Comprehensive compilation of congener profiles to support health assessment of environmental exposures to polychlorinated biphenyl mixtures.

Exposure to polychlorinated biphenyls (PCBs) remains a potential human health risk due to their persistence in the environment, despite a global ban on their production. Understanding the composition of PCB mixtures is essential for the application of a mixtures-based approach to assessing health risks of PCB exposure. This work represents the most extensive effort to date to compile and make publicly available the PCB congener profiles for mixtures with toxicological data, providing a foundation for understanding toxicological potency of PCB mixtures in the environment. We searched for published congener profiles across 29 commercial and simulated environmental PCB mixtures, including various Aroclors, Phenoclors, Clophens, and Kanechlors, among others. A total of 117 references containing 401 distinct complete or partial tabularized profiles were found. Aroclor 1254 had the most published profiles, with 79 unique datasets characterizing multiple mixture lots. In contrast, no congener-specific composition data were identified for Fenclors, Clophen C, or Pyralenes. Eighty-seven of the most complete and clearly reported profiles underwent a detailed extraction of the congener data, PCB mixture source, and analytical methods. Challenges encountered during data extraction included congener coelutions, incomplete methods reporting, and inconsistencies in PCB nomenclature. These factors complicate data visualization, comparisons across datasets, and use of the data in subsequent analyses. Where possible, we have converted profiles to the same units and congener numbering convention to allow for easier comparison. The extracted data are publicly available online as interactive visuals and as a downloadable Microsoft Excel® workbook. This dataset provides researchers with an overview of the current PCB mixture profile landscape that can serve as a tool to support efforts to minimize the health impacts of environmental PCB exposure, including the exploration of links between mixture composition and toxicity and the identification of the most efficient and effective remediation strategies at contaminated sites.

A systematic evidence map for the evaluation of noncancer health effects and exposures to polychlorinated biphenyl mixtures.

Assessing health outcomes associated with exposure to polychlorinated biphenyls (PCBs) is important given their persistent and ubiquitous nature. PCBs are classified as a Group 1 carcinogen, but the full range of potential noncancer health effects from exposure to PCBs has not been systematically summarized and evaluated. We used systematic review methods to identify and screen the literature using combined manual review and machine learning approaches. A protocol was developed that describes the literature search strategy and Populations, Exposures, Comparators, and Outcomes (PECO) criteria used to facilitate subsequent screening and categorization of literature into a systematic evidence map of PCB exposure and noncancer health endpoints across 15 organs/systems. A comprehensive literature search yielded 62,599 records. After electronic prioritization steps, 17,037 studies were manually screened at the title and abstract level. An additional 900 studies identified by experts or supplemental searches were also included. After full-text screening of 3889 references, 1586 studies met the PECO criteria. Relevant study details such as the endpoints assessed, exposure duration, and species were extracted into literature summary tables. This review compiles and organizes the human and mammalian studies from these tables into an evidence map for noncancer health endpoints and PCB mixture exposure to identify areas of robust research as well as areas of uncertainty that would benefit from future investigation. Summary data are available online as interactive visuals with downloadable metadata. Sufficient research is available to inform PCB hazard assessments for most organs/systems, but the amount of data to inform associations with specific endpoints differs. Furthermore, despite many years of research, sparse data exist for inhalation and dermal exposures, which are highly relevant human exposure routes. This evidence map provides a foundation for future systematic reviews and noncancer hazard assessments of PCB mixtures and for strategic planning of research to inform areas of greater uncertainty.

