Faculty Bibliography

Synthetic phenolic antioxidants (SPAs), including 2,6-di-tert-butyl-4-hydroxytoluene (BHT), are extensively used in food, cosmetic and plastic industries. Nevertheless, limited information is available on human exposures, other than the dietary sources, to SPAs. In this study, occurrence of 9 SPAs and their metabolites/degradation products was determined in 339 indoor dust collected from 12 countries. BHT was found in 99.5% of indoor dust samples from homes and microenvironments at concentrations that ranged from < LOQ to 118 μg/g and 0.10 to 3460 μg/g, respectively. This is the first study to measure BHT metabolites in house dust (0.01-35.1 μg/g) and their concentrations accounted for 9.2-58% of the sum concentrations (∑SPAs). 3,5-di-tert-butyl-4-hydroxybenzaldehyde (BHT-CHO), 2,6-di-tert-butyl-4-(hydroxymethyl)phenol (BHT-OH), 2,6-di-tert-butyl-1,4-benzoquinone (BHT-Q) were the major derivatives of BHT found in dust samples. The concentrations of gallic acid esters (gallates) in dust from homes and microenvironments ranged from < LOQ to 18.2 and < LOQ to 684 μg/g, respectively. The concentrations and profiles of SPAs varied among countries and microenvironments. Significantly elevated concentrations of SPAs were found in dust from an e-waste workshop (1530 μg/g). The estimated daily intake (EDI) of BHT via house dust ingestion ranged from 0.40 to 222 ng/kg/d (95th percentile).

BACKGROUND:Perfluoroalkyl substances (PFASs), including perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), perfluorohexane sulfonic acid (PFHxS), and perfluorononanoic acid (PFNA), are detectable in the serum of 95% of the U.S. OBJECTIVE:Considering the role of PFASs as endocrine disruptors, we examined their relationships with bone health. METHODS:The association between serum PFAS concentration and bone mineral density at total femur (TFBMD), femoral neck (FNBMD), lumbar spine (LSBMD), and physician-diagnosed osteoporosis was assessed in 1,914 participants using data from the National Health and Nutritional Examination Survey 2009-2010. RESULTS:The mean age of the participants was 43 years. Men had higher serum PFAS concentrations than women (p < 0.001) except for PFNA. In both sexes, serum PFOS concentrations were inversely associated with FNBMD (p < 0.05). In women, significant negative associations were observed for natural log (ln)-transformed PFOS exposure with TFBMD and FNBMD, and for ln-transformed PFOA exposure with TFBMD (p < 0.05). In postmenopausal women, serum PFOS was negatively associated with TFBMD and FNBMD, and PFNA was negatively associated with TFBMD, FNBMD, and LSBMD (all p < 0.05). With one log unit increase in serum PFOA, PFHxS, and PFNA, osteoporosis prevalence in women increased as follows: [adjusted odds ratios (aORs)] 1.84 (95% CI: 1.17, 2.905), 1.64 (95% CI: 1.14, 2.38), and 1.45 (95% CI: 1.02, 2.05), respectively. In women, the prevalence of osteoporosis was significantly higher in the highest versus the lowest quartiles of PFOA, PFHxS, and PFNA, with aORs of 2.59 (95% CI: 1.01, 6.67), 13.20 (95% CI: 2.72, 64.15), and 3.23 (95% CI: 1.44, 7.21), respectively, based on 77 cases in the study sample. CONCLUSION/CONCLUSIONS:In a representative sample of the U.S. adult population, serum PFAS concentrations were associated with lower bone mineral density, which varied according to the specific PFAS and bone site assessed. Most associations were limited to women. Osteoporosis in women was also associated with PFAS exposure, based on a small number of cases. CITATION/BACKGROUND:Khalil N, Chen A, Lee M, Czerwinski SA, Ebert JR, DeWitt JC, Kannan K. 2016. Association of perfluoroalkyl substances, bone mineral density, and osteoporosis in the U.S. population in NHANES 2009-2010. Environ Health Perspect 124:81-87; http://dx.doi.org/10.1289/ehp.1307909.

As health concerns over bisphenol A (BPA) in consumer products are mounting, this weak estrogen mimicking compound is gradually being replaced with structural analogs, whose environmental occurrence and estrogen risks are not well understood yet. We used high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) to determine the concentrations of eight bisphenol analogs in 76 sewage sludge samples collected by the U.S. Environmental Protection Agency (EPA) in 2006/2007 from 74 wastewater treatment plants (WWTPs) in 35 states. Bisphenols were detected at the following concentration ranges (ng/g dry weight) and detection frequencies: BPA (6.5-4700; 100%); bisphenol S (BPS; <1.79-1480; 84%); bisphenol F (BPF; <1.79-242; 68%); bisphenol AF (BPAF; <1.79-72.2; 46%); bisphenol P (BPP; <1.79-6.42; <5%), bisphenol B (BPB; <1.79-5.60; <5%), and bisphenol Z (BPZ; <1.79--66.7; <5%). Bisphenol AP (BPAP) was not detected in any of the samples (<1.79 ng/g dw). Concentrations of BPA in sewage sludge were an order of magnitude higher than those reported in China but similar to those in Germany. The calculated 17β-estradiol equivalents (E2EQ) of bisphenols present in sludge samples were 7.74 (0.26-90.5) pg/g dw, which were three orders of magnitude lower than the estrogenic activity contributed by natural estrogens present in the sludge. The calculated mass loading of bisphenols through the disposal of sludge and wastewater was <0.02% of the total U.S. production. As the usage of BPA is expected to decline further, environmental emissions of BPS, BPF, and BPAF are likely to increase in the future. This study establishes baseline levels and estrogenic activity of diverse bisphenol analogs in sewage sludge.

