Perfluoroalkyl chemicals and elevated serum uric acid in US adults

Anoop Shankar, Jie Xiao, Alan DucatmanDepartment of Community Medicine, West Virginia University School of Medicine, Morgantown, WV, USABackground: Perfluoroalkyl chemicals, including perfluorooctanoic acid and perfluorooctane sulfonate, are man-made chemicals that have been detected in the blood of over 98% of the US population. Serum uric acid is a novel biomarker, even mild elevations of which has been implicated in the development of hypertension, diabetes mellitus, cardiovascular disease, and chronic kidney disease. We examined the relationship of serum perfluoroalkyl chemicals, including perfluorooctanoic acid and perfluorooctane sulfonate, and elevated uric acid levels in a representative sample of US adults.Methods: We examined 3883 participants from the 1999–2000 and 2003–2006 National Health and Nutritional Examination Surveys,a representative, multiethnic population-based survey of noninstitutionalized US adults. Serum perfluorooctanoic acid and perfluorooctane sulfonate were analyzed as quartiles. The main outcome was hyperuricemia.Results: We found that serum levels of perfluoroalkyl chemicals, including perfluorooctanoic acid and perfluorooctane sulfonate, were positively associated with hyperuricemia. This association appeared to be independent of confounders such as age, gender, race-ethnicity, body mass index, diabetes, hypertension, and serum cholesterol. Compared with subjects in quartile 1 (referent), the multivariate odds ratio for hyperuricemia among subjects in quartile 4 was 1.97 (95% confidence interval 1.44–2.70, P < 0.0001) for perfluorooctanoic acid and 1.48% (95% confidence interval 0.99–2.22, P = 0.0433) for perfluorooctane sulfonate. This observed association persisted in subgroup analysis by gender and body mass index.Conclusion: Our results demonstrate that elevated levels of perfluoroalkyl chemicals are associated with hyperuricemia even at low perfluoroalkyl chemical exposure levels as seen in the US general population.Keywords: perfluoroalkyl chemicals, perfluorooctanoic acid, perfluorooctane sulfonate, uric aci

Association between Six Environmental Chemicals and Lung Cancer Incidence in the United States

Background. An increased risk of lung cancer has been observed at exposure to certain industrial chemicals in occupational settings; however, less is known about their carcinogenic potential to the general population when those agents are released into the environment. Methods. We used the Toxics Release Inventory (TRI) database and Surveillance, Epidemiology, and End Results (SEER) data to conduct an ecological study at the county level. We used multiple linear regression to assess the association of age-adjusted lung cancer incidence with the quantities of on-site air and water releases of six selected industrial chemicals including arsenic, 1,3 butadiene, cadmium, chromium, formaldehyde, and nickel after controlling for other risk variables. Results. Overall, we observed a significantly increased risk of lung cancer incidence associated with releases of chromium, formaldehyde, and nickel. The links were present for both males and females. Significant effects were present in nonmetropolitan but not metropolitan counties. Releases of arsenic, 1,3 butadiene, and cadmium were reported by small numbers of facilities, and no relationships to lung cancer incidence were detected. Conclusions. Our results suggest that environmental exposure to chromium, formaldehyde, and nickel from TRI sites may increase population risk of lung cancer. These findings need to be confirmed in individual-level studies, but in congruence with the precautionary principle in environmental science, support prudent efforts to limit release of these agents into the environment

Association of Perfluorooctanoic Acid (PFOA) and Perfluorooctane Sulfonate (PFOS) with Uric Acid among Adults with Elevated Community Exposure to PFOA

