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Background: The need to identify and try to prevent adverse health impacts of climate change has risen to the forefront of climate change policy debates and become a top priority of the public health community. Given the observed and projected changes in climate and weather patterns, their current and anticipated health impacts, and the significant degree of regulatory discussion underway in the U.S. government, it is reasonable to determine the extent of federal investment in research to understand, avoid, prepare for, and respond to the human health impacts of climate change in the United States.
Objective: In this commentary we summarize the health risks of climate change in the United States and examine the extent of federal funding devoted to understanding, avoiding, preparing for, and responding to the human health risks of climate change.
Discussion: Future climate change is projected to exacerbate various current health problems, including heat-related mortality, diarrheal diseases, and diseases associated with exposure to ozone and aeroallergens. Demographic trends and geophysical and socioeconomic factors could increase overall vulnerability. Despite these risks, extramural federal funding of climate change and health research is estimated to be < $3 million per year.
Conclusions: Given the real risks that climate change poses for U.S. populations, the National Institutes of Health, Centers for Disease Control and Prevention, U.S. Environmental Protection Agency, and other agencies need to have robust intramural and extramural programs, with funding of > $200 million annually. Oversight of the size and priorities of these programs could be provided by a standing committee within the National Academy of Sciences.
Objectives: Traditional hazards such as poor sanitation currently account for most of Africa’s environmentally related disease burden. However, with rapid development absent appropriate safeguards for environment and health, modern environmental health hazards (MEHHs) may emerge as critical contributors to the continent’s disease burden. We review recent evidence of human exposure to and health effects from MEHHs, and their occurrence in environmental media and consumer products. Our purpose is to highlight the growing significance of these hazards as African countries experience urbanization, industrial growth, and development.
Data sources: We reviewed published epidemiologic, exposure, and environmental studies of chemical agents such as heavy metals and pesticides.
Data synthesis: The body of evidence demonstrates ongoing environmental releases of MEHHs and human exposures sometimes at toxicologically relevant levels. Several sources of MEHHs in environmental media have been identified, including natural resource mining and processing and automobile exhaust. Biomonitoring studies provided direct evidence of human exposure to metals such as mercury and lead and pesticides such as p,p′-dichlorodiphenyltrichloroethane (DDT) and organophosphates. Land and water resource pollution and industrial air toxics are areas of significant data gaps, notwithstanding the presence of several emitting sources.
Conclusion: Unmitigated MEHH releases and human exposure have implications for Africa’s disease burden. For Africans encumbered by conditions such as malnutrition that impair resilience to toxicologic challenges, the burden may be higher. A shift in public health policy toward accommodating the emerging diversity in Africa’s environmental health issues is necessary to successfully alleviate the burden of avoidable ill health and premature death for all its communities now and in the future.
Objective: Concern for children exposed to elemental mercury prompted the Agency for Toxic Substances and Disease Registry and the Centers for Disease Control and Prevention to review the sources of elemental mercury exposures in children, describe the location and proportion of children affected, and make recommendations on how to prevent these exposures. In this review, we excluded mercury exposures from coal-burning facilities, dental amalgams, fish consumption, medical waste incinerators, or thimerosal-containing vaccines.
Data sources: We reviewed federal, state, and regional programs with information on mercury releases along with published reports of children exposed to elemental mercury in the United States. We selected all mercury-related events that were documented to expose (or potentially expose) children. We then explored event characteristics (i.e., the exposure source, location).
Data synthesis: Primary exposure locations were at home, at school, and at other locations such as industrial property not adequately remediated or medical facilities. Exposure to small spills from broken thermometers was the most common scenario; however, reports of such exposures are declining.
Discussion and conclusions: Childhood exposures to elemental mercury often result from inappropriate handling or cleanup of spilled mercury. The information reviewed suggests that most releases do not lead to demonstrable harm if the exposure period is short and the mercury is properly cleaned up.
Recommendations: Primary prevention should include health education and policy initiatives. For larger spills, better coordination among existing surveillance systems would assist in understanding the risk factors and in developing effective prevention efforts.
Background: Exposure to endocrine-disrupting chemicals during critical developmental periods causes adverse consequences later in life; an example is prenatal exposure to the pharmaceutical diethylstilbestrol (DES). Bisphenol A (BPA), an environmental estrogen used in the synthesis of plastics, is of concern because its chemical structure resembles that of DES, and it is a “high-volume production” chemical with widespread human exposure.
Objectives: In this study we investigated whether prenatal BPA causes long-term adverse effects in female reproductive tissues in an experimental animal model previously shown useful in studying effects of prenatal DES.
Methods: Timed pregnant CD-1 mice were treated on days 9–16 of gestation with BPA (0.1, 1, 10, 100, or 1,000 μg/kg/day). After delivery, pups were held for 18 months; reproductive tissues were then evaluated.
