Ana Navas-Acien

The effect of the Environmental Protection Agency maximum contaminant level on arsenic exposure in the USA from 2003 to 2014: an analysis of the National Health and Nutrition Examination Survey (NHANES)

Background The current US Environmental Protection Agency (EPA) maximum contaminant level (MCL) for arsenic in public water systems (10 µg/L) took effect in 2006. Arsenic is not federally regulated in private wells. The impact of the 2006 MCL on arsenic exposure in the US, as confirmed through biomarkers, is presently unknown. We evaluated national trends in water arsenic exposure in the US, hypothesizing that urinary arsenic levels would decrease over time among participants using public water systems but not among those using well water. We further estimated the expected number of avoided lung, bladder, and skin cancer cases. Methods We evaluated 14,127 participants in the National Health and Nutrition Examination Survey (NHANES) 2003–2014 with urinary dimethylarsinate (DMA) and total arsenic available. To isolate water exposure, we expanded a residual-based method to remove tobacco and dietary contributions of arsenic. We applied EPA risk assessment approaches to estimate the expected annual number of avoided cancer cases comparing arsenic exposure in 2013–2014 vs. 2003–2004. Findings Among public water users, fully adjusted geometric means (GMs) of DMA decreased from 3.01 µg/L in 2003–2004 to 2.49 µg/L in 2013–2014 (17% reduction; 95% confidence interval 10%, 24%; p-trend<0.01); no change was observed among well water users (p-trend= 0.35). Assuming these estimated exposure reductions will remain similar across a lifetime, we estimate a reduction of 200 to 900 lung and bladder cancer cases per year depending on the approach used. Interpretation The decline in urinary arsenic among public water but not private well users in NHANES 2003–2014 indicates that the implementation of the current MCL has reduced arsenic exposure in the US population. Our study supports prior work showing that well water users are inadequately protected against drinking water arsenic, and confirms the critical role of federal drinking water regulations in reducing toxic exposures and protecting human health. Funding This work was supported by the National Institute of Environmental Health Sciences (1R01ES025216, R01ES021367, 5P30ES009089 and P42ES010349). A. E. Nigra was supported by 5T32ES007322.

Environmental Metals and Cardiovascular Disease in Adults: A Systematic Review Beyond Lead and Cadmium

Published systematic reviews concluded that there is moderate to strong evidence to infer a potential role of lead and cadmium, widespread environmental metals, as cardiovascular risk factors. For other non-essential metals, the evidence has not been appraised systematically. Our objective was to systematically review epidemiologic studies on the association between cardiovascular disease in adults and the environmental metals antimony, barium, chromium, nickel, tungsten, uranium, and vanadium. We identified a total of 4 articles on antimony, 1 on barium, 5 on chromium, 1 on nickel, 4 on tungsten, 1 on uranium, and 0 on vanadium. We concluded that the current evidence is not sufficient to inform on the cardiovascular role of these metals because of the small number of studies. Few experimental studies have also evaluated the role of these metals in cardiovascular outcomes. Additional epidemiologic and experimental studies, including prospective cohort studies, are needed to understand the role of metals, including exposure to metal mixtures, in cardiovascular disease development.

The consumption of canned food and beverages and urinary Bisphenol A concentrations in NHANES 2003-2008.

BACKGROUNDnExposure to Bisphenol A (BPA) is ubiquitous and includes dietary and environmental pathways. BPA is rapidly glucuronidated in the body, and both BPA and its conjugates can be readily measured in urine.nnnOBJECTIVESnTo investigate the contribution of canned food and beverages, known sources of BPA contamination, to BPA biomarkers of exposure using dietary and urinary BPA concentration information in a representative sample of the U.S.nnnMETHODSnWe evaluated 7669 NHANES 2003-2008 participants 6 years and older with 24-h dietary recall information and urinary BPA concentrations available. Using linear regression models, we evaluated the associations between recent canned food and beverage consumption and urinary BPA concentrations, adjusting for potential confounders.nnnRESULTSnWe found 9% of our participants consumed one canned food in the past 24h and 2% consumed two or more canned foods. The consumption of one canned food vs. none was associated with 24% (95% CI 1.11, 1.38) higher urinary BPA concentrations. The consumption of two or more canned foods vs. none was associated with 54% (95% CI 1.27, 1.88) higher urinary BPA concentrations. The consumption of one or more of some specific types of canned foods vs. none were associated with higher urinary BPA concentrations: 41% (95% CI 1.23, 1.63) higher BPA for vegetable and fruit, 70% (95% CI 1.18, 2.44) higher for canned pasta, and 229% (95% CI 1.22, 4.30) higher for canned soup. Canned beverages were not associated with urinary BPA concentrations.nnnCONCLUSIONSnCanned food, including some specific types such as canned vegetable and fruit, canned pasta, and canned soup were associated with higher levels of urinary BPA concentrations.

