Longitudinal trajectories and determinants of plasma per- and polyfluoroalkyl substance (PFAS) levels from birth to early childhood and metabolomic associations: A pilot study in the Boston Birth Cohort.

Background: Per- and polyfluoroalkyl substances (PFAS) are a major public health concern worldwide due to their ubiquitous exposures, environmental persistence, maternal-to-fetal transfer, and multi-organ toxicity. This pilot study aimed to generate preliminary data to inform future studies to address data gaps in the field, including early life PFAS exposure levels, longitudinal changes, determinants, and associated metabolomic alterations in understudied Black and Hispanic children in the United States (U.S.). Methods: This study leveraged existing biosamples and data in the Boston Birth Cohort and measured 12 legacy and emerging PFAS, including Me-PFOSA-AcOH, PFDA, PFDoA, PFHxS, PFNA, PFOA, PFOS, PFUnA, GenX, ADONA, 9Cl-PF3ONS, and PFHpS, in paired cord and early childhood plasma samples. Summary statistics and graphic plots were used to depict PFAS levels at the two time points and their longitudinal changes. Linear regression models were used to identify the early-life factors associated with cord and early childhood PFAS levels. Associations of cord PFAS with cord metabolites were explored using a metabolome-wide association approach and a targeted approach. Results: This study included 39 children, of whom 25 (64%) were Black, 14 (36%) were Hispanic, and 15 (38%) were female. PFOA, PFOS, PFNA, and PFHpS were detectable in all cord and early childhood plasma samples, while GenX and ADONA were not detectable in any sample. Cord PFAS levels were weakly-to-moderately correlated with early childhood PFAS levels (r = -0.03 to 0.40). Several maternal and child factors, including gestational age, year at blood collection, and race/ethnicity, were associated with cord and early childhood PFAS levels. The metabolome-wide association study and the targeted study identified several cord metabolites that may have been affected by in utero PFAS exposure. Conclusions: This pilot study found ubiquitous exposure to multiple PFAS in cord plasma (reflects in utero exposure) and in early childhood plasma (reflects both prenatal and postnatal exposure) among U.S. Black and Hispanic children. Metabolomic analysis suggests that in utero PFAS exposures may alter fetal metabolism. Future large-scale studies are needed to replicate the findings and further examine the associations of fetal PFAS exposure with long-term health outcomes and underlying metabolic pathways.

Maternal prenatal selenium levels and child risk of neurodevelopmental disorders: A prospective birth cohort study.

Selenium (Se) is an essential trace element involved in various biological processes, including neurodevelopment. Available literature indicates that both Se deficiency and excess may be detrimental to health. It is also known that Se can cross the placenta from maternal to fetal circulation. To date, the role of maternal Se status in child long-term neurodevelopment is largely unexplored. This study investigated the temporal and dose-response associations between maternal Se status and child risk of neurodevelopmental disorders including autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD). It consisted of 1550 mother-infant dyads from the Boston Birth Cohort. Maternal red blood cell (RBC) Se levels were measured in samples collected within 72 h of delivery (biomarker of third trimester Se status). Pediatric neurodevelopmental diagnoses were obtained from electronic medical records. Data analyses showed that maternal RBC Se levels were positively associated with child risk of developing ASD, with an adjusted odds ratio of 1.49 for ASD (95% CI: 1.09, 2.02) per IQR increase in Se. There was also a positive association between maternal Se and ADHD (OR: 1.29; 95% CI: 1.04, 1.56, per IQR increase in Se). These associations remained robust even after adjusting for pertinent covariables; and there was no significant interaction between Se and these covariables. Our findings suggest that prenatal exposure to high maternal Se levels may adversely affect child neurodevelopment. Our findings warrant further investigation; if confirmed, optimizing maternal prenatal Se levels may be necessary to maximize its health benefits while preventing undue risk. LAY SUMMARY: Selenium (Se) is an essential nutrient for the health of the pregnant mother and her baby. While Se can readily cross the placenta from maternal to fetal circulation, little is known about maternal Se status on her child's neurodevelopmental outcomes. We studied over 1500 mother-child dyads from birth to school age of the child. We found that babies born from mothers with high blood Se levels may be at increased risk of developing autism spectrum disorder or attention deficit hyperactivity disorder. Given this is the first study of the kind, more study is needed to confirm our findings.