Results: Ovarian cysts were significantly increased in the 1-μg/kg BPA group; ovarian cyst-adenomas were seen in the other three BPA-treated groups but not in corn-oil controls. We observed increased progressive proliferative lesions of the oviduct after BPA treatment, similar to those described in response to DES. Further, although not statistically different from the controls, prominent mesonephric (Wolffian) remnants and squamous metaplasia of the uterus, as well as vaginal adenosis, were present in BPA-treated mice, similar to lesions reported following DES treatment. More severe pathologies observed in some BPA-treated animals included atypical hyperplasia and stromal polyps of the uterus; sarcoma of the uterine cervix; and mammary adenocarcinoma. We did not observe these lesions in controls.
Conclusions: These data suggest that BPA causes long-term adverse reproductive and carcinogenic effects if exposure occurs during critical periods of differentiation.
Background: Studies of chronic health effects due to exposures to particulate matter with aerodynamic diameters ≤ 2.5 μm (PM2.5) are often limited by sparse measurements. Satellite aerosol remote sensing data may be used to extend PM2.5 ground networks to cover a much larger area.
Objectives: In this study we examined the benefits of using aerosol optical depth (AOD) retrieved by the Geostationary Operational Environmental Satellite (GOES) in conjunction with land use and meteorologic information to estimate ground-level PM2.5 concentrations.
Methods: We developed a two-stage generalized additive model (GAM) for U.S. Environmental Protection Agency PM2.5 concentrations in a domain centered in Massachusetts. The AOD model represents conditions when AOD retrieval is successful; the non-AOD model represents conditions when AOD is missing in the domain.
Results: The AOD model has a higher predicting power judged by adjusted R2 (0.79) than does the non-AOD model (0.48). The predicted PM2.5 concentrations by the AOD model are, on average, 0.8–0.9 μg/m3 higher than the non-AOD model predictions, with a more smooth spatial distribution, higher concentrations in rural areas, and the highest concentrations in areas other than major urban centers. Although AOD is a highly significant predictor of PM2.5, meteorologic parameters are major contributors to the better performance of the AOD model.
Conclusions: GOES aerosol/smoke product (GASP) AOD is able to summarize a set of weather and land use conditions that stratify PM2.5 concentrations into two different spatial patterns. Even if land use regression models do not include AOD as a predictor variable, two separate models should be fitted to account for different PM2.5 spatial patterns related to AOD availability.
Background: During the last week of June 2008, central and northern California experienced thousands of forest and brush fires, giving rise to a week of severe fire-related particulate air pollution throughout the region. California experienced PM10–2.5 (particulate matter with mass median aerodynamic diameter > 2.5 μm to < 10 μm; coarse ) and PM2.5 (particulate matter with mass median aerodynamic diameter < 2.5 μm; fine) concentrations greatly in excess of the air quality standards and among the highest values reported at these stations since data have been collected.
Objectives: These observations prompt a number of questions about the health impact of exposure to elevated levels of PM10–2.5 and PM2.5 and about the specific toxicity of PM arising from wildfires in this region.
Methods: Toxicity of PM10–2.5 and PM2.5 obtained during the time of peak concentrations of smoke in the air was determined with a mouse bioassay and compared with PM samples collected under normal conditions from the region during the month of June 2007.
Results: Concentrations of PM were not only higher during the wildfire episodes, but the PM was much more toxic to the lung on an equal weight basis than was PM collected from normal ambient air in the region. Toxicity was manifested as increased neutrophils and protein in lung lavage and by histologic indicators of increased cell influx and edema in the lung.
Conclusions: We conclude that the wildfire PM contains chemical components toxic to the lung, especially to alveolar macrophages, and they are more toxic to the lung than equal doses of PM collected from ambient air from the same region during a comparable season.
Background: Although many studies have examined the effects of air pollution on mortality, data limitations have resulted in fewer studies of both particulate matter with an aerodynamic diameter of ≤ 2.5 μm (PM2.5; fine particles) and of coarse particles (particles with an aerodynamic diameter > 2.5 and < 10 μm; PM coarse). We conducted a national, multicity time-series study of the acute effect of PM2.5 and PM coarse on the increased risk of death for all causes, cardiovascular disease (CVD), myocardial infarction (MI), stroke, and respiratory mortality for the years 1999–2005.
Method: We applied a city- and season-specific Poisson regression in 112 U.S. cities to examine the association of mean (day of death and previous day) PM2.5 and PM coarse with daily deaths. We combined the city-specific estimates using a random effects approach, in total, by season and by region.
Results: We found a 0.98% increase [95% confidence interval (CI), 0.75–1.22] in total mortality, a 0.85% increase (95% CI, 0.46–1.24) in CVD, a 1.18% increase (95% CI, 0.48–1.89) in MI, a 1.78% increase (95% CI, 0.96–2.62) in stroke, and a 1.68% increase (95% CI, 1.04–2.33) in respiratory deaths for a 10-μg/m3 increase in 2-day averaged PM2.5. The effects were higher in spring. For PM coarse, we found significant but smaller increases for all causes analyzed.
