Association of Occupational Exposures and Chronic Obstructive Pulmonary Disease Morbidity.

OBJECTIVE: The aim of the study is to determine whether aggregate measures of occupational exposures are associated with chronic obstructive pulmonary disease (COPD) outcomes in the Subpopulations and Intermediate Outcome Measures in COPD study cohort. METHODS: Individuals were assigned to six predetermined exposure hazard categories based on self-reported employment history. Multivariable regression, adjusted for age, sex, race, current smoking status, and smoking pack-years determined the association of such exposures to odds of COPD and morbidity measures. We compared these with the results of a single summary question regarding occupational exposure. RESULTS: A total of 2772 individuals were included. Some exposure estimates, including "gases and vapors" and "dust and fumes" exposures resulted in associations with effect estimates over two times the estimated effect size when compared with a single summary question. CONCLUSIONS: Use of occupational hazard categories can identify important associations with COPD morbidity while use of single-point measures may underestimate important differences in health risks.

Peak Exposures in Epidemiologic Studies and Cancer Risks: Considerations for Regulatory Risk Assessment.

We review approaches for characterizing "peak" exposures in epidemiologic studies and methods for incorporating peak exposure metrics in dose-response assessments that contribute to risk assessment. The focus was on potential etiologic relations between environmental chemical exposures and cancer risks. We searched the epidemiologic literature on environmental chemicals classified as carcinogens in which cancer risks were described in relation to "peak" exposures. These articles were evaluated to identify some of the challenges associated with defining and describing cancer risks in relation to peak exposures. We found that definitions of peak exposure varied considerably across studies. Of nine chemical agents included in our review of peak exposure, six had epidemiologic data used by the U.S. Environmental Protection Agency (US EPA) in dose-response assessments to derive inhalation unit risk values. These were benzene, formaldehyde, styrene, trichloroethylene, acrylonitrile, and ethylene oxide. All derived unit risks relied on cumulative exposure for dose-response estimation and none, to our knowledge, considered peak exposure metrics. This is not surprising, given the historical linear no-threshold default model (generally based on cumulative exposure) used in regulatory risk assessments. With newly proposed US EPA rule language, fuller consideration of alternative exposure and dose-response metrics will be supported. "Peak" exposure has not been consistently defined and rarely has been evaluated in epidemiologic studies of cancer risks. We recommend developing uniform definitions of "peak" exposure to facilitate fuller evaluation of dose response for environmental chemicals and cancer risks, especially where mechanistic understanding indicates that the dose response is unlikely linear and that short-term high-intensity exposures increase risk.

An investigation of mercury sources in the Puyango-Tumbes River: Using stable Hg isotopes to characterize transboundary Hg pollution.

Mercury (Hg) concentrations and stable isotopes along with other trace metals were examined in environmental samples from Ecuador and Peru's shared Puyango-Tumbes River in order to determine the extent to which artisanal- and small-scale gold mining (ASGM) in Portovelo-Zaruma, Ecuador contributes to Hg pollution in the downstream aquatic ecosystem. Prior studies investigated the relationship between ASGM activities and downstream Hg pollution relying primarily on Hg concentration data. In this study, Hg isotopes revealed an isotopically heavy Hg signature with negligible mass independent fractionation (MIF) in downstream sediments, which was consistent with the signature observed in the ASGM source endmember. This signature was traced as far as ∼120 km downstream of Portovelo-Zaruma, demonstrating that Hg stable isotopes can be used as a tool to fingerprint and trace sources of Hg over vast distances in freshwater environments. The success of Hg isotopes as a source tracer in fresh waters is largely due to the particle-reactive nature of Hg. Furthermore, the magnitude and extent of downstream Hg, lead, copper and zinc contamination coupled with the Hg isotopes suggest that it is unlikely that the smaller artisanal-scale activities, which do not use cyanidation, are responsible for the pollution. More likely it is the scale of ores processed and the cyanide leaching, which can release other metals and enhance Hg transport, used during small-scale gold mining that is responsible. Thus, although artisanal- and small-scale gold mining occur in tandem in Portovelo-Zaruma, a distinction should be made between these two activities.

Environmental and occupational risk factors for progressive supranuclear palsy: Case-control study.