Epidemiology Evidence for Health Effects of 150 per- and Polyfluoroalkyl Substances: A Systematic Evidence Map.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) comprise a large class of chemicals with widespread use and persistence in the environment and in humans; however, most of the epidemiology research has focused on a small subset. OBJECTIVES: The aim of this systematic evidence map (SEM) is to summarize the epidemiology evidence on approximately 150 lesser studied PFAS prioritized by the EPA for tiered toxicity testing, facilitating interpretation of those results as well as identification of priorities for risk assessment and data gaps for future research. METHODS: The Populations, Exposure, Comparators, and Outcomes (PECO) criteria were intentionally broad to identify studies of any health effects in humans with information on associations with exposure to the identified PFAS. Systematic review methods were used to search for literature that was screened using machine-learning software and manual review. Studies meeting the PECO criteria underwent quantitative data extraction and evaluation for risk of bias and sensitivity using the Integrated Risk Information System approach. RESULTS: 193 epidemiology studies were identified, which included information on 15 of the PFAS of interest. The most commonly studied health effect categories were metabolic (n=37), endocrine (n=30), cardiovascular (30), female reproductive (n=27), developmental (n=26), immune (n=22), nervous (n=21), male reproductive (n=14), cancer (n=12), and urinary (n=11) effects. In study evaluation, 120 (62%) studies were considered High/Medium confidence for at least one outcome. DISCUSSION: Most of the PFAS in this SEM have little to no epidemiology data available to inform evaluation of potential health effects. Although exposure to the 15 PFAS that had data was fairly low in most studies, these less-studied PFAS may be used as replacements for "legacy" PFAS, leading to potentially greater exposure. It is impractical to generate epidemiology evidence to fill the existing gaps for all potentially relevant PFAS. This SEM highlights some of the important research gaps that currently exist. https://doi.org/10.1289/EHP11185.

An evidence map of polychlorinated biphenyl exposure and health outcome studies among residents of the Akwesasne Mohawk Nation.

From the 1950s to the 1970s, three Superfund sites discharged polychlorinated biphenyl (PCB)-contaminated waste upstream of the Mohawk Nation at Akwesasne, resulting in PCB contamination of groundwater, soil, and sediment in the surrounding area. Given the persistence of PCBs in the environment and in human tissues, there are continued concerns regarding PCB exposures and the potential for adverse health effects in the community. We developed an evidence map of PCB research at Akwesasne in order to characterize the available data and to highlight potential research needs. Human health and exposure biomarker studies were identified from a literature search based on population, exposure, comparator, and outcome (PECO) criteria. Data extracted from references that met the inclusion criteria after full-text review included study characteristics (e.g., sample size, study design, sampling years), details on PCB measurements (e.g., analytical method, number of congeners analyzed, method detection limits), and results (e.g., PCB levels and summary of study conclusions). We identified 33 studies, conducted between 1986 and 2013, that examined PCB exposure characteristics and health effects in residents of the Akwesasne Mohawk Nation. Organizing this literature into an evidence map including information on study cohort, congener groupings, exposure biomarker characteristics, and health effects allowed us to identify research gaps and to suggest future research priorities for the community. We identified current PCB exposure levels and PCB source characterization as major uncertainties, both of which could be addressed by new studies of PCB concentrations in environmental media.

Prenatal exposure to multiple metals and birth outcomes: An observational study within the National Children's Study cohort.

BACKGROUND: Prenatal exposure to metals may play an important role in fetal growth. However, the epidemiologic evidence for certain metals is sparse, and most of the existing research has focused on evaluating single metals in highly exposed target populations. OBJECTIVES: We evaluated associations of cadmium, lead, manganese, selenium, and total mercury exposures during pregnancy with fetal growth using data from mother-infant pairs participating in the National Children's Study. METHODS: Prenatal metal exposures were measured using maternal blood collected from 6 to 32 weeks of gestation. Birth outcomes, including gestational age, birthweight, birth length, head circumference, and ponderal index, were ascertained through physical measurement at birth or abstraction from medical records. Regression coefficients and their 95% confidence intervals were estimated from multivariable linear regression models in the overall study population as well as among male and female infants. We further evaluated pairwise metal-metal interactions. RESULTS: Sex-specific associations were observed for lead, with inverse associations for birthweight, birth length, head circumference, and gestational age observed only among female infants. Sex-specific associations were also observed for selenium, with a positive association for birthweight observed among male infants; selenium was also positively associated with ponderal index and inversely associated with birth length among female infants. Overall, total mercury was inversely associated with birthweight and ponderal index, and the association with birthweight was stronger among female infants. No significant associations were observed with cadmium and manganese. In the metal-metal interaction analyses, we found evidence of a synergistic interaction between lead and total mercury and antagonistic interaction between selenium and total mercury with selected birth outcomes. CONCLUSIONS: Our findings suggest that prenatal exposure to metals may be related to birth outcomes, and infant sex may modify these associations.

The role of epidemiology studies in human health risk assessment of polychlorinated biphenyls.

