Faculty Bibliography

BACKGROUND:Epidemiological evidence for gestational polycyclic aromatic hydrocarbon (PAH) exposure and adverse child cognitive outcomes is mixed; little is known about critical windows of exposure. OBJECTIVE:We investigated associations between prenatal PAH exposure and child cognition in a large, multi-site study. METHODS:We included mother-child dyads from two pooled prospective pregnancy cohorts (CANDLE and TIDES, N = 1,223) in the ECHO-PATHWAYS Consortium. Seven urinary mono-hydroxylated PAH metabolites were measured in mid-pregnancy in both cohorts as well as early and late pregnancy in TIDES. Child intelligence quotient (IQ) was assessed between ages 4-6. Associations between individual PAH metabolites and IQ were estimated with multivariable linear regression. Interaction terms were used to examine effect modification by child sex and maternal obesity. We explored associations of PAH metabolite mixtures with IQ using weighted quantile sum regression. In TIDES, we averaged PAH metabolites over three periods of pregnancy and by pregnancy period to investigate associations between PAH metabolites and IQ. RESULTS: = 0.04). In analyses across pregnancy (TIDES-only), inverse associations with IQ were observed for 2-hydroxyphenanthrene averaged across pregnancy (β = -1.28 [95%CI:-2.53,-0.03]) and in early pregnancy (β = -1.14 [95%CI:-2.00,-0.28]). SIGNIFICANCE/CONCLUSIONS:In this multi-cohort analysis, we observed limited evidence of adverse associations of early pregnancy PAHs with child IQ. Analyses in the pooled cohorts were null. However, results also indicated that utilizing more than one exposure measures across pregnancy could improve the ability to detect associations by identifying sensitive windows and improving the reliability of exposure measurement. More research with multiple timepoints of PAH assessment is warranted.

Marginalized populations experience disproportionate rates of preterm birth and early term birth. Exposure to per- and polyfluoroalkyl substances (PFAS) has been reported to reduce length of gestation, but the underlying mechanisms are unknown. In the present study, we characterized the molecular signatures of prenatal PFAS exposure and gestational age at birth outcomes in the newborn dried blood spot metabolome among 267 African American dyads in Atlanta, Georgia between 2016 and 2020. Pregnant people with higher serum perfluorooctanoic acid and perfluorohexane sulfonic acid concentrations had increased odds of an early birth. After false discovery rate correction, the effect of prenatal PFAS exposure on reduced length of gestation was associated with 8 metabolomic pathways and 52 metabolites in newborn dried blood spots, which suggested perturbed tissue neogenesis, neuroendocrine function, and redox homeostasis. These mechanisms explain how prenatal PFAS exposure gives rise to the leading cause of infant death in the United States.

Occurrence of volatile organic compounds (VOCs) such as benzene in personal care products is a topic of public health concern. Sunscreen products are extensively used to protect skin and hair from UV radiation from sun light. Nevertheless, little is known about exposure doses and risks of VOCs present in sunscreens. In this study, we determined the concentrations of and exposure to three VOCs, namely benzene, toluene and styrene, in 50 sunscreen products marketed in the United States. Benzene, toluene and styrene were found in 80 %, 92 % and 58 %, respectively, of the samples analyzed at mean concentrations of 45.8 ng/g (range: 0.007-862), 89.0 ng/g (range: 0.006-470) and 161 ng/g (range: 0.006-1650), respectively. The mean dermal exposure doses (DEDs) to benzene, toluene and styrene of children/teenagers were 68.3, 133 and 441 ng/kg-bw/d, respectively, whereas those of adults were 48.7, 94.6 and 171 ng/kg-bw/d, respectively. The lifetime cancer risk from benzene concentrations present in 22 sunscreen products (44 % of the samples) for children/teenagers and 19 sunscreen products (38 %) for adults, exceeded the acceptable benchmark risk level (1.0 × 10^-6). This is the first study to comprehensively assess the concentrations of and risks to benzene, toluene and styrene present in sunscreen products.

