Faculty Bibliography

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.

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.

BACKGROUND: Endocrine-disrupting chemicals (EDCs) contribute to disease and dysfunction and incur high associated costs (>1% of the gross domestic product [GDP] in the European Union). Exposure to EDCs varies widely between the USA and Europe because of differences in regulations and, therefore, we aimed to quantify disease burdens and related economic costs to allow comparison. METHODS: We used existing models for assessing epidemiological and toxicological studies to reach consensus on probabilities of causation for 15 exposure-response relations between substances and disorders. We used Monte Carlo methods to produce realistic probability ranges for costs across the exposure-response relation, taking into account uncertainties. Estimates were made based on population and costs in the USA in 2010. Costs for the European Union were converted to US$ (euro1=$1.33). FINDINGS: The disease costs of EDCs were much higher in the USA than in Europe ($340 billion [2.33% of GDP] vs $217 billion [1.28%]). The difference was driven mainly by intelligence quotient (IQ) points loss and intellectual disability due to polybrominated diphenyl ethers (11 million IQ points lost and 43 000 cases costing $266 billion in the USA vs 873 000 IQ points lost and 3290 cases costing $12.6 billion in the European Union). Accounting for probability of causation, in the European Union, organophosphate pesticides were the largest contributor to costs associated with EDC exposure ($121 billion), whereas in the USA costs due to pesticides were much lower ($42 billion). INTERPRETATION: EDC exposure in the USA contributes to disease and dysfunction, with annual costs taking up more than 2% of the GDP. Differences from the European Union suggest the need for improved screening for chemical disruption to endocrine systems and proactive prevention. FUNDING: Endocrine Society, Ralph S French Charitable Foundation, and Broad Reach Foundation.

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.

Evidence increasingly confirms that synthetic chemicals disrupt the endocrine system and contribute to disease and disability across the lifespan. Despite a United Nations Environment Programme/WHO report affirmed by over 100 countries at the Fourth International Conference on Chemicals Management, 'manufactured doubt' continues to be cast as a cloud over rigorous, peer-reviewed and independently funded scientific data. This study describes the sources of doubt and their social costs, and suggested courses of action by policymakers to prevent disease and disability. The problem is largely based on the available data, which are all too limited. Rigorous testing programmes should not simply focus on oestrogen, androgen and thyroid. Tests should have proper statistical power. 'Good laboratory practice' (GLP) hardly represents a proper or even gold standard for laboratory studies of endocrine disruption. Studies should be evaluated with regard to the contamination of negative controls, responsiveness to positive controls and dissection techniques. Flaws in many GLP studies have been identified, yet regulatory agencies rely on these flawed studies. Peer-reviewed and unbiased research, rather than 'sound science', should be used to evaluate endocrine-disrupting chemicals.

BACKGROUND: Few studies have used GPS data to analyze the relationship between Walk Score, transportation choice and walking. Additionally, the influence of Walk Score is understudied using trips rather than individuals as statistical units. The purpose of this study is to examine associations at the trip level between Walk Score, transportation mode choice, and walking among Paris adults who were tracked with GPS receivers and accelerometers in the RECORD GPS Study. METHODS: In the RECORD GPS Study, 227 participants were tracked during seven days with GPS receivers and accelerometers. Participants were also surveyed with a GPS-based web mapping application on their activities and transportation modes for all trips (6969 trips). Walk Score, which calculates neighborhood walkability, was assessed for each origin and destination of every trip. Multilevel logistic and linear regression analyses were conducted to estimate associations between Walk Score and walking in the trip or accelerometry-assessed number of steps for each trip, after adjustment for individual/neighborhood characteristics. RESULTS: The mean overall Walk Scores for trip origins were 87.1 (SD = 14.4) and for trip destinations 87.1 (SD = 14.5). In adjusted trip-level associations between Walk Score and walking only in the trip, we found that a walkable neighborhood in the trip origin and trip destination was associated with increased odds of walking in the trip assessed in the survey. The odds of only walking in the trip were 3.48 (95% CI: 2.73 to 4.44) times higher when the Walk Score for the trip origin was "Walker's Paradise" compared to less walkable neighborhoods (Very/Car-Dependent or Somewhat Walkable), with an identical independent effect of trip destination Walk Score on walking. The number of steps per 10 min (as assessed with accelerometry) was cumulatively higher for trips both originating and ending in walkable neighborhoods (i.e., "Very Walkable"). CONCLUSIONS: Walkable neighborhoods were associated with increases in walking among adults in Paris, as documented at the trip level. Creating walkable neighborhoods (through neighborhood design increased commercial activity) may increase walking trips and, therefore, could be a relevant health promotion strategy to increase physical activity.