Conclusions: We conclude that our analysis showed an increased risk of mortality for all and specific causes associated with PM2.5, and the risks are higher than what was previously observed for PM10. In addition, coarse particles are also associated with more deaths.
Background: Recent research highlights the promise of remotely sensed aerosol optical depth (AOD) as a proxy for ground-level particulate matter with aerodynamic diameter ≤ 2.5 μm (PM2.5). Particular interest lies in estimating spatial heterogeneity using AOD, with important application to estimating pollution exposure for public health purposes. Given the correlations reported between AOD and PM2.5, it is tempting to interpret the spatial patterns in AOD as reflecting patterns in PM2.5.
Objectives: We evaluated the degree to which AOD can help predict long-term average PM2.5 concentrations for use in chronic health studies.
Methods: We calculated correlations of AOD and PM2.5 at various temporal aggregations in the eastern United States in 2004 and used statistical models to assess the relationship between AOD and PM2.5 and the potential for improving predictions of PM2.5 in a subregion, the mid-Atlantic.
Results: We found only limited spatial associations of AOD from three satellite retrievals with daily and yearly PM2.5. The statistical modeling shows that monthly average AOD poorly reflects spatial patterns in PM2.5 because of systematic, spatially correlated discrepancies between AOD and PM2.5. Furthermore, when we included AOD as a predictor of monthly PM2.5 in a statistical prediction model, AOD provided little additional information in a model that already accounts for land use, emission sources, meteorology, and regional variability.
Conclusions: These results suggest caution in using spatial variation in currently available AOD to stand in for spatial variation in ground-level PM2.5 in epidemiologic analyses and indicate that when PM2.5 monitoring is available, careful statistical modeling outperforms the use of AOD.
Background: Bisphenol A (BPA) is widely used in the manufacture of polycarbonate plastics, including infant formula bottles.
Objectives: Based on the reported endocrine disruptor activity of this polyphenol, we hypothesized that exposure to BPA early in life would elicit developmental changes in the mammary tissue and cause a predisposition for mammary cancer.
Methods: We exposed neonatal/prepubertal rats to BPA via lactation from nursing dams treated orally with 0, 25, and 250 μg BPA/kg body weight/day. For tumorigenesis studies, female offspring were exposed to 30 mg dimethylbenzanthracene (DMBA)/kg body weight at 50 days of age.
Results: The combination of DMBA treatment with lactational exposure to BPA demonstrated a dose-dependent increase in mammary tumor multiplicity and reduced tumor latency compared with controls. In the absence of DMBA treatment, lactational BPA exposure resulted in increased cell proliferation and decreased apoptosis at 50 but not 21 days postpartum (shortly after last BPA treatment). Using Western blot analysis, we determined that steroid receptor coactivators (SRCs) 1–3, Akt, phosphorylated Akt, progesterone receptor A (PR-A), and erbB3 proteins were significantly up-regulated at 50 days of age.
Conclusions: The data presented here provide the first evidence that maternal exposure to BPA during lactation increases mammary carcinogenesis in a DMBA-induced model of rodent mammary cancer. Changes in PR-A, SRC 1–3, erbB3, and Akt activity are consistent with increased cell proliferation and decreased apoptosis playing a role in mammary cancer susceptibility. These alterations provide an explanation of enhanced mammary carcinogenesis after lactational BPA exposure.
Background: Developmental exposure to a wide variety of developmental neurotoxicants, including organophosphate pesticides, evokes late-emerging and persistent abnormalities in acetylcholine (ACh) systems. We are seeking interventions that can ameliorate or reverse the effects later in life.
Objectives: We administered parathion to neonatal rats and then evaluated whether a high-fat diet begun in adulthood could reverse the effects on ACh systems.
Methods: Neonatal rats received parathion on postnatal days 1–4 at 0.1 or 0.2 mg/kg/day, straddling the cholinesterase inhibition threshold. In adulthood, half the animals were switched to a high-fat diet for 8 weeks. We assessed three indices of ACh synaptic function: nicotinic ACh receptor binding, choline acetyltransferase activity, and hemicholinium-3 binding. Determinations were performed in brain regions comprising all the major ACh projections and cell bodies.
Results: Neonatal parathion exposure evoked widespread abnormalities in ACh synaptic markers, encompassing effects in brain regions possessing ACh projections and ACh cell bodies. In general, males were affected more than females. Of 17 regional ACh marker abnormalities (10 male, 7 female), 15 were reversed by the high-fat diet.
Conclusions: A high-fat diet reverses neurodevelopmental effects of neonatal parathion exposure on ACh systems. This points to the potential for nonpharmacologic interventions to offset the effects of developmental neurotoxicants. Further, cryptic neurodevelopmental deficits evoked by environmental exposures may thus engender a later preference for a high-fat diet to maintain normal ACh function, ultimately contributing to obesity.
