Environmental exposure to metals and the development of tauopathies, synucleinopathies, and TDP-43 proteinopathies: A systematic evidence map protocol.

BACKGROUND: Neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis are incurable and expected to increase in prevalence in the upcoming decades. Environmental exposure to metals has been suggested as a contributing factor to the development of neurodegenerative disease. This systematic evidence map will identify and characterize the epidemiological and experimental data available on the intersection of eighteen metals of environmental concern (i.e., aluminum, antimony, arsenic, barium, beryllium, cadmium, chromium, cobalt, copper, lead, manganese, mercury, nickel, palladium, radium, silver, vanadium, and zinc) and three neurodegenerative disease clusters (i.e., tauopathies, synucleinopathies, and TDP-43 proteinopathies). We aim to describe the type and amount of evidence available (or lack thereof) for each metal and neurodegenerative disease combination and highlight important knowledge gaps and knowledge clusters for future research. METHODS: We will conduct a thorough search using two databases (MEDLINE and Web of Science Core Collection) and grey literature resources. Pre-defined criteria have been developed to identify studies which evaluate at least one of the selected metals and neurodegenerative disease-relevant outcomes (e.g., neuropathology, cognitive function, motor function, disease mortality). At each phase of review, studies will be evaluated by two reviewers. Studies determined to be relevant will be extracted for population, exposure, and outcome information. We will conduct a narrative review of the included studies, and the extracted data will be available in a database hosted on Tableau Public. CONCLUSION: This protocol documents the decisions made a priori to data collection regarding these objectives.

The relationship between childhood blood lead levels below 5 µg/dL and childhood intelligence quotient (IQ): Protocol for a systematic review and meta-analysis.

BACKGROUND: The causal association between childhood lead (Pb) exposure and decrements in intelligence quotient (IQ) is well-established, and no safe blood lead level (BLL) in children has been identified. An international pooled analysis of seven prospective studies published by Lanphear et al. in 2005 quantified the relationship between childhood BLL and IQ. Further studies of Pb and IQ have been published more recently with mean BLLs generally lower than in the studies analyzed by Lanphear et al. In this article, we present the protocol for a systematic review to estimate an updated Pb-IQ relationship focusing on BLLs below 5 µg per deciliter (µg/dL). STUDY QUESTION: What is the quantitative relationship between childhood BLLs and IQ at ages 3-17 years at BLLs below 5 µg/dL? DATA SOURCES: A comprehensive search of the scientific literature will utilize citation mapping and key word searching. In the citation mapping approach, we will identify seed references that are relevant to our study question, and will then identify more recent references that have cited at least one of the seed references. The key word search will be conducted in the PubMed, Biosis Previews, Scopus, and Web of Science databases. We will also search electronic grey literature databases for conference proceedings, dissertations, and preprints. STUDY ELIGIBILITY CRITERIA, STUDY SCREENING AND DATA EXTRACTION: We will include studies that measured BLL in children at any age, assessed full-scale IQ of the same children (concurrent with or subsequent to BLL sample collection) at ages 3-17, and estimated a continuous quantitative relationship between BLL and IQ. We will consider only studies with a central tendency BLL < 10 µg/dL. The title and abstract of each record will be reviewed independently by two authors to determine whether the study in question satisfies the inclusion criteria. The full text of each article remaining after title-abstract screening will be reviewed independently by two authors to determine whether the study in question satisfies the inclusion criteria. Two authors will independently extract study characteristics and data from each included study. RISK OF BIAS ASSESSMENT: Studies meeting inclusion criteria will be evaluated for risk of bias (RoB) using the Navigation Guide method applied in a previous systematic review of neurodevelopmental effects (Lam et al., 2017), with adaptation to our study question. Each study will be independently evaluated by two review authors. DATA ANALYSIS AND SYNTHESIS: We intend to conduct a random-effects meta-analysis to summarize the effects of children's exposure to Pb on IQ scores. Additionally, we plan to perform sensitivity analyses using sub-group analyses and/or meta-regression techniques to assess the impact of study design and study population characteristics to examine potential heterogeneity of results across studies. We will assign a confidence level rating (high, moderate, low, or very low) to the effect estimate from the meta-analyses/meta-regressions.