Benzophenone-3 (BP-3) is a widespread environmental contaminant and an estrogenic compound. Very little is known with regard to the occurrence in indoor air and the inhalation exposure of humans to BP-3. In this study, 81 indoor air samples were collected from various locations in Albany, New York, USA, in 2014 and analyzed for BP-3 by high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). BP-3 was found in all indoor air samples and the overall concentrations in bulk air (vapor plus particulate phases) were in the range of 0.19-72.0 ng/m(3) (geometric mean: 2.67 ng/m(3)). The highest concentrations (geometric mean: 10.7 ng/m(3)) were found in cars, followed by barber shops (6.57) ˃ public places (5.75)>homes (3.27) ˃ offices (1.96) ˃ garages (1.04) ˃ laboratories (0.47). The estimated geometric mean daily intake (EDI) of BP-3 for infants, toddlers, children, teenagers, and adults through indoor air inhalation from homes was 1.83, 1.74, 1.18, 0.69, and 0.51 ng/kg-bw/day, respectively. Although high concentrations of BP-3 were measured in some microenvironments, the estimated contribution of indoor air to total BP-3 intake was <5% of the total BP-3 intake in humans. This is the first survey on the occurrence of BP-3 in indoor air.

Bisphenol A (BPA) is an endocrine disruptor associated with poor pregnancy outcomes in human and rodents. The effects of butterfat diets on embryo implantation and whether it modifies BPA's actions are currently unknown. We aimed to determine the effects of butterfat diet on embryo implantation success in female rats exposed to an environmentally relevant dose of BPA. Female Sprague-Dawley rats were exposed to dietary butterfat (10% or 39% kcal/kg body weight [BW]) in the presence or absence of BPA (250 μg/kg BW) or ethinylestradiol (0.1 μg/kg BW) shortly before and during pregnancy to assess embryo implantation potentials by preimplantation development and transport, in vitro blastulation, outgrowth, and implantation. On gestational day (GD) 4.5, rats treated with BPA alone had higher serum total BPA level (2.3-3.7 ng/ml). They had more late-stage preimplantation embryos, whereas those receiving high butterfat (HBF) diet had the most advanced-stage embryos; dams cotreated with HBF and BPA had the most number of advanced embryos. BPA markedly delayed embryo transport to the uterus, but neither amount of butterfat had modifying effects. An in vitro implantation assay showed HBF doubled the outgrowth area, with BPA having no effect. In vivo, BPA reduced the number of implanted embryos on GD8, and cotreatment with HBF eliminated this adverse effect. HBF diet overall resulted in more and larger GD8 embryos. This study reveals the implantation disruptive effects of maternal exposure to an environmentally relevant dose of BPA and identifies HBF diet as a modifier of BPA in promoting early embryonic health.

Concentrations of eight bisphenol analogues (BPs) including BPA, BPS, and BPF were determined in surface waters collected from select rivers in Japan, Korea, China, and India. BPA was found at a concentration in the range of several tens to several hundreds of nanograms per liter in most of the rivers surveyed and some of the highest concentrations (54-1950 ng/L) were found in rivers in Chennai, India. Concentrations of BPF were one to two orders of magnitude higher than those of BPA in river and sea waters collected from Japan, Korea and China, which suggested that BPF is a major contaminant in surface waters in several Southeast Asian countries. BPF concentrations as high as 2850 ng/L were found in the Tamagawa River in Japan. The flux of BPs through riverine discharges into Tokyo Bay was calculated to be approximately 5.5 t per year. Based on the flux estimates and the mass of BPF found in water column and sediment in Tokyo Bay, it was found that BPF degrades faster than BPA in the environment. Elevated concentrations of BPF found in surface waters suggest the need for further studies to determine the fate and toxicity of this compound.