Biomonitoring: A tool to assess PFNA body burdens and evaluate the effectiveness of drinking water intervention for communities in New Jersey.

Elevated perfluorononanoic acid (PFNA) levels, one of many manmade per- and polyfluoroalkyl substances (PFAS), were detected in public water systems/private wells in New Jersey communities. Interventions to end exposure through drinking water were carried out from 2014 to 2016. To evaluate the effectiveness of interventions, a community biomonitoring study was conducted for the communities between 2017 and 2020. A convenience sampling design was used with 120 participants in Year 1 between ages of 20-74 who consumed PFNA-contaminated water. Three blood samples, one year apart, were drawn from each participant and completed for 99 participants. Separated serum samples were measured for 12 PFAS including PFNA. Questionnaires were administered to collect information on demographics and potential sources. Drinking water and house dust collected at the first visit were analyzed for 14 PFAS including PFNA. The PFNA sera levels (Year 1) found 84 out of 120 (70%) participants were higher than the 95th percentile of a nationally representative sample of US adults (NHANES2015-16). Current drinking water and house dust were not significant contributing sources for the study participants. On average, PFNA sera levels were 12 ± 16% (Year 2) and 27 ± 16% (Year 3) lower than the level measured in Year 1 (p < 0.01). The PFNA half-life was estimated around 3.52 years, using a mixed model from 68 high-exposed participants (>95th percentile of NHANES2015-16) with controlling for physiological covariates. The decline in adult serum PFNA levels seen in the years following a community drinking water intervention suggests the intervention effectively reduced PFNA exposure via drinking water.

Concentration of polychlorinated biphenyls in serum from New Jersey biomonitoring study: 2016-2018.

The first statewide New Jersey Biomonitoring (NJBM) of serum polychlorinated biphenyls (PCBs) was conducted from 2016 to 2018. Forty ortho-substituted PCBs were measured in serum samples collected from 920 NJ residents in compliance with the CDC method. The lipid adjusted geometric mean (GM) of ∑40PCB concentration for all the 920 measured subjects was 65.5 ng/g lipid (95% CIs: 56.9-75.4 ng/g lipid). Age stratified serum concentration showed that the lowest GM (33.3 ng/g lipid) was observed in the 20-39 years age group (n = 282), followed by a concentration of 76.05 ng/g lipid (n = 382) in the 40-59 years age group, and the highest GM (168.4 ng/g lipid) was found in the 60-74 years age group (n = 256). A survey regression model revealed that ∑40PCBs was significantly associated with age, moderately associated with geographic region, and not significantly associated with sex. The comparison of serum PCB levels in NJBM with the sequential National Health and Nutrition Examination Survey (NHANES) data suggested that the serum PCBs in NJ adults declined 52-59% at all age groups over the last decade. Positive Matrix Factorization (PMF) suggests that ongoing and recent exposure to lower molecular weight PCBs contributes about 15% to total serum PCB levels and more in younger subjects, while higher molecular weight PCBs contribute 52% of the total serum PCB levels and more in older subjects.

Biomonitoring of emerging contaminants, perfluoroalkyl and polyfluoroalkyl substances (PFAS), in New Jersey adults in 2016-2018.