Lead exposure and antisocial behavior: A systematic review protocol.

BACKGROUND: Lead exposure remains highly prevalent worldwide despite decades of research highlighting its link to numerous adverse health outcomes. In addition to well-documented effects on cognition, there is growing evidence of an association with antisocial behavior, including aggression, conduct problems, and crime. An updated systematic review on this topic, incorporating study evaluation and a developmental perspective on the outcome, can advance the state of the science on lead and inform global policy interventions to reduce exposure. OBJECTIVES: We aim to evaluate the link between lead exposure and antisocial behavior. This association will be investigated via a systematic review of human epidemiological and experimental nonhuman mammalian studies. METHODS: The systematic review protocol presented in this publication is informed by recommendations for the conduct of systematic reviews in toxicology and environmental health research (COSTER) and follows the study evaluation approach put forth by the U.S. EPA Integrated Risk Information System (IRIS) program. DATA SOURCES: We will search the following electronic databases for relevant literature: PubMed, BIOSIS and Web of Science. Search results will be stored in EPA's Health and Environmental Research Online (HERO) database. STUDY ELIGIBILITY AND CRITERIA: Eligible human epidemiological studies will include those evaluating any population exposed to lead at any lifestage via ingestion or inhalation exposure and considering an outcome of antisocial behavior based on any of the following criteria: psychiatric diagnoses (e.g., oppositional defiant disorder (ODD), conduct disorder (CD), disruptive behavior disorders (DBD)); violation of social norms (e.g., delinquency, criminality); and aggression. Eligible experimental animal studies will include those evaluating nonhuman mammalian studies exposed to lead via ingestion, inhalation, or injection exposure during any lifestage. The following outcomes will be considered relevant: aggression; antisocial behavior; and altered fear, anxiety, and stress response. STUDY APPRAISAL AND SYNTHESIS METHODS: Screening will be conducted with assistance from an artificial intelligence application. Two independent reviewers for each data stream (human, animal) will screen studies with highest predicted relevance against pre-specified inclusion criteria at the title/abstract and full-text level. Study evaluation will be conducted using methods adapted from the U.S. EPA IRIS program. After data extraction, we will conduct a narrative review and quantitative meta-analysis on the human epidemiological studies as well as a narrative review of the experimental animal studies. We will evaluate the strength of each evidence stream separately and then will develop a summary evidence integration statement based on inference across evidence streams.

Estimating the Effects of Soil Remediation on Children's Blood Lead near a Former Lead Smelter in Omaha, Nebraska, USA.

BACKGROUND: Lead exposures from legacy sources threaten children's health. Soil in Omaha, Nebraska, was contaminated by emissions from a lead smelter and refinery. The U.S. Environmental Protection Agency excavated and replaced contaminated soil at the Omaha Lead Superfund Site between 1999 and 2016. OBJECTIVES: The goal of this study was to assess the association of soil lead level (SLL) and soil remediation status with blood lead levels (BLLs) in children living near or on the site. METHODS: We linked information on SLL at residential properties with children's BLLs and assigned remediation status to children's BLL measurements based on whether their measurements occurred during residence at remediated or unremediated properties. We examined the association of SLL and remediation status with elevated BLL (EBLL). We distinguished the roles of temporal trend and the intervention with time-by-intervention-status interaction contrasts. All analyses estimated odds ratios (ORs) with a generalized estimating equations approach to ensure robustness under the complex correlations among BLL measurements. All analyses controlled for relevant covariates including children's characteristics. RESULTS: EBLL (>5µg/dL) was associated with both residential SLL [e.g., OR=2.00; 95% confidence interval (CI): 1.83, 2.19; >400-800 vs. ≤200 ppm] and neighborhood SLL [e.g., OR=1.85 (95% CI: 1.62, 2.11; >400-800 vs. ≤200 ppm)] before remediation but only with neighborhood SLL after remediation. The odds of EBLL were higher before remediation [OR 1.52 (95% CI: 1.34, 1.72)]. Similarly, EBLL was positively associated with preremediation status in our interaction analysis [interaction OR=1.18 (95%CI: 1.02, 1.37)]. DISCUSSION: Residential and neighborhood SLLs were important predictors of EBLLs in children residing near or on this Superfund site. Neighborhood SLL remained a strong predictor following remediation. Our data analyses showed the benefit of soil remediation. Results from the interaction analyses should be interpreted cautiously due to imperfect correspondence of remediation times between remediation and comparison groups. https://doi.org/10.1289/EHP8657.

