Faculty Bibliography

The occurrence and profiles of 15 organophosphate flame retardants/plasticizers (OPFRs) (3 chlorinated [Cl-], 2 aryl-, 5 non-Cl alkyl-, and 5 other types of OPFRs) were investigated in indoor air and dust collected from various microenvironments, including homes in the Albany area of New York State, United States. Concurrent indoor air and dust were collected from floors and window sills at homes and fire stations to investigate the partitioning of OPFRs between the vapor and particulate phases of air and dust. The total concentrations of OPFRs in bulk air (vapor plus particulate phases) were found at several tens to hundreds of ng/m³, with mean concentrations that ranged from 0.12 ng/m³ for tripropyl phosphate (TPP) to 43.8 ng/m³ for tris(1-chloro-2-propyl)phosphate (TCIPP). TCIPP, triethyl phosphate (TEP) and tris(2-butoxyethyl)phosphate (TBOEP) were the predominant compounds found in bulk air, vapor phase, and dust. Among the ten types of microenvironments studied, indoor air samples collected from automobile parts shops contained the highest concentrations of OPFRs (mean: 258 ng/m³), followed by electronics shops, nail salons/shops that sell nail polish, and home construction/interior products shops. Estimated daily intakes of OPFRs via inhalation of air, dermal sorption, and ingestion of dust were 149, 279, and 390 ng/kg bw/day, respectively, which suggested that dust ingestion is an important source of human exposure to OPFRs among the indoor exposure pathways studied.

OBJECTIVES:Exposome-wide association studies (EWAS) are a systematic and unbiased way to investigate multiple environmental factors associated with phenotype. We applied EWAS to study semen quality and queried the sample size requirements to detect modest associations in a reproductive cohort. STUDY DESIGN AND SETTING:We conducted 1) a multivariate EWAS of 128 endocrine disrupting chemicals (EDCs) from 15 chemical classes measured in urine/serum relative to 7 semen quality endpoints in a prospective cohort study comprising 473 men and 2) estimated the sample size requirements for EWAS etiologic investigations. RESULTS:None of the EDCs were associated with semen quality endpoints after adjusting for multiple tests. However, several EDCs (e.g., polychlorinated biphenyl congeners 99, 105, 114, and 167) were associated with raw p < 0.05. In a post hoc statistical power analysis with the observed effect sizes, we determined that EWAS research in male fertility will require a mean sample size of 2696 men (1795-3625) to attain a power of 0.8. The average size of four published studies is 201 men. CONCLUSION:Existing cohort studies with hundreds of participants are underpowered (<0.8) for EWAS-related investigations. Merging cohorts to ensure a sufficient sample size can facilitate the use of EWAS methods for assessing EDC mixtures that impact semen quality.

Bisphenol A (BPA), S (BPS), and F (BPF) are among the most abundant bisphenols detected in humans, yet pregnancy toxicokinetics for BPS or BPF remain unknown. Because gestational BPS can disrupt placental function and result in reproductive and metabolic disorders in the progeny, the aim of the study was to investigate BPS and BPF toxicokinetics during pregnancy using an in vivo approach. Fetal catheterizations were conducted in pregnant sheep (n = 6) at mid-pregnancy and injected with either a single dose of BPS (n = 3, 0.5 mg/kg, s.c.), or a combination of BPS, BPF, and BPA (n = 3, 0.5 mg/kg for each chemical, s.c.). Maternal and fetal blood and urine and amniotic fluid were collected over 72 h and analyzed for bisphenols by HPLC-MS/MS. We observed significant differences in half-life, maximum concentration, and total body clearance in maternal circulation among bisphenols. Longer half-lives were observed in fetal vs. maternal circulation for all bisphenols. Fetal toxicokinetics differed among bisphenols with BPS having the longest fetal half-life. All bisphenols reached basal levels at 48 h in maternal plasma, but were still detectable in amniotic fluid, fetal urine, and fetal plasma at 72 h. In this first pregnancy toxicokinetic study of BPS and BPF we have demonstrated maternal and fetal toxicokinetic differences among all three bisphenols. Higher BPS persistence in the fetal compartment warrants studies into progeny adverse outcomes following gestational exposure. Additionally, toxicokinetic differences among bisphenols call for a more careful approach when extrapolating kinetic information from one bisphenol chemical to another.

