Justin A. Colacino

Perfluorinated Compounds, Polychlorinated Biphenyls, and Organochlorine Pesticide Contamination in Composite Food Samples from Dallas, Texas, USA

Objectives The objective of this article is to extend our previous studies of persistent organic pollutant (POP) contamination of U.S. food by measuring perfluorinated compounds (PFCs), organochlorine pesticides, and polychlorinated biphenyls (PCBs) in composite food samples. This study is part of a larger study reported in two articles, the other of which reports levels of polybrominated diphenyl ethers and hexabromocyclododecane brominated flame retardants in these composite foods [Schecter et al. 2010. Polybrominated diphenyl ethers (PBDEs) and hexabromocyclodecane (HBCD) in composite U.S. food samples, Environ Health Perspect 118:357–362]. Methods In this study we measured concentrations of 32 organochlorine pesticides, 7 PCBs, and 11 PFCs in composite samples of 31 different types of food (310 individual food samples) purchased from supermarkets in Dallas, Texas (USA), in 2009. Dietary intake of these chemicals was calculated for an average American. Results Contamination varied greatly among chemical and food types. The highest level of pesticide contamination was from the dichlorodiphenyltrichloroethane (DDT) metabolite p,p′- dichlorodiphenyldichloroethylene, which ranged from 0.028 ng/g wet weight (ww) in whole milk yogurt to 2.3 ng/g ww in catfish fillets. We found PCB congeners (28, 52, 101, 118, 138, 153, and 180) primarily in fish, with highest levels in salmon (PCB-153, 1.2 ng/g ww; PCB-138, 0.93 ng/g ww). For PFCs, we detected perfluorooctanoic acid (PFOA) in 17 of 31 samples, ranging from 0.07 ng/g in potatoes to 1.80 ng/g in olive oil. In terms of dietary intake, DDT and DDT metabolites, endosulfans, aldrin, PCBs, and PFOA were consumed at the highest levels. Conclusion Despite product bans, we found POPs in U.S. food, and mixtures of these chemicals are consumed by the American public at varying levels. This suggests the need to expand testing of food for chemical contaminants.

Phthalate Concentrations and Dietary Exposure from Food Purchased in New York State

Background: Phthalates have been found in many personal care and industrial products, but have not previously been reported in food purchased in the United States. Phthalates are ubiquitous synthetic compounds and therefore difficult to measure in foods containing trace levels. Phthalates have been associated with endocrine disruption and developmental alteration. Objectives: Our goals were to report concentrations of phthalates in U.S. food for the first time, specifically, nine phthalates in 72 individual food samples purchased in Albany, New York, and to compare these findings with other countries and estimate dietary phthalate intake. Methods: A convenience sample of commonly consumed foods was purchased from New York supermarkets. Methods were developed to analyze these foods using gas chromatography–mass spectroscopy. Dietary intakes of phthalates were estimated as the product of the food consumption rate and concentration of phthalates in that food. Results: The range of detection frequency of individual phthalates varied from 6% for dicyclohexyl phthalate (DCHP) to 74% for di-2-ethylhexyl phthalate (DEHP). DEHP concentrations were the highest of the phthalates measured in all foods except beef [where di-n-octyl phthalate (DnOP) was the highest phthalate found], with pork having the highest estimated mean concentration of any food group (mean 300 ng/g; maximum, 1,158 ng/g). Estimated mean adult intakes ranged from 0.004 μg/kg/day for dimethyl phthalate (DMP) to 0.673 μg/kg/day for DEHP. Conclusions: Phthalates are widely present in U.S. foods. While estimated intakes for individual phthalates in this study were more than an order of magnitude lower than U.S. Environmental Protection Agency reference doses, cumulative exposure to phthalates is of concern and a more representative survey of U.S. foods is indicated.

Polybrominated diphenyl ethers (PBDEs) and hexabromocyclodecane (HBCD) in composite U.S. food samples.