CONTEXT AND OBJECTIVE/OBJECTIVE:Effects of prenatal exposure to bisphenol A (BPA) on gestational and birth outcomes are controversial. The aim of the study was to evaluate the relationship between prenatal exposure to BPA and birth and gestational outcomes. design, setting, participants, and outcome: Levels of unconjugated (uBPA) and BPA glucuronide in 80 matching samples of pregnant women during the first trimester of pregnancy and at delivery and matching term cord blood obtained from a prospective study conducted at the University of Michigan Hospitals were determined using a methodology validated in the National Institutes of Environmental Health Sciences funded Round Robin study and related to pregnancy outcomes. RESULTS:Highest levels of uBPA were found in maternal term samples followed by first trimester maternal (M1) samples and cord blood. A 2-fold increase in M1 uBPA was associated with 55-g less birth weight when male and female pregnancies were combined and 183-g less birth weight with only female pregnancies. A 2-fold increase in maternal term uBPA was associated with an increased gestational length of 0.7 days for all pregnancies and 1.1 days for only female pregnancies. CONCLUSION/CONCLUSIONS:Higher uBPA exposure levels during first trimester and term are associated with sex-specific reduction in birth weight and increase in gestational length, respectively. Race, parity, and employment have an effect on BPA exposure. Because low birth weight is associated with adverse health outcomes, effect of early pregnancy BPA levels on reducing birth weight highlights the risk posed by developmental exposure to BPA.

BACKGROUND:Charleston Harbor has elevated concentrations of PFAS in dolphins, but local human exposure data are limited. OBJECTIVES/OBJECTIVE:We sought to describe PFAS serum concentrations' temporal trends among Gullah African American residents of coastal South Carolina. METHODS:Longitudinal measures of PFAS in blood serum from a Gullah clinical sample, without lupus, were examined using spaghetti plots and visit-to-visit change scores (e.g., differences in concentrations between visits) among the 68 participants with repeated measures available. We also modeled population-level trends among the 71 participants with any data using proportionate percentile models, accounting for clustering through robust standard errors. In a post-hoc analysis we examined heterogeneity of temporal trends by age through mixed-effects models for the log-transformed PFAS compounds. RESULTS:Population concentrations of PFOS dropped approximately 9 (95% CI: 8, 10) percent each year over 2003-2013. This was concordant with individual PFOS trajectories (median PFOS change score -21.7 ng/g wet weight, interquartile range of PFOS change scores: -32.8, -14.9) and reports for other populations over this time period. Several other compounds including PFOA, PFHxS, and PFuNDA also showed a population-level decrease. However, examination of individual trajectories suggested substantial heterogeneity. Post-hoc analyses indicated that PFAS trajectories were heterogeneous by age. CONCLUSIONS:Many PFAS compounds are decreasing in a sample of Gullah African Americans from coastal South Carolina. There may be age differences in the elimination kinetics of PFASs. The possible role of age as a modifier of PFAS serum trends merits further research.

The widespread exposure of humans to parabens present in personal care products is well-known. Nevertheless, little is known about the accumulation of parabens in marine organisms. In this study, six parabens and four common metabolites of parabens were measured in 121 tissue samples from eight species of marine mammals collected along the coastal waters of Florida, California, Washington, and Alaska. Methyl paraben (MeP) was the predominant compound found in the majority of the marine mammal tissues analyzed, and the highest concentration found was 865 ng/g (wet weight [wet wt]) in the livers of bottlenose dolphins from Sarasota Bay, FL. 4-Hydroxybenzoic acid (4-HB) was the predominant paraben metabolite found in all tissue samples. The measured concentrations of 4-HB were on the order of hundreds to thousands of ng/g tissue, and these values are some of the highest ever reported in the literature. MeP and 4-HB concentrations showed a significant positive correlation (p < 0.05), which suggested a common source of exposure to these compounds in marine mammals. Trace concentrations of MeP and 4-HB were found in the livers of polar bears from the Chuckchi Sea and Beaufort Sea, which suggested widespread distribution of MeP and 4-HB in the oceanic environment.

Water samples collected along the Japanese coast and in the open Pacific Ocean in 2010, 2011, and 2012 were analyzed for perfluoroalkyl substances (PFASs) to evaluate the effect of Great East Japan Earthquake (EQ 3.11), which occurred on March 11, 2011, on the dispersion of chemical pollutants. Ultratrace analysis of PFASs in water, a super computer simulation, and an inventory analysis from industrial records revealed the sources and dynamics of PFASs during the EQ 3.11 disaster. In this respect, EQ 3.11 destroyed solid infrastructure on land, and within minutes, PFASs stocked therein were released into the open environment. The historically significant tsunami backwash swept them away from their origin to the coastal water within several hours. It was estimated that from 0.8 to 1.0 tons of perfluorooctanesulfonate (PFOS) and 4.8 to 5.1 tons of PFOA were discharged into the coastal waters after EQ 3.11 and the tsunami that followed. The reconstruction of EQ 3.11 also traced the influence of this pollution in open ocean water until March 2012, and a statistical and finger printing analysis revealed that there were different distribution mechanisms in coastal regions than in the open ocean for PFOS, other shorter chain perfluorinated sulfonic acids and perfluorinated carboxylic acids.