New Jersey (NJ) residents in some areas may be exposed to perfluoroalkyl and polyfluoroalkyl substances (PFAS) due to PFAS contamination of public drinking water. This contamination stems from industrial discharges and the use of aqueous film-foaming foams at military bases and commercial airports for drills and locations where fires occurred. Exposure to PFAS has raised significant public health concerns due to its persistence both in the environment and human body. The potential toxicity of these chemicals may pose risks to human health. Statewide biomonitoring data is needed to establish a baseline of exposure and to identify the subpopulations at risk. The NJ Department of Health (NJDOH) conducted a statewide NJ Biomonitoring (NJBM) study for PFAS utilizing a cost-effective sampling approach, i.e. acquiring remnant sera from both clinical laboratories and blood banks across NJ. This convenience sampling approach was adopted as an alternative to a costly and labor-intensive probability-based population sampling. One thousand and thirty human sera were collected from NJ adults between 20 and 74 years of age from 2016 to 2018, with additional information of county, sex, and age. The serum collection was demographically and geographically dispersed across four seasons. Twelve PFAS analytes were measured for the specimens collected. The data were post-stratified by county, sex, and age groups (20-39, 40-59, and 60-74 years old). Stratified individual sample weights were developed and used to estimate population means, compare least-squared mean differences, and examine contributing variables. Geometric means (GMs) and percentiles with 95% confidence intervals (CIs) of the target analytes are presented, providing preliminary baselines of the statewide PFAS exposure for NJ adults. PFOA, PFNA, PFHxS, and PFOS were selected for in-depth analyses because their GMs were greater than 0.5 ng/mL and they were detected over 99% in study population. Subjects from this study had higher serum levels of PFOA, PFNA, and PFHxS compared to the general U.S. population reported by the latest National Health and Nutrition Examination Survey (NHANES in 2015-2016). However, the distributions of PFOA, PFNA, PFHxS, and PFOS across sex and age groups were consistent with the patterns found in NHANES, i.e. all differed by sex and age group. Further sex and age stratification showed significantly lower concentrations of the 4 analytes in younger females (20-59 years old) than in older females (60-74 years old) and males (20-74 years old). Future research is needed to identify PFAS exposure sources and to develop effective intervention strategies. Continuing PFAS biomonitoring using population sampling is recommended for tracking trends and better identifying subpopulations at risk.

Qualitative and quantitative measurement of cannabinoids in cannabis using modified HPLC/DAD method.

This study presents an accurate and high throughput method for the quantitative determination of various cannabinoids in cannabis plant material using high pressure liquid chromatography (HPLC) with a diode array detector (DAD). Sample extraction and chromatographic analysis conditions for the measurement of cannabinoids in the complex cannabis plant material matrix were optimized. The Agilent Poroshell 120 SB-C18 column provided high resolution for all target analytes with a short run time (10minutes) given the core shell technology. The aqueous buffer mobile phase was optimized with ammonium acetate at pH 4.75. The change in the mobile phase and the new column ensured a separation between cannabidiol (CBD and cannabigerol (CBG) along with cannabigerol and tetrahydrocannabinolic acid (THCA), which were not well separated by previous publications, improved buffering capacity, and provided analytical performance stability. Moreover, baseline drifting was significantly minimized by the use of a low concentration buffer solution (25mM ammonium acetate). In addition, evaporation and reconstitution of the sample residue with a methanol-organic pure (OP) water solution (65:35) significantly reduced the matrix interference. The modified extraction produced good recoveries (>91%) for each of the eight cannabinoids. The optimized method was validated for specificity, linearity, sensitivity, precision, accuracy, and stability. The combined relative standard deviation (%RSD) for intra-day and inter-day precision for all eight analytes varied from 2.5% to 5.2% and 0.28% to 5.5%, respectively. The %RSD for the repeatability study varied from 1.1% to 5.5%. The recoveries from spiked cannabis matrix samples were greater than 90% for all analytes, except delta-8-tetrahydrocannabinol (Δ8-THC), which was 80%. The recoveries varied from 81% to 107% with a precision of 0.7-8.1%RSD. Delta-9-tetrahydrocannabinol (Δ9-THC) in all of the cannabis samples (n=635) was less than 10%, which is in compliance with the NJ Medicinal Marijuana regulation. Analysis of samples from two cultivars, which included ten individual samples, four composite samples, seven calibration standards, and four quality control standards, can be performed within 24hours by this high throughput method.

A sensitive and accurate method for the determination of perfluoroalkyl and polyfluoroalkyl substances in human serum using a high performance liquid chromatography-online solid phase extraction-tandem mass spectrometry.

