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Exposure to per- and polyfluoroalkyl substances (PFAS) during pregnancy and lactation is of increasing public health concern, but little is known about longitudinal changes in maternal PFAS concentrations from pregnancy to a few years postpartum. We quantified 11 PFAS in 251 serum samples prospectively collected from 42 Northern California mothers during the first, second, and third trimesters of pregnancy and at 3, 6, and 24 months after delivery over 2009-2017. We fit separate linear mixed models during pregnancy, early postpartum, and late postpartum to estimate percent changes of PFAS for each subperiod. Among five PFAS detected in more than 99% of samples, linear and branched perfluorooctanesulfonate (

Background A growing body of literature investigated childhood exposure to environmental chemicals in association with attention deficit hyperactivity disorder (ADHD) symptoms, but limited studies considered urinary mixtures of multiple chemical classes. This study examined associations of concurrent exposure to non-persistent chemicals with ADHD symptoms in children diagnosed with autism spectrum disorder (ASD), developmental delay, and typical development. Methods A total of 574 children aged 2–5 years from the Childhood Autism Risks from Genetics and Environment (CHARGE) case-control study was administered the Aberrant Behavior Checklist (ABC). This study focused on the Hyperactivity subscale and its two subdomains (hyperactivity/impulsivity, inattention). Sixty-two chemicals from four classes (phenols/parabens, phthalates, organophosphate pesticides, trace elements) were quantified in child urine samples, and 43 chemicals detected in > 70% samples were used in statistical analyses. Weighted quantile sum regression for negative binomial outcomes with repeated holdout validation was performed to investigate covariate-adjusted associations between mixtures and ABC scores in 574 children. The mixture analyses were further restricted to 232 children with ASD. Results Phthalate metabolite mixtures, weighted for mono-n-butylphthalate (MNBP), mono-2-heptyl phthalate, and mono-carboxy isononyl phthalate, were associated with the Hyperactivity subscale (mean incidence rate ratio [mIRR] = 1.11; 2.5th, 97.5th percentile: 1.00, 1.23), especially the hyperactivity/impulsivity subdomain (mIRR = 1.14; 2.5th, 97.5th percentile: 1.06, 1.26). These associations remained similar after restricting to children with ASD. The inattention subdomain was associated with a phenols/parabens mixture, weighted for several parabens and bisphenols (mIRR = 1.13; 2.5th, 97.5th percentile: 1.00, 1.28) and a total mixture, weighted for 3,4-dihydroxy benzoic acid, MNBP, and mono-(2-ethyl-5-carboxypentyl) phthalate (mIRR = 1.11; 2.5th, 97.5th percentile: 1.01, 1.25) only among children with ASD. Conclusions Concurrent exposure to phthalate mixtures was associated with hyperactivity in early childhood. Though causal inference cannot be made based on our cross-sectional findings, this study warrants further research on mixtures of larger number of chemicals from multiple classes in association with ADHD-related behaviors in young children.

Urinary concentrations of phenols, parabens, and triclocarban have been extensively used as biomarkers of exposure. However, because these compounds are quickly metabolized and excreted in urine, characterizing participants' long-term average exposure from a few spot samples is challenging. To examine the variability of urinary concentrations of these compounds during pregnancy, we quantified four phenols, four parabens, and triclocarban in 357 first morning voids (FMVs) and 203 pooled samples collected during the second and third trimesters of 173 pregnancies. We computed intraclass correlation coefficients (ICCs) by the sample type (FMV and pool) across two trimesters and by the number of composite samples in pools, ranging from 2 to 4, within the same trimester. Among the three compounds detected in more than 50% of the samples, the ICCs across two trimesters were higher in pools (0.29-0.68) than in FMVs (0.17-0.52) and the highest ICC within the same trimester was observed when pooling either two or three composites. Methyl paraben and propyl paraben primarily exposed via cosmetic use had approximately 2-3 times higher ICCs than bisphenol A primarily exposed via diet. Our findings support that within-subject pooling of biospecimens can increase the reproducibility of pregnant women's exposure to these compounds and thus could potentially minimize exposure misclassification.

The Environmental Influences on Child Health Outcomes (ECHO) Program will evaluate environmental factors affecting children’s health (perinatal, neurodevelopmental, obesity, respiratory, and positive health outcomes) by pooling cohorts composed of >50,000 children in the largest US study of its kind. Our objective was to identify opportunities for studying chemicals and child health using existing or future ECHO chemical exposure data. We described chemical-related information collected by ECHO cohorts and reviewed ECHO-relevant literature on exposure routes, sources, and environmental and human monitoring. Fifty-six ECHO cohorts have existing or planned chemical biomonitoring data for mothers or children. Environmental phenols/parabens, phthalates, metals/metalloids, and tobacco biomarkers are each being measured by ≥15 cohorts, predominantly during pregnancy and childhood, indicating ample opportunities to study child health outcomes. Cohorts are collecting questionnaire data on multiple exposure sources and conducting environmental monitoring including air, dust, and water sample collection that could be used for exposure assessment studies. To supplement existing chemical data, we recommend biomonitoring of emerging chemicals, non-targeted analysis to identify novel chemicals, and expanded measurement of chemicals in alternative biological matrices and dust samples. ECHO’s rich data and samples represent an unprecedented opportunity to accelerate environmental chemical research to improve the health of US children.

