Faculty Bibliography

Volatile organic compounds (VOCs) are ubiquitous environmental pollutants, exposure to which is associated with birth defects, neurocognitive and reproductive impairments, and cancer. Little is known, however, about VOC exposure in pet dogs and cats, which represent sentinels for human exposure as well as having value as companion animals. In this study, we determined 38 VOC metabolites (VOCMs) in urine samples collected from 47 dogs and 42 cats from the Albany area of New York State. Seventeen (in cats) to twenty (in dogs) VOCMs were found at detection frequencies (DFs) above 60%. The creatinine-adjusted geometric mean (GM) concentrations of individual VOCMs ranged from 5.43 (EMA) to 761 μg/g (3HPMA) in dog urine and 0.824 (SBMA) to 278 μg/g (ATCA) in cat urine. The ∑20 VOCM concentration in dog urine was 2280 μg/g (geometric mean) and the ∑17 VOCM concentration in cat urine was 847 μg/g. Eight individual VOCMs were significantly more abundant in dog than in cat urine, and the urinary concentrations of several VOCMs in dogs were comparable to those reported for human tobacco smokers. Metabolites of acrolein accounted for 43% of ∑20 VOCM concentration in dogs, whereas those of cyanide and benzene accounted for 60% of ∑17 VOCM concentration in cats. Based on acrylamide exposure doses, calculated hazard quotients were above 1 in 77% of dogs and 50% of cats studied, and cancer risk values (using a benchmark of 10^-6) from exposure to acrylamide exceeded 1 for all dogs and cats. This is the first study to report VOCM concentrations in urine collected from pet dogs and cats and highlights the need to identify sources and health implications of VOCs exposure in these animals.

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/OBJECTIVE: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/CONCLUSIONS: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.

Legacy [e.g., brominated- (BFRs)] and alternative [e.g., organophosphate- (OPFRs) and nitrogenous- (NFRs)] flame retardants have a propensity to migrate out of consumer products, and thus are dispersed in indoor microenvironments. In this study, simultaneous presence of 11 BFRs, 18 OPFRs and 11 NFRs were measured in house dust collected from Tianjin, China. OPFRs were found at the highest concentrations, with a median value of 3200 ng/g, followed by NFRs (2600) and BFRs (1600). Tris(2-butoxyethyl) phosphate (median: 1800 ng/g), melamine (1100), and BDE-209 (870) were the top three most abundant chemicals in the respective groups. Location-specific patterns of flame retardant concentrations were found with 30%, 20% and 10% of samples were predominated by OPFRs, NFRs and BFRs, respectively, and the remaining samples contained by two or more of the chemical groups occurring concurrently. Network and cluster analysis results indicated the existence of multiple sources of flame retardants in the indoor microenvironment. Estimated human daily intakes via indoor dust ingestion were approximately several tens of ng/kg bw/day and were below their respective reference dose values. Our results indicate widespread occurrence of multiple flame retardant families in indoor dust and suggest need for continued monitoring and efforts to reduce exposures through dust ingestion.

BACKGROUND:African Americans (AAs) experience high rates of adverse pregnancy outcomes relative to Whites. Differential in utero exposure to environmental chemicals and psychosocial stressors may explain some of the observed health disparities, as exposures to per- and polyfluoroalkyl substances (PFAS) and experiences of discrimination have been linked to adverse birth outcomes. Few studies have examined chemicals and non-chemical stressors together as an exposure mixture, which may better reflect real-life exposure patterns. Here, we adapted methods designed for the analysis of exposure mixtures to examine joint effects of PFAS and psychosocial stress on birth outcomes among AAs. METHODS:348 participants from the Atlanta African American Maternal-Child cohort were included in this study. Four PFAS were measured in first trimester serum samples. Self-report questionnaires were administered during the first trimester and were used to assess psychosocial stress (perceived stress, depression, anxiety, gendered racial stress). Quantile g-computation and Bayesian kernel machine regression (BKMR) were used to estimate the joint effects between PFAS and psychosocial stressors on gestational age at delivery and birthweight for gestational age z-scores. All models were adjusted for maternal education, maternal age, parity, and any alcohol, tobacco and marijuana use. RESULTS:Our analytic sample included a socioeconomically diverse group of pregnant women, with 79 % receiving public health insurance. In quantile g-computation models, a simultaneous one-quartile increase in all PFAS, perceived stress, depression, anxiety, and gendered racial stress was associated with a reduction in birthweight z-scores (mean %change per quartile increase = -0.24, 95 % confidence interval = -0.43, -0.06). BKMR similarly showed that increasing all exposures in the mixture was associated with a modest decrease in birthweight z-scores, but not a reduced length of gestation. DISCUSSION/CONCLUSIONS:Using methods designed for analyzing exposure mixtures, we found that a simultaneous increase in in utero PFAS and psychosocial stressors was associated with reduced birthweight for gestational age z-scores.