1,3-Diphenylguanidine (DPG), benzothiazole (BTH), benzotriazole (BTR), and their derivatives are high-production-volume chemicals widely used in tires, corrosion inhibitors and plastic products. Vehicular traffic is an important source of these chemicals in the environment. Despite this, little is known about the occurrence of these chemicals in roadside soils. In this study, we determined the concentrations, profiles, and distribution patterns of 3 DPGs, 5 BTHs, and 7 BTRs in 110 soil samples collected from northeastern United States. We found widespread occurrence of 12 out of the 15 analytes measured in roadside soils, at detection frequencies ≥71 % and median concentrations in the range of 0.38-380 ng/g (dry weight). DPGs were the predominant chemicals accounting for 63 % of the sum concentrations of three chemical classes determined, followed by BTHs (28 %) and BTRs (9 %). The concentrations of all analytes (except for 1-, 4-, and 5-OH-BTRs) exhibited significant positive correlations (r: 0.1-0.9, p < 0.01), suggestive of their common sources and/or similar environmental fates. Higher concentrations of DPGs, BTHs and BTRs were found in soils from highways, rubberized playgrounds, and indoor parking lots than those from gardens, parks, and residential areas. Our findings suggest the release of DPGs, BTHs and BTRs from rubber products, especially automobile tires. Further studies are needed to investigate the environmental fate and toxicities of these chemicals to humans and wildlife.

Human exposure to pesticides is a topic of public health concern for decades. Pesticide exposures have been assessed through the analysis of urine or blood matrices, but little is known on the accumulation of these chemicals in cerebrospinal fluid (CSF). CSF plays an important role in maintaining physical and chemical balance of the brain and central nervous system and any perturbation can have adverse effects on health. In this study, we investigated the occurrence of 222 pesticides in CSF from 91 individuals using gas chromatography-tandem mass spectrometry (GC-MS/MS). Measured pesticide concentrations in CSF were compared with those in 100 serum and urine specimens from individuals living in the same urban location. Twenty pesticides were found in CSF, serum and urine, at levels above the limit of detection. Three most frequently detected pesticides in CSF were biphenyl (100%), diphenylamine (75%), and hexachlorobenzene (63%). Median concentrations of biphenyl in CSF, serum and urine were 1.11, 10.6, and 1.10 ng/mL, respectively. Six triazole fungicides were found only in CSF, but not in other matrices. To our knowledge, this is the first study to report pesticide concentrations in CSF in a general urban population.

BACKGROUND:Fibroids (hormonally responsive benign tumors) often undergo volume changes in pregnancy. Because per- and polyfluoroalkyl substances (PFAS) disrupt hormonal signaling, they might affect fibroid growth. We assessed associations between PFAS and fibroid changes in pregnancy. METHODS: RESULTS: DISCUSSION:Certain PFAS were associated with fibroid growth among women with small fibroids and decreases among women with medium fibroids. PFAS were not associated with fibroid prevalence or number; therefore, PFAS may influence prevalent fibroids rather than initiating fibroid development. https://doi.org/10.1289/EHP11606.

1,3-Diphenylguanidine (DPG), 1,3-di-o-tolylguanidine (DTG), and 1,2,3-triphenylguanidine (TPG) are synthetic chemicals widely used in rubber and other polymers. Nevertheless, limited information is available on their occurrence in indoor dust. We measured these chemicals in 332 dust samples collected from 11 countries. DPG, DTG, and TPG were found in 100%, 62%, and 76% of the house dust samples, at median concentrations of 140, 2.3, and 0.9 ng/g, respectively. The sum concentrations of DPG and its analogues varied among the countries in the following decreasing order: Japan (median: 1300 ng/g) > Greece (940) > South Korea (560) > Saudi Arabia (440) > the United States (250) > Kuwait (160) > Romania (140) > Vietnam (120) > Colombia (100) > Pakistan (33) > India (26). DPG accounted for ≥87% of the sum concentrations of the three compounds in all countries. DPG, DTG, and TPG exhibited significant correlations (r: 0.35-0.73; p < 0.001). Elevated concentrations of DPG were found in dust from certain microenvironments (e.g., offices and cars). Human exposure to DPG through dust ingestion were in the ranges 0.07-4.40, 0.09-5.20, 0.03-1.70, 0.02-1.04, and 0.01-0.87 ng/kg body weight (BW)/day for infants, toddlers, children, teenagers, and adults, respectively.