One-hundred seventy-two households were recruited from regions with high outdoor air pollution (Fresno and Riverside, CA) to participate in a randomized, sham-controlled, cross-over study to determine the effectiveness of high-efficiency air filtration to reduce indoor particle exposures. In 129 households, stand-alone HEPA air cleaners were placed in a bedroom and in the main living area. In 43 households, high-efficiency MERV 16 filters were installed in central forced-air heating and cooling systems and the participating households were asked to run the system on a clean-air cycle for 15 min per hour. Participating households that completed the study received true air filtration for a year and sham air filtration for a year. Air pollution samples were collected at approximately 6-month intervals, with two measurements in each of the sham and true filtration periods. One week indoor and outdoor time-integrated samples were collected for measurement of PM

BACKGROUND: Melamine, melamine derivatives, and aromatic amines are nitrogen-containing compounds with known toxicity and widespread commercial uses. Nevertheless, biomonitoring of these chemicals is lacking, particularly during pregnancy, a period of increased susceptibility to adverse health effects. OBJECTIVES: We aimed to measure melamine, melamine derivatives, and aromatic amine exposure in pregnant women across the United States (U.S.) and evaluate associations with participant and urine sample collection characteristics. METHODS: We measured 43 analytes, representing 45 chemicals (i.e., melamine, three melamine derivatives, and 41 aromatic amines), in urine from pregnant women in nine diverse ECHO cohorts during 2008–2020 (N=171). To assess relations with participant and urine sample collection characteristics, we used generalized estimating equations to estimate prevalence ratios (PRs) for analytes dichotomized at the detection limit, % differences (%Δ) for continuous analytes, and 95% confidence intervals. Multivariable models included age, race/ethnicity, marital status, urinary cotinine, and year of sample collection. RESULTS: Twelve chemicals were detected in >60% of samples, with near ubiquitous detection of cyanuric acid, melamine, aniline, 4,4’-methylenedianiline, and a composite of o-toluidine and m-toluidine (99–100%). In multivariable adjusted models, most chemicals were associated with higher exposures among Hispanic and non-Hispanic Black participants. For example, concentrations of 3,4-dichloroaniline were higher among Hispanic (%Δ: +149, 95% CI: +17, +431) and non-Hispanic Black (%Δ: +136, 95% CI: +35, +311) women compared with non-Hispanic White women. We observed similar results for ammelide, o-/m-toluidine, 4,4’-methylenedianiline, and 4-chloroaniline. Most chemicals were positively associated with urinary cotinine, with strongest associations observed for o-/m-toluidine (%Δ: +23; 95% CI: +16, +31) and 3,4-dichloroaniline (%Δ: +25; 95% CI: +17, +33). Some chemicals exhibited annual trends (e.g., %Δ in melamine per year: −11; 95% CI: −19, −1) or time of day, seasonal, and geographic variability. DISCUSSION: Exposure to melamine, cyanuric acid, and some aromatic amines was ubiquitous in this first investigation of these analytes in pregnant women. Future research should expand biomonitoring, identify sources of exposure disparities by race/ethnicity, and evaluate potential adverse health effects.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are shown to have neurotoxic effects on animals, but epidemiological evidence for associations between childhood PFAS exposure and neurodevelopment is inconclusive. We examined if childhood PFAS concentrations are associated with a diagnosis of autism spectrum disorder (ASD), developmental delay (DD), and other early concerns (OEC) in development. METHODS: We included 551 children 2 to 5 years old from the CHildhood Autism Risks from Genetics and Environment (CHARGE) case-control study. Children were clinically diagnosed and classified as having ASD, DD, OEC, and typical development (TD). Fourteen PFAS were quantified in child serum samples collected when diagnostic assessments were performed. We used multinomial logistic regression models to investigate the cross-sectional associations of individual PFAS concentrations with neurodevelopmental outcomes and weighted quantile sum (WQS) regression models with repeated holdout validation to investigate the associations with PFAS mixtures. RESULTS: Childhood perfluorooctanoic acid (PFOA) was associated with increased odds of ASD (odds ratio [OR] per ln ng/mL increase: 1.99, 95% confidence interval [CI]: 1.20, 3.29) and DD (OR: 2.16, 95% CI: 1.21, 3.84) versus TD. Perfluoroheptanoic acid (PFHpA) was associated with increased odds of ASD (OR: 1.61, 95% CI: 1.21, 2.13). However, perfluroundecanoic acid (PFUnDA) was associated with decreased odds of ASD (OR: 0.43, 95% CI: 0.26, 0.69). From mixture analyses, the WQS index was associated with increased odds of ASD (average OR: 1.57, 5(th) and 95(th) percentile: 1.16, 2.13). Child’s sex and homeownership modified associations of perfluorodecanoic acid (PFDA) with DD and ASD, respectively. CONCLUSIONS: In this case-control study, childhood PFOA, PFHpA, and a PFAS mixture was associated with increased odds of ASD, while PFUnDA was associated with decreased odds of ASD. Because we used concurrent measurements of PFAS, our results do not imply causal relationships and thus need to be interpreted with caution.

BACKGROUND AND AIM: Prenatal chemical exposures are ubiquitous, can influence maternal, fetal and child health, and lead to adverse pregnancy and child health outcomes. The NIH Environmental influe...

Little is known about temporal trends of pregnant women's exposures to environmental phenols and parabens. We quantified four phenols [bisphenol A (BPA), bisphenol F, bisphenol S, and triclosan), four parabens [butyl paraben, ethyl paraben (ETPB), methyl paraben (MEPB), and propyl paraben (PRPB)], and triclocarban in 760 urine samples collected during 2007-2014 from 218 California pregnant women participating in a high-familial risk autism spectrum disorder cohort. We applied multiple regression to compute least square geometric means of urinary concentrations and computed average annual percent changes. We compared our urinary concentrations with those of other study populations to examine geographic variations in pregnant women's exposure to these target compounds. Urinary concentrations of BPA, MEPB, ETPB, and PRPB in this study population decreased over the study period [percent change per year (95% confidence interval): -5.7% (-8.2%, -3.2%); -13.0% (-18.1%, -7.7%); -5.5% (-11.0%, 0.3%); and -13.3% (-18.3%, -8.1%), respectively] and were consistently lower than those in pregnant women in other U.S. regions during the same study period. In recent years, certain phenols and parabens with known adverse health effects are being regulated or replaced with alternatives, which explains decreased body burdens observed in this study population. Either the national regulations or the advocacy campaigns in California may have influenced exposures or consumer product choices.