Novel text analytics approach to identify relevant literature for human health risk assessments: A pilot study with health effects of in utero exposures.

BACKGROUND: Systematic reviews involve mining literature databases to identify relevant studies. Identifying potentially relevant studies can be informed by computational tools comparing text similarity between candidate studies and selected key (i.e., seed) references. Challenge Using computational approaches to identify relevant studies for risk assessments is challenging, as these assessments examine multiple chemical effects across lifestages (e.g., human health risk assessments) or specific effects of multiple chemicals (e.g., cumulative risk). The broad scope of potentially relevant literature can make selection of seed references difficult. Approach We developed a generalized computational scoping strategy to identify human health relevant studies for multiple chemicals and multiple effects. We used semi-supervised machine learning to prioritize studies to review manually with training data derived from references cited in the hazard identification sections of several US EPA Integrated Risk Information System (IRIS) assessments. These generic training data or seed studies were clustered with the unclassified corpus to group studies based on text similarity. Clusters containing a high proportion of seed studies were prioritized for manual review. Chemical names were removed from seed studies prior to clustering resulting in a generic, chemical-independent method for identifying potentially human health relevant studies. We developed a case study that focused on identifying the array of chemicals that have been studied with respect to in utero exposure to test the recall of this novel literature searching strategy. We then evaluated the general strategy of using generic, chemical-independent training data with two previous IRIS assessments by comparing studies predicted relevant to those used in the assessments (i.e., total relevant). Outcome A keyword search designed to retrieve studies that examined the in utero effects of environmental chemicals identified over 54,000 candidate references. Clustering algorithms were applied using 1456 studies from multiple IRIS assessments with chemical names removed as training data or seeds (i.e., semi-supervised learning). Using a six-algorithm ensemble approach 2602 articles, or approximately 5% of candidate references, were "voted" relevant by four or more clustering algorithms and manual review confirmed nearly 50% of these studies were relevant. Further evaluations on two IRIS assessments, using a nine-algorithm ensemble approach and a set of generic, chemical-independent, externally-derived seed studies correctly identified 77-83% of hazard identification studies published in the assessments and eliminated the need to manually screen more than 75% of search results on average. Limitations The chemical-independent approach used to build the training literature set provides a broad and unbiased picture across a variety of endpoints and environmental exposures but does not systematically identify all available data. Variance between actual and predicted relevant studies will be greater because of the external and non-random origin of seed study selection. This approach depends on access to readily available generic training data that can be used to locate relevant references in an unclassified corpus. Impact A generic approach to identifying human health relevant studies could be an important first step in literature evaluation for risk assessments. This initial scoping approach could facilitate faster literature evaluation by focusing reviewer efforts, as well as potentially minimize reviewer bias in selection of key studies. Using externally-derived training data has applicability particularly for databases with very low search precision where identifying training data may be cost-prohibitive.

Epidemiology: a foundation of environmental decision making.

Many epidemiologic studies are designed so they can be drawn upon to provide scientific evidence for evaluating hazards of environmental exposures, conducting quantitative assessments of risk, and informing decisions designed to reduce or eliminate harmful exposures. However, experimental animal studies are often relied upon for environmental and public health policy making despite the expanding body of observational epidemiologic studies that could inform the relationship between actual, as opposed to controlled, exposures and health effects. This paper provides historical examples of how epidemiology has informed decisions at the U.S. Environmental Protection Agency, discusses some challenges with using epidemiology to inform decision making, and highlights advances in the field that may help address these challenges and further the use of epidemiologic studies moving forward.

A systematic review of cardiovascular emergency department visits, hospital admissions and mortality associated with ambient black carbon.