Background: Perfluoroalkyl acids (PFAAs) are found globally in wildlife and humans and are suspected to act as endocrine disruptors. There are no previous reports of PFAA levels in adult men from Denmark or of a possible association between semen quality and PFAA exposure.
Objectives: We investigated possible associations between PFAAs and testicular function. We hypothesized that higher PFAA levels would be associated with lower semen quality and lower testosterone levels.
Methods: We analyzed serum samples for levels of 10 different PFAAs and reproductive hormones and assessed semen quality in 105 Danish men from the general population (median age, 19 years).
Results: Considerable levels of perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), and perfluorohexane sulfonic acid were found in all young men (medians of 24.5, 4.9, and 6.6 ng/mL, respectively). Men with high combined levels of PFOS and PFOA had a median of 6.2 million normal spermatozoa in their ejaculate in contrast to 15.5 million among men with low PFOS–PFOA (p = 0.030). In addition, we found nonsignificant trends with regard to lower sperm concentration, lower total sperm counts, and altered pituitary–gonadal hormones among men with high PFOS–PFOA levels.
Conclusion: High PFAA levels were associated with fewer normal sperm. Thus, high levels of PFAAs may contribute to the otherwise unexplained low semen quality often seen in young men. However, our findings need to be corroborated in larger studies.
Background: There is concern about the potential risk posed by compounds with estrogen-like activity present in the environment. As previous studies have shown that combined exposure to such compounds results in dose additivity, it should be possible to assess estrogen exposure with suitable biomarkers of effect.
Objectives: Our goal was to identify candidate protein biomarkers of effect for estrogenic compounds.
Methods: In the search for biomarkers, we assessed the effect of several estrogenic compounds on the expression profile of proteins in breast-derived cell lines varying in their estrogen receptor (ER) phenotype using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry. We identified responsive proteins, after separating them by SDS-polyacrylamide gel electrophoresis, and analyzing the trypsin-digested proteins by tandem mass spectrometry.
Results: The estrogenic compounds 17β-estradiol, genistein, bisphenol A, and endosulfan produced similar protein profile changes in MCF-7 cells (phenotype: ERα+/ERβ+), but had no effect on MDA-MB-231 (ERα−/ERβ+), MCF-10F (ERα−/ERβ+), or MCF-10A (ERα−/ERβ−) cells. The most responsive proteins in MCF-7 cells were identified as histones H2A, H2B, H3, and H4. Histone levels were not increased in cell lines that showed no proliferative response to estrogens despite their rapid intrinsic growth rate in culture.
Conclusion: Our results indicate that ER-mediated cell proliferation results in up-regulation of core histone proteins.
Background: Fine particulate matter [aerodynamic diameter ≤ 2.5 μm (PM2.5)] has been associated with autonomic dysregulation.
Objective: We hypothesized that PM2.5 influences postural changes in systolic blood pressure (ΔSBP) and in diastolic blood pressure (ΔDBP) and that this effect is modified by genes thought to be related to chronic lung disease.
Methods: We measured blood pressure in participants every 3–5 years. ΔSBP and ΔDBP were calculated as sitting minus standing SBP and DBP. We averaged PM2.5 over 48 hr before study visits and analyzed 202 single nucleotide polymorphisms (SNPs) in 25 genes. To address multiple comparisons, data were stratified into a split sample. In the discovery cohort, the effects of SNP × PM2.5 interactions on ΔSBP and ΔDBP were analyzed using mixed models with subject-specific random intercepts. We defined positive outcomes as p < 0.1 for the interaction; we analyzed only these SNPs in the replicate cohort and confirmed them if p < 0.025 with the same sign. Confirmed associations were analyzed within the full cohort in models adjusted for anthropometric and lifestyle factors.
Results: Nine hundred forty-five participants were included in our analysis. One interaction with rs9568232 in PHD finger protein 11 (PHF11) was associated with greater ΔDBP. Interactions with rs1144393 in matrix metalloprotease 1 (MMP1) and rs16930692, rs7955200, and rs10771283 in inositol 1,4,5-triphosphate receptor, type 2 (ITPR2) were associated with significantly greater ΔSBP. Because SNPs associated with ΔSBP in our analysis are in genes along the renin–angiotensin pathway, we then examined medications affecting that pathway and observed significant interactions for angiotensin receptor blockers but not angiotensin-converting enzyme inhibitors with PM2.5.
Conclusions: PM2.5 influences blood pressure and autonomic function. This effect is modified by genes and drugs that also act along this pathway.
Background: Lead is known to be a health hazard to the human brain and nervous system based on data from epidemiologic studies. However, few studies have examined the mechanism or biochemical changes caused by lead in the human brain, although recently some have used magnetic resonance spectroscopy (MRS) to test brain metabolism in vivo.
Objectives: In this study, we used 3-T MRS to investigate brain metabolism in workers chronically exposed to lead and matched nonexposed controls.