Importance/UNASSIGNED:Greater caffeine consumption in pregnancy is associated with reduced birth size, but potential associations with childhood growth are unclear. Objective/UNASSIGNED:To evaluate the associations of pregnancy caffeine and paraxanthine measures with child growth in a contemporary cohort with low caffeine consumption and a historical cohort with high caffeine consumption. Design, Setting, and Participants/UNASSIGNED:The Environmental Influences on Child Health Outcomes cohort of the National Institute of Child Health and Human Development Fetal Growth Studies (ECHO-FGS; 10 sites, 2009-2013) was a pregnancy cohort with 1 child measurement between ages 4 and 8 years (follow-up in 2017-2019). The Collaborative Perinatal Project (CPP) was a pregnancy cohort (12 sites, 1959-1965) with child follow-up through 8 years (1960-1974). The current secondary analysis was conducted in 2021 and 2022. Exposures/UNASSIGNED:Concentrations of caffeine and its primary metabolite, paraxanthine, were quantified from plasma (ECHO-FGS) and serum (CPP) collected in the first trimester. Cut points for analyses were defined by quartiles in ECHO-FGS and quintiles in CPP. Main Outcomes and Measures/UNASSIGNED:Child z scores for body mass index, weight, and height were evaluated, as well as fat mass index and percentage and obesity risk measured at 1 time between age 4 and 8 years in ECHO-FGS. In a secondary analysis of the CPP cohort, child z scores and obesity risk longitudinally through age 8 years were evaluated. Results/UNASSIGNED:In ECHO-FGS (median caffeine intake <50 mg/d), 788 children (mean [SD] age, 6.8 [1.0] years; 411 boys [52.2%]) of women in the fourth vs first quartile of plasma caffeine concentrations had lower height z scores (β = -0.21; 95% CI, -0.41 to -0.02), but differences in weight z scores were only observed in the third quartile (β = -0.27; 95% CI, -0.47 to -0.07). In CPP, beginning at age 4 years, 1622 children (805 boys [49.7%]) of women in the highest caffeine quintile group had lower height z scores than their peers from the lowest group, with the gap widening with each successive year of age (β = -0.16 [95% CI, -0.31 to -0.01] at 4 years; β = -0.37 [95% CI, -0.57 to -0.16] at 8 years). There were slight reductions in weight at ages 5 to 8 years for children in the third vs first caffeine quintile (β = -0.16 to -0.22). Results were consistent for paraxanthine concentrations in both cohorts. Conclusions and Relevance/UNASSIGNED:Intrauterine exposure to increasing levels of caffeine and paraxanthine, even in low amounts, was associated with shorter stature in early childhood. The clinical implication of reductions in height and weight is unclear; however, the reductions were apparent even with levels of caffeine consumption below clinically recommended guidelines of less than 200 mg per day.

BACKGROUND/UNASSIGNED:fetal growth trajectories and assessed whether maternal stress modified these associations. METHODS/UNASSIGNED:= 833 scans, GA range 10-42 weeks, mean 2.4 scans/participant). Adjusted linear mixed models with a GA quadratic growth curve were used for each PFAS exposure and growth outcome. PFOS and PFHxS were modeled continuously (100% sample detection), while PFOA, PFNA, and PFDA were modeled categorically (57-70% sample detection). Scores on the Perceived Stress Scale (PSS) measured in pregnancy were dichotomized at the median (<13 vs. ≥ 13) in stratified models. RESULTS/UNASSIGNED:= -0.8, 95% CI -1.6, -1.1). CONCLUSIONS/UNASSIGNED:Prenatal PFOA exposure adversely impacted fetal head biometric parameters in participants experiencing higher stress during pregnancy.