BACKGROUND: Black carbon (BC) is a ubiquitous component of particulate matter (PM) emitted from combustion-related sources and is associated with a number of health outcomes. OBJECTIVES: We conducted a systematic review to evaluate the potential for cardiovascular morbidity and mortality following exposure to ambient BC, or the related component elemental carbon (EC), in the context of what is already known about the associations between exposure to fine particulate matter (PM2.5) and cardiovascular health outcomes. DATA SOURCES: We conducted a stepwise systematic literature search of the PubMed database and employed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for reporting our results. STUDY ELIGIBILITY CRITERIA: Studies meeting inclusion criteria (i.e., include a quantitative measurement of BC or EC used to characterize exposure and an effect estimate of the association of the exposure metric with ED visits, hospital admissions, or mortality due to cardiovascular disease) were evaluated for risk of bias in study design and results. STUDY APPRAISAL AND SYNTHESIS METHODS: Risk of bias evaluations assess some aspects of internal validity of study findings based on study design, conduct, and reporting and identify potential issues related to confounding or other biases. RESULTS: The results of our systematic review demonstrate similar results for BC or EC and PM2.5; that is, a generally modest, positive association of each pollutant measurement with cardiovascular emergency department visits, hospital admissions, and mortality. There is no clear evidence that health risks are greater for either BC or EC when compared to one another, or when either is compared to PM2.5. LIMITATIONS: We were unable to adequately evaluate the role of copollutant confounding or differential spatial heterogeneity for BC or EC compared to PM2.5. CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS: Overall, the evidence at present indicates that BC or EC is consistently associated with cardiovascular morbidity and mortality but is not sufficient to conclude that BC or EC is independently associated with these effects rather than being an indicator for PM2.5 mass. SYSTEMATIC REVIEW REGISTRATION NUMBER: Not available.

Framework for assessing causality of air pollution-related health effects for reviews of the National Ambient Air Quality Standards.

To inform regulatory decisions on the risk due to exposure to ambient air pollution, consistent and transparent communication of the scientific evidence is essential. The United States Environmental Protection Agency (U.S. EPA) develops the Integrated Science Assessment (ISA), which contains evaluations of the policy-relevant science on the effects of criteria air pollutants and conveys critical science judgments to inform decisions on the National Ambient Air Quality Standards. This article discusses the approach and causal framework used in the ISAs to evaluate and integrate various lines of scientific evidence and draw conclusions about the causal nature of air pollution-induced health effects. The framework has been applied to diverse pollutants and cancer and noncancer effects. To demonstrate its flexibility, we provide examples of causality judgments on relationships between health effects and pollutant exposures, drawing from recent ISAs for ozone, lead, carbon monoxide, and oxides of nitrogen. U.S. EPA's causal framework has increased transparency by establishing a structured process for evaluating and integrating various lines of evidence and uniform approach for determining causality. The framework brings consistency and specificity to the conclusions in the ISA, and the flexibility of the framework makes it relevant for evaluations of evidence across media and health effects.

Associations of Ozone and PM2.5 Concentrations With Parkinson's Disease Among Participants in the Agricultural Health Study.

OBJECTIVE: This study describes associations of ozone and fine particulate matter with Parkinson's disease observed among farmers in North Carolina and Iowa. METHODS: We used logistic regression to determine the associations of these pollutants with self-reported, doctor-diagnosed Parkinson's disease. Daily predicted pollutant concentrations were used to derive surrogates of long-term exposure and link them to study participants' geocoded addresses. RESULTS: We observed positive associations of Parkinson's disease with ozone (odds ratio = 1.39; 95% CI: 0.98 to 1.98) and fine particulate matter (odds ratio = 1.34; 95% CI: 0.93 to 1.93) in North Carolina but not in Iowa. CONCLUSIONS: The plausibility of an effect of ambient concentrations of these pollutants on Parkinson's disease risk is supported by experimental data demonstrating damage to dopaminergic neurons at relevant concentrations. Additional studies are needed to address uncertainties related to confounding and to examine temporal aspects of the associations we observed.

Cross-species coherence in effects and modes of action in support of causality determinations in the U.S. Environmental Protection Agency's Integrated Science Assessment for Lead.