Nitarsone, Inorganic Arsenic, and Other Arsenic Species in Turkey Meat: Exposure and Risk Assessment Based on a 2014 U.S. Market Basket Sample

Background: Use of nitarsone, an arsenic-based poultry drug, may result in dietary exposures to inorganic arsenic (iAs) and other arsenic species. Nitarsone was withdrawn from the U.S. market in 2015, but its use in other countries may continue. Objectives: We characterized the impact of nitarsone use on arsenic species in turkey meat and arsenic exposures among turkey consumers, and we estimated cancer risk increases from consuming turkey treated with nitarsone before its 2015 U.S. withdrawal. Methods: Turkey from three cities was analyzed for total arsenic, iAs, methylarsonate (MA), dimethylarsinate, and nitarsone, which were compared across label type and month of purchase. Turkey consumption was estimated from NHANES data to estimate daily arsenic exposures for adults and children 4–30 months of age and cancer risks among adult consumers. Results: Turkey meat from conventional producers not prohibiting nitarsone use showed increased mean levels of iAs (0.64 μg/kg) and MA (5.27 μg/kg) compared with antibiotic-free and organic meat (0.39 μg/kg and 1.54 μg/kg, respectively) and meat from conventional producers prohibiting nitarsone use (0.33 μg/kg and 0.28 μg/kg, respectively). Samples with measurable nitarsone had the highest mean iAs and MA (0.92 μg/kg and 10.96 μg/kg, respectively). Nitarsone was higher in October samples than in March samples, possibly resulting from increased summer use. Based on mean iAs concentrations in samples from conventional producers with no known policy versus policies prohibiting nitarsone, estimated lifetime daily consumption by an 80-kg adult, and a recently proposed cancer slope factor, we estimated that use of nitarsone by all turkey producers would result in 3.1 additional cases of bladder or lung cancer per 1,000,000 consumers. Conclusions: Nitarsone use can expose turkey consumers to iAs and MA. The results of our study support the U.S. Food and Drug Administration’s removal of nitarsone from the U.S. market and further support its removal from the global marketplace. Citation: Nachman KE, Love DC, Baron PA, Nigra AE, Murko M, Raber G, Francesconi KA, Navas-Acien A. 2017. Nitarsone, inorganic arsenic, and other arsenic species in turkey meat: exposure and risk assessment based on a 2014 U.S. market basket sample. Environ Health Perspect 125:363–369;u2002http://dx.doi.org/10.1289/EHP225

Racial/Ethnic Differences in Duration of Smoking among Former Smokers in the National Health and Nutrition Examination Surveys (NHANES).

IntroductionnThe burden of tobacco-related disease is not uniformly distributed across racial/ethnic groups. Differences in smoking duration by race/ethnicity may contribute to this disparity. Previous studies have examined racial/ethnic differences in smoking duration among ever smokers (former and current smokers combined). It is unknown if racial/ethnic differences in smoking duration are evident among quitters. This study examined racial/ethnic differences in duration of smoking among former smokers in the United States.nnnMethodsnWe studied 6030 white, black, and Mexican-American former smokers (3647 men and 2383 women) aged 20-79 years who participated in the National Health and Nutrition Examination Survey (NHANES) from 1999 through 2012. Mean differences in smoking duration by race/ethnicity were estimated using linear regression models.nnnResultsnAfter adjustment for demographics, age at smoking initiation and smoking intensity, compared to white men, black men smoked for 2.3 (95% confidence interval [CI]: 1.3, 3.3) years longer before quitting and Mexican-American men for 0.2 (95% CI: -1.6, 1.2) years less before quitting. Compared to white women, black women smoked for 1.9 (95% CI: 0.7, 3.0) years longer before quitting and Mexican-American women for 0.9 (95% CI: -2.4, 0.5) years less before quitting.nnnConclusionsnIn a representative sample of US adults, black former smokers continued smoking for longer periods before quitting compared to white former smokers. These findings support the need for smoking cessation efforts that address racial/ethnic differences in smoking behaviors. The longer time to quit among black former smokers should be investigated as an explanation for racial/ethnic disparities in smoking-associated diseases.nnnImplicationsnIn a representative sample of US adults that successfully quit smoking, the timing of smoking cessation differed by race/ethnicity with blacks smoking for longer periods before quitting compared to whites. Racial/ethnic differences in duration of smoking among former smokers differed by participant age and age at smoking initiation. These findings support the need for smoking cessation efforts that address racial/ethnic differences in smoking behaviors.