Polychlorinated biphenyls (PCBs) are a public health concern given evidence that they persist and accumulate in the environment and can cause toxic effects in animals and humans. However, evaluating adverse effects of PCBs in epidemiologic studies is complicated by the characteristics of PCB exposure. PCBs exist as mixtures in the environment; the mixture changes over time due to degradation, and given physicochemical differences between specific PCB congeners, the mixture that an individual is exposed to (via food, air, or other sources) is likely different from that which can be measured in biological tissues. This is particularly problematic when evaluating toxicity of shorter-lived congeners that may not be measurable by the time biological samples are collected. We review these and other issues that arise when evaluating epidemiologic studies of PCBs and discuss how epidemiology data can still be used to inform both hazard identification and dose-response evaluation.

Dietary carotenoids and cognitive function among US adults, NHANES 2011-2014.

Objectives: Dietary carotenoids may limit neuronal damage from free radicals, potentially serving as a modifiable risk factor for cognitive decline. We examined intake of lutein and zeaxanthin (L and Z) in relation to cognitive performance among 2011-2014 National Health and Nutrition Examination Survey participants aged ≥60 years. Methods: L and Z intake from foods and supplements was estimated from two non-consecutive 24-hour diet recalls. Outcomes included the CERAD Word Learning sub-test score, Animal Fluency test score, and Digit Symbol Substitution test score. Regression models were adjusted for survey design variables, year, sex, age, race/ethnicity, body mass index, family income, education, alcohol, and smoking. Results: Among the 2796 participants, higher dietary intake of L and Z was associated with higher score on each test. For example, the highest quartile of L and Z intake was associated with a 2.52 point increase (SE=0.86 points, P=0.01) on the digit symbol score test, compared with the lowest quartile. There were differences by race/ethnicity, with positive associations generally stronger for Black compared to white participants. Discussion: Further research from longitudinal studies is needed, but increasing L and Z intake may help to prevent or slow cognitive decline.

Dietary Carotenoids and Non-Alcoholic Fatty Liver Disease among US Adults, NHANES 2003⁻2014.

Non-alcoholic fatty liver disease (NAFLD) is highly prevalent worldwide. Oxidative stress is thought to be a major mechanism, and previous epidemiological studies found higher serum levels of antioxidant carotenoids were associated with reduced risk for development and progression of NAFLD. The objective of this analysis is to examine cross-sectional associations between dietary and serum levels of carotenoids in relation to NAFLD among a nationally representative sample of US adults. We used data from the 2003-2014 National Health and Nutrition Examination Survey (NHANES). Dietary carotenoid intake was estimated from a 24-hour recall, while serum carotenoids were measured from 2003 to 2006. The NAFLD status was determined based upon US Fatty Liver Index (FLI) value ≥30. Regression models were used to estimate associations between carotenoids and NAFLD by controlling for covariates and adjusting for survey design variables. Overall, 33% of participants were classified as having NAFLD. Intake of all carotenoids, with the exception of lycopene, was lower among those with NAFLD. This association was significant for the highest quartiles of intake of α-carotene, ß-carotene, ß-cryptoxanthin, and lutein/zeaxanthin. For serum measures, the highest level of all carotenoids was associated with significantly reduced odds of NAFLD. In conclusion, higher intake and serum levels of most carotenoids were associated with lower odds of having NAFLD. Identification of such modifiable lifestyle factors provide an opportunity to limit or prevent the disease and its progression.

Childhood Lead Poisoning in Wisconsin.

INTRODUCTION: In 2016, 4,353 Wisconsin children under 6 years of age were identified with elevated blood lead levels (≥ 5 µg/dL). There is no safe level of lead in the human body; extensive research shows that children with blood lead levels < 5 µg/dL may still be at risk for adverse health effects including developmental delays. DISCUSSION: Physicians should follow current guidelines and consider factors such as the child's age, socioeconomic status, and housing situation when determining need for testing. In addition to Wisconsin's screening recommendations, federal requirements exist for testing Medicaidenrolled children. Under state statute, all blood lead test results and specified demographic information must be reported to the Wisconsin Childhood Lead Poisoning Prevention Program. To eliminate elevated blood lead levels, primary prevention is key. Physicians play an important role by educating parents, prospective parents, and caregivers about lead poisoning risks and prevention measures. Physicians are also vital in secondary prevention-mitigating the adverse effects in children already exposed to lead. Secondary prevention requires first identifying children with elevated blood lead levels through appropriate testing. Use of the Wisconsin Blood Lead Registry can alert providers about children with elevated blood lead levels and reduce duplicate testing. Recent surveillance data show current screening is inadequate; in 2015, only 32% of Medicaid-enrolled children received appropriate testing. Physicians should provide clinical management for children with elevated blood levels and their families. CONCLUSIONS: Physicians are a vital partner in preventing, identifying, and mitigating the effects of elevated blood lead levels for Wisconsin's children.