Background Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) are compounds that do not occur in nature, have been widely used since World War II, and persist indefinitely in most environments. Median serum levels in the United States are 4 ng/mL for PFOA and 21 ng/mL for PFOS. PFOA has been associated with elevated uric acid in two studies of chemical workers. Uric acid is a risk factor for hypertension and possibly other cardiovascular outcomes. Methods We conducted a cross-sectional study of PFOA and PFOS and uric acid among 54,951 adult community residents in Ohio and West Virginia, who lived or worked in six water districts contaminated with PFOA from a chemical plant. Analyses were conducted by linear and logistic regression, adjusted for confounders. Results Both PFOA and PFOS were significantly associated with uric acid. An increase of 0.2–0.3 mg/dL uric acid was associated with an increase from the lowest to highest decile of either PFOA or PFOS. Hyperuricemia risk increased modestly with increasing PFOA; the odds ratios by quintile of PFOA were 1.00, 1.33 [95% confidence interval (CI), 1.24–1.43], 1.35 (95% CI, 1.26–1.45), 1.47 (95% CI, 1.37–1.58), and 1.47 (95% CI, 1.37–1.58; test for trend, p \u3c 0.0001). We saw a less steep trend for PFOS. Inclusion of both correlated fluorocarbons in the model indicated PFOA was a more important predictor than was PFOS. Conclusion Higher serum levels of PFOA were associated with a higher prevalence of hyperuricemia, but the limitations of cross-sectional data and the possibility of noncausal mechanisms prohibit conclusions regarding causality

Perfluoroalkyl substance excretion: Effects of organic anion-inhibiting and resin-binding drugs in a community setting.

BACKGROUND: Longer serum half-lives of perfluoroalkyl substances (PFAS) in humans compared to other species has been attributed to differences in the activity of organic anion transporters (OAT). METHODS: Among 56,175 adult participants in the community-based C8 Health Project, 23 subjects were taking the uricosuric OAT-inhibitor probenecid, and 36 subjects were taking the bile acid sequestrant cholestyramine. In regression models of log transformed serum PFAS, medication effects were estimated in terms of mean ratios, adjusting for age, gender, BMI, estimated glomerular filtration rate (eGFR) and water-district of residence. RESULTS: Probenecid was associated with modest, but not statistically significant increases in serum PFAS concentrations. In contrast, cholestyramine significantly lowered serum PFAS concentrations, notably for perfluorooctane sulfonic acid (PFOS). CONCLUSIONS: The effectiveness of cholestyramine in a community setting supports the importance of gastrointestinal physiology for PFAS excretion kinetics, especially for PFOS. We did not find clear evidence that probenecid, an inhibitor of OAT, affects PFAS clearance

Tetryl Exposure: Forgotten Hazards Of Antique Munitions

Background: Older yet still abundant munitions such as tetryl present easily forgotten health hazards and associated needs for worker protection. Case presentation: Symptoms and findings from 22 workers who were exposed to tetryl are summarized. Conclusions: This study highlights the health hazards from exposure to tetryl. Occupational health professionals need to maintain vigilance to protect workers from the risks of handling older munitions

Predictors of PFOA Levels in a Community Surrounding a Chemical Plant

BACKGROUND. Perfluorooctanoic acid (PFOA) is considered a probable human carcinogen by the U.S. Environmental Protection Agency. It does not exist in nature but has been used widely since World War II. It is present in the serum of most Americans at about 4-5 ng/mL, although the routes of exposure remain unknown. OBJECTIVES. We examined predictors of PFOA in mid-Ohio Valley residents living near a chemical plant that until recently released large quantities of PFOA into the environment, contaminating drinking water. METHODS. We studied 69,030 residents in six contaminated water districts who participated in a 2005-2006 survey involving a questionnaire and blood tests. Of these, 64,251 had complete data on PFOA and covariates. We also analyzed a subset (71%) for whom we had occupational history. We ran linear regression models to determine serum PFOA predictors. RESULTS. Mean PFOA serum level was 83.0 ng/mL (median, 28.2). The most important predictors were current (median for all districts, 38.4; highest district, 224.1) and past (median, 18.6) residence in contaminated water districts, and current (median, 147.8) and past (median, 74.9) employment at the chemical plant (R^2 model = 0.55). PFOA was higher for males, those consuming local vegetables, and those using well water rather than public water, and lower for those using bottled water. PFOA was higher at younger and older ages. CONCLUSIONS. PFOA levels in this population varied with distance of residence from the plant and employment at the plant. Effects of age and sex reflected prior findings. Effects of other demographic and lifestyle covariates were relatively weak