Materials : Methods: Twenty-two workers at a lead paint factory served as chronically exposed subjects of this study. These workers did not have any clinical syndromes. Eighteen age- and sex-matched nonexposed healthy volunteers served as controls. We measured blood and bone lead and used a 3-T MRS to measure their levels of brain N-acetyl aspartate (NAA), choline (Cho), and total creatine (tCr). A structural questionnaire was used to collect demographic, work, and health histories and information about their life habits.
Results: All the MRS measures were lower in the lead-exposed group. Increased blood and bone lead levels correlated with declines in Cho:tCr ratios, especially in the occipital lobe, where changes in all gray, subcortical, and white matter were significant. Increases in blood and patella lead in every layer of the frontal lobe correlated with significant decreases in NAA:tCr ratios. One of the strongest regression coefficients was −0.023 (SE = 0.005, p < 0.001), which was found in the NAA:tCr ratio of frontal gray matter.
Discussion: We conclude that chronic exposure to lead might upset brain metabolism, especially NAA:tCr and Cho:tCr ratios. Brain NAA and Cho are negatively correlated to blood and bone lead levels, suggesting that lead induces neuronal and axonal damage or loss. The most significant changes occurred in frontal and occipital lobes, areas in which previous neurobehavioral studies have shown memory and visual performance to be adversely affected by lead toxicity.
Background: Recent evidence has shown that humans metabolize benzene more efficiently at environmental air concentrations than at concentrations > 1 ppm. This led us to speculate that an unidentified metabolic pathway was mainly responsible for benzene metabolism at ambient levels.
Objective: We statistically tested whether human metabolism of benzene is better fitted by a kinetic model having two pathways rather than one.
Methods: We fit Michaelis-Menten-like models to levels of urinary benzene metabolites and the corresponding air concentrations for 263 nonsmoking Chinese females. Estimated benzene concentrations ranged from less than 0.001 ppm to 299 ppm, with 10th and 90th percentile values of 0.002 ppm and 8.97 ppm, respectively.
Results: Using values of Akaike’s information criterion obtained under the two models, we found strong statistical evidence favoring two metabolic pathways, with respective affinities (benzene air concentrations analogous to Km values) of 301 ppm for the low-affinity pathway (probably dominated by cytochrome P450 enzyme 2E1) and 0.594 ppm for the high-affinity pathway (unknown). The exposure-specific metabolite level predicted by our two-pathway model at nonsaturating concentrations was 184 μM/ppm of benzene, a value close to an independent estimate of 194 μM/ppm for a typical nonsmoking Chinese female. Our results indicate that a nonsmoking woman would metabolize about three times more benzene from the ambient environment under the two-pathway model (184 μM/ppm) than under the one-pathway model (68.6 μM/ppm). In fact, 73% of the ambient benzene dose would be metabolized via the unidentified high-affinity pathway.
Conclusion: Because regulatory risk assessments have assumed nonsaturating metabolism of benzene in persons exposed to air concentrations well above 10 ppm, our findings suggest that the true leukemia risks could be substantially greater than currently thought at ambient levels of exposure—about 3-fold higher among nonsmoking females in the general population.
Background: As part of an ongoing medical surveillance program for U.S. veterans exposed to depleted uranium (DU), biological monitoring of urine uranium (U) concentrations is offered to any veteran of the Gulf War and those serving in more recent conflicts (post-Gulf War veterans).
Objectives: Since a previous report of surveillance findings in 2004, an improved methodology for determination of the isotopic ratio of U in urine (235U:238U) has been developed and allows for more definitive evaluation of DU exposure. This report updates previous findings.
Methods: Veterans provide a 24-hr urine specimen and complete a DU exposure questionnaire. Specimens are sent to the Baltimore Veterans Affairs Medical Center for processing. Uranium concentration and isotopic ratio are measured using ICP-MS at the Armed Forces Institute of Pathology.
Results: Between January 2003 and June 2008, we received 1,769 urine specimens for U analysis. The mean urine U measure was 0.009 μg U/g creatinine. Mean urine U concentrations for Gulf War and post-Gulf War veterans were 0.008 and 0.009 μg U/g creatinine, respectively. Only 3 of the 1,700 (0.01%) specimens for which we completed isotopic determination showed evidence of DU. Exposure histories confirmed that these three individuals had been involved in “friendly fire” incidents involving DU munitions or armored vehicles.
Conclusions: No urine U measure with a “depleted” isotopic signature has been detected in U.S. veterans without a history of retained DU embedded fragments from previous injury. These findings suggest that future DU-related health harm is unlikely in veterans without DU fragments.
Background: Population-based studies have estimated health risks of short-term exposure to fine particles using mass of PM2.5 (particulate matter ≤ 2.5 μm in aerodynamic diameter) as the indicator. Evidence regarding the toxicity of the chemical components of the PM2.5 mixture is limited.
Objective: In this study we investigated the association between hospital admission for cardiovascular disease (CVD) and respiratory disease and the chemical components of PM2.5 in the United States.