Dietary Antioxidants, Macular Pigment, and Glaucomatous Neurodegeneration: A Review of the Evidence.

Primary open-angle glaucoma (POAG) is a leading cause of irreversible blindness worldwide, and the prevalence is projected to increase to 112 million worldwide by 2040. Intraocular pressure is currently the only proven modifiable risk factor to treat POAG, but recent evidence suggests a link between antioxidant levels and risk for prevalent glaucoma. Studies have found that antioxidant levels are lower in the serum and aqueous humor of glaucoma patients. In this review, we provide a brief overview of the evidence linking oxidative stress to glaucomatous pathology, followed by an in-depth discussion of epidemiological studies and clinical trials of antioxidant consumption and glaucomatous visual field loss. Lastly, we highlight a possible role for antioxidant carotenoids lutein and zeaxanthin, which accumulate in the retina to form macular pigment, as evidence has emerged supporting an association between macular pigment levels and age-related eye disease, including glaucoma. We conclude that the evidence base is inconsistent in showing causal links between dietary antioxidants and glaucoma risk, and that prospective studies are needed to further investigate the possible relationship between macular pigment levels and glaucoma risk specifically.

Perfluoroalkyl substances and metabolic syndrome.

BACKGROUND: Perfluoroalkyl substances (PFAS) are a class of contaminants used in many industrial applications and consumer products. Certain PFAS are regulated or voluntarily limited due to concern about environmental persistence and adverse health effects. OBJECTIVES: In this analysis we examine PFAS levels and their association with metabolic syndrome and its components, using a representative sample of the U.S. METHODS: Data on PFAS levels and metabolic syndrome components were collected from the 2007-2008, 2009-2010, 2011-2012, and 2013-2014 cycles of the National Health and Nutrition Examination Survey. Twelve different PFAS were measured in serum samples from participants. Logistic regression models were used to identify associations between metabolic syndrome, its individual components, and serum PFAS concentrations. RESULTS: Over one-third (37%) of participants met the definition for metabolic syndrome, with increased waist circumference and elevated glucose being the most commonly reported components. Seven PFAS were detected in at least 30% of participants and were examined in subsequent analyses (PFDA, PFOA, PFOS, PFHxS, MPAH, PFNA, PFUnDA). The PFAS with the highest concentrations was PFOS (median 8.4 ng/mL), followed by PFOA, PFHxS and PFNA. After adjusting for potential confounders, PFNA was associated with increased risk of metabolic syndrome and well as several individual components, while the highest levels of PFHxS were associated with elevated triglycerides. Other PFAS were associated with decreased risk of at least one outcome. CONCLUSIONS: Associations between PFAS and metabolic syndrome are inconsistent within and across studies. PFNA was consistently associated with increased risk for components of the syndrome, a finding that warrants further investigation.

Using Medicaid Data to Improve Childhood Lead Poisoning Prevention Program Outcomes and Blood Lead Surveillance.

