Michael Lewin

Variability of urinary concentrations of polycyclic aromatic hydrocarbon metabolite in general population and comparison of spot, first-morning, and 24-h void sampling.

Urinary mono-hydroxy polycyclic aromatic hydrocarbons (OH-PAHs) are commonly used in biomonitoring to assess exposure to polycyclic aromatic hydrocarbons (PAHs). Similar to other biologically non-persistent chemicals, OH-PAHs have relatively short biological half-lives (4.4-35 h). Little information is available on their variability in urinary concentrations over time in non-occupationally exposed subjects. This study was designed to (i) examine the variability of nine urinary OH-PAH metabolite concentrations over time and (ii) calculate sample size requirements for future epidemiological studies on the basis of spot urine, first-morning void, and 24-h void sampling. Individual urine samples (n=427) were collected during 1 week from 8 non-occupationally exposed adults. We recorded the time and volume of each urine excretion, dietary details, and driving activities of the participants. Within subjects, the coefficients of variation (CVs) for the wet-weight concentration of OH-PAHs in all samples ranged from 45% to 297%; creatinine adjustment reduced the CV to 19-288% (P<0.001; paired t-test). The simulated 24-h void concentrations were the least variable measure, with CVs ranging from 13% to 182% for the 9 OH-PAHs. Within-day variability contributed on average 84%, and between-day variability accounted for 16% of the total variance of 1-hydroxypyrene (1-PYR). Intraclass correlation coefficients of 1-PYR levels were 0.55 for spot urine samples, 0.65 [corrected] for first-morning voids, and 0.77 [corrected] for 24-h voids, indicating a high degree of correlation between urine measurements collected from the same subject over time. Sample size calculations were performed to estimate the number of subjects required for detecting differences in the geometric mean at a statistical power of 80% for spot urine, first-morning, and 24-h void sampling. These data will aid in the design of future studies of PAHs and possibly other biologically non-persistent chemicals and in the interpretation of their analytical results.Urinary mono-hydroxy polycyclic aromatic hydrocarbons (OH-PAHs) are commonly used in biomonitoring to assess exposure to polycyclic aromatic hydrocarbons (PAHs). Similar to other biologically non-persistent chemicals, OH-PAHs have relatively short biological half-lives (4.4–35 h). Little information is available on their variability in urinary concentrations over time in non-occupationally exposed subjects. This study was designed to (i) examine the variability of nine urinary OH-PAH metabolite concentrations over time and (ii) calculate sample size requirements for future epidemiological studies on the basis of spot urine, first-morning void, and 24-h void sampling. Individual urine samples (n=427) were collected during 1 week from 8 non-occupationally exposed adults. We recorded the time and volume of each urine excretion, dietary details, and driving activities of the participants. Within subjects, the coefficients of variation (CVs) for the wet-weight concentration of OH-PAHs in all samples ranged from 45% to 297%; creatinine adjustment reduced the CV to 19–288% (P<0.001; paired t-test). The simulated 24-h void concentrations were the least variable measure, with CVs ranging from 13% to 182% for the 9 OH-PAHs. Within-day variability contributed on average 84%, and between-day variability accounted for 16% of the total variance of 1-hydroxypyrene (1-PYR). Intraclass correlation coefficients of 1-PYR levels were 0.55 for spot urine samples, 0.60 for first-morning voids, and 0.76 for 24-h voids, indicating a high degree of correlation between urine measurements collected from the same subject over time. Sample size calculations were performed to estimate the number of subjects required for detecting differences in the geometric mean at a statistical power of 80% for spot urine, first-morning, and 24-h void sampling. These data will aid in the design of future studies of PAHs and possibly other biologically non-persistent chemicals and in the interpretation of their analytical results.

Associations between radiographic findings and spirometry in a community exposed to Libby amphibole

Background Among asbestos-exposed individuals, abnormal spirometry is usually associated with parenchymal abnormalities or diffuse pleural thickening. Localised pleural thickening (LPT), the most common abnormality associated with asbestos exposure, is typically thought to be a marker of exposure with little clinical consequence. Our objective was to determine if abnormal spirometry is associated with LPT independent of other abnormalities, using data from community-based screening conducted in Libby, Montana. Methods Subjects were a subset of screening participants comprising persons with interpretable spirometry and chest radiograph results (n=6475). Chest radiographs were independently evaluated by two or three B readers, and participants were classified by mutually exclusive categories of spirometry outcome: normal, restriction, obstruction or mixed defect. Results Restrictive spirometry was strongly associated with parenchymal abnormalities (OR 2.9; 95% CI 1.4 to 6.0) and diffuse pleural thickening (OR 4.1; 95% CI 2.1 to 7.8). Controlling for the presence of these abnormalities as well as age, smoking status and other covariates, restrictive spirometry was also associated with LPT (OR 1.4; 95% CI 1.1 to 1.8). The risk of restrictive spirometric findings correlated with the severity of LPT. Conclusions In this large community-based screening cohort, restrictive spirometry is significantly associated with LPT, indicating that this abnormality may result in lung function impairment. Physicians treating patients exposed to Libby amphibole should be aware that LPT may have functional consequences.