Quality Improvement Intervention for Reduction of Redundant Testing

Laboratory data are critical to analyzing and improving clinical quality. In the setting of residual use of creatine kinase M and B isoenzyme testing for myocardial infarction, we assessed disease outcomes of discordant creatine kinase M and B isoenzyme +/troponin I (−) test pairs in order to address anticipated clinician concerns about potential loss of case-finding sensitivity following proposed discontinuation of routine creatine kinase and creatine kinase M and B isoenzyme testing. Time-sequenced interventions were introduced. The main outcome was the percentage of cardiac marker studies performed within guidelines. Nonguideline orders dominated at baseline. Creatine kinase M and B isoenzyme testing in 7496 order sets failed to detect additional myocardial infarctions but was associated with 42 potentially preventable admissions/quarter. Interruptive computerized soft stops improved guideline compliance from 32.3% to 58% (P \u3c .001) in services not receiving peer leader intervention and to \u3e80% (P \u3c .001) with peer leadership that featured dashboard feedback about test order performance. This successful experience was recapitulated in interrupted time series within 2 additional services within facility 1 and then in 2 external hospitals (including a critical access facility). Improvements have been sustained postintervention. Laboratory cost savings at the academic facility were estimated to be ≥US$635 000 per year. National collaborative data indicated that facility 1 improved its order patterns from fourth to first quartile compared to peer norms and imply that nonguideline orders persist elsewhere. This example illustrates how pathologists can provide leadership in assisting clinicians in changing laboratory ordering practices. We found that clinicians respond to local laboratory data about their own test performance and that evidence suggesting harm is more compelling to clinicians than evidence of cost savings. Our experience indicates that interventions done at an academic facility can be readily instituted by private practitioners at external facilities. The intervention data also supplement existing literature that electronic order interruptions are more successful when combined with modalities that rely on peer education combined with dashboard feedback about laboratory order performance. The findings may have implications for the role of the pathology laboratory in the ongoing pivot from quantity-based to value-based health care

Suicide and unintentional poisoning mortality trends in the United States, 1987-2006: two unrelated phenomena?

Background Two counter trends in injury mortality have been separately reported in the US in recent times - a declining suicide rate and a rapidly rising unintentional poisoning mortality rate. Poisoning suicides are especially difficult to detect, and injury of undetermined intent is the underlying cause-of-death category most likely to reflect this difficulty. We compare suicide and poisoning mortality trends over two decades in a preliminary assessment of their independence and implications for suicide misclassification. Methods Description of overall and gender- and age-specific trends using national mortality data from WISQARS, the Web-based Injury Statistics Query and Reporting System, maintained by the Centers for Disease Control and Prevention (CDC). Subjects were the 936,633 residents dying in the 50 states and the District of Columbia between 1987 and 2006 whose underlying cause of death was classified as suicide, unintentional poisoning, or injury mortality of undetermined intent. Results The official US suicide rate declined 18% between 1987 and 2000, from 12.71 to 10.43 deaths per 100,000 population. It then increased to 11.15 deaths per 100,000 by 2006, a 7% rise. By contrast to these much smaller rate changes for suicide, the unintentional poisoning mortality rate rose more than fourfold between 1987 and 2006, from 2.19 to 9.22 deaths per 100,000. Only the population aged 65 years and older showed a sustained decline in the suicide rate over the entire observation period. Consistently highest in gender-age comparisons, the elderly male rate declined by 35%. The elderly female rate declined by 43%. Unlike rate trends for the non-elderly, both declines appeared independent of corresponding mortality trends for unintentional poisoning and poisoning of undetermined intent. The elderly also deviated from younger counterparts by having a smaller proportion of their injury deaths of undetermined intent classified as poisoning. Poisoning manifested as a less common method of suicide for this group than other decedents, except for those aged 15-24 years. Although remaining low, the undetermined poisoning mortality rate increased over the observation period. Conclusions The official decline in the suicide rate between 1987 and 2000 may have been a partial artifact of misclassification of non-elderly suicides within unintentional poisoning mortality. We recommend in-depth national, regional, and local population-based research investigations of the poisoning-suicide nexus, and endorse calls for widening the scope of the definition of suicide and evaluation of its risk factors

Serum Perfluorooctanoate (PFOA) and Perfluorooctane Sulfonate (PFOS) Concentrations and Liver Function Biomarkers in a Population with Elevated PFOA Exposure

Background: Perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS) persist in the environment and are found in relatively high concentrations in animal livers. Studies in humans have reported inconsistent associations between PFOA and liver enzymes