CONTEXT: Wisconsin-specific data revealed that not all Medicaid providers were testing children appropriately for blood lead levels and not all blood lead tests were reported to the Department of Health Services, Childhood Lead Poisoning Prevention Program. The Medicaid program requires blood lead screening for all Medicaid-enrolled children at specific ages. Wisconsin state law requires reporting of all blood lead test results. Projects were implemented to encourage appropriate testing for Medicaid-enrolled children and improve blood lead surveillance. METHODS: Medicaid billing data were linked to blood lead data to identify Medicaid-enrolled children who had not received the required tests. Medicaid provider report cards were distributed annually from 2006 to 2011 to inform providers of their compliance with federal testing requirements and of the names of children within their practice who had not been tested. Blood lead tests billed to Medicaid but not in the blood lead database were identified and billing providers were contacted to obtain the test report. RESULTS: The number of children tested increased from 81 834 children per year in 2006 to 106 003 children per year in 2010. Testing of Medicaid-enrolled children increased by 31% from 2006 to 2010. The percentage of Medicaid-enrolled children receiving an age-appropriate test increased from 46% in 2004 to a high of 55% in 2010. There were 9035 blood lead tests identified in the Medicaid billing data that had not been reported from 2007 to 2015. There were 468 billing providers who had unreported tests. All sites with unreported tests were contacted, 84% of test results were obtained, and 14% of test records could not be retrieved. Outpatient clinics accounted for the majority of all unreported tests (72%) and irretrievable test records (74%). DISCUSSION: Childhood lead poisoning prevention programs can effectively utilize Medicaid data to increase testing and improve blood lead surveillance. Primary health care providers should ensure that Medicaid-enrolled children in their care receive the age-appropriate tests. Many Wisconsin health care providers lack awareness of blood lead test reporting requirements. Outpatient clinics account for the largest proportion of unreported tests and highest priority should be given working with these sites to improve reporting practices.

An Occupational Legacy: Malignant Mesothelioma Incidence and Mortality in Wisconsin.

OBJECTIVES: The aim of the study was to describe mesothelioma occurrence in Wisconsin from 1997 to 2013 by usual industry and occupation (I&O), including occupations generally considered low risk. METHODS: Population-based rates and standardized incidence and mortality ratios were calculated. Two case-control analyses were designed to compare mesothelioma incidence and mortality in specific I&O groups with occurrence of (1) brain and central nervous system cancers and (2) other causes of death, using logistic regression. RESULTS: Mesothelioma incidence and mortality were elevated in Wisconsin (SIRadj = 1.20 [1.13 to 1.28]; SMRadj = 1.30 [1.22 to 1.38]). Certain industry (construction, manufacturing) and occupation (construction and extraction) groups were associated with increased odds of mesothelioma, with some evidence of increased risk among teachers. CONCLUSIONS: Forty years after the Occupational and Safety Health Act, mesothelioma incidence and mortality remain elevated in Wisconsin, with increased risk continuing for certain I&O groups.

Lead Exposure Among Workers at a Shipyard-Wisconsin, 2015 to 2016.

OBJECTIVE: In March 2016, the state health departments of Wisconsin and Minnesota learned of three shipyard workers with blood lead levels (BLLs) more than 40 µg/dL. An investigation was conducted to determine the extent of and risk factors for the exposure. METHODS: We defined a case as an elevated BLL more than or equal to 5 µg/dL in a shipyard worker. Workers were interviewed regarding their symptoms and personal protective equipment (PPE) use. RESULTS: Of 357 workers, 65.0% had received more than or equal to 1 BLL test. Among tested workers, 171 (73.7%) had BLLmax more than or equal to 5 µg/dL. Workers who received respirator training or fit testing had a median BLLmax of 18.0 µg/dL, similar to the median BLLmax of workers who did not receive such training (22.6 µg/dL, P = 0.20). CONCLUSIONS: Our findings emphasize the importance of adequate provision and use of PPE to prevent occupational lead exposure.

Changes in Hair Mercury Levels Among Women of Child-Bearing Age Following an Educational Intervention.

OBJECTIVE: Describe mercury exposures among women of childbearing age before and after an educational intervention. METHODS: Women age 18 to 45 were recruited to participate in an educational intervention concerning fish consumption. Fish consumption habits and total mercury concentration in hair were assessed pre- and post-intervention. Regression models examined associations between mercury, fish consumption, and demographics. RESULTS: Overall, 234 women completed the study. On average, mercury concentrations increased by 0.01 ppm (parts per million) following the intervention, despite declines in fish consumption; however, women in the 90th percentile for mercury at baseline decreased concentrations significantly while maintaining high rates of fish consumption. Mercury concentrations were positively correlated with fish consumption and certain demographic characteristics. CONCLUSIONS: The intervention reached individuals most at-risk. Healthcare providers should discuss fish consumption habits with women to encourage consumption of low-risk fish, and identify women needing education and counseling.