Objectives This study was designed to update previous U.S. market basket surveys of levels and polybrominated diphenyl ether (PBDE) dietary intake calculations. This study also quantifies hexabromocyclododecane (HBCD) levels in U.S.-purchased foods for the first time and estimates U.S. dietary intake of HBCD. This is part of a larger market basket study reported in two companion articles, of current levels of certain persistent organic pollutants (POPs) PBDEs, HBCD, perfluorinated compounds, polychlorinated biphenyls, and pesticides in composite food samples collected in 2008–2009. Methods In this study, we measured concentrations of 24 PBDE congeners and total HBCD in composite samples of 31 food types (310 samples). U.S. dietary intake of PBDEs and HBCD was estimated referencing the most current U.S. Department of Agriculture loss-adjusted food availability report. Results Total PBDE concentrations in food varied by food type, ranging from 12 pg/g wet weight (ww) in whole milk to 1,545 pg/g ww in canned sardines and 6,211 pg/g ww in butter. Total HBCD concentrations also varied substantially within and among food groups, ranging from 23 pg/g in canned beef chili to 593 pg/g in canned sardines. HBCD was not detected in any dairy samples. Dietary intake of all PBDE congeners measured was estimated to be 50 ng/day, mostly from dairy consumption but also from meat and fish. HBCD intake was estimated at 16 ng/day, primarily from meat consumption. Conclusion PBDEs and HBCDs currently contaminate some food purchased in the United States, although PBDE intake estimated in this study is lower than reported in our previous market basket surveys. HBCD is in food at higher levels than expected based on previously reported levels in milk and blood compared with PBDE levels and is comparable to European levels.

Dietary intake is associated with phthalate body burden in a nationally representative sample.

Background Phthalates are compounds that are used in a wide range of consumer products. However, the contribution of dietary intake to phthalate exposure has not been well defined. Objective The objective of this study was to assess the contribution of different food types to phthalate exposure. Phthalates are chemicals of concern because of the high levels measured in people and the environment, as well as the demonstrated toxicity in animal studies and limited epidemiological studies. Previous research, although limited, has suggested that phthalates contaminate food in various countries. Methods We conducted an exploratory analysis of data collected as part of the 2003–2004 National Health and Nutrition Examination Survey (NHANES). Associations between dietary intake (assessed by a 24-hr dietary recall) for a range of food types (meat, poultry, fish, fruit, vegetable, and dairy) and phthalate metabolites measured in urine were analyzed using multiple linear regression modeling. Results We found that metabolites of di-(2-ethylhexyl) phthalate (DEHP) and high-molecular-weight phthalate metabolites were associated with the consumption of poultry. Monoethyl phthalate, the metabolite of diethyl phthalate (DEP), was associated with vegetable consumption, specifically tomato and potato consumption. Discussion These results, combined with results from previous studies, suggest that diet is an important route of intake for phthalates. Further research is needed to determine the sources of food contamination with these toxic chemicals and to describe the levels of contamination of U.S. food in a large, representative U.S. sample.

Genome-wide methylation and expression differences in HPV(+) and HPV(-) squamous cell carcinoma cell lines are consistent with divergent mechanisms of carcinogenesis

