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Identifying Subpopulations Vulnerable to the Thyroid-Blocking Effects of Perchlorate and Thiocyanate

McMullen, Jenica; Ghassabian, Akhgar; Kohn, Brenda; Trasande, Leonardo
Context: Common environmental contaminants can disrupt normal thyroid function, which plays essential but varying roles at different ages. Objective: To evaluate the relationship of perchlorate, thiocyanate, and nitrate, three sodium-iodide symporter (NIS) inhibitors, and thyroid function in different age-sex-stratified populations. Design, Setting, Participants, and Intervention: This was a cross-sectional analysis of data from the 2009-2012 National Health and Nutrition Examination Surveys (NHANES) evaluating the exposure to perchlorate, thiocyanate, and nitrate in 3,151 participants aged 12-80. Main Outcome Measure: Blood serum free thyroxine (FT4) as both a continuous and categorical variable. We also assessed blood serum thyroid stimulating hormone (TSH). Results: Controlling for serum cotinine, BMI, total daily energy consumption, race/ethnicity, and poverty-to-income ratio, for each log unit increase in perchlorate, FT4 decreased by 0.03 ng/dL in both the general population (p=0.004) and in all women (p=0.005), and by 0.06 ng/dL in adolescent girls (p=0.029), corresponding to 4% and 8% decreases relative to median FT4, respectively. For each log unit increase thiocyanate, FT4 decreased by 0.07 ng/dL in adolescent boys (p=0.003), corresponding to a 9% decrease relative to median FT4, respectively. Conclusions: Our results indicate that adolescent boys and girls represent vulnerable subpopulations to the thyroid-blocking effects of NIS symporter inhibitors. These results suggest a valuable screening and intervention opportunity.
PMID: 28430972
ISSN: 1945-7197
CID: 2532822

Comparison of methods for calculating the health costs of endocrine disrupters: a case study on triclosan

Prichystalova, Radka; Fini, Jean-Baptiste; Trasande, Leonardo; Bellanger, Martine; Demeneix, Barbara; Maxim, Laura
BACKGROUND: Socioeconomic analysis is currently used in the Europe Union as part of the regulatory process in Regulation Registration, Evaluation and Authorisation of Chemicals (REACH), with the aim of assessing and managing risks from dangerous chemicals. The political impact of the socio-economic analysis is potentially high in the authorisation and restriction procedures, however, current socio-economic analysis dossiers submitted under REACH are very heterogeneous in terms of methodology used and quality. Furthermore, the economic literature is not very helpful for regulatory purposes, as most published calculations of health costs associated with chemical exposures use epidemiological studies as input data, but such studies are rarely available for most substances. The quasi-totality of the data used in the REACH dossiers comes from toxicological studies. METHODS: This paper assesses the use of the integrated probabilistic risk assessment, based on toxicological data, for the calculation of health costs associated with endocrine disrupting effects of triclosan. The results are compared with those obtained using the population attributable fraction, based on epidemiological data. RESULTS: The results based on the integrated probabilistic risk assessment indicated that 4894 men could have reproductive deficits based on the decreased vas deferens weights observed in rats, 0 cases of changed T3 levels, and 0 cases of girls with early pubertal development. The results obtained with the Population Attributable Fraction method showed 7,199,228 cases of obesity per year, 281,923 girls per year with early pubertal development and 88,957 to 303,759 cases per year with increased total T3 hormone levels. The economic costs associated with increased BMI due to TCS exposure could be calculated. Direct health costs were estimated at euro5.8 billion per year. CONCLUSIONS: The two methods give very different results for the same effects. The choice of a toxicological-based or an epidemiological-based method in the socio-economic analysis will therefore significantly impact the estimated health costs and consequently the political risk management decision. Additional work should be done for understanding the reasons of these significant differences.
PMCID:5466740
PMID: 28599657
ISSN: 1476-069x
CID: 2592252

Exposure to Bisphenols and Phthalates and Association with Oxidant Stress, InsulinN Resistance, and Endothelial Dysfunction in Children