Upholstered furniture has been a major source of chemical flame retardant (FR) exposures in US homes since the 1970s. FRs are a large group of chemicals, many of which are associated with adverse health effects, including cancer, reproductive toxicity, and neurotoxicity. California homes have some of the highest dust concentrations of FRs, due to Technical Bulletin 117 (TB117), California’s outdated flammability standard for furniture foam that was generally followed across the US and Canada. In 2014, this standard was updated to a smolder standard for furniture fabric called TB117-2013, and it is no longer reliant on FRs. This update provided an opportunity to measure differences in FR dust levels in California homes before and after residents replaced older upholstered furniture, or its foam, with products that met the new standard and were expected to be FR-free. We collected dust from homes of participants who had plans to replace older upholstered furniture, or furniture foam, with FR-free options. We returned for follow-up dust collection six, 12, and 18 months following replacement. Concentrations of three polybrominated diphenyl ethers (PBDEs) (BDE-47, BDE-99, BDE-100), three chlorinated organophosphate ester FRs (tris(2-chloroethyl) phosphate (TCEP), tris(2-chloroisopropyl) phosphate (TCIPP), and tris(1,3-dichloroisopropyl) phosphate (TDCIPP)), and one aryl organophosphate ester FR triphenyl phosphate (TPHP), were widely detected in participant homes. All measured FRs decreased in nearly all homes after the older upholstered furniture was replaced. The decreases in FRs were significant in both homes that replaced entire pieces of furniture and those that replaced only the furniture foam. This study demonstrates that replacing older upholstered furniture or foam significantly reduces concentrations of a range of FRs in the home. Foam replacement offers a potentially more economic alternative that produces a lower volume of waste.

Household dust is a reservoir of various consumer product chemicals. Thus, characterizing comprehensive chemical profiles of house dust may help improve our understanding of residential chemical exposure. We have previously developed a method for detecting a broad spectrum of chemicals in dust by applying a combination of target, suspect screening, and non-target methods with mass spectrometry preceded by liquid chromatography and gas chromatography. Building upon a previous study that detected 271 compounds in 38 dust samples, we presented concentrations of 144 compounds that were confirmed and quantified by standards in the same set of samples. Ten compounds were measured with median concentrations greater than 10000ng/g of dust: cis-hexadec-6-enoic acid, squalene, cholesterol, vitamin E, bis(2-ethylhexyl) phthalate, dioctyl terephthalate, linoleic acid, tricaprylin, tris(1-chloroisopropyl) phosphate, and oxybenzone. We also reviewed in vitro toxicity screening data to identify compounds that were not previously detected in indoor dust but have potential for adverse health effects. Among 119 newly detected compounds, 13 had endocrine-disrupting potential and 7 had neurotoxic potential. Toxicity screening data were not available for eight biocides, which may adversely affect health. Our results strive to provide more comprehensive chemical profiles of house dust and identified information gaps for future health studies.

Semivolatile organic compounds (SVOCs) are ubiquitous in the indoor environment and a priority for exposure assessment because of the environmental health concerns that they pose. Direct air-to-skin dermal uptake has been shown to be comparable to the inhalation intake for compounds with certain chemical properties. In this study, we aim to further understand the transport of these types of chemicals through the skin, specifically through the stratum corneum (SC). Our assessment is based on collecting three sequential forehead skin wipes, each hypothesized to remove pollutants from successively deeper skin layers, and using these wipe analyses to determine the skin concentration profiles. The removal of SVOCs with repeated wipes reveals the concentration profiles with depth and provides a way to characterize penetration efficiency and potential transfer to blood circulation. We used a diffusion model applied to surface skin to simulate concentration profiles of SVOCs and compared them with the measured values. We found that two phthalates, dimethyl and diethyl phthalates, penetrate deeper into skin with similar exposure compared to other phthalates and targeted SVOCs, an observation supported by the model results as well. We also report the presence of statistically significant declining patterns with skin depth for most SVOCs, indicating that their diffusion through the SC is relevant and eventually can reach the blood vessels in the vascularized dermis. Finally, using a nontarget approach, we identified skin oxidation products, linked to respiratory irritation symptoms, formed from the reaction between ozone and squalene.

Farm workers are at risk of heat related illness (HRI), but their work rates that contribute to HRI have not been objectively assessed. The CHIPS study collected accelerometer data and characterized the physical activity of major farm tasks. Demographic information, work characteristics, and accelerometer data were collected from 575 farm workers in California. Each participating worker contributed measurements over one work shift. An Actical accelerometer was attached securely to a belt worn at the hip. Data were collected at one-minute intervals throughout the work shift. A total of 13 major work-task categories were defined. The mean physical activity counts per minute (cpm) and percentage of the shift spent at moderate and/or vigorous levels of activity were described for each task. Multiple linear regression models were constructed to determine the worker and environmental characteristics contributing to the physical activity level. Mean levels of physical activity ranged from 700 cpm (workers who carry produce) to a low of 150 cpm "ground pruners" who tend low-level plants, with an overall mean of 345 cpm or "light" activity (2 to ≤3 metabolic equivalents). The environmental temperature was the major factor associated with physical activity. A 10°C increase in the median temperature reduced the mean cpm by 135 (95% CI = 87, 193). Age and the tasks of sorting, ground pruning, and harvesting low-level crops were also negatively and independently associated with mean cpm. Incentivized (piece rate) pay, multi-task work, and irrigator work were positively associated with cpm. An interaction was found between piece rate and sex. Men's activity significantly increased (p0.001) by a mean of 95 cpm, (95% CI = 38.3, 150.7) if they were paid by the piece, but there was a non-significant association with women's activity level. Workers conducting multiple tasks, irrigators, men, and those earning incentivized (piece rate) pay had higher adjusted mean physical activity levels and are likely at increased risk of heat-related illness on hot days.

Objective Determine compliance with and effectiveness of California regulations in reducing farmworkers' heat-related illness (HRI) risk and identify main factors contributing to HRI. Methods In a cross-sectional study of Latino farmworkers, core body temperature (CBT), work rate, and environmental temperature (WBGT) were monitored over a work shift by individual ingestible thermistors, accelerometers, and weather stations, respectively. Multiple logistic modeling was used to identify risk factors for elevated CBT. Results Although farms complied with Cal/OSHA regulations, worker training of HRI prevention and hydration replacement rates were insufficient. In modeling (AOR [95% CI]) male sex (3.74 [1.22 - 11.54]), WBGT (1.22 [1.08 - 1.38]), work rate (1.004 [1.002 - 1.006]), and increased BMI (1.11 [1.10 - 1.29]) were all independently associated with elevated CBT. Conclusion Risk of HRI was exacerbated by work rate and environmental temperature despite farms following Cal/OSHA regulations.