INTRODUCTION:Iodine is essential for thyroid function, and iodine deficiency during pregnancy is common in Europe and the USA. However, no published studies have examined the role of iodine deficiency in the relation between thyroid function and gestational diabetes mellitus (GDM). MATERIAL AND METHODS:We conducted a population-based, nested case-control study within the Finnish Maternity Cohort using pregnancy and perinatal outcome data from the Finnish Maternal Birth Register. We randomly selected 224 GDM cases with singleton pregnancies and 224 controls without GDM from all singleton births occurring in Finland during 2012-2013. Blood was drawn at 10-14 weeks' gestation and analyzed for serum iodide, thyroglobulin, and thyroid-stimulating hormone (TSH) concentrations. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CI) of GDM. RESULTS:Very high thyroglobulin concentration (>95% percentile; >83 μg/L) was not associated with significantly altered odds of GDM compared to those with normal levels (OR 0.41; 95% CI: 0.12, 1.38). High concentrations of TSH were also not associated with increased odds of GDM compared to normal levels of TSH (OR 0.45; 95% CI: 0.06, 3.18). Women in the lowest 5th percentile (<1.58 ng/mL) of iodine did not have increased odds of GDM compared to those with iodide in the highest quartile (OR 0.39; 95% CI: 0.11, 1.35). CONCLUSIONS:Low levels of iodide and thyroid function in early pregnancy are not associated with increased risk of GDM in this mildly iodine-deficient population.

Concentrations of 11 PFASs were determined in muscle and whole fish for six species collected from Charleston, South Carolina (SC) for the assessment of potential health risks to humans and wildlife. Across all species and capture locations, total PFAS levels in whole fish were significantly higher than fillets by a factor of two- to three-fold. Mean ∑PFAS concentrations varied from 12.7 to 33.0 ng/g wet weight (ww) in whole fish and 6.2-12.7 ng/g ww in fillets. For individual whole fish, ∑PFASs ranged from 12.7 ng/g ww in striped mullet to 85.4 ng/g ww in spotted seatrout, and in fillets individual values ranged from 6.2 ng/g ww in striped mullet to 27.9 ng/g ww in spot. The most abundant compound in each species was perfluorooctane sulfonate (PFOS), comprising 25.5-69.6% of the ∑PFASs. Striped mullet had significantly lower relative amounts of PFOS compared to all other species and higher relative amounts of PFUnDA compared to Atlantic croaker, spotted seatrout, and spot. Unlike whole fish, PFAS levels in fillets varied significantly by location with higher ∑PFOS from the Ashley River than the Cooper River and Charleston Harbor, which reflects the levels of PFASs contamination in these systems. In whole fish, differences in relative concentrations of PFOS, PFNA, and PFDA occurred by capture location, suggestive of different sources. PFOS concentrations for southern flounder and spotted seatrout fillets were within the advisory range to limit fish consumption to 4 meals a month. PFOS levels exceeded screening values to protect mammals in 83% of whole fish examined and represent a potential risk to wildlife predators such as dolphins.

Organophosphate esters (OPEs) are used as flame retardants and plasticizers in a wide range of consumer products. Nevertheless, studies on the occurrence and inventory of OPEs in sewage sludge are limited. In this study, 20 OP triesters and 11 diesters were measured in 75 archived sewage sludge samples collected from 67 wastewater treatment plants (WWTPs) across the United States (US). The median concentrations of ∑₂₀OP-triesters and ∑₁₁OP-diesters in sludge were 1290 and 78.4 ng/g dry weight (dw), respectively. Sludge samples originating from the Western and Northeastern US contained higher concentrations of OP triesters than did those from the Midwestern and Southern US. Sludge samples from WWTPs with larger treatment capacity (>38 million liters per day) contained higher concentrations of OP diesters (p < 0.05). OP diesters in sludge originated from two sources, triester degradation and direct inputs. Land application of sludge to US soils was estimated to result in annual mass inputs of 12,400-14,900 kg/year of OP triesters and 663-796 kg/year of OP diesters. A hazard assessment was performed for 14 OPEs found in sludge, which suggested a low level of risk at the current land application practices of sludge.

Iodine deficiency in pregnancy is a common problem in the United States and parts of Europe, but whether iodine deficiency is associated with increased pregnancy loss has not been well studied. The LIFE study provided an excellent opportunity to examine the relationship between iodine status and pregnancy loss because women were monitored prospectively to ensure excellent ascertainment of conceptions. The LIFE study, a population-based prospective cohort study, monitored 501 women who had discontinued contraception within two months to become pregnant; 329 became pregnant, had urinary iodine concentrations measured on samples collected at enrollment, and were followed up to determine pregnancy outcomes. Of the 329, 196 had live births (59.5%), 92 (28.0%) had losses, and 41 (12.5%) withdrew or were lost to follow up. Urinary iodine concentrations were in the deficiency range in 59.6% of the participants. The risk of loss, however, was not elevated in the mildly deficient group (hazard ratio 0.69, 95% confidence interval 0.34, 1.38), the moderately deficient group (hazard ratio 0.81, 95% confidence interval 0.43, 1.51), or the severely deficient group (hazard ratio 0.69, 95% confidence interval 0.32, 1.50). Iodine deficiency, even when moderate to severe, was not associated with increased rates of pregnancy loss. This study provides some reassurance that iodine deficiency at levels seen in many developed countries does not increase the risk of pregnancy loss.