Kataria, Anglina; Levine, Dov; Wertenteil, Sara; Vento, Suzanne; Xue, Jingchuan; Rajendiran, Karthikraj; Kannan, Kurunthachalam; Thurman, Joshua M; Morrison, Debra; Brody, Rachel; Urbina, Elaine; Attina, Teresa; Trasande, Leonardo; Trachtman, Howard
BACKGROUND: The health effects of bisphenol A (BPA) and di-(2-ethylhexyl) phthalate (DEHP) have been studied extensively in children. The impact of other chemicals in these two classes has not been investigated as fully. METHODS: We conducted a cross-sectional pilot study of 10-13 year old healthy children. We assessed descriptive, univariable and multivariable associations of urinary metabolites of bisphenols and phthalates with oxidant stress, insulin resistance, body mass, and endothelial dysfunction. Possible associations with brachial artery distensibility, pulse wave velocity (markers of vascular stiffness), and serum endothelial cell-derived microparticle levels were also assessed. RESULTS: We enrolled 41 participants, 12.1 +/- 1.0 years, most of whom were Mexican-Americans (42%) or other Hispanics (34%). Increased BPA levels were associated with increased levels of F2-isoprostane (ng/ml) (P=0.02), with a similar trend for DEHP metabolites. Each log unit increase of high molecular weight (HMW) phthalate metabolites was associated with 0.550 increase in HOMA-IR units (p=0.019) and altered circulating levels of activated endothelial cell-derived microparticles (% per ml) (P=0.026). Bisphenol S (BPS), a replacement for BPA, was associated with increased albumin (mg):creatinine (g) ratio (P=0.04). Metabolites of HMW phthalates were also associated with decreased brachial artery distensibility (P=0.047). CONCLUSIONS: Exposure to bisphenols and phthalates, including a BPA replacement, is associated with increased oxidant stress, insulin resistance, albuminuria, as well as disturbances in vascular function in healthy children.Pediatric Research (2017); doi:10.1038/pr.2017.16.
PMCID:5618435
PMID: 28099427
ISSN: 1530-0447
CID: 2413952

Exploring regrettable substitution: replacements for bisphenol A

Trasande, Leonardo
PMID: 29851613
ISSN: 2542-5196
CID: 3136372

Serum perfluoroalkyl substances in children exposed to the world trade center disaster

Trasande, Leonardo; Koshy, Tony T; Gilbert, Joseph; Burdine, Lauren K; Attina, Teresa M; Ghassabian, Akhgar; Honda, Masato; Marmor, Michael; Chu, Dinh Binh; Han, Xiaoxia; Shao, Yongzhao; Kannan, Kurunthachalam
The World Trade Center (WTC) disaster released large amounts of various chemical substances into the environment, including perfluoroalkyl substances (PFASs). Yet, no studies have examined exposures in children living or attending schools near the disaster site. We measured serum PFASs in WTC Health Registry (WTCHR) respondents who were
PMCID:5328959
PMID: 28104511
ISSN: 1096-0953
CID: 2414042

Effects of early exposure to phthalates and bisphenols on cardiometabolic outcomes in pregnancy and childhood

Philips, Elise M; Jaddoe, Vincent W V; Trasande, Leonardo
Pregnant women are exposed to various chemicals, including endocrine-disrupting chemicals (EDCs) such as phthalates and bisphenols. Increasing evidence suggests that early life exposures to phthalates and bisphenols may contribute to cardiometabolic risks. The aim of this narrative review was to summarize current knowledge of the effects of fetal and childhood exposure to phthalates and bisphenols on child growth and child cardiometabolic outcomes and the effects on maternal outcomes. In total, 54 studies were identified and included. The majority of studies found effects of phthalates and bisphenols on maternal, child growth, and cardiometabolic outcomes. Currently results suggest that early life exposure to phthalates and bisphenols may have a substantial influence on perinatal and postnatal cardiometabolic programming. In a large part of the investigated outcomes studies show contradictory results. However, the majority of the existing evidence is based on non-cohort studies with single samples neglecting time-variant effects and complicating conclusions regarding causal inference. More studies are needed investigating the mechanisms and its potential interactions.
PMCID:5336527
PMID: 27596818
ISSN: 1873-1708
CID: 2238542