OBJECTIVE: To determine if higher exposures measured in early childhood to environmental phenols, phthalates, pesticides, and/or trace elements, are associated with increased odds of having a diagnosis of Autism Spectrum Disorder (ASD), Developmental Delay (DD), or Other Early Concerns (OEC) compared to typically developing children (TD). METHODS: This study included 627 children between the ages of 2–5 who participated in the Childhood Autism Risks from Genetics and Environment (CHARGE) study. Urine samples were collected at the same study visit where diagnostic assessments to confirm diagnosis indicated during the recruitment process were performed. Adjusted multinomial regression models of each chemical with diagnosis as the outcome were conducted. Additionally, two methods were used to analyze mixtures: repeated holdout multinomial weighted quantile sum (WQS) regression for each chemical class; and a total urinary mixture effect was assessed with repeated holdout random subset WQS. RESULTS: Many urinary chemicals were associated with increased odds of ASD, DD or OEC compared to TD; however, most did not remain significant after false discovery rate adjustment. Repeated holdout WQS indices provided evidence for associations of both a phenol/paraben mixture effect and a trace element mixture effect on DD independently. In analyses adjusted for confounders and other exposures, results suggested an association of a pesticide mixture effect with increased risk for ASD. Results also suggested associations of a total urinary mixture with greater odds of both ASD and DD separately.. CONCLUSION: Higher concentrations of urinary biomarkers were associated with ASD, DD, and OEC compared to TD, with consistency of the results comparing single chemical analyses and mixture analyses. Given that the biospecimens used for chemical analysis were generally collected many months after diagnoses were made, the direction of any causal association is unknown. Hence findings may reflect higher exposures among children with non-typical development than TD children due to differences in behaviors, metabolism, or toxicokinetics.

Existing methods for the analysis of pesticides in human breast milk involve multiple extraction steps requiring large sample and solvent volumes, which can be a major obstacle in large epidemiologic studies. Here, we developed a simple, low-volume method for extracting organophosphates, pyrethroids, carbamates, atrazine, and imidacloprid from 100 to 200 μL of human breast milk. Multiple extraction protocols were tested including microwave-assisted acid/base digestion and double-solvent extraction with 2 or 20 mL of 2:1 (v/v) dichloromethane/hexane, with or without subsequent solid-phase extraction (SPE) cleanup. Samples were analyzed by liquid chromatography tandem mass spectrometry. Analyte recoveries and reproducibility were highest when 100-200 μL of milk were extracted with 2 mL of dichloromethane/hexane without subsequent SPE steps. Analysis of 79 breast milk samples using this method revealed the presence of carbamates, organophosphates, pyrethroids, and imidacloprid at detection frequencies of 79-96, 53-90, 1-7, and 61%, respectively. This study demonstrates the feasibility of a simple low-volume extraction method for measuring pesticides in human breast milk.

BACKGROUND/OBJECTIVE: Polyurethane foam (PUF), a proven sampling medium for measuring air concentrations of organic compounds, is widely used in upholstered home furniture. We evaluated the potential utility of couch PUF as a passive sampler and as a reservoir for non-flame retardant semivolatile organic compounds (SVOCs). METHODS: We collected PUF samples from 13 California home couches, measured concentrations (C(PUF)) of 64 SVOCs at three different depths (i.e., top, top-middle, and middle from couch surfaces facing outward), and examined concentration changes with depth. To calculate the PUF-air partition coefficient (K(PUF-air) = C(PUF)/C(air) = C(PUF) × K(dust-air)/C(dust)), we used the calculated dust-air partition coefficient (K(dust-air)) with the octanol-air partition coefficient (K(oa)) and dust concentrations (C(dust)) simultaneously collected and measured. We used K(PUF-air) to compute fugacity capacity of PUF and chemical mass distribution among various indoor compartments and PUF. RESULTS: Among 29 detected compounds, 11 compounds were detected in more than 50% of the samples at all depths. Among the 11 compounds, concentrations of phenanthrene, 2-benzylideneoctanal, galaxolide, tonalide, and homosalate decreased with depth. Among the studied SVOCs, more than 20% of the total mass was distributed to couch PUF for phenol and compounds in skin-applied products (i.e., 2-benzylideoneoctanal, galaxolide, and homosalate). CONCLUSIONS: Our results showed that couch PUF can absorb many SVOCs and may be an important reservoir for some SVOCs. However, it may not be an effective passive sampling medium for those that have relatively high K(oa) values. Direct dermal contact with couch seats may be an important exposure route for non-users of skin-applied compounds.

The determinants of the temporal variability of indoor dust concentrations of semivolatile organic compounds (SVOCs) remain mostly unexplored. We examined temporal variability of dust concentrations and factors affecting dust concentrations for a wide range of SVOCs. We collected dust samples three times from 29 California homes during a period of 22months and quantified concentrations of 47 SVOCs in 87 dust samples. We computed intraclass correlation coefficients (ICCs) using three samples collected within the same house. We calculated correlation coefficients (r) between two seasons with similar climate (spring and fall) and between two seasons with opposite climate (summer and winter). Among 26 compounds that were detected in more than 50% of the samples at all three visits, 20 compounds had ICCs above 0.50 and 6 compounds had ICCs below 0.50. For 19 out of 26 compounds, correlation coefficients between spring and fall (r=0.48-0.98) were higher than those between summer and winter (r=0.09-0.92), implying seasonal effects on dust concentrations. Our study showed that within-home temporal variability of dust concentrations was small (ICC>0.50) for most SVOCs, but dust concentrations may vary over time for some SVOCs with seasonal variations in source rates, such as product use.