Perfluoroalkyl substances and fish consumption.

BACKGROUND: Perfluoroalkyl substances (PFAS) are an emerging class of contaminants. Certain PFAS are regulated or voluntarily limited due to concern about environmental persistence and adverse health effects, including thyroid disease and dyslipidemia. The major source of PFAS exposure in the general population is thought to be consumption of seafood. OBJECTIVES: In this analysis we examine PFAS levels and their determinants, as well as associations between PFAS levels and self-reported fish and shellfish consumption, using a representative sample of the U.S. METHODS: Data on PFAS levels and self-reported fish consumption over the past 30 days were collected from the 2007-2008, 2009-2010, 2011-2012, and 2013-2014 cycles of the National Health and Nutrition Examination Survey. Twelve different PFAS were measured in serum samples from participants. Ordinary least squares regression models were used to identify factors (demographic characteristics and fish consumption habits) associated with serum PFAS concentrations. Additional models were further adjusted for other potential exposures including military service and consumption of ready-to-eat and fast foods. RESULTS: Seven PFAS were detected in at least 30% of participants and were examined in subsequent analyses (PFDA, PFOA, PFOS, PFHxS, MPAH, PFNA, PFUA). The PFAS with the highest concentrations were PFOS, followed by PFOA, PFHxS and PFNA (medians of 8.3, 2.7, 1.5 and 1.0ng/mL). Fish consumption was generally low, with a median of 1.2 fish meals and 0.14 shellfish meals, reported over the past 30 days. After adjusting for demographic characteristics, total fish consumption was associated with reduced MPAH, and with elevated PFDE, PFNA and PFuDA. Shellfish consumption was associated with elevations of all PFAS examined except MPAH. Certain specific fish and shellfish types were also associated with specific PFAS. Adjustment for additional exposure variables resulted in little to no change in effect estimates for seafood variables. CONCLUSIONS: PFAS are emerging contaminants with widespread exposure, persistence, and potential for adverse health effects. In the general population, fish and shellfish consumption are associated with PFAS levels, which may indicate an avenue for education and outreach.

Associations Between Fish Consumption and Contaminant Biomarkers With Cardiovascular Conditions Among Older Male Anglers in Wisconsin.

OBJECTIVE: The aim of this study was to determine fish consumption habits and contaminant exposures associated with adverse cardiovascular outcomes among older male anglers. METHODS: One hundred fifty-four men aged 50 years and older living and fishing in Wisconsin completed a detailed survey and provided hair and blood samples. Associations between fish consumption and body burdens of several contaminants, with self-reported cardiovascular outcomes, were evaluated. RESULTS: Consuming fish species with higher methyl mercury content was positively associated with odds of angina, coronary heart disease (CHD), or heart attack, while consuming fattier species was negatively associated with high blood pressure or high cholesterol. Total mercury in blood was associated with 27% higher odds of heart attack, and certain classes of polychlorinated biphenyls were positively associated with CHD. CONCLUSION: Total mercury exposures may affect cardiovascular outcomes. Educational interventions promoting consumption of fish low in methyl mercury among older male anglers are needed.

Fish Consumption, Levels of Nutrients and Contaminants, and Endocrine-Related Health Outcomes Among Older Male Anglers in Wisconsin.

OBJECTIVE: The aim of this study was to examine associations between endocrine disorders, fish consumption habits, and biomarkers of contaminants and nutrients METHODS: : Male anglers aged at least 50 years living in Wisconsin (n = 154) completed a questionnaire and provided biological samples. Adjusted logistic regression models were used to evaluate risk factors for endocrine outcomes. RESULTS: Nineteen percent of anglers reported either pre-diabetes or diabetes, while 4.6% reported thyroid disease. There were few associations between endocrine disease and fish consumption, fish meal source, or species, aside from a notable increase in diabetes risk with lake trout consumption. Docosahexaenoic acid, certain polychlorinated biphenyls (PCBs), and perfluorinated compounds were associated with an increased risk of diabetes or pre-diabetes. PCBs were associated with a decreased risk of thyroid disease. CONCLUSION: Fish consumption patterns may affect risk for endocrine outcomes, but direction and magnitude of association may depend on the balance of the contaminants and nutrients in the individual diet.