/MS). Values were divided by molecular weight and summed to obtain a composite DINCH value (nmol/ml). Outcomes were child's body mass index (BMI) z-score, waist circumference z-score, percent body fat, and categorized BMI percentiles (85, 85 to 95, ≥95). Multivariable linear and logistic regression models adjusted for urine specific gravity, gender, age, race/ethnicity, birth weight, prolonged exclusive breastfeeding, reported physical activity level, frequency of fast-food consumption, cigarette smoke exposure, neighborhood traffic, mother's education and pre-pregnancy BMI were used to analyze the association between natural log transformed DINCH levels and outcomes. RESULTS:88% of children had DINCH levels at or above the limit of detection. For each unit increase in natural log transformed DINCH there was a significant decrease in BMI z-score (β [95% CI]: -0.103 [-0.180, -0.026]), waist circumference z-score (β [95% CI]: -0.126 [-0.198, -0.054]) and percent body fat (β [95% CI]: -0.022 [-0.035, -0.009]). DINCH levels were not associated with overweight [OR=0.82 (95% CI: 0.66, 1.02)] or obese [OR=0.88 (95% CI: 0.69, 1.12)] versus normal BMI percentile categories. CONCLUSIONS:In this cross-sectional analysis there were significant inverse associations between children's DINCH exposure levels and adiposity measures. Additional research is needed to confirm this association and identify possible interactions between DINCH and joint exposure to other related chemicals. KEYWORDS: Phthalates, Obesity and metabolic disorders, Children's environmental health

Recent advancement in lower-cost air monitoring technology has resulted in an increased interest in community-based air quality studies. However, non-reference monitoring (NRM; e.g., low-cost sensors) is imperfect and approaches that improve data quality are highly desired. Herein, we illustrate a framework for adjusting continuous NRM measures of particulate matter (PM) with field-based comparisons and non-linear statistical modeling as an example of instrument evaluation prior to exposure assessment. First, we collected continuous measurements of PM with a NRM technology collocated with a US EPA federal equivalent method (FEM). Next, we fit a generalized additive model (GAM) to establish a non-linear calibration curve that defines the relationship between the NRM and FEM data. Then, we used our fitted model to generate calibrated NRM PM data. Evaluation of raw NRM PM2.5 data revealed strong correlation with FEM (R = 0.9) but an average bias (AB) of −2.84 µg/m3 and a root mean square error (RMSE) of 2.85 µg/m3, with 406 h of data. Fitting of our GAM revealed that the correlation structure was maintained (r = 0.9) and that average bias (AB = 0) and error (RMSE = 0) were minimized. We conclude that field-based statistical calibration models can be used to reduce bias and improve NRM data used for community air monitoring studies.