A selective, sensitive, and accurate analytical method for the measurement of perfluoroalkyl and polyfluoroalkyl substances (PFASs) in human serum, utilizing LC-MS/MS (liquid chromatography-tandem mass spectrometry), was developed and validated according to the Centers for Disease Control and Prevention (CDC) guidelines for biological sample analysis. Tests were conducted to determine the optimal analytical column, mobile phase composition and pH, gradient program, and cleaning procedure. The final analytical column selected for analysis was an extra densely bonded silica-packed reverse-phase column (Agilent XDB-C8, 3.0×100mm, 3.5µm). Mobile phase A was an aqueous buffer solution containing 10mM ammonium acetate (pH=4.3). Mobile phase B was a mixture of methanol and acetonitrile (1:1, v/v). The gradient program was programmed by initiating a fast elution (%B, from 40 to 65%) between 1.0 and 1.5min, followed by a slow elution (%B: 65-80%) in the period of 1.5-7.5min. The cleanup procedures were augmented by cleaning with (1) various solvents (isopropyl alcohol, methanol, acetonitrile, and reverse osmosis-purified water); (2) extensive washing steps for the autosampler and solid phase extraction (SPE) cartridge; and (3) a post-analysis cleaning step for the whole system. Under the above conditions, the resolution and sensitivity were significantly improved. Twelve target PFASs were baseline-separated (2.5-7.0min) within a 10-min of acquisition time. The limits of detection (LODs) were 0.01ng/mL or lower for all of the target compounds, making this method 5 times more sensitive than previously published methods. The newly developed method was validated in the linear range of 0.01-50ng/mL, and the accuracy (recovery between 80 and 120%) and precision (RSD<20%) were acceptable at three spiked levels (0.25, 2.5, and 25ng/mL). The method development and validation results demonstrated that this method was precise, accurate, and robust, with high-throughput (∼10min per sample); thus suitable for large-scale epidemiological studies.

Measurement of Soluble and Total Hexavalent Chromium in the Ambient Airborne Particles in New Jersey.

Hexavalent chromium (Cr(VI)) in ambient airborne particulate matter (PM) is a known pulmonary carcinogen and may have both soluble and insoluble forms. The sum of the two forms is defined as total Cr(VI). Currently, there were no methods suitable for large-scale monitoring of total Cr(VI) in ambient PM. This study developed a method to measure total Cr(VI) in ambient PM. This method includes PM collection using a Teflon filter, microwave extraction with 3% Na2CO3-2% NaOH at 95°C for 60 minutes, and Cr(VI) analysis by 1,5-diphenylcarbazide colorimetry at 540 nm. The recoveries of total Cr(VI) were 119.5 ± 10.4% and 106.3 ± 16.7% for the Cr(VI)-certified reference materials, SQC 012 and SRM 2700, respectively. Total Cr(VI) in the reference urban PM (NIST 1648a) was 26.0 ± 3.1 mg/kg (%CV = 11.9%) determined by this method. The method detection limit was 0.33 ng/m3. This method and the one previously developed to measure ambient Cr(VI), which is soluble in pH ~9.0 aqueous solution, were applied to measure Cr(VI) in ambient PM10 collected from three urban areas and one suburban area in New Jersey. The total Cr(VI) concentrations were 1.05-1.41 ng/m3 in the winter and 0.99-1.56 ng/m3 in the summer. The soluble Cr(VI) concentrations were 0.03-0.19 ng/m3 in the winter and 0.12-0.37 ng/m3 in the summer. The summer mean ratios of soluble to total Cr(VI) were 14.3-43.7%, significantly higher than 4.2-14.4% in the winter. The winter concentrations of soluble and total Cr(VI) in the suburban area were significantly lower than in the three urban areas. The results suggested that formation of Cr(VI) via atmospheric chemistry may contribute to the higher soluble Cr(VI) concentrations in the summer.

Interconversion of chromium species during air sampling: effects of O3, NO2, SO2, particle matrices, temperature, and humidity.

The interconversion between Cr(VI), a pulmonary carcinogen, and Cr(III), an essential human nutrient, poses challenges to the measurement of Cr(VI) in airborne particles. Chamber and field tests were conducted to identify the factors affecting Cr(VI)-Cr(III) interconversion in the basic filter medium under typical sampling conditions. In the chamber tests, isotopically enriched (53)Cr(VI) and (50)Cr(III) were spiked on diesel particulate matter (DPM) and secondary organic aerosol (SOA) that were precollected on a basic MCE filter. The filter samples were then exposed to clean air or the air containing SO2 (50 and 160 ppb), 100 ppb O3, or 150 ppb NO2 for 24 h at 16.7 LPM flow rate at designated temperature (20 and 31 °C) and RH (40% and 70%) conditions. Exposure to 160 ppb SO2 had the greatest effect on (53)Cr(VI) reduction, with (53)Cr(VI) recovery of 31.7 ± 15.8% (DPM) and 42.0 ± 7.9% (SOA). DPM and SOA matrix induced (53)Cr(VI) reduction when exposed to clean air while reactive oxygen species in SOA could promote (50)Cr(III) oxidation. Deliquescence when RH increased from 40% to 70% led to conversion of Cr(III) in SOA, whereas oxidized organics in DPM and SOA enhanced hygroscopicity and thus facilitated Cr(VI) reduction. Field tests showed seasonal variation of Cr(VI)-Cr(III) interconversion during sampling. Correction of the interconversion using USEPA method 6800 is recommended to improve accuracy of ambient Cr(VI) measurements.