The peer-reviewed literature on the health and ecological effects of lead (Pb) indicates common effects and underlying modes of action across multiple organisms for several endpoints. Based on such observations, the United States (U.S.) Environmental Protection Agency (EPA) applied a cross-species approach in the 2013 Integrated Science Assessment (ISA) for Lead for evaluating the causality of relationships between Pb exposure and specific endpoints that are shared by humans, laboratory animals, and ecological receptors (i.e., hematological effects, reproductive and developmental effects, and nervous system effects). Other effects of Pb (i.e., cardiovascular, renal, and inflammatory responses) are less commonly assessed in aquatic and terrestrial wildlife limiting the application of cross-species comparisons. Determinations of causality in ISAs are guided by a framework for classifying the weight of evidence across scientific disciplines and across related effects by considering aspects such as biological plausibility and coherence. As illustrated for effects of Pb where evidence across species exists, the integration of coherent effects and common underlying modes of action can serve as a means to substantiate conclusions regarding the causal nature of the health and ecological effects of environmental toxicants.

Effect measure modification of blood lead-air lead slope factors.

There is abundant literature finding that susceptibility factors, including race and ethnicity, age, and housing, directly influence blood lead levels. No study has explored how susceptibility factors influence the blood lead-air lead relationship nationally. The objective is to evaluate whether susceptibility factors act as effect measure modifiers on the blood lead-air lead relationship. Participant level blood lead data from the 1999 to 2008 National Health and Nutrition Examination Survey were merged with air lead data from the US Environmental Protection Agency. Linear mixed effects models were run with and without an air lead interaction term for age group, sex, housing age, or race/ethnicity to determine whether these factors are effect measure modifiers for all ages combined and for five age brackets. Age group and race/ethnicity were determined to be effect measure modifiers in the all-age model and for some age groups. Being a child (1-5, 6-11, and 12-19 years) or of Mexican-American ethnicity increased the effect estimate. Living in older housing (built before 1950) decreased the effect estimate for all models except for the 1-5-year group, where older housing was an effect measure modifier. These results are consistent with the peer-reviewed literature of time-activity patterns, ventilation, and toxicokinetics.

Joint effects of ambient air pollutants on pediatric asthma emergency department visits in Atlanta, 1998-2004.

BACKGROUND: Because ambient air pollution exposure occurs as mixtures, consideration of joint effects of multiple pollutants may advance our understanding of the health effects of air pollution. METHODS: We assessed the joint effect of air pollutants on pediatric asthma emergency department visits in Atlanta during 1998-2004. We selected combinations of pollutants that were representative of oxidant gases and secondary, traffic, power plant, and criteria pollutants, constructed using combinations of criteria pollutants and fine particulate matter (PM2.5) components. Joint effects were assessed using multipollutant Poisson generalized linear models controlling for time trends, meteorology, and daily nonasthma upper respiratory emergency department visit counts. Rate ratios (RRs) were calculated for the combined effect of an interquartile range increment in each pollutant's concentration. RESULTS: Increases in all of the selected pollutant combinations were associated with increases in warm-season pediatric asthma emergency department visits (eg, joint-effect RR = 1.13 [95% confidence interval = 1.06-1.21] for criteria pollutants, including ozone, carbon monoxide, nitrogen dioxide, sulfur dioxide, and PM2.5). Cold-season joint effects from models without nonlinear effects were generally weaker than warm-season effects. Joint-effect estimates from multipollutant models were often smaller than estimates based on single-pollutant models, due to control for confounding. Compared with models without interactions, joint-effect estimates from models including first-order pollutant interactions were largely similar. There was evidence of nonlinear cold-season effects. CONCLUSIONS: Our analyses illustrate how consideration of joint effects can add to our understanding of health effects of multipollutant exposures and also illustrate some of the complexities involved in calculating and interpreting joint effects of multiple pollutants.

The influence of declining air lead levels on blood lead-air lead slope factors in children.