Background Prenatal exposure to per- and polyfluoroalkyl substances (PFAS) has shown potential to adversely affect child brain development, but epidemiologic evidence remains inconsistent. We examined whether prenatal exposure to PFAS was associated with increased risk of autism spectrum disorder (ASD). Methods Participants were 173 mother–child pairs from MARBLES ( M arkers of A utism R isk in B abies – L earning E arly S igns), a high-risk ASD cohort. At 3 years old, children were clinically confirmed for ASD and classified into ASD (n = 57) and typical development (TD, n = 116). We quantified nine PFAS in maternal serum collected during pregnancy. We examined associations of ASD with individual PFAS as well as the combined effect of PFAS on ASD using scores of the first principal component (PC-1) accounting for the largest variance. Results Prenatal perfluorooctanoate (PFOA) and perfluorononanoate (PFNA) showed positive associations (per 2-fold relative increase in concentration: relative risk (RR) = 1.20, 95% CI: 0.90, 1.61 [PFOA]; RR = 1.24, 95% CI: 0.91, 1.69 [PFNA]), while perfluorohexane sulfonate (PFHxS) showed a negative association (RR = 0.88, 95% CI: 0.77, 1.01) with ASD risk. When examining associations of ASD with untransformed PFAS concentrations, PFOA, PFNA, and PC-1 were associated with increased ASD risk (per nanogram per milliliter increase: RR = 1.31, 95% CI: 1.04, 1.65; RR = 1.79, 95% CI: 1.13, 2.85; RR = 1.10, 95% CI: 0.97, 1.25, respectively), while the RR of PFHxS moved toward the null. Conclusions From this high-risk ASD cohort, we observed increased risk of ASD in children exposed to PFOA and PFNA. Further studies should be conducted in the general population because this population may have a larger fraction of cases resulting from genetic sources.

Background We assessed the relationships between prenatal pyrethroid pesticide exposure and autism spectrum disorders (ASD) or non-typical development (non-TD) at 3 years. Methods Participants were mother-child pairs (n = 201) in the MARBLES (Markers of Autism Risk in Babies-Learning Early Signs) cohort. Because familial recurrence risk is high, MARBLES enrolls pregnant women with a family history of ASD. Children from these pregnancies were clinically assessed at 3 years of age and classified into 3 outcome categories: ASD, typically developing (TD), or non-TD (neither TD or ASD). Repeated maternal second and third trimester urine samples were analyzed for pyrethroid metabolite 3-phenoxybenzoic acid (3-PBA). Multinomial logistic regression was used to obtain relative risk ratios (RRR) linking 3-PBA concentrations averaged across each trimester and over pregnancy with child's outcome: ASD or non-TD vs. TD. Models were adjusted for specific gravity, maternal pre-pregnancy BMI, prenatal vitamin use, birth year, home-ownership, and pregnancy concentrations of TCPy (3,5,6-trichloro-2-pyridinol, a metabolite of chlorpyrifos). Results The median specific gravity corrected 3-PBA concentration of all samples was 1.46 ng/mL. Greater second trimester 3-PBA concentrations were associated with a relative risk ratio (RRR) for ASD of (RRR: 1.50 (95% CI 0.89 to 2.51), p = 0.12). There were no differences between non-TD and TD. Conclusions This study found no evidence for differences in 3-PBA comparing non-TD with TD. A modestly elevated RRR was found comparing second trimester urinary 3-PBA concentrations for ASD versus TD; however, the confidence interval was wide and hence, these findings cannot be considered definitive.

The Environmental influences on Child Health Outcomes (ECHO) Program is a research initiative funded by the National Institutes of Health that capitalizes on existing cohort studies to investigate the impact of early life environmental factors on child health and development from infancy through adolescence. In the initial stage of the program, extant data from 70 existing cohort studies are being uploaded to a database that will be publicly available to researchers. This new database will represent an unprecedented opportunity for researchers to combine data across existing cohorts to address associations between prenatal chemical exposures and child neurodevelopment. Data elements collected by ECHO cohorts were determined via a series of surveys administered by the ECHO Data Analysis Center. The most common chemical classes quantified in multiple cohorts include organophosphate pesticides, polychlorinated biphenyls, polybrominated diphenyl ethers, environmental phenols (including bisphenol A), phthalates, and metals. For each of these chemicals, at least four ECHO cohorts also collected behavioral data during infancy/early childhood using the Child Behavior Checklist. For these chemicals and this neurodevelopmental assessment (as an example), existing data from multiple ECHO cohorts could be pooled to address research questions requiring larger sample sizes than previously available. In addition to summarizing the data that will be available, the article also describes some of the challenges inherent in combining existing data across cohorts, as well as the gaps that could be filled by the additional data collection in the ECHO Program going forward.

Background/Objective Human exposure to per- and polyfluoroalkyl substances (PFAS) has changed since the early 2000s, in part, because of the phase-out and replacement of some long-chain PFAS. Studies of PFAS exposure and its temporal changes have been limited to date mostly to adults and pregnant women. We examined temporal trends and determinants of PFAS serum concentrations among mothers with a young child who participated in the CHARGE ( CH ildhood A utism R isk from G enetics and E nvironment) case-control study. Methods We quantified nine PFAS in serum samples collected from 2009 to 2016 in 450 Northern California mothers when their child was 2–5 years old. With five compounds that were detected in more than 50% of the samples, we performed multiple regression to estimate least square geometric means (LSGMs) of PFAS concentrations with adjustment for sampling year and other characteristics that may affect maternal concentrations (e.g., breastfeeding duration). We also used time-related regression coefficients to calculate percent changes over the study period. Results LSGM concentrations of perfluorooctanoate (PFOA), perfluorooctane sulfonate (PFOS), and perfluorohexane sulfonate (PFHxS) decreased over the study period [percent change (95% confidence interval): −10.7% (−12.7%, −8.7%); −10.8% (−12.9%, −8.5%); −8.0% (−10.5%, −5.5%), respectively]. On the other hand, perfluorononanoate (PFNA) and perfluorodecanoate (PFDA) showed mixed time trends. Among the selected covariates, longer breastfeeding duration was associated with decreased maternal serum concentrations of PFOA, PFOS, PFHxS, PFNA and PFDA. Conclusions Our study demonstrated that body burden of some common long-chain PFAS among California mothers with a young child decreased over the study period and that breastfeeding appears to contribute to the elimination of PFAS in lactating mothers.