Exposures to volatile organic compounds (VOCs) and associated health risks of socio-economically disadvantaged population in a "hot spot" in Camden, New Jersey.

To address disparities in health risks associated with ambient air pollution for racial/ethnic minority groups, this study characterized personal and ambient concentrations of volatile organic compounds (VOCs) in a suspected hot spot of air pollution - the Village of Waterfront South (WFS), and an urban reference community - the Copewood/Davis Streets (CDS) neighborhood in Camden, New Jersey. Both are minority-dominant, impoverished communities. We collected 24-h integrated personal air samples from 54 WFS residents and 53 CDS residents, with one sample on a weekday and one on a weekend day during the summer and winter seasons of 2004-2006. Ambient air samples from the center of each community were also collected simultaneously during personal air sampling. Toluene, ethylbenzene, and xylenes (TEX) presented higher (p < 0.05) ambient levels in WFS than in CDS, particularly during weekdays. A stronger association between personal and ambient concentrations of MTBE and TEX was found in WFS than in CDS. Fourteen to forty-two percent of the variation in personal MTBE, hexane, benzene, and TEX was explained by local outdoor air pollution. These observations indicated that local sources impacted the community air pollution and personal exposure in WFS. The estimated cancer risks resulting from two locally emitted VOCs, benzene and ethylbenzene, and non-cancer neurological and respiratory effects resulting from hexane, benzene, toluene, and xylenes exceeded the US EPA risk benchmarks in both communities. These findings emphasized the need to address disparity in health risks associated with ambient air pollution for the socio-economically disadvantaged groups. This study also demonstrated that air pollution hot spots similar to WFS can provide robust setting to investigate health effects of ambient air pollution.

Ambient concentrations and personal exposure to polycyclic aromatic hydrocarbons (PAH) in an urban community with mixed sources of air pollution.

Assessment of the health risks resulting from exposure to ambient polycyclic aromatic hydrocarbons (PAH) is limited by a lack of environmental exposure data among the general population. This study characterized personal exposure and ambient concentrations of PAH in the Village of Waterfront South (WFS), an urban community with many mixed sources of air toxics in Camden, New Jersey, and CopeWood/Davis Streets (CDS), an urban reference area located ∼1 mile east of WFS. A total of 54 and 53 participants were recruited from non-smoking households in WFS and CDS, respectively. In all, 24-h personal and ambient air samples were collected simultaneously in both areas on weekdays and weekends during summer and winter. The ambient PAH concentrations in WFS were either significantly higher than or comparable to those in CDS, indicating the significant impact of local sources on PAH pollution in WFS. Analysis of diagnostic ratios and correlation suggested that diesel truck traffic, municipal waste combustion and industrial combustion were the major sources in WFS. In such an area, ambient air pollution contributed significantly to personal PAH exposure, explaining 44-96% of variability in personal concentrations. This study provides valuable data for examining the impact of local ambient PAH pollution on personal exposure and therefore potential health risks associated with environmental PAH pollution.

Time-location patterns of a population living in an air pollution hotspot.

This study characterized the time-location pattern of 107 residents living in air pollution hotspots, the Waterfront South and Copewood/Davis Streets communities in Camden, NJ. Most residents in the two communities are minority and impoverished individuals. Results showed that employment status played the fundamental role in determining time-location patterns of this study population, and the variations of time-location pattern by season and by day-type were partially attributed to employment status. Compared to the National Human Activity Pattern Survey, the Camden cohort spent significantly more time outdoors (3.8 hours versus 1.8 hours) and less time indoors (19.4 hours versus 20.9 hours) than the general US population, indicating a higher risk of exposure to ambient air pollution for the Camden cohort. The findings of the study are important for understanding exposure routes and sources for the socioeconomically disadvantaged subgroup and ultimately help develop effective strategies to reduce community exposure to ambient air pollution in "hotspots".