Oncogenic human papillomaviruses (HPV) are associated with nearly all cervical cancers and are increasingly important in the etiology of oropharyngeal tumors. HPV-associated head and neck squamous cell carcinomas (HNSCC) have distinct risk profiles and appreciate a prognostic advantage compared to HPV-negative HNSCC. Promoter hypermethylation is widely recognized as a mechanism in the progression of HNSCC, but the extent to which this mechanism is consistent between HPV(+) and HPV(-) tumors is unknown. To investigate the epigenetic regulation of gene expression in HPV-induced and carcinogen-induced cancers, we examined genome-wide DNA methylation and gene expression in HPV(+) and HPV(-) SCC cell lines. We used two platforms: the Illumina Infinium Methylation BeadArray and tiling arrays, and confirmed illustrative examples with pyrosequencing and quantitative PCR. These analyses indicate that HPV(+) cell lines have higher DNA methylation in genic and LINE-1 regions than HPV(-) cell lines. Differentially methylated loci between HPV(+) and HPV(-) cell lines significantly correlated with HPV-typed HNSCC primary tumor DNA methylation levels. Novel findings include higher promoter methylation of polycomb repressive complex 2 target genes in HPV(+) cells compared to HPV(-) cells and increased expression of DNMT3A in HPV(+) cells. Additionally, CDKN2A and KRT8 were identified as interaction hubs among genes with higher methylation and lower expression in HPV(-) cells. Conversely, RUNX2, IRS-1 and CCNA1 were major hubs with higher methylation and lower expression in HPV(+) cells. Distinct HPV(+) and HPV(-) epigenetic profiles should provide clues to novel targets for development of individualized therapeutic strategies.

Relationship between urinary triclosan and paraben concentrations and serum thyroid measures in NHANES 2007–2008

Triclosan and parabens are broad spectrum antimicrobials used in a range of consumer products. In vitro and animal studies have suggested the potential for these compounds to disrupt thyroid function, though studies in humans have been limited. The objective of the study was to assess the relationship of urinary concentrations of triclosan and parabens with serum thyroid measures in a large, representative sample of the US population. We conducted an exploratory, cross-sectional analysis of data on urinary biomarkers of triclosan and paraben exposure and serum thyroid measures obtained from 1831 subjects (ages≥12 years) as part of the 2007-2008 National Health and Nutrition Examination Survey (NHANES). We found evidence of some inverse associations between parabens and circulating thyroid hormone levels in adults, with the strongest and most consistent associations among females. We also observed a positive association between triclosan and total triiodothyonine (T3) concentrations in adolescents. These results, in accordance with the in vitro and animal literature, suggest that paraben, and potentially triclosan, exposures may be associated with altered thyroid hormone levels in humans. Further research is needed for confirmation and to determine the potential clinical and public health significance of these findings.

Partitioning of polybrominated diphenyl ethers (PBDEs) in serum and milk from the same mothers.

We and others have previously described partitioning of chemicals, including polychlorinated-p-dioxins, dibenzofurans, and biphenyls in different types of human tissues and fluids, including blood and milk. Additionally, we previously reported the blood to milk partitioning of polybrominated diphenyl ethers (PBDEs) in a group of 11 women. Partitioning is of importance in understanding the toxicokinetics of these compounds and also in clinical medicine in improving estimates of levels in different matrices including blood and milk. In this study we extend these findings, describing the levels of PBDEs detected in the serum and milk of 29 women from Texas. The median sum of the levels of the four most detected congeners (BDE 47, 99, 100, and 153) in serum was 27.8 ng g(-1) lipid (range 6.7-501.6 ng g(-1) lipid). In milk, the median sum of the levels of the same congeners was 39.7 ng g(-1) lipid (range 12.9-580.3 ng g(-1) lipid). The levels detected in breast milk in this study are similar to those we reported in 2003, where a median total PBDE level of 34 ng g(-1) lipid was reported. When congener specific blood to milk partitioning ratios were calculated for BDEs 47, 99, 100, and 153, the relatively small tetrabrominated congener, BDE 47, was found in higher concentrations in milk compared to blood, while the higher molecular weight hexabrominated congener, BDE 153, was found in approximately equal quantities in blood and milk, on a lipid normalized basis. The reason for the differential partitioning of PBDE congeners in milk and blood could be due to variation in toxicokinetics, specifically distribution based on molecular size or molecular weight.