Methods: We used a national database comprising daily data for 2000–2006 on emergency hospital admissions for cardiovascular and respiratory outcomes, ambient levels of major PM2.5 chemical components [sulfate, nitrate, silicon, elemental carbon (EC), organic carbon matter (OCM), and sodium and ammonium ions], and weather. Using Bayesian hierarchical statistical models, we estimated the associations between daily levels of PM2.5 components and risk of hospital admissions in 119 U.S. urban communities for 12 million Medicare enrollees (≥ 65 years of age).
Results: In multiple-pollutant models that adjust for the levels of other pollutants, an interquartile range (IQR) increase in EC was associated with a 0.80% [95% posterior interval (PI), 0.34–1.27%] increase in risk of same-day cardiovascular admissions, and an IQR increase in OCM was associated with a 1.01% (95% PI, 0.04–1.98%) increase in risk of respiratory admissions on the same day. Other components were not associated with cardiovascular or respiratory hospital admissions in multiple-pollutant models.
Conclusions: Ambient levels of EC and OCM, which are generated primarily from vehicle emissions, diesel, and wood burning, were associated with the largest risks of emergency hospitalization across the major chemical constituents of PM2.5.
Background: Research suggests that independent and joint effects of genetic variability in the dopamine transporter (DAT) locus and pesticides may influence Parkinson’s disease (PD) risk.
Materials : Methods: In 324 incident PD patients and 334 population controls from our rural California case–control study, we genotyped rs2652510, rs2550956 (for the DAT 5′ clades), and the 3′ variable number of tandem repeats (VNTR). Using geographic information system methods, we determined residential exposure to agricultural maneb and paraquat applications. We also collected occupational pesticide use data. Employing logistic regression, we calculated odds ratios (ORs) for clade diplotypes, VNTR genotype, and number of susceptibility (A clade and 9-repeat) alleles and assessed susceptibility allele–pesticide interactions.
Results: PD risk was increased separately in DAT A clade diplotype carriers [AA vs. BB: OR = 1.66; 95% confidence interval (CI), 1.08–2.57] and 3′ VNTR 9/9 carriers (9/9 vs. 10/10: OR = 1.8; 95% CI, 0.96–3.57), and our data suggest a gene dosing effect. Importantly, high exposure to paraquat and maneb in carriers of one susceptibility allele increased PD risk 3-fold (OR = 2.99; 95% CI, 0.88–10.2), and in carriers of two or more alleles more than 4-fold (OR = 4.53; 95% CI, 1.70–12.1). We obtained similar results for occupational pesticide measures.
Discussion: Using two independent pesticide measures, we a) replicated previously reported gene–environment interactions between DAT genetic variants and occupational pesticide exposure in men and b) overcame previous limitations of nonspecific pesticide measures and potential recall bias by employing state records and computer models to estimate residential pesticide exposure.
Conclusion: Our results suggest that DAT genetic variability and pesticide exposure interact to increase PD risk.
Background: Understanding the progression from beryllium exposure (BeE) to chronic beryllium disease (CBD) is essential for optimizing screening and early intervention to prevent CBD.
Methods: We developed an analytic Markov model of progression to CBD that assigns annual probabilities for progression through three states: from BeE to beryllium sensitization and then to CBD. We used calculations of the number in each state over time to assess which of several alternative progression models are most consistent with the limited available empirical data on prevalence and incidence. We estimated cost-effectiveness of screening considering both incremental (cost/case) and cumulative program costs.
Results: No combination of parameters for a simple model in which risk of progression remains constant over time can meet the empirical constraints of relatively frequent early cases and continuing development of new cases with long latencies. Modeling shows that the risk of progression is initially high and then declines over time. Also, it is likely that there are at least two populations that differ significantly in risk. The cost-effectiveness of repetitive screening declines over time, although new cases will still be found with long latencies. However, screening will be particularly cost-effective when applied to persons with long latencies who have not been previously screened.
Conclusions: To optimize use of resources, the intensity of screening should decrease over time. Estimation of lifetime cumulative CBD risk should consider the declining risk of progression over time.
Background: Respiratory symptoms, either newly reported after the World Trade Center (WTC) disaster on 11 September 2001 (9/11) or increased in severity, have been well documented in WTC-exposed workers and New York City residents. However, considerable uncertainty exists over the persistence of symptoms.
Objectives: In this study, our goals were to describe trends in post-9/11 respiratory and gastro-esophageal reflux disease (GERD) symptoms in WTC-exposed firefighters and to examine symptom progression in the cohort that completed both year 1 and year 4 questionnaires.
Methods: We analyzed questionnaire responses from 10,378 firefighters in yearly intervals, from 2 October 2001 to 11 September 2005, defining exposure based on arrival time at the WTC site. For the cohort of 3,722 firefighters who completed the two questionnaires, we also calculated exposure duration summing months of work at the site.