Background: The National Institutes of Health’s Environmental influences on Child Health Outcomes (ECHO) initiative aims to understand the impact of environmental factors on childhood disease. Over 40,000 chemicals are approved for commercial use. The challenge is to prioritize chemicals for biomonitoring that may present health risk concerns. Objectives: Our aim was to prioritize chemicals that may elicit child health effects of interest to ECHO but that have not been biomonitored nationwide and to identify gaps needing additional research. Methods: We searched databases and the literature for chemicals in environmental media and in consumer products that were potentially toxic. We selected chemicals that were not measured in the National Health and Nutrition Examination Survey. From over 700 chemicals, we chose 155 chemicals and created eight chemical panels. For each chemical, we compiled biomonitoring and toxicity data, U.S. Environmental Protection Agency exposure predictions, and annual production usage. We also applied predictive modeling to estimate toxicity. Using these data, we recommended chemicals either for biomonitoring, to be deferred pending additional data, or as low priority for biomonitoring. Results: For the 155 chemicals, 97 were measured in food or water, 67 in air or house dust, and 52 in biospecimens. We found in vivo endocrine, developmental, reproductive, and neurotoxic effects for 61, 74, 47, and 32 chemicals, respectively. Eighty-six had data from high-throughput in vitro assays. Positive results for endocrine, developmental, neurotoxicity, and obesity were observed for 32, 11, 35, and 60 chemicals, respectively. Predictive modeling results suggested 90% are toxicants. Biomarkers were reported for 76 chemicals. Thirty-six were recommended for biomonitoring, 108 deferred pending additional research, and 11 as low priority for biomonitoring. Discussion: The 108 deferred chemicals included those lacking biomonitoring methods or toxicity data, representing an opportunity for future research. Our evaluation was, in general, limited by the large number of unmeasured or untested chemicals. https://doi.org/10.1289/EHP5133

Background: The National Institutes of Health’s Environmental influences on Child Health Outcomes (ECHO) initiative aims to understand the impact of environmental factors on childhood disease. More...

Background Variability of short-lived urinary pesticide metabolites during pregnancy raises challenges for exposure assessment. Objectives For urinary metabolite concentrations 3-phenoxybenzoic acid (3-PBA) and 3,5,6-trichloro-2-pyridinol (TCPy), we assessed: (1) temporal variability; (2) variation of two urine specimens within a trimester; (3) reliability for pesticide concentrations from a single urine specimen to classify participants into exposure tertiles; and (4) seasonal or year variations. Methods Pregnant mothers (N = 166) in the MARBLES (Markers of Autism Risk in Babies-Learning Early Signs) Study provided urine specimens (n = 528). First morning void (FMV), pooled, and 24-h specimens were analyzed for 3-PBA and TCPy. For 9 mothers (n = 88 specimens), each urine specimen was analyzed separately (not pooled) to estimate within- and between-person variance components expressed as intraclass correlation coefficients (ICC). Pesticide concentrations from two specimens within a trimester were also assessed using ICC's. Agreement for exposure classifications was assessed with weighted Cohen's kappa statistics. Longitudinal mixed effect models were used to assess seasonal or year variations. Results Urinary pesticide metabolites were detected in ≥ 93% of specimens analyzed. The highest ICC from repeated individual specimens was from specific gravity-corrected FMV specimens for 3-PBA (ICC=0.13). Despite high within-person variability, the median concentrations did not differ across trimesters. Concentrations from pooled specimens had substantial agreement predicting exposure categories for TCPy (K = 0.67, 95% CI (0.59, 0.76)) and moderate agreement for 3-PBA (K = 0.59, 95% CI (0.49, 0.69)). TCPy concentrations significantly decreased from 2007 to 2014. Conclusions Pooled specimens may improve exposure classification and reduce laboratory costs for compounds with short biological half-lives in epidemiological studies.

Chemical exposure in household dust poses potential risks to human health but has been studied incompletely thus far. Most analytical studies have focused on one or several compound classes, with analysis performed by either liquid or gas chromatography coupled with mass spectrometry (LC-MS or GC-MS). However, a comprehensive investigation of individual dust samples is missing. The present study comprehensively characterizes chemicals in dust by applying a combination of target, suspect, and nontarget screening approaches using both LC and GC with quadrupole time-of-flight (Q/TOF) MS. First, the extraction method was optimized to streamline detection of LC-Q/TOF and GC-Q/TOF amenable compounds and was successfully validated with over 100 target compounds. Nontarget screening with GC-Q/TOF was done by spectral deconvolution followed by a library search. Suspect screening by LC-Q/TOF was carried out with an accurate mass spectral library. Finally, LC-Q/TOF nontarget screening was carried out by extracting molecular features, acquiring tandem mass spectrometric (MS/MS) spectra, and performing compound identification by use of in silico fragmentation software tools. In total, 271 chemicals could be detected in 38 dust samples, 163 of which could be unambiguously confirmed by a reference standard. Many of them, such as the plastic leachable 7,9-di- tert-butyl-1-oxaspiro(4,5)deca-6,9-diene-2,8-dione (CAS 82304-66-3) and three organofluorine compounds, are of emerging concern and their presence in dust has been underestimated. Advantages and drawbacks of the different approaches and analytical instruments are critically discussed.

ObjectiveThe California heat illness prevention study (CHIPS) devised methodology and collected physiological data to assess heat related illness (HRI) risk in Latino farmworkers.MethodsBilingual researchers monitored HRI across a workshift, recording core temperature, work rate (metabolic equivalents [METs]), and heart rate at minute intervals. Hydration status was assessed by changes in weight and blood osmolality. Personal data loggers and a weather station measured exposure to heat. Interviewer administered questionnaires were used to collect demographic and occupational information.ResultsCalifornia farmworkers (n = 588) were assessed. Acceptable quality data was obtained from 80% of participants (core temperature) to 100% of participants (weight change). Workers (8.3%) experienced a core body temperature more than or equal to 38.5 °C and 11.8% experienced dehydration (lost more than 1.5% of body weight).ConclusionsMethodology is presented for the first comprehensive physiological assessment of HRI risk in California farmworkers.