Polyfluoroalkyl compounds in Texas children from birth through 12 years of age

Background: For > 50 years, polyfluoroalkyl compounds (PFCs) have been used worldwide, mainly as surfactants and emulsifiers, and human exposure to some PFCs is widespread. Objectives: Our goal was to report PFC serum concentrations from a convenience sample of Dallas, Texas, children from birth to < 13 years of age, and to examine age and sex differences in PFC concentrations. Methods: We analyzed 300 serum samples collected in 2009 for eight PFCs by online solid phase extraction–high performance liquid chromatography–isotope dilution–tandem mass spectrometry. Results: Perfluorohexane sulfonic acid (PFHxS), perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), and perfluorononanoic acid (PFNA) were detected in > 92% of participants; the other PFCs measured were detected less frequently. Overall median concentrations of PFOS (4.1 ng/mL) were higher than those for PFOA (2.85 ng/mL), PFNA (1.2 ng/mL), and PFHxS (1.2 ng/mL). For PFOS, PFOA, PFNA, and PFHxS, we found no significant differences (p < 0.05) by sex, significantly increasing concentrations for all four chemicals by age, and significantly positive correlations between all four compounds. Conclusions: We found no significant differences in the serum concentrations of PFOS, PFOA, PFNA, and PFHxS by sex, but increasing concentrations with age. Our results suggest that these 300 Texas children from birth through 12 years of age continued to be exposed to several PFCs in late 2009, years after changes in production of some PFCs in the United States.

Cancer Epigenetics: A Brief Review

Cancer is a disease that results from the successive accumulation of genetic and epigenetic alterations. Despite intense study, many unanswered questions about the nature of the contribution of epigenetic changes to carcinogenesis remain. In this review, we describe principles of epigenetics as they relate to our current understanding of carcinogenesis. There are a number of in vivo models of specific pathways of carcinogenesis that are very useful for the characterization of epigenetic mechanisms that link environmental exposures or genetic susceptibility and cancer progression. Because epigenetic alterations are thought to be reversible, they offer great promise for treatment of cancer. The use of animal models to evaluate the effects of decitabine and zebularine has elucidated the mechanisms of action and indicated the potential for these types of treatment. Ultimately, the greatest challenge lies in the integration of laboratory and epidemiologic data to best prevent and treat this deadly disease.

Bisphenol A-associated epigenomic changes in prepubescent girls: a cross-sectional study in Gharbiah, Egypt

BackgroundThere is now compelling evidence that epigenetic modifications link adult disease susceptibility to environmental exposures during specific life stages, including pre-pubertal development. Animal studies indicate that bisphenol A (BPA), the monomer used in epoxy resins and polycarbonate plastics, may impact health through epigenetic mechanisms, and epidemiological data associate BPA levels with metabolic disorders, behavior changes, and reproductive effects. Thus, we conducted an environmental epidemiology study of BPA exposure and CpG methylation in pre-adolescent girls from Gharbiah, Egypt hypothesizing that methylation profiles exhibit exposure-dependent trends.MethodsUrinary concentrations of total (free plus conjugated) species of BPA in spot samples were quantified for 60 girls aged 10 to 13. Genome-wide CpG methylation was concurrently measured in bisulfite-converted saliva DNA using the Infinium HumanMethylation27 BeadChip (N = 46). CpG sites from four candidate genes were validated via quantitative bisulfite pyrosequencing.ResultsCpG methylation varied widely among girls, and higher urinary BPA concentrations were generally associated with less genomic methylation. Based on pathway analyses, genes exhibiting reduced methylation with increasing urinary BPA were involved in immune function, transport activity, metabolism, and caspase activity. In particular, hypomethylation of CpG targets on chromosome X was associated with higher urinary BPA. Using the Comparative Toxicogenomics Database, we identified a number of candidate genes in our sample that previously have been associated with BPA-related expression change.ConclusionsThese data indicate that BPA may affect human health through specific epigenomic modification of genes in relevant pathways. Thus, epigenetic epidemiology holds promise for the identification of biomarkers from previous exposures and the development of epigenetic-based diagnostic strategies.