Results: In cross-sectional analyses, the prevalence of dyspnea, wheeze, rhinosinusitis, and GERD remained relatively stable, whereas cough and sore throat declined, especially between 1 and 2 years post-9/11. We found a dose–response relationship between arrival time and symptoms in all years (p < 0.01). Logistic models of symptoms at year 4 in the cohort demonstrated independent effects of earlier arrival and longer work duration: each additional month of work increased the odds of symptoms 8–11%.
Conclusions: Protracted work exposures increased the odds of respiratory and GERD symptoms 4 years later. In most large disasters, exposures may be unavoidable during the rescue phase, but our data strongly suggest the need to minimize additional exposures during recovery and cleanup phases.
Background: Exposure to arsenic is a critical risk factor in the complex interplay among genetics, the environment, and human disease. Despite the potential for in utero exposure, the mechanism of arsenic action on vertebrate development and disease is unknown.
Objectives: The objective of this study was to identify genes and gene networks perturbed by arsenic during development in order to enhance understanding of the molecular mechanisms of arsenic action.
Methods: We exposed zebrafish embryos at 0.25–1.25 hr postfertilization to 10 or 100 ppb arsenic for 24 or 48 hr. We then used total RNA to interrogate genome microarrays and to test levels of gene expression changes by quantitative real-time polymerase chain reaction (QPCR). Computational analysis was used to identify gene expression networks perturbed by arsenic during vertebrate development.
Results: We identified a set of 99 genes that responded to low levels of arsenic. Nineteen of these genes were predicted to function in a common regulatory network that was significantly associated with immune response and cancer (p < 10−41). Arsenic-mediated expression changes were validated by QPCR.
Conclusions: In this study we demonstrated that arsenic significantly down-regulates expression levels of multiple genes potentially critical for regulating the establishment of an immune response. The data also provide molecular evidence consistent with phenotypic observations reported in other model systems. Additional mechanistic studies will help explain molecular events regulating early stages of the immune system and long-term consequences of arsenic-mediated perturbation of this system during development.
Background: Agricultural workers are exposed to airborne pollutants, including organic and inorganic (mineral) dusts.
Objectives: Lung autopsy specimens from consecutive coroner’s cases of Hispanic males in Fresno County, California, (n = 112) were obtained to determine whether mineral dust exposure in agricultural work leads to pneumoconiosis.
Methods: The left lung was fixed by inflation. We evaluated airway and parenchymal pathology using standardized diagnostic criteria and semiquantitative grading schemata, including the grading of small airways for fibrosis and birefringent mineral dust particles. We analyzed lung dust burden on a subset of 37 lungs following bleach digestion, using scanning electron microscopy (SEM), X-ray spectrometry (XRS) and image analysis, and by X-ray diffraction for crystalline silica (CSi). Farmworkers comprised 51.5% and nonfarmworkers 48.5% of the samples.
Results: Proximal airways demonstrated little mineral dust accumulation, but membranous and respiratory bronchioles had wall thickening, remodeling, and inflammation associated with carbonaceous and mineral dust deposition. These changes were independently associated with agricultural work, cigarette smoking, and increased age. Mineral dust small airways disease, pneumoconiosis (macules and nodules), and pathologic changes consistent with chronic bronchitis, emphysema, and interstitial fibrosis predominated in farmworkers compared with nonfarmworkers. CSi, determined gravimetrically, and aluminum silicate particles, determined by SEM/XRS, were increased in the lungs of farmworkers compared with nonfarmworkers and were significantly (p < 0.05) associated with small airway disease and pneumoconiosis.
Conclusion: Mineral dust exposure is associated with increased small airway disease and pneumoconiosis among California farmworkers; however, the clinical significance and natural history of these changes remains to be determined.
Background: Air pollution has consistently been associated with increased morbidity and mortality due to respiratory and cardiovascular disease. Underlying biological mechanisms are not entirely clear, and hemostasis and inflammation are suggested to be involved.
Objectives: Our aim was to study the association of the variation in local concentrations of airborne particulate matter (PM) with aerodynamic diameter < 10 μm, carbon monoxide, nitrogen monoxide, nitrogen dioxide, and ozone with platelet aggregation, thrombin generation, fibrinogen, and C-reactive protein (CRP) levels in healthy individuals.
Methods: From 40 healthy volunteers, we collected 13 consecutive blood samples within a 1-year period and measured light-transmittance platelet aggregometry, thrombin generation, fibrinogen, and CRP. We performed regression analysis using generalized additive models to study the association between the hemostatic and inflammatory variables, and local environmental concentrations of air pollutants for time lags within 24 hr before blood sampling or 24–96 hr before blood sampling.
Results: In general, air pollutants were associated with platelet aggregation [average, +8% per interquartile range (IQR), p < 0.01] and thrombin generation (average, +1% per IQR, p < 0.05). Platelet aggregation was not affected by in vitro incubation of plasma with PM. We observed no relationship between any of the air pollutants and fibrinogen or CRP levels.
Conclusions: Air pollution increased platelet aggregation as well as coagulation activity but had no clear effect on systemic inflammation. These prothrombotic effects may partly explain the relationship between air pollution and the risk of ischemic cardiovascular disease.