BACKGROUND: It is difficult to discern the proportion of blood lead (PbB) attributable to ambient air lead (PbA), given the multitude of lead (Pb) sources and pathways of exposure. The PbB-PbA relationship has previously been evaluated across populations. This relationship was a central consideration in the 2008 review of the Pb national ambient air quality standards. OBJECTIVES: The objectives of this study were to evaluate the relationship between PbB and PbA concentrations among children nationwide for recent years and to compare the relationship with those obtained from other studies in the literature. METHODS: We merged participant-level data for PbB from the National Health and Nutrition Examination Survey (NHANES) III (1988-1994) and NHANES 9908 (1999-2008) with PbA data from the U.S. Environmental Protection Agency. We applied mixed-effects models, and we computed slope factor, d[PbB]/d[PbA] or the change in PbB per unit change in PbA, from the model results to assess the relationship between PbB and PbA. RESULTS: Comparing the NHANES regression results with those from the literature shows that slope factor increased with decreasing PbA among children 0-11 years of age. CONCLUSION: These findings suggest that a larger relative public health benefit may be derived among children from decreases in PbA at low PbA exposures. Simultaneous declines in Pb from other sources, changes in PbA sampling uncertainties over time largely related to changes in the size distribution of Pb-bearing particulate matter, and limitations regarding sampling size and exposure error may contribute to the variability in slope factor observed across peer-reviewed studies.

Contribution of particle-size-fractionated airborne lead to blood lead during the National Health and Nutrition Examination Survey, 1999-2008.

The objective of this work is to examine associations between blood lead (PbB) and air lead (PbA) in particulate matter measured at different size cuts by use of PbB concentrations from the National Health and Nutrition Examination Survey and PbA concentrations from the U.S. Environmental Protection Agency for 1999-2008. Three size fractions of particle-bound PbA (TSP, PM10, and PM2.5) data with different averaging times (current and past 90-day average) were utilized. A multilevel linear mixed effect model was used to characterize the PbB-PbA relationship. At 0.15 µg/m(3), a unit decrease in PbA in PM10 was significantly associated with a decrease in PbB of 0.3-2.2 µg/dL across age groups and averaging times. For PbA in PM2.5 and TSP, slopes were generally positive but not significant. PbB levels were more sensitive to the change in PbA concentrations for children (1-5 and 6-11 years) and older adults (≥ 60 years) than teenagers (12-19 years) and adults (20-59 years). For the years following the phase-out of Pb in gasoline and a resulting upward shift in the PbA particle size distribution, PbA in PM10 was a statistically significant predictor of PbB. The results also suggest that age could affect the PbB-PbA association, with children having higher sensitivity than adults.

A multi-level model of blood lead as a function of air lead.

National and local declines in lead (Pb) in blood (PbB) over the past several years coincide with the decline in ambient air Pb (PbA) concentrations. The objective of this work is to evaluate how the relationship between PbB levels and PbA levels has changed following the phase out of leaded gasoline and tightened controls on industrial Pb emissions over the past 30 years among a national population sample. Participant-level data from the National Health and Nutrition Examination Survey (NHANES) were employed for two time periods (1988-1994 and 1999-2008), and the model was corrected for housing, demographic, socioeconomic, and other covariates present in NHANES. NHANES data for PbB and covariates were merged with PbA data from the U.S. Environmental Protection Agency. Linear mixed effects models (LMEs) were run to assess the relationship of PbB with PbA; sample weights were omitted, given biases encountered with the use of sample weights in LMEs. The 1988-1994 age-stratified results found that ln(PbB) was statistically significantly associated with ln(PbA) for all age groups. The consistent influence of PbA on PbB across age groups for the years 1988-1994 suggests a ubiquitous exposure unrelated to age of the sample population. The comparison of effect estimates for ln(PbA) shows a statistically significant effect estimate and ANOVA results for ln(PbB) for the 6- to 11-year and 12- to 19-year age groups during 1999-2008. The more recent finding suggests that PbA has less consistent influence on PbB compared with other factors.

Comments on: Chari, R.; Burke, T.A.; White, R.H.; Fox, M.A. Integrating Susceptibility into environmental policy: an analysis of the national ambient air quality standard for lead. Int. J. Environ. Res. Public Health 2012, 9, 1077-1096.