We present a screening-level exposure assessment method which integrates exposure from all plausible exposure pathways as a result of indoor residential use of cleaning products. The exposure pathways we considered are (1) exposure to a user during product use via inhalation and dermal, (2) exposure to chemical residues left on clothing, (3) exposure to all occupants from the portion released indoors during use via inhalation and dermal, and (4) exposure to the general population due to down-the-drain disposal via inhalation and ingestion. We use consumer product volatilization models to account for the chemical fractions volatilized to air (fvolatilized) and disposed down the drain (fdown-the-drain) during product use. For each exposure pathway, we use a fate and exposure model to estimate intake rates (iR) in mg/kg/day. Overall, the contribution of the four exposure pathways to the total exposure varies by the type of cleaning activities and with chemical properties. By providing a more comprehensive exposure model and by capturing additional exposures from often-overlooked exposure pathways, our method allows us to compare the relative contribution of various exposure routes and could improve high-throughput exposure assessment for chemicals in cleaning products. This article is protected by copyright. All rights reserved.

Chemical exposure via dust ingestion is of great interest to researchers and regulators because children are exposed to dust through their daily activities, and as a result, to the many chemicals contained within dust. Our goal was to develop a workflow to identify and rank organic chemicals that could be used as tracers to calculate children's dust ingestion rates. We proposed a set of criteria for a chemical to be considered a promising tracer. The best tracers must be (1) ubiquitous in dust, (2) unique to dust, (3) detectable as biomarkers in accessible biological samples, and (4) have available or obtainable ADME information for biomarker-based exposure reconstruction. To identify compounds meeting these four criteria, we developed a workflow that encompasses non-targeted analysis approaches, literature and database searching, and multimedia modeling. We then implemented an ad hoc grading system and ranked candidate chemicals based on fulfillment of our criteria (using one small, publicly available dataset to show proof of concept). Initially, five chemicals (1,3-diphenylguanidine, leucine, piperine, 6:2/8:2 fluorotelomer phosphate diester, 6:2 fluorotelomer phosphate diester) appeared to satisfy many of our criteria. However, a rigorous manual investigation raised many questions about the applicability of these chemicals as tracers. Based on the results of this initial pilot study, no individual compounds can be unequivocally considered suitable tracers for calculating dust ingestion rates. Future work must therefore consider larger datasets, generated from broader measurement studies and literature searches, as well as refinements to selection criteria, to identify robust and defensible tracer compounds.

Background Evidence from experimental and observational studies suggests that prenatal phthalate exposures may be associated with autism spectrum disorder (ASD). We examined whether prenatal phthalate exposures were associated with an increased risk of ASD. Methods We quantified 14 metabolites of eight phthalates in 636 multiple maternal urine samples collected during 2nd and 3rd trimesters of pregnancy from 201 mother-child pairs in MARBLES (Markers of Autism Risk in Babies – Learning Early Signs), a high-risk ASD longitudinal cohort. At 3 years old, children were clinically assessed for ASD and classified into three diagnostic categories: ASD (n = 46), non-typical development (Non-TD, n = 55), and typical development (TD, n = 100). We used multinomial logistic regression to evaluate the association of phthalate metabolite concentrations with ASD and Non-TD. Results Most associations of phthalate biomarkers with both ASD and Non-TD were null, with the exception that monoethyl phthalate (MEP) was significantly associated with an increased risk of Non-TD (per 2.72-fold relative increase in concentration: Relative risk ratio (RRR) = 1.38; 95% confidence interval (CI): 1.01, 1.90). When stratified by prenatal vitamin use during the first month of pregnancy, among mothers who took vitamins, ASD risk was inversely associated with mono-isobutyl phthalate (MiBP, RRR = 0.44; 95% CI: 0.21, 0.88), mono(3-carboxypropyl) phthalate (MCPP, RRR = 0.41; 95% CI: 0.20, 0.83) and mono-carboxyisooctyl phthalate (MCOP, RRR = 0.49; 95% CI: 0.27, 0.88), but among mothers who did not take prenatal vitamins, Non-TD risk was positively associated with MCPP (RRR = 5.09; 95% CI: 2.05, 12.6), MCOP (RRR = 1.86; 95% CI: 1.01, 3.39), and mono-carboxyisononyl phthalate (MCNP, RRR = 3.67; 95% CI: 1.80, 7.48). When stratified by sex, among boys, MEP, monobenzyl phthalate, MCPP, MCNP, and sum of di(2-ethylhexyl) phthalate metabolites (ΣDEHP) were positively associated with Non-TD risk, but associations with ASD were null. Among girls, associations with both ASD and Non-TD were null. Conclusions Our study showed that phthalate exposures in mid- to late pregnancy were not associated with ASD in children from this high-risk ASD cohort. Further studies should be conducted in the general population without high-risk genes to confirm our findings. Electronic supplementary material The online version of this article (10.1186/s12940-018-0428-4) contains supplementary material, which is available to authorized users.

There have been many studies to reduce ozone formation mostly from volatile organic compound (VOC) sources. However, the role of low vapor pressure (LVP)-VOCs from consumer products remains mostly unexplored and unaddressed. This study explores the impact of high production volume LVP-VOCs on ozone formation from three cleaning products-associated activities (dishwashing, clothes washing, and surface cleaning). We develop a model framework to account for the portion available for ozone formation during the use phase and from the down-the-drain disposal. We apply experimental studies that measured emission rates or models that were developed for estimating emission rates of organic compounds during the use phase. Then, the fraction volatilized (fvolatilized) and the fraction disposed down the drain (fdown-the-drain) are multiplied by the portion available for ozone formation for releases to the outdoor air (fO3|volatilized) and down-the-drain (fO3|down-the-drain), respectively. Overall, for chemicals used in three specific cleaning-product uses, fvolatilized is less than 0.6% for all studied LVP-VOCs. Because greater than 99.4% of compounds are disposed of down the drain during the use phase, when combined with fO3|volatilized and fO3|down-the-drain, the portion available for ozone formation from the direct releases to outdoor air and the down-the-drain disposal is less than 0.4% and 0.2%, respectively. The results from this study indicate that the impact of the studied LVP-VOCs on ozone formation is very sensitive to what occurs during the use phase and suggest the need for future research on experimental work at the point of use.