Population attributable risks and costs of diabetogenic chemical exposures in the elderly

Trasande, Leonardo; Lampa, Erik; Lind, Lars; Lind, P Monica
BACKGROUND: A previous analysis examined the contribution of endocrine disruptor exposures (endocrine-disrupting chemicals, EDCs) to adult diabetes, but was limited to effects of phthalates in middle-aged women and did not simultaneously examine multiple EDCs which are known to coexist in the environment. We therefore endeavoured to quantify potential reductions in diabetes and disease costs that could result from reducing synthetic chemical diabetogenic exposures in the elderly in Europe. METHODS: We leveraged the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study ( approximately 1000 participants), which has measured exposure to phthalates; dichlorodiphenyltrichloroethylene; polychlorinated biphenyls (PCBs) and perfluoroalkyl substances to examine their independent contribution to diabetes. We estimated risk reductions assuming identical 25% reductions across levels of 4 selected compounds (PCB 153, monoethylphthalate, dichlorodiphenyldichloroethylene and perfluorononanoic acid), and diabetes costs saved in European men and women if diabetogenic exposures are limited. RESULTS: Reduction of chemical exposures was associated with a 13% (95% CI 2% to 22%) reduction in prevalent diabetes, compared with 40% resulting from an identical (25%) reduction in body mass index (BMI) in cross-sectional analyses. Extrapolating to Europe, 152 481 cases of diabetes in Europe and euro4.51 billion/year in associated costs could be prevented, compared with 469 172 cases prevented by reducing BMI. CONCLUSIONS: These findings support regulatory and individual efforts to reduce chemical exposures to reduce the burden and costs of diabetes.
PMCID:5284466
PMID: 27789757
ISSN: 1470-2738
CID: 2297632

Geographic Variations and Temporal Trends in Cesarean Delivery Rates in China, 2008-2014

Li, Hong-Tian; Luo, Shusheng; Trasande, Leonardo; Hellerstein, Susan; Kang, Chuyun; Li, Jia-Xin; Zhang, Yali; Liu, Jian-Meng; Blustein, Jan
Importance: The increasing use of cesarean delivery is an emerging global health issue. Prior estimates of China's cesarean rate have been based on surveys with limited geographic coverage. Objective: To provide updated information about cesarean rates and geographic variation in cesarean use in China. Design, Setting, and Data Sources: Descriptive study, covering every county (n = 2865) in mainland China's 31 provinces, using county-level aggregated information on the number of live births, cesarean deliveries, maternal deaths, and perinatal deaths, collected by the Office for National Maternal & Child Health Statistics of China, from 2008 through 2014. Exposures: Live births. Main Outcomes and Measures: Annual rate of cesarean deliveries. Results: Over the study period, there were 100873051 live births, of which 32947229 (32.7%) were by cesarean delivery. In 2008, there were 13160634 live births, of which 3788029 (28.8%) were by cesarean delivery and in 2014 there were 15123276 live births, of which 5280124 (34.9%) were by cesarean delivery. Rates varied markedly by province, from 4.0% to 62.5% in 2014. Despite the overall increase, by 2014 rates of cesarean delieries in 14 of the nation's 17 "super cities" had declined by 4.1 to 17.5 percentage points from their earlier peak values (median, 11.4; interquartile range, 6.3-15.4). In 4 super cities with the largest decreases, there was no increase in maternal or perinatal mortality. Conclusions and Relevance: Between 2008 and 2014, the overall annual rate of cesarean deliveries increased in China, reaching 34.9%. There was major geographic variation in rates and trends over time, with rates declining in some of the largest urban areas.
PMID: 28030701
ISSN: 1538-3598
CID: 2383322

Economic implications of mercury exposure in the context of the global mercury treaty: Hair mercury levels and estimated lost economic productivity in selected developing countries