Acute exposure to elevated PM2.5 generated by traffic and cardiopulmonary health effects in healthy older adults.

There are evidences for exposure to vehicular emissions and adverse cardiopulmonary health effects. This study attempted to further explore these effects on elderly. This study monitored personal PM(2.5) concentrations and ambulatory electrocardiograms continuously for 24 h on 1 working day in 3 separate weeks for 11 school crossing guards. Spirometry was also performed before and after the morning shift. The traffic at each work location was video recorded during one of the three morning shifts. The increases in the average personal PM(2.5) concentrations (baseline PM(2.5) was subtracted) of 1.2-87 and 1.1-98 microg/m(3) were observed during the 1-h morning (DeltaPM(2.5-ave-m)) and afternoon shift (DeltaPM(2.5-ave-a)), respectively. Traffic count was not a significant predictor of the DeltaPM(2.5-ave-m) (P=0.78). Mean heart rate variability (HRV), measured as 5-min standard deviation of normal-to-normal (SDNN) beats during the 10-min rest periods, decreased 18-26% (P<0.02) 15 min, 2 and 4 h after the morning shift, but changes in SDNN (DeltaSDNN) were insignificant post-afternoon exposure (-0.3 to -7% with P>0.53). DeltaSDNN were negatively associated with DeltaPM(2.5-ave-m), with the strongest association at 2 h after the morning shift (P<0.01) but insignificant 4 h after the morning exposure. The peak PM(2.5) concentration (DeltaPM(2.5-peak), baseline PM(2.5) was subtracted) was not a significant predictor for DeltaSDNN, and no clear effect of PM(2.5) exposure on heart rate was observed. There was no effect of PM exposure on lung function (P>0.16), either. In conclusion, acute exposure to the PM(2.5) resulting from mobile sources can cause acute decline in HRV in healthy older adults, suggesting one of the biological mechanisms for the adverse cardiovascular health effects associated with traffic-related air pollution. Traffic count may not be an appropriate surrogate measure of acute personal exposure to vehicular emission in traffic congested areas.

Spatial variation of volatile organic compounds in a "Hot Spot" for air pollution.

The spatial variations of volatile organic compounds (VOCs) were characterized in the Village of Waterfront South neighborhood (WFS), a "hot spot" for air toxics in Camden, NJ. This was accomplished by conducting "spatial saturation sampling" for 11 VOCs using 3500 OVM passive samplers at 22 sites in WFS and 16 sites in Copewood/Davis Streets (CDS) neighborhood, an urban reference area located ∼1000 m east of the WFS. Sampling durations were 24 and 48 h. For all 3 sampling campaigns (2 in summer and 1 in winter), the spatial variations and median concentrations of toluene, ethylbenzene, and xylenes (TEX) were found significantly higher (p < 0.05) in WFS than in CDS, where the spatial distributions of these compounds were relatively uniform. The highest concentrations of methyl tert-butyl ether (MTBE) (maximum of 159 µg m(-3)) were always found at one site close to a car scrapping facility in WFS during each sampling campaign. The spatial variation of benzene in WFS was found to be marginally higher (p = 0.057) than in CDS during one sampling campaign, but similar in the other two sampling periods. The results obtained from the analyses of correlation among all species and the proximity of sampling site to source indicated that local stationary sources in WFS have significant impact on MTBE and BTEX air pollution in WFS, and both mobile sources and some of the stationary sources in WFS contributed to the ambient levels of these species measured in CDS. The homogenous spatial distributions (%RSD < 24%) and low concentrations of chloroform (0.02-0.23 µg m(-3)) and carbon tetrachloride (0.45-0.51 µg m(-3)) indicated no significant local sources in the study areas. Further, results showed that the sampling at the fixed monitoring site may under- or over-estimate air pollutant levels in a "hot spot" area, suggesting that the "spatial saturation sampling" is necessary for conducting accurate assessment of air pollution and personal exposure in a community with a high density of sources.