Exposure of pet dogs and cats to pesticides used in and around homes (e.g., lawns and gardens) is a significant health concern. Furthermore, some pesticides are directly used on dogs and cats for flea, lice, and tick control. Despite this, little is known regarding the extent of pesticide exposure in pets. In this study, we determined the concentrations of 30 biomarkers of pesticide exposure in urine collected from dogs and cats in New York State, USA: 6 dialkylphosphate (DAP) metabolites of organophosphates (OPs); 14 neonicotinoids (neonics); 3 specific metabolites of OPs; 5 pyrethroids (PYRs); and 2 phenoxy acids (PAs). The sum median concentrations of these 30 pesticide biomarkers (ΣPesticides) in dog and cat urine were 35.2 and 38.1 ng/mL, respectively. Neonics were the most prevalent in dogs (accounting for 43% of the total concentrations), followed by DAPs (17%), PYRs (16%), OPs (13%), and PAs (∼10%). In cat urine, neonics alone accounted for 83% of the total concentrations. Elevated concentrations of imidacloprid were found in the urine of certain dogs (max: 115 ng/mL) and cats (max: 1090 ng/mL). Some pesticides showed gender- and sampling location- related differences in urinary concentrations. We calculated daily exposure doses of pesticides from the measured urinary concentrations through a reverse dosimetry approach. The estimated daily intakes (DIs) of chlorpyrifos, diazinon, and cypermethrin were above the chronic reference doses (cRfDs) in 22, 76, and 5%, respectively, of dogs. The DIs of chlorpyrifos, parathion, diazinon, and imidacloprid were above the cRfDs in 33, 14, 100, and 29%, respectively, of cats. This study thus provides evidence that pet dogs and cats are exposed to certain pesticides at levels that warrant immediate attention.

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 2-5 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, 5th and 95th 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.

Benzophenone (BP)-type ultraviolet (UV) filters are estrogenic chemicals used extensively in sunscreen products, leading to concerns over human exposure. To assess exposure to BP derivatives in sunscreens, we tested 14 BP UV filters in 50 products representing 44 brands marketed in the United States in 2021, finding BP, 2-hydroxy-4-methoxybenzophenone (BP-3 or oxybenzone), 2,2'-dihydroxy-4-methoxybenzophenone (BP-8), 2-hydroxy-4-methoxy-4'-methylbenzophenone (BP-10), 2,3,4-trihydroxybenzophenone (2,3,4-OH-BP), and 4-methylbenzophenone (4-Me-BP) in ≥70% of the samples. The geometric mean (GM) concentration of the sum of these BPs (∑₁₄BPs) in the 50 products was 6600 ng/g. BP-3 was the predominant BP in oxybenzone-containing products (accounting for >99% of the total concentration), with a concentration 5-6 orders of magnitude higher than that in "oxybenzone-free" products (GM: 35 600 000 vs 113 ng/g). BP was present in >90% of products analyzed, including those labeled "oxybenzone-free" (GM: 2100 ng/g). BP concentrations were ∼100-fold higher in octocrylene-containing vs "octocrylene-free" products (GM: 15900 vs 151 ng/g). Dermal exposure doses of BP-3 from oxybenzone-containing products (GM: 4140 000 ng/kg body weight (BW)/day) and of BP in some (24%) octocrylene-containing products (GM: 12 200 ng/kg BW/day) were above reference values (2 000 000 and 30 000 ng/kg BW/day for BP-3 and BP, respectively). This study provides evidence that BP and BP-3 concentrations in sunscreen products vary widely and may be noteworthy even in products labeled oxybenzone- or octocrylene-free, making dermal exposure a continuing concern.

BACKGROUND:Prenatal exposure to polycyclic aromatic hydrocarbons (PAH) may increase risk of pediatric asthma, but existing human studies are limited. OBJECTIVES/OBJECTIVE:We estimated associations between gestational PAHs and pediatric asthma in a diverse US sample and evaluated effect modification by child sex, maternal asthma, and prenatal vitamin D status. METHODS:We pooled two prospective pregnancy cohorts in the ECHO PATHWAYS Consortium, CANDLE and TIDES, for an analytic sample of N = 1296 mother-child dyads. Mono-hydroxylated PAH metabolites (OH-PAHs) were measured in mid-pregnancy urine. Mothers completed the International Study on Allergies and Asthma in Childhood survey at child age 4-6 years. Poisson regression with robust standard errors was used to estimate relative risk of current wheeze, current asthma, ever asthma, and strict asthma associated with each metabolite, adjusted for potential confounders. We used interaction models to assess effect modification. We explored associations between OH-PAH mixtures and outcomes using logistic weighted quantile sum regression augmented by a permutation test to control Type 1 errors. RESULTS: = 0.004). There was no consistent evidence of modification by vitamin D status or maternal asthma. DISCUSSION/CONCLUSIONS:This analysis, the largest cohort study of gestational PAH exposure and childhood asthma to date, suggests adverse associations for females only. These preliminary findings are consistent with hypothesized endocrine disruption properties of PAHs, which may lead to sexually dimorphic effects.