Trasande, Leonardo; DiGangi, Joseph; Evers, David C; Petrlik, Jindrich; Buck, David G; Samanek, Jan; Beeler, Bjorn; Turnquist, Madeline A; Regan, Kevin
Several developing countries have limited or no information about exposures near anthropogenic mercury sources and no studies have quantified costs of mercury pollution or economic benefits to mercury pollution prevention in these countries. In this study, we present data on mercury concentrations in human hair from subpopulations in developing countries most likely to benefit from the implementation of the Minamata Convention on Mercury. These data are then used to estimate economic costs of mercury exposure in these communities. Hair samples were collected from sites located in 15 countries. We used a linear dose-response relationship that previously identified a 0.18 IQ point decrement per part per million (ppm) increase in hair mercury, and modeled a base case scenario assuming a reference level of 1 ppm, and a second scenario assuming no reference level. We then estimated the corresponding increases in intellectual disability and lost Disability-Adjusted Life Years (DALY). A total of 236 participants provided hair samples for analysis, with an estimated population at risk of mercury exposure near the 15 sites of 11,302,582. Average mercury levels were in the range of 0.48 ppm-4.60 ppm, and 61% of all participants had hair mercury concentrations greater than 1 ppm, the level that approximately corresponds to the USA EPA reference dose. An additional 1310 cases of intellectual disability attributable to mercury exposure were identified annually (4110 assuming no reference level), resulting in 16,501 lost DALYs (51,809 assuming no reference level). A total of $77.4 million in lost economic productivity was estimated assuming a 1 ppm reference level and $130 million if no reference level was used. We conclude that significant mercury exposures occur in developing and transition country communities near sources named in the Minamata Convention, and our estimates suggest that a large economic burden could be avoided by timely implementation of measures to prevent mercury exposures.
PMID: 27594689
ISSN: 1095-8630
CID: 2254142

Particulate Matter Exposure and Preterm Birth: Estimates of U.S. Attributable Burden and Economic Costs

Trasande, Leonardo; Malecha, Patrick; Attina, Teresa M
BACKGROUND: Preterm birth (PTB) rates (11.4% in 2013) in the United States (US) remain high and are a substantial cause of morbidity. Studies of prenatal exposure have associated particulate matter <2.5microns in diameter (PM2.5) and other ambient air pollutants with adverse birth outcomes, yet, to our knowledge, burden and costs of PM 2.5-attributable PTB have not been estimated in the US. OBJECTIVES: To estimate burden of PTB in the US and economic costs attributable to PM2.5 exposure in 2010. METHODS: Annual deciles of PM2.5 were obtained from US EPA. We converted PTB odds ratio (OR), identified in a previous meta-analysis (1.15 per 10microg/m3 for our base case, 1.07-1.16 for low- and high-end scenarios) to relative risk (RRs), to obtain an estimate that better represents the true relative risk. A reference level (RL) of 8.8microg/m3 was applied. We then used the RR estimates and county-level PTB prevalence to quantify PM2.5 attributable PTB. Direct medical costs were obtained from the 2007 Institute of Medicine report, and lost economic productivity (LEP) was estimated using a meta-analysis of PTB-associated IQ loss, and well-established relationships of IQ loss with LEP. All costs were calculated using 2010 dollars. RESULTS: An estimated 3.32% of PTBs nationally (corresponding to15,808 PTBs) in 2010 could be attributed to PM2.5 (PM2.5>8.8 microg/m3). Attributable PTBs cost were estimated at $4.33 billion (SA: $2.06-8.22B), of which $760 million were spent for medical care (SA: $362M-1.44B). The estimated PM2.5-attributable fraction (AF) of PTB was highest in urban counties, with highest AFs in the Ohio valley and Southern US. CONCLUSIONS: PM2.5 may contribute substantially to burden and costs of PTB in the US, and considerable health and economic benefits could be achieved through environmental regulatory interventions that reduce PM2.5 exposure in pregnancy.
PMCID:5132647
PMID: 27022947
ISSN: 1552-9924
CID: 2059112