Secondhand Tobacco Smoke Exposure Associations With DNA Methylation of the Aryl Hydrocarbon Receptor Repressor

IntroductionnCigarette smoking is inversely associated with DNA methylation of the aryl hydrocarbon receptor repressor (AHRR; cg05575921). However, the association between secondhand tobacco smoke (SHS) exposure and AHRR methylation is unknown.nnnMethodsnDNA methylation of AHRR cg05575921 in CD14+ monocyte samples, from 495 never-smokers and 411 former smokers (having quit smoking ≥15 years) from the Multi-Ethnic Study of Atherosclerosis (MESA), was cross-sectionally compared with concomitantly ascertained self-reported SHS exposure, urine cotinine concentrations, and estimates of air pollutants at participants homes. Linear regression was used to test for associations, and covariates included age, sex, race, education, study site, and previous smoking exposure (smoking status, time since quitting, and pack-years).nnnResultsnRecent indoor SHS exposure (hours per week) was inversely associated with cg05575921 methylation (β ± SE = -0.009 ± 0.003, p = .007). The inverse effect direction was consistent (but did not reach significance) in the majority of stratified analyses (by smoking status, sex, and race). Categorical analysis revealed high levels of recent SHS exposure (≥10 hours per week) inversely associated with cg05575921 methylation (β ± SE = -0.28 ± 0.09, p = .003), which remained significant (p < .05) in the majority of stratified analyses. cg05575921 methylation did not significantly (p < .05) associate with low to moderate levels of recent SHS exposure (1-9 hours per week), urine cotinine concentrations, years spent living with people smoking, years spent indoors (not at home) with people smoking, or estimated levels of air pollutants.nnnConclusionsnHigh levels of recent indoor SHS exposure may be inversely associated with DNA methylation of AHRR in human monocytes.nnnImplicationsnDNA methylation is a biochemical alteration that can occur in response to cigarette smoking; however, little is known about the effect of SHS on human DNA methylation. In the present study, we evaluated the association between SHS exposure and DNA methylation in human monocytes, at a site (AHRR cg05575921) known to have methylation inversely associated with current and former cigarette smoking compared to never smoking. Results from this study suggest high levels of recent SHS exposure inversely associate with DNA methylation of AHRR cg05575921 in monocytes from nonsmokers, albeit with weaker effects than active cigarette smoking.

Arsenic metabolism and one-carbon metabolism at low-moderate arsenic exposure: Evidence from the Strong Heart Study

B-vitamins involved in one-carbon metabolism (OCM) can affect arsenic metabolism efficiency in highly arsenic exposed, undernourished populations. We evaluated whether dietary intake of OCM nutrients (including vitamins B2, B6, folate (B9), and B12) was associated with arsenic metabolism in a more nourished population exposed to lower arsenic than previously studied. Dietary intake of OCM nutrients and urine arsenic was evaluated in 405 participants from the Strong Heart Study. Arsenic exposure was measured as the sum of iAs, monomethylarsonate (MMA) and dimethylarsenate (DMA) in urine. Arsenic metabolism was measured as the individual percentages of each metabolite over their sum (iAs%, MMA%, DMA%). In adjusted models, increasing intake of vitamins B2 and B6 was associated with modest but significant decreases in iAs% and MMA% and increases in DMA%. A significant interaction was found between high folate and B6 with enhanced arsenic metabolism efficiency. Our findings suggest OCM nutrients may influence arsenic metabolism in populations with moderate arsenic exposure. Stronger and independent associations were observed with B2 and B6, vitamins previously understudied in relation to arsenic. Research is needed to evaluate whether targeting B-vitamin intake can serve as a strategy for the prevention of arsenic-related health effects at low-moderate arsenic exposure.