Exposure to fine particulate matter (PM2.5) is a major contributor to the global human disease burden. The indoor environment is of particular importance when considering the health effects associated with PM2.5 exposures because people spend the majority of their time indoors and PM2.5 exposures per unit mass emitted indoors are two to three orders of magnitude larger than exposures to outdoor emissions. Variability in indoor PM2.5 intake fraction (iFin,total), which is defined as the integrated cumulative intake of PM2.5 per unit of emission, is driven by a combination of building-specific, human-specific, and pollutant-specific factors. Due to a limited availability of data characterizing these factors, however, indoor emissions and intake of PM2.5 are not commonly considered when evaluating the environmental performance of product life cycles. With the aim of addressing this barrier, a literature review was conducted and data characterizing factors influencing iFin,total were compiled. In addition to providing data for the calculation of iFin,total in various indoor environments and for a range geographic regions, this paper discusses remaining limitations to the incorporation of PM2.5-derived health impacts into life cycle assessments and makes recommendations regarding future research.This article is protected by copyright. All rights reserved.

Background/objectivePer- and polyfluoroalkyl substances (PFAS) display neurobehavioral toxicity in laboratory animal studies. We examined associations of modeled prenatal maternal exposure to PFAS with child diagnosis of autism spectrum disorder (ASD).MethodsParticipants were 453 mother-child pairs from CHARGE (CHildhood Autism Risk from Genetics and Environment), a population-based case-control study. Children underwent psychometric testing and were clinically confirmed for ASD (n=239) or typical development (TD, n=214). At the end of the clinic visit, maternal blood specimens were collected. We quantified nine PFAS in maternal serum samples collected when their child was 2-5 years old. As surrogate in utero exposure, we used a model built from external prospective data in pregnancy and 24 months post-partum and then reconstructed maternal PFAS serum concentrations during pregnancy in this case-control sample. We used logistic regression to evaluate associations of modeled prenatal maternal PFAS concentrations with child ASD.ResultsModeled prenatal maternal perfluorohexane sulfonate (PFHxS) and perfluorooctane sulfonate (PFOS) were borderline associated with increased odds of child diagnosis of ASD (per nanogram per milliliter increase: odds ratio [OR]=1.46; 95% confidence interval [CI]: 0.98, 2.18 for PFHxS, OR=1.03; 95% CI: 0.99, 1.08 for PFOS). When compared to the lowest quartile (reference category), the highest quartile of modeled prenatal maternal PFHxS was associated with increased odds of child diagnosis of ASD (OR=1.95; 95% CI: 1.02, 3.72).ConclusionsIn analyses where modeled prenatal maternal PFAS serum concentrations served as in utero exposure, we observed that prenatal PFHxS and PFOS exposure, but not other PFAS, were borderline associated with increased odds of child diagnosis of ASD. Further studies in which PFAS concentrations are prospectively measured in mothers and children at a range of developmental stages are needed to confirm these findings.

BACKGROUND: Until recently, environmental factors in autism spectrum disorder (ASD) were largely ignored. Over the last decade, altered risks from lifestyle, medical, chemical, and other factors have emerged through various study designs: whole population cohorts linked to diagnostic and/or exposure-related databases, large case-control studies, and smaller cohorts of children at elevated risk for ASD. OBJECTIVES: This study aimed to introduce the MARBLES (Markers of Autism Risk in Babies-Learning Early Signs) prospective study and its goals, motivate the enhanced-risk cohort design, describe protocols and main exposures of interest, and present initial descriptive results for the study population. METHODS: Families having one or more previous child with ASD were contacted before or during a pregnancy, and once the woman became pregnant, were invited to enroll. Data and biological samples were collected throughout pregnancy, at birth, and until the child's third birthday. Neurodevelopment was assessed longitudinally. The study began enrolling in 2006 and is ongoing. RESULTS: As of 30 June 2018, 463 pregnant mothers have enrolled. Most mothers ([Formula: see text]) were thirty years of age or over, including 7.9% who are fourty years of age or over. The sample includes 22% Hispanic and another 25% nonHispanic Black, Asian, or multiracial participants; 24% were born outside the United States. Retention is high: 84% of participants whose pregnancies did not end in miscarriage completed the study or are still currently active. Among children evaluated at 36 months of age, 24% met criteria for ASD, and another 25% were assessed as nonASD nontypical development. CONCLUSION: Few environmental studies of ASD prospectively obtain early-life exposure measurements. The MARBLES study fills this gap with extensive data and specimen collection beginning in pregnancy and has achieved excellent retention in an ethnically diverse study population. The 24% familial recurrence risk is consistent with recent reported risks observed in large samples of siblings of children diagnosed with ASD. https://doi.org/10.1289/EHP535.

In a Policy Forum, Irva Hertz-Picciotto and colleagues review the scientific evidence linking organophosphate pesticides to cognitive, behavioral, and neurological deficits in children and recommend actions to reduce exposures.

Background The primary aim of this study was to investigate the effects of work rate, hydration status, and clothing on core body temperature (CBT) on California farmworkers. Methods Two hundred and eighty-seven farmworkers were recruited in Summer 2015, with 259 participants having sufficient data for analysis. We collected CBT, ambient temperature, work rate, body weight loss, and clothing worn by each participant throughout the work day and demographic data from a questionnaire. Results Multiple regression with CBT as the outcome was used to determine the adjusted associations between CBT, environmental heat load, and worker characteristics. The multivariate regression model showed statistically significant associations of CBT with work rate (β = .006, 95% CI [0.004, 0.009]) and wet-bulb globe temperature (β = .03, 95% CI [0.017, 0.05]). Conclusion Results suggest that among our population workload is the primary modifiable risk factor for heat-related illness. As expected, the ambient temperature was also associated with higher risk.