In their recent article [1], Chari et al. call attention to the important subject of setting National Ambient Air Quality Standards (NAAQS) to provide requisite protection for public health, including the health of sensitive groups, as specified under the Clean Air Act (73 FR 66965) [2]. The authors focus on consideration of susceptibility to inform policy choices, using lead (Pb)-related neurocognitive effects and children from low socioeconomic status (SES) families in the context of alternative Pb standard levels. Our comments focus on the authors' analysis of the scientific evidence and not on policy. We agree with the authors that the health effects evidence for Pb indicates a role (or roles) for SES-related factors in influencing childhood Pb exposure and associated health effects. We disagree, however, with the authors' interpretation of the literature on SES influence on the shape of the concentration-response (C-R) relationship between children's blood Pb and IQ (e.g., steepness of the slope). We further address aspects of the scientific evidence that are important to the consideration of sensitive populations in the context of the Pb NAAQS, and how the U.S. Environmental Protection Agency (EPA) considered this evidence in setting the Pb NAAQS in 2008.

Personal exposure to benzene from fuel emissions among commercial fishers: comparison of two-stroke, four-stroke and diesel engines.

Commercial fishers are exposed to unburned hydrocarbon vapors and combustion products present in the emissions from their boat engines. The objective of this study was to measure personal exposure to benzene as a marker of fuel exposure, and to predict exposure levels across categories of carbureted two-stroke, four-stroke and diesel engines. A self-monitoring approach, employing passive monitors, was used to obtain measurements of personal exposure to benzene over time. Mixed-effect linear regression models were used to predict exposure levels, identify significant effects and determine restricted maximum likelihood estimates for within- and between-person variance components. Significant fixed effects for engine type and refueling a car or truck were identified. After controlling for refueling, predicted benzene exposure levels to fishers on boats equipped with two-stroke, four-stroke and diesel engines were 58.4, 38.9 and 15.7 microg/m3, respectively. The logged within-person variance component was 1.43, larger than the between-person variance component of 1.13, indicating that the total variation may be attributable to monitor placement, environmental conditions and other factors that change over time as well as differences between individual work practices. The health consequences of exposure to marine engine emissions are not known. The predicted levels are well below those at which health effects have been attributed, however.

Retinal degeneration and other eye disorders in wives of farmer pesticide applicators enrolled in the agricultural health study.

Retinal degeneration is the leading cause of visual impairment in older adults. An association between retinal degeneration and fungicide use was observed previously among farmer pesticide applicators in the Agricultural Health Study, a large study of farm families from Iowa and North Carolina. The objective of this investigation was to determine whether wives of these farmer pesticide applicators were at increased risk of retinal degeneration. Self-reported cross-sectional data obtained via questionnaire between 1993 and 1997 from 31,173 wives were used. Associations of specific pesticides and groups of pesticides based on function (fungicides, herbicides, insecticides, and fumigants) or chemical structure (organophosphates, organochlorines, and carbamates) with eye disorders were evaluated using logistic and hierarchical logistic regression analyses. Self-reported retinal degeneration was associated with the wife's fungicide use (odds ratio = 1.9, 95% confidence interval: 1.2, 3.1) after adjustment for age and state of residence. Specific fungicides that appeared to drive this association were maneb or mancozeb and ziram. No associations between pesticide use and other eye disorders were found. Although these findings for retinal degeneration are based solely on self-reported disease, they are consistent with those reported for farmer pesticide applicators. These findings suggest that exposure to some fungicides and other pesticides may increase the risk of retinal degeneration and warrant further investigation.

Patterns of pesticide use and their determinants among wives of farmer pesticide applicators in the Agricultural Health Study.

Pesticide exposure among farmers' wives is poorly characterized. Using questionnaire data from a cohort study of licensed pesticide applicators and their spouses, we investigated patterns of pesticide use among farmers' wives (n = 31,173). Wives reported a wide range of pesticide use: 36% never used pesticides during their lifetimes, whereas the heaviest pesticide users (10%) reported lifetime use of 3 or more agricultural pesticides plus commonly used residential pesticides. We identified 5 ordinal pesticide-use categories and studied factors associated with each category through polytomous logistic regression. Engaging in field work and household hygiene practices that could increase exposure were associated with pesticide use, and associations appeared to strengthen with increasing pesticide use category. Farm women reporting the heaviest pesticide use could exacerbate their exposure by engaging in practices that could increase pesticide contact.