BACKGROUND: The cause of progressive supranuclear palsy (PSP) is largely unknown. Based on evidence for impaired mitochondrial activity in PSP, we hypothesized that the disease may be related to exposure to environmental toxins, some of which are mitochondrial inhibitors. METHODS: This multicenter case-control study included 284 incident PSP cases of 350 cases and 284 age-, sex-, and race-matched controls primarily from the same geographical areas. All subjects were administered standardized interviews to obtain data on demographics, residential history, and lifetime occupational history. An industrial hygienist and a toxicologist unaware of case status assessed occupational histories to estimate past exposure to metals, pesticides, organic solvents, and other chemicals. RESULTS: Cases and controls were similar on demographic factors. In unadjusted analyses, PSP was associated with lower education, lower income, more smoking pack-years, more years of drinking well water, more years living on a farm, more years living 1 mile from an agricultural region, more transportation jobs, and more jobs with exposure to metals in general. However, in adjusted models, only more years of drinking well water was significantly associated with PSP. There was an inverse association with having a college degree. CONCLUSIONS: We did not find evidence for a specific causative chemical exposure; higher number of years of drinking well water is a risk factor for PSP. This result remained significant after adjusting for income, smoking, education and occupational exposures. This is the first case-control study to demonstrate PSP is associated with environmental factors. © 2016 International Parkinson and Movement Disorder Society.

Serial Free Bisphenol A and Bisphenol A Glucuronide Concentrations in Neonates.

OBJECTIVE: To determine the balance of metabolism of free bisphenol A (BPA) to the inactive conjugate, BPA glucuronide (BPAG), in neonates. STUDY DESIGN: Free BPA and BPAG concentrations were measured in 78 urine samples collected between December 2012 and August 2013 from a cohort of 44 healthy full term (≥ 37 weeks' gestation) neonates at 2 intervals (3-6 days and 7-27 days of age). A questionnaire was administered at the time of sample collection. Neonates recruited into the study were born in an urban, tertiary care hospital. RESULTS: Only BPAG was detected in the urine samples; concentrations ranged from <0.1 µg/L to 11.21 µg/L (median: 0.27 µg/L). Free BPA concentrations were below the limit of quantification of 0.1 µg/L. Age, but not sex or type of diet, was significantly associated with urinary BPAG concentration (P = .002). CONCLUSIONS: Our results illustrate widespread BPA exposure in healthy full-term neonates and efficient conjugation of BPA to its readily excretable and biologically inactive form (BPAG) as early as 3 days of age. Factors other than type of diet may be important contributors to BPA exposure in neonates.

Laceration injuries and infections among workers in the poultry processing and pork meatpacking industries.

BACKGROUND: Workers in poultry processing and pork meatpacking have high rates of acute injuries and chronic disease among. The presence of zoonotic pathogens in these workplaces may interact with injury. METHODS: We investigated incidence of worker injuries, lacerations, and infections reported by 10 companies from 2004 to 2009 and calculated annual incidence rates by industry and company along with temporal trends and job-related risk factors. RESULTS: Average annual mean total injury rates were 6.4 per 100 workers (poultry) and 13.2 per 100 workers (pork). Average annual mean rates for lacerations were 1.8 per 100 workers (poultry) and 1.9 per 100 (pork). Sharp tools and animal products were most frequently reported as sources for lacerations. Animal products were most frequently reported as sources of infected lacerations. CONCLUSIONS: The results indicate that these industries continue to have high injury rates. The results also suggest that zoonotic pathogens may be preventable health and safety risks.

Early Life Metabolism of Bisphenol A: A Systematic Review of the Literature.

When a comprehensive report on BPA was published in 2008, few data were available to assess the extent to which known poor glucuronidation capacity impacts BPA internal dose in infants and young children. In this paper, evidence that has emerged since the 2008 report is summarized, including: 1) human biomarker studies in children aged 0-5 years; 2) animal studies of neonatal toxicokinetics; and 3) physically based pharmacokinetic (PBPK) models. To address limitations in these studies, we recommend more human biomonitoring studies in children aged 0-5 years in which unmetabolized (free) BPA and BPA metabolites are separately quantified and detailed quality-control data are reported, investigation of metabolic differences between humans and animal species used for the study of BPA metabolism, and enzyme ontogeny studies, which along with biomonitoring studies would reduce uncertainty in PBPK models of early-life BPA metabolism.