BACKGROUND:Persistent organic pollutants (POPs) are linked with insulin resistance and type-2 diabetes (T2D) in the general population. However, their associations with gestational diabetes (GDM) are inconsistent. OBJECTIVE:We prospectively evaluated the associations of POPs measured in early pregnancy with GDM risk. We also assessed whether pre-pregnancy BMI (ppBMI) and family history of T2D modify this risk. METHODS:In NICHD Fetal Growth Study, Singletons, we measured plasma concentration of 76 POPs, including 11 organochlorine pesticides (OCPs), 9 polybrominated diphenylethers (PBDEs), 44 polychlorinated biphenyls (PCBs), and 11 per-and polyfluoroalkyl substances (PFAS) among 2334 healthy non-obese women at 8-13 weeks of gestation. GDM was diagnosed by Carpenter and Coustan criteria. We constructed chemical networks using a weighted-correlation algorithm and examined the associations of individual chemical and chemical networks with GDM using multivariate Poisson regression with robust variance. RESULTS:Higher concentrations of PCBs with six or more chlorine atoms were associated with increased risk of GDM in the overall cohort (risk ratios [RRs] range: 1.08-1.13 per 1-standard deviation [SD] increment) and among women with a family history of T2D (RRs range: 1.08-1.48 per 1-SD increment) or normal ppBMI (RRs range: 1.08-1.22 per 1-SD increment). Similar associations were observed for the chemical network comprised of PCBs with ≥6 chlorine atoms and the summary measure of total PCBs and non-dioxin like PCBs (138, 153, 170, 180). Furthermore, four PFAS congeners - perfluorononanoic acid (PFNA), perfluorooctanoic acid (PFOA), perfluoroheptanoic acid (PFHpA), and perfluorododecanoic acid (PFDoDA) - showed significant positive associations with GDM among women with a family history of T2D (RRs range:1.22-3.18 per 1-SD increment), whereas BDE47 and BDE153 showed significant positive associations among women without a family history of T2D. CONCLUSIONS:Environmentally relevant levels of heavily chlorinated PCBs and some PFAS and PBDEs were positively associated with GDM with suggestive effect modifications by family history of T2D and body adiposity status.

Information on the occurrence and bioaccumulation of bisphenols and benzophenones in coastal marine invertebrates is limited. In this study, concentrations of eight bisphenol and five benzophenone analogues were determined in 186 mollusks collected from coastal areas of the Chinese Bohai Sea during the period 2006-2015. Total concentrations of bisphenols and benzophenones were in range of not detected (nd)-58 (geometric mean: 13.0 ng/g) and nd-59.1 (2.06 ng/g) on a dry-weight basis, respectively. BPA and BPF were the major bisphenols, collectively accounting for >90% of the total concentrations. BP-3 was the predominant benzophenone, representing 74% of the total concentrations. The mollusk species, Meretrix meretrix, accumulated high concentrations of both bisphenols and benzophenones. A steady increase in bisphenol concentrations in mollusks was observed in recent years, whereas no obvious temporal trend was found for benzophenones. The estimated daily intakes of bisphenols through consumption of mollusks were lower than the current reference dose. This study establishes a baseline concentration for bisphenols and benzophenones in mollusks in Chinese coastal waters.

The effects of childhood exposure to perfluoroalkyl substances (PFASs) on lung function remain mostly unknown. Previous research indicates that children living or going to school near the World Trade Center (WTC) disaster were exposed to high levels of PFASs, among other toxic chemicals. To explore the effects of PFAS exposure on lung function, we measured serum PFASs in a cohort of children from the WTC Health Registry and a matched control group. Perfluorooctanesulfonate had the highest median concentrations in both groups (WTCHR = 3.72 ng/mL, Comparison = 2.75 ng/mL), while the lowest median concentrations were seen for perfluoroundecanoic acid (WTCHR = 0.12 ng/mL, Comparison = 0.01 ng/mL). Lung function outcomes were measured by spirometry, plethysmography, and oscillometry. Asthma diagnosis and serum eosinophil count were also recorded. We examined the relationships of each PFAS with lung function parameters and eosinophil count using linear regressions. Odds ratios for asthma were obtained for each PFAS using logistic regression. The effect of total PFASs on these outcomes was also assessed. All regression models were adjusted for sex, race/ethnicity, age, body mass index (BMI) and tobacco smoke exposure. We found that serum PFASs were not statistically associated with the measured lung function parameters, asthma diagnosis, or eosinophil count in this cohort (p < 0.05). These findings highlight the need for more longitudinal studies to explore the long-term effects of childhood PFAS exposure on lung function past adolescence and early adulthood.