Background: The etiology of childhood brain cancer remains largely unknown. However, previous studies have yielded suggestive associations with parental pesticide use.
Objectives: We aimed to evaluate parental exposure to pesticides at home and on the job in relation to the occurrence of brain cancer in children.
Methods: We included 526 one-to-one–matched case–control pairs. Brain cancer cases were diagnosed at < 10 years of age, and were identified from statewide cancer registries of four U.S. Atlantic Coast states. We selected controls by random digit dialing. We conducted computer-assisted telephone interviews with mothers. Using information on residential pesticide use and jobs held by fathers during the 2-year period before the child’s birth, we assessed potential exposure to insecticides, herbicides, and fungicides. For each job, two raters independently classified the probability and intensity of exposure; 421 pairs were available for final analysis. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) using conditional logistic regression, after adjustment for maternal education.
Results: A significant risk of astrocytoma was associated with exposures to herbicides from residential use (OR = 1.9; 95% CI, 1.2–3.0). Combining parental exposures to herbicides from both residential and occupational sources, the elevated risk remained significant (OR = 1.8; 95% CI, 1.1–3.1). We observed little association with primitive neuroectodermal tumors (PNET) for any of the pesticide classes or exposure sources considered.
Conclusions: Our observation is consistent with a previous literature reporting suggestive associations between parental exposure to pesticides and risk of astrocytoma in offspring but not PNET. However, these findings should be viewed in light of limitations in exposure assessment and effective sample size.
Background: Incidence of childhood leukemia in industrialized countries rose significantly during 1975–2004, and the reasons for the increase are not understood.
Objectives: We used carpet dust as an exposure indicator to examine the risk of childhood leukemia in relation to residential exposure to persistent organochlorine chemicals: six polychlorinated biphenyl (PCB) congeners and the pesticides α- and γ-chlordane, p,p′-DDT (dichlorodiphenyltrichloroethane), p,p′-DDE (dichlorodiphenyldichloroethylene), methoxychlor, and pentachlorophenol.
Methods: We conducted a population-based case–control study in 35 counties in northern and central California in 2001–2006. The study included 184 acute lymphocytic leukemia (ALL) cases 0–7 years of age and 212 birth certificate controls matched to cases by birth date, sex, race, and Hispanic ethnicity. We collected carpet dust samples from the room where the child spent the most time before diagnosis (similar date for controls) using a specialized vacuum.
Results: Detection of any PCB congener in the dust conferred a 2-fold increased risk of ALL [odds ratio (OR) = 1.97; 95% confidence interval (CI), 1.22–3.17]. Compared with those in the lowest quartile of total PCBs, the highest quartile was associated with about a 3-fold risk (OR = 2.78; 95% CI, 1.41–5.48), and the positive trend was significant (p = 0.017). Significant positive trends in ALL risk were apparent with increasing concentrations of PCB congeners 118, 138, and 153. We observed no significant positive associations for chlordane, DDT, DDE, methoxychlor, or pentachlorophenol. The associations with PCBs were stronger among non-Hispanic whites than among Hispanics despite similar distributions of PCB levels among controls in each racial/ethnic group.
Conclusions: Our findings suggest that PCBs, which are considered probable human carcinogens and cause perturbations of the immune system, may represent a previously unrecognized risk factor for childhood leukemia.
Background: An increasing number of studies have shown that several ubiquitous environmental contaminants possess thyroid hormone–disrupting capacities. Prenatal exposure to some of them, such as polychlorinated biphenyls (PCBs), has also been associated with adverse neurodevelopmental effects in infants.
Objectives: In this study we examined the relationship between exposure to potential thyroid hormone–disrupting toxicants and thyroid hormone status in pregnant Inuit women from Nunavik and their infants within the first year of life.
Methods: We measured thyroid hormone parameters [thyroid stimulating hormone (TSH), free thyroxine (fT4), total triiodothyronine (T3), thyroxine-binding globulin (TBG)] and concentrations of several contaminants [PCB-153, hydroxylated metabolites of PCBs (HO-PCBs), pentachlorophenol (PCP) and hexachlorobenzene (HCB)] in maternal plasma at delivery (n = 120), in umbilical cord plasma (n = 95), and in infant plasma at 7 months postpartum (n = 130).
Results: In pregnant women, we found a positive association between HO-PCBs and T3 concentrations (β = 0.57, p = 0.02). In umbilical cord blood, PCB-153 concentrations were negatively associated with TBG levels (β = −0.26, p = 0.01). In a subsample analysis, a negative relationship was also found between maternal PCP levels and cord fT4 concentrations in neonates (β = −0.59, p = 0.02). No association was observed between contaminants and thyroid hormones at 7 months of age.
Conclusion: Overall, there is little evidence that the environmental contaminants analyzed in this study affect thyroid hormone status in Inuit mothers and their infants. The possibility that PCP may decrease thyroxine levels in neonates requires further investigation.