Characterization of a portable method for the collection of exhaled breath condensate and subsequent analysis of metal content.

Using exhaled breath condensate (EBC) as a biological media for analysis of biomarkers of exposure may facilitate the understanding of inhalation exposures. In this study, we present method validation for the collection of EBC and analysis of metals in EBC. The collection method was designed for use in a small scale longitudinal study with the goal of improving reproducibility while maintaining economic feasibility. We incorporated the use of an Rtube with additional components as an assembly, and trained subjects to breathe into the apparatus. EBC was collected from 8 healthy adult subjects with no known elevated exposures to Mn, Cr, Ni, and Cd repeatedly (10 times) within 7 days and analyzed for these metals via ICP-MS. Method detection limits were obtained by mimicking the process of EBC collection with ultrapure water, and resulted in 46-62% of samples falling in a range less than the method detection limit. EBC metal concentrations were found to be statistically significantly associated (p < 0.05) with room temperature and relative humidity during collection, as well as with the gender of the subject. The geometric mean EBC metal concentrations in our unexposed subjects were 0.57 µg Mn per L, 0.25 µg Cr per L, 0.87 µg Ni per L, and 0.14 µg Cd per L. The overall standard deviation was greater than the mean estimate, and the major source in EBC metals concentrations was due to fluctuations in subjects' measurements over time rather than to the differences between separate subjects. These results suggest that measurement and control of EBC collection and analytical parameters are critical to the interpretation of EBC metals measurements. In particular, rigorous estimation of method detection limits of metals in EBC provides a more thorough evaluation of accuracy.

Urinary free bisphenol A and bisphenol A-glucuronide concentrations in newborns.

Infants are exposed to the endocrine disruptor bisphenol A (BPA) through breast milk and baby formula. Detoxication by conjugation of BPA may be limited in infants. We demonstrate BPA exposure in 11 neonates and 1 young infant, but find no evidence of a low capacity for BPA conjugation.

Prenatal secondhand smoke exposure and infant birth weight in China.

Epidemiologic evidence provides some support for a causal association between maternal secondhand smoke (SHS) exposure during pregnancy and reduction in infant birth weight. The purpose of this cross-sectional study is to examine the magnitude of this association in China, where both prevalence and dose of SHS exposure are thought to be higher than in U.S. populations. Women who gave birth in Beijing and Changchun September 2000-November 2001 were interviewed to quantify self-reported prenatal SHS exposure. Their medical records were reviewed for data on pregnancy complications and birth outcomes. Non-smoking women who delivered term babies (≥37 weeks gestation) were included in the study (N = 2,770). Nearly a quarter of the women (24%) reported daily SHS exposure, 47% reported no prenatal exposure, and 75% denied any SHS exposure from the husband smoking at home. Overall, no deficit in mean birth weight was observed with exposure from all sources of SHS combined (+11 grams, 95% CI: +2, +21). Infants had higher mean birth weights among the exposed than the unexposed for all measures of SHS exposure. Future studies on SHS exposure and infant birth weight in China should emphasize more objective measures of exposure to quantify and account for any exposure misclassification.

Evaluation of the interactions between multiwalled carbon nanotubes and Caco-2 cells.

The aim of this study was to determine whether multiwalled carbon nanotubes (MWNCT) are taken up by and are toxic to human intestinal enterocytes using the Caco-2 cell model. Caco-2 cells were exposed to 50 µg/ml MWCNT (oxidized or pristine) for 24 h, and experiments were repeated in the presence of 2.5 mg/L natural organic matter. Cells displayed many of the properties that characterize enterocytes, such as apical microvilli, basolateral basement membrane, and glycogen. The cell monolayers also displayed tight junctions and electrical resistance. Exposure to pristine and oxidized MWCNT, with or without natural organic matter, did not markedly affect viability, which was assessed by measuring activity of released lactate dehydrogenase (LDH) and staining with propidium iodide. Ultrastructural analysis revealed some damage to microvilli colocalized with the MWCNT; however, neither type of MWCNT was taken up by Caco-2 cells. In contrast, pristine and oxidized MWCNT were taken up by the macrophage RAW 264.7 line. Our study suggests that intestinal enterocytes cells do not take up MWCNT.

Evaluation of antineoplastic drug exposure of health care workers at three university-based US cancer centers.