Smoking intensity (pack/day) is a better measure than pack-years or smoking status for modeling cardiovascular disease outcomes

OBJECTIVESnSmoking as an epidemiological exposure can be quantified in many ways including duration, intensity, pack-years, recency, and age at initiation. However, it is not clear which of these are most important for cardiovascular disease (CVD) and how they should be modeled.nnnSTUDY DESIGN AND SETTINGnUsing the Multi-Ethnic Study of Atherosclerosis, Cox models for time to incident CVD adjusted for age, sex, race/ethnicity, education category, and income category were compared which included various characterizations of smoking history.nnnRESULTSnDuration, age at starting, time since quitting, and noncigarette forms of smoking were not independently associated with CVD, whereas baseline current intensity was associated with CVD [e.g., hard CVD hazard ratio 1 pack/d of 1.85 95% confidence interval (1.33, 2.57)]. Former smokers, regardless of duration, intensity, or recency, were not at increased risk, suggesting that risk may risk may drop precipitously from the time of quitting. For CVD events, representing smoking exposure as baseline smoking intensity produced better model fit as measured by Akaike information criterion than models using smoking status or pack-years.nnnCONCLUSIONnThe association of smoking with incident CVD events was well captured by including a simple term for baseline smoking intensity.

A dose-response meta-analysis of chronic arsenic exposure and incident cardiovascular disease

BackgroundnConsistent evidence at high levels of water arsenic (≥100 µg/l), and growing evidence at low-moderate levels (<100 µg/l), support a link with cardiovascular disease (CVD). The shape of the dose-response across low-moderate and high levels of arsenic in drinking water is uncertain and critical for risk assessment.nnnMethodsnWe conducted a systematic review of general population epidemiological studies of arsenic and incident clinical CVD (all CVD, coronary heart disease (CHD) and stroke) with three or more exposure categories. In a dose-response meta-analysis, we estimated the pooled association between log-transformed water arsenic (log-linear) and restricted cubic splines of log-transformed water arsenic (non-linear) and the relative risk of each CVD endpoint.nnnResultsnTwelve studies (pooled N = 408 945) conducted at high (N = 7) and low-moderate (N = 5) levels of water arsenic met inclusion criteria, and 11 studies were included in the meta-analysis. Compared with 10 µg/l, the estimated pooled relative risks [95% confidence interval (CI)] for 20 µg/l water arsenic, based on a log-linear model, were 1.09 (1.03, 1.14) (N = 2) for CVD incidence, 1.07 (1.01, 1.14) (N = 6) for CVD mortality, 1.11 (1.05, 1.17) (N = 4) for CHD incidence, 1.16 (1.07, 1.26) (N = 6) for CHD mortality, 1.08 (0.99, 1.17) (N = 2) for stroke incidence and 1.06 (0.93, 1.20) (N = 6) for stroke mortality. We found no evidence of non-linearity, although these tests had low statistical power.nnnConclusionsnAlthough limited by the small number of studies, this analysis supports quantitatively including CVD in inorganic arsenic risk assessment, and strengthens the evidence for an association between arsenic and CVD across low-moderate to high levels.

Dietary determinants of cadmium exposure in the Strong Heart Family Study

Urinary cadmium (Cd) concentrations in the Strong Heart Family Study (SHFS) participants are higher than in the general US population. This difference is unlikely to be related to tobacco smoking. We evaluated the association of consumption of processed meats and other dietary products with urinary Cd concentrations in the SHFS, a family-based study conducted in American Indian communities. We included 1725 participants with urine Cd concentrations (standardized to urine creatinine) and food frequency questionnaire data grouped in 24 categories, including processed meat. Median (IQR) urinary Cd concentrations were 0.42 (0.20-0.85) μg/g creatinine. The age, sex, smoking, education, center, body mass index, and total kcal adjusted geometric mean ratio (GMR) (95%CI) of urinary cadmium concentrations per IQR increase in each dietary category was 1.16 (1.04-1.29) for processed meat, 1.10 (1.00-1.21) for fries and chips, 0.87 (0.80-0.95) for dairy products, and 0.89 (0.82-0.97) for fruit juices. The results remained similar after further adjustment for the dietary categories associated with urinary Cd in the previous model except for fries and chips, which was no longer statistically significant. These findings revealed the potential importance of processed meat products as a dietary source of cadmium.