The fate of environmental chemicals in maternal and fetal tissues might be affected by pregnancy-related hemodynamic changes that occur across gestation. Specifically, hemodilution and renal function are hypothesized to confound associations between per- and polyfluoroalkyl substances (PFAS) exposure measures in late pregnancy with gestational length and fetal growth. We sought to analyze two pregnancy-related hemodynamic biomarkers, creatinine and estimated glomerular filtration rate (eGFR), as confounders of the trimester-specific relationships between maternal serum PFAS concentrations and adverse birth outcomes. Participants were enrolled in the Atlanta African American Maternal-Child Cohort between 2014 and 2020. Biospecimens were collected at up to two timepoints, which were categorized into the 1st trimester (N = 278; 11 mean weeks gestation), 2nd trimester (N = 162; 24 mean weeks gestation), and 3rd trimester (N = 110; 29 mean weeks gestation). We quantified six PFAS in serum, creatinine in serum and urine, and eGFR using the Cockroft-Gault equation. Multivariable regression models estimated the associations between single PFAS and their sum with gestational age at delivery (weeks), preterm birth (PTB, <37 gestational weeks), birthweight z-scores, and small for gestational age (SGA). Primary models were adjusted for sociodemographics. We additionally adjusted for serum creatinine, urinary creatinine, or eGFR in the confounding assessments. An interquartile range increase in perfluorooctanoic acid (PFOA) produced a non-significant reduction in birthweight z-score during the 1st and 2nd trimesters (β = -0.01 g [95% CI = -0.14, 0.12] and β = -0.07 g [95% CI = -0.19, 0.06], respectively) whereas the relationship was significant and positive during the 3rd trimester (β = 0.15 g; 95% CI = 0.01, 0.29). Trimester-specific effects were similar for the other PFAS and adverse birth outcomes, which persisted after adjusting for creatinine or eGFR. The relationships between prenatal PFAS exposure and adverse birth outcomes were not strongly confounded by renal function or hemodilution. However, 3rd trimester samples consistently exhibited different effects than those collected during the 1st and 2nd trimesters.

Little is known about exposure of infants to neonicotinoid insecticides (NEOs). In this study, concentrations of six parent NEOs (p-NEOs) and N-desmethyl-acetamiprid (N-dm-ACE) were measured in urine and whole blood samples from infants, in addition to breast milk, infant formula, and tap water collected in South China. The p-NEO with the highest median concentration in urine (0.25 ng/mL) and blood (1.30) samples was dinotefuran (DIN), while imidacloprid (IMI) was abundant in breast milk (median: 0.27 ng/mL), infant formula (0.22), and tap water (0.028). The older infants (181-360 days) might face higher NEO and N-dm-ACE exposure than younger infants (0-180 days). Blood samples contained a significantly (p < 0.01) higher median concentration of ∑₆

BACKGROUND:Bisphenols and phthalates are high production volume chemicals used as additives in a variety of plastic consumer products leading to near ubiquitous human exposure. These chemicals have established endocrine disrupting properties and have been linked to a range of adverse reproductive and developmental outcomes. Here, we investigated exposure in relation to fetal growth. METHODS:Participants included 855 mother-fetal pairs enrolled in the population-based New York University Children's Health and Environment Study (NYU CHES). Bisphenols and phthalates were measured in maternal urine collected repeatedly during pregnancy. Analyses included 15 phthalate metabolites and 2 bisphenols that were detected in 50 % of participants or more. Fetal biometry data were extracted from electronic ultrasonography records and estimated fetal weight (EFW) was predicted for all fetuses at 20, 30, and 36 weeks gestation. We used quantile regression adjusted for covariates to model exposure-outcome relations across percentiles of fetal weight at each gestational timepoint. We examined sex differences using stratified models. RESULTS:Few statistically significant associations were observed across chemicals, gestational time periods, percentiles, and sexes. However, within gestational timepoints, we found that among females, the molar sums of the phthalates DiNP and DnOP were generally associated with decreases in EFW among smaller babies and increases in EFW among larger babies. Among males, the opposite trend was observed. However, confidence intervals were generally wide at the tails of the distribution. CONCLUSION/CONCLUSIONS:In this sample, exposure to bisphenols and phthalates was associated with small sex-specific shifts in fetal growth; however, few associations were observed at the median of fetal weight and confidence intervals in the tails were wide. Findings were strongest for DiNP and DnOP, which are increasingly used as replacements for DEHP, supporting the need for future research on these contaminants.