OBJECTIVE: This study evaluated health care worker exposure to antineoplastic drugs. METHODS: A cross-sectional study examined environmental samples from pharmacy and nursing areas. A 6-week diary documented tasks involving those drugs. Urine was analyzed for two specific drugs, and blood samples were analyzed by the comet assay. RESULTS: Sixty-eight exposed and 53 nonexposed workers were studied. Exposed workers recorded 10,000 drug-handling events during the 6-week period. Sixty percent of wipe samples were positive for at least one of the five drugs measured. Cyclophosphamide was most commonly detected, followed by 5-fluorouracil. Three of the 68 urine samples were positive for one drug. No genetic damage was detected in exposed workers using the comet assay. CONCLUSIONS: Despite following recommended safe-handling practices, workplace contamination with antineoplastic drugs in pharmacy and nursing areas continues at these locations.

Chemosensory loss: functional consequences of the world trade center disaster.

BACKGROUND: Individuals involved in rescue, recovery, demolition, and cleanup at the World Trade Center (WTC) site were exposed to a complex mixture of airborne smoke, dust, combustion gases, acid mists, and metal fumes. Such exposures have the potential to impair nasal chemosensory (olfactory and trigeminal) function. OBJECTIVE: The goal of this study was to evaluate the prevalence of chemosensory dysfunction and nasal inflammation among these individuals. METHODS: We studied 102 individuals who worked or volunteered at the WTC site in the days and weeks during and after 11 September 2001 (9/11) and a comparison group with no WTC exposure matched to each participant on age, sex, and job title. Participants were comprehensively evaluated for chemosensory function and nasal inflammation in a single session. Individual exposure history was obtained from self-reported questionnaires. RESULTS: The prevalence of olfactory and trigeminal nerve sensitivity loss was significantly greater in the WTC-exposed group relative to the comparison group [prevalence ratios (95% confidence intervals) = 1.96 (1.2-3.3) and 3.28 (2.7-3.9) for odor and irritation thresholds, respectively]. Among the WTC responders, however, individuals caught in the dust cloud from the collapse on 9/11 exhibited the most profound trigeminal loss. Analysis of the nasal lavage samples supported the clinical findings of chronic nasal inflammation among the WTC-exposed cohort. CONCLUSIONS: The prevalence of significant chemosensory impairment in the WTC-exposed group more than 2 years after their exposure raises concerns for these individuals when the ability to detect airborne odors or irritants is a critical safety factor. RELEVANCE TO CLINICAL PRACTICE: This outcome highlights the need for chemosensory evaluations among individuals with exposure to acute high or chronic levels of airborne pollutants.

Circumstances of fatal lockout/tagout-related injuries in manufacturing.

BACKGROUND: Over the past few decades, hundreds of manufacturing workers have suffered fatal injuries while performing maintenance and servicing on machinery and equipment. Using lockout/tagout procedures could have prevented many of these deaths. METHODS: A narrative text analysis of OSHA accident investigation report summaries was conducted to describe the circumstances of lockout/tagout-related fatalities occurring in the US manufacturing industry from 1984 to 1997. RESULTS: The most common mechanisms of injury were being caught in or between parts of equipment, electrocution, and being struck by or against objects. Typical scenarios included cleaning a mixer or blender, cleaning a conveyor, and installing or disassembling electrical equipment. Lockout procedures were not even attempted in the majority (at least 58.8%) of fatal incidents reviewed. CONCLUSIONS: Lockout/tagout-related fatalities occur under a wide range of circumstances. Enhanced training and equipment designs that facilitate lockout and minimize worker contact with machine parts may prevent many lockout/tagout-related injuries.

Effects of the Occupational Safety and Health Administration's control of hazardous energy (lockout/tagout) standard on rates of machinery-related fatal occupational injury.

OBJECTIVE: To evaluate the impact of the United States' federal Occupational Safety and Health Administration's control of hazardous energy (lockout/tagout) standard on rates of machinery-related fatal occupational injury. The standard, which took effect in 1990, requires employers in certain industries to establish an energy control program and sets minimum criteria for energy control procedures, training, inspections, and hardware. DESIGN: An interrupted time-series design was used to determine the standard's effect on fatality rates. Machinery-related fatalities, obtained from the National Traumatic Occupational Fatalities surveillance system for 1980 through 2001, were used as a proxy for lockout/tagout-related fatalities. Linear regression was used to control for changes in demographic and economic factors. RESULTS: The average annual crude rate of machinery-related fatalities in manufacturing changed little from 1980 to 1989, but declined by 4.59% per year from 1990 to 2001. However, when controlling for demographic and economic factors, the regression model estimate of the standard's effect is a small, non-significant increase of 0.05 deaths per 100 000 production worker full-time equivalents (95% CI -0.14 to 0.25). When fatality rates in comparison groups that should not have been affected by the standard are incorporated into the analysis, there is still no significant change in the rate of machinery-related fatalities in manufacturing. CONCLUSIONS: There is no evidence that the lockout/tagout standard decreased fatality rates relative to other trends in occupational safety over the study period. A possible explanation is voluntary use of lockout/tagout by some employers before introduction of the standard and low compliance by other employers after.

Evaluation of long-term occupational exposure to styrene vapor on olfactory function.

The primary sensory neurons of the olfactory system are chronically exposed to the ambient environment and may therefore be susceptible to damage from occupational exposure to many volatile chemicals. To investigate whether occupational exposure to styrene was associated with olfactory impairment, we examined olfactory function in 2 groups: workers in a German reinforced-plastics boat-manufacturing facility having a minimum of 2 years of styrene exposure (15-25 ppm as calculated from urinary metabolite concentrations, with historical exposures up to 85 ppm) and a group of age-matched workers from the same facility with lower styrene exposures. The results were also compared with normative data previously collected from healthy, unexposed individuals. Multiple measures of olfactory function were evaluated using a standardized battery of clinical assessments from the Monell-Jefferson Chemosensory Clinical Research Center that included tests of threshold sensitivity for phenylethyl alcohol (PEA) and odor identification ability. Thresholds for styrene were also obtained as a measure of occupational olfactory adaptation. Styrene exposure history was calculated through the use of past biological monitoring results for urinary metabolites of styrene (mandelic acid [MA], phenylglyoxylic acid [PGA]); current exposure was determined for each individual using passive air sampling for styrene and biological monitoring for styrene urinary metabolites. Current mean effective styrene exposure during the day of olfactory testing for the group of workers who worked directly with styrene resins was 18 ppm styrene (standard deviation [SD] = 14), 371 g/g creatinine MA + PGA (SD = 289) and that of the group of workers with lower exposures was 4.8 ppm (SD = 5.2), 93 g/g creatinine MA+PGA (SD = 100). Historic annual average exposures for all workers were greater by a factor of up to 6x. No differences unequivocally attributable to exposure status were observed between the Exposed and Comparison groups or between performance of either group and normative population values on thresholds for PEA or odor identification. Although odor identification performance was lower among workers with higher ongoing exposures, performance on this test is not a pure measure of olfactory ability and is influenced by familiarity with the stimuli and their sources. Consistent with exposure-induced sensory adaptation, however, elevated styrene thresholds were significantly associated with higher occupational exposures to styrene. In summary, the present study found no evidence among a cross-section of reinforced-plastics workers that current or historical exposure to styrene was associated with a general impairment of olfactory function. When taken together with prior studies of styrene-exposed workers, these results suggest that styrene is not a significant olfactory toxicant in humans at current exposure levels.

Inter-rater agreement of assessed prenatal maternal occupational exposures to lead.

BACKGROUND: Industrial hygienists' assessments of prenatal occupational exposures based on parental job histories is a promising approach for population-based case-control studies of birth defects and other perinatal outcomes. However, evaluations of inter-rater agreement of such assessments have been limited. METHODS: We examined inter-rater agreement of occupational lead exposure assessments of maternal job reports by industrial hygienists in a population-based case-control study of parental occupational lead exposure and low birth weight. A total of 178 jobs with potential exposure to lead during the 6 months before pregnancy to the end of pregnancy were examined. Three industrial hygienists evaluated these jobs independently for exposure to lead including probability of exposure, type of exposure, route of entry, exposure frequency, duration, and intensity. Inter-rater agreement of these assessments beyond chance was evaluated using the kappa statistic (kappa). RESULTS: In general, inter-rater agreement was greater for assessment of direct exposures than assessment of indirect exposures. However, inter-rater agreement varied with the lead exposure metric under consideration, being: 1) fair to good for type of direct exposure (i.e., inorganic or organic), respiratory exposure and frequency of exposure to direct inorganic lead, hours per day of direct (i.e., inorganic or organic), and intensity of direct inorganic exposure; 2) poor for probability and type of indirect exposure (inorganic or organic); and 3) indeterminate for frequency of direct organic exposure, frequency of indirect exposures (organic or inorganic), and intensity of direct exposures (organic or inorganic). CONCLUSION: Retrospective assessment of maternal prenatal exposures to lead by industrial hygienists can provide some reliable metrics of exposure for studies of perinatal outcomes. Reliability studies of such exposure assessments may be useful for: quantifying the reliability of derived exposure metrics; identifying exposure metrics for exposure-outcome analyses; and determining the reliability of prenatal occupational exposures to other agents of interest.

Health status of Army Chemical Corps Vietnam veterans who sprayed defoliant in Vietnam.

BACKGROUND: U.S. Army Chemical Corps veterans handled and sprayed herbicides in Vietnam resulting in exposure to Agent Orange and its contaminant 2,3,7, 8-tetrachlorodibenzo-p-dioxin (TCDD or dioxin). This study examined the long-term health effects associated with herbicide exposure among these Vietnam veterans. METHODS: A health survey of these 1,499 Vietnam veterans and a group of 1,428 non-Vietnam veterans assigned to chemical operations jobs was conducted using a computer-assisted telephone interview (CATI) system. Exposure to herbicides was assessed by analyzing serum specimens from a sample of 897 veterans for dioxin. Logistic regression analyses were used to estimate the risk of selected medical outcomes associated with herbicide exposure. RESULTS: Odds ratios for diabetes, heart disease, hypertension, and chronic respiratory disease were elevated, but not significantly (P>0.05) for those who served in Vietnam. However, they were significantly elevated among those Vietnam veterans who sprayed herbicides: diabetes, odds ratio (OR)=1.50 (95% confidence interval [95%CI]=1.15-1.95); heart disease, OR=1.52 (1.18-1.94); hypertension, OR=1.32 (1.08-1.61); and chronic respiratory condition, OR=1.62 (1.28-2.05). Hepatitis was associated with Vietnam service, but not with herbicide application. CONCLUSIONS: Vietnam veterans who were occupationally exposed to herbicide experienced a higher risk of several chronic medical conditions relative to other non-Vietnam veterans. A potential selection bias is of concern. However, there were relatively high participation rates in both the Vietnam and non-Vietnam veteran groups, and the prevalence rates of some of these medical conditions among non-Vietnam veterans were comparable to general populations. Therefore, self-selection factors are considered unlikely to have biased the study results.

Development of a questionnaire to assess worker knowledge, attitudes and perceptions underlying dermal exposure.

OBJECTIVES: Workers' behavior is identified as an important determinant of dermal exposure and is influenced by knowledge, attitudes, and risk perceptions. Because behavior may be a significant predictor of exposure, its assessment provides a means for examining exposure and designing strategies and incentives that encourage worker protective behavior. Currently, there are no psychosocial instruments examining worker knowledge, attitudes, and perceptions with respect to dermal hazards. Accordingly, a questionnaire was developed and tested to provide an instrument for measuring worker knowledge, attitudes, and perceptions. METHODS: The questionnaire was developed on the basis of a literature review and expert consultation. Scales were constructed based on standard methods. Two worker focus groups were used to evaluate worker understanding and content validity of the KAP (knowledge, attitudes, perceptions) questionnaire. The resulting 115-item questionnaire that included scales for knowledge (N=13), attitudes (N=27), perceptions (N=15), behavior (N=8), behavioral intentions (N=15), barriers (N=13), and facilitators (N=5) was tested on 89 workers from 19 facilities. RESULTS: The concepts identified in the focus groups included worker perception of higher risk due to a poor fit and replacement frequency for personal protective equipment and cross-contamination by workers moving into work zones. Field testing of the questionnaire (N=89) yielded Cronbach's alpha reliability scores ranging from 0.87 for the self-efficacy personal protective equipment scale to 0.92 for the overall belief scale, indicating high internal reliability. CONCLUSIONS: Although further testing and refinement is needed, this survey instrument provides an initial and conceptually unique means for evaluating behavioral determinants of worker dermal exposure.