Dioxin exposure in a residential community

The Agency for Toxic Substances and Disease Registry (ATSDR) conducted biological testing to assess dioxin exposure in residents of a community who lived in an area with heavy chemical industry. Dioxin concentrations were measured in blood serum samples from 28 adult residents of the community. Fourteen of those tested had blood dioxin concentrations that exceeded the 95th percentile prediction level of an age-matched comparison population. Specific congener analyses indicated that the elevated dioxin concentrations were primarily due to high concentrations of 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD), 1,2,3,7,8 pentachlorodibenzo-p-dioxin (PeCDD), and hexachlorodibenzo-p-dioxins (HxCDs). Principal components analysis (PCA) indicated that the profiles of dioxin congeners were different in people with elevated blood dioxin concentrations compared to those with background concentrations. Elevated blood dioxin concentrations were detected only in older members of the population, which suggests that dioxin exposures were higher in the past. The sources of the dioxin exposure have not been identified.

Mortality from asbestos-associated disease in Libby, Montana 1979-2011.

Research on asbestos exposure in Libby, MT, has focused on occupational exposure in vermiculite mining and processing, but less attention has been paid to asbestos-related mortality among community members without vermiculite mining occupational history. Our study reports on asbestos-related mortality in Libby over 33 years (1979–2011) while controlling for occupational exposure. We calculated sex-specific 33-year standardized mortality ratios (SMRs) for Libby residents who died from 1979 to 2011 with an asbestos-related cause of death. Decedent address at time of death was geocoded to confirm inclusion in the Libby County Division. We controlled for past W.R. Grace employment by including and then removing them from the SMR analysis. Six hundred and ninety-four decedents were identified as having at least one asbestos-related cause of death and residing in our study area boundary. Statistically significant (P<0.05) 33-year SMRs, both before and after controlling for W.R. Grace employment, were found for: male and female non-malignant respiratory diseases, female COPD, and asbestosis for both sexes combined. Eighty-five men and two women were matched to employment records. We observed elevated asbestos-related mortality rates among males and females. SMR results for asbestosis were high for both sexes, even after controlling for past W.R. Grace employment. These results suggest that the general population may be experiencing asbestos-related effects, not just former vermiculite workers. Additional research is needed to determine whether SMRs remain elevated after controlling for secondary exposure, such as living with vermiculite workers.

Biomonitoring Human Exposure to Household Air Pollution and Association with Self-reported Health Symptoms – A Stove Intervention Study in Peru

BACKGROUND Household air pollution (HAP) from indoor biomass stoves contains harmful pollutants, such as polycyclic aromatic hydrocarbons (PAHs), and is a leading risk factor for global disease burden. We used biomonitoring to assess HAP exposure and association with self-reported symptoms in 334 non-smoking Peruvian women to evaluate the efficacy of a stove intervention program. METHODS We conducted a cross-sectional study within the framework of a community randomized control trial. Using urinary PAH metabolites (OH-PAHs) as the exposure biomarkers, we investigated whether the intervention group (n=155, with new chimney-equipped stoves) were less exposed to HAP compared to the control group (n=179, with mostly open-fire stoves). We also estimated associations between the exposure biomarkers, risk factors, and self-reported health symptoms, such as recent eye conditions, respiratory conditions, and headache. RESULTS We observed reduced headache and ocular symptoms in the intervention group than the control group. Urinary 2-naphthol, a suggested biomarker for inhalation PAH exposure, was significantly lower in the intervention group (GM with 95% CI: 13.4 [12.3, 14.6] μg/g creatinine) compared to control group (16.5 [15.0, 18.0] μg/g creatinine). Stove type and/or 2-naphthol was associated with a number of self-reported symptoms, such as red eye (adjusted OR with 95% CI: 3.80 [1.32, 10.9]) in the past 48h. CONCLUSIONS Even with the improved stoves, the biomarker concentrations in this study far exceeded those of the general populations and were higher than a no-observed-genotoxic-effect-level, indicating high exposure and a potential for increased cancer risk in the population.

Prevalence and associated demographic characteristics of exposure to multiple metals and their species in human populations: The United States NHANES, 2007–2012

ABSTRACT Lead (Pb), cadmium (Cd), mercury (Hg), and arsenic (As) are among the top 10 pollutants of global health concern. Studies have shown that exposures to these metals produce severe adverse effects. However, the mechanisms underlying these effects, particularly joint toxicities, are poorly understood in humans. The objective of this investigation was to identify and characterize prevalent combinations of these metals and their species in the U.S. NHANES population to provide background data for future studies of potential metal interactions. Exposure was defined as urine or blood levels ≥ medians of the NHANES 2007–2012 participants ≥6 years (n = 7408). Adjusted-odds ratios (adj-OR) and 95% confidence intervals were determined for covariates (age, gender, and race/ethnicity, cotinine and body mass index). Species-specific analysis was also conducted for As and Hg including iAs (urinary arsenous acid and/or arsenic acid), met-iAs (urinary monomethylarsonic acid and/or dimethylarsinic acid), and oHg (blood methyl-mercury and/or ethyl-mercury). For combinations of As and Hg species, age- and gender-specific prevalence was determined among NHANES 2011–2012 participants (n = 2342). Data showed that approximately 49.3% of the population contained a combination of three or more metals. The most prevalent unique specific combinations were Pb/Cd/Hg/As, Pb/Cd/Hg, and Pb/Cd. Age was consistently associated with these combinations: adj-ORs ranged from 10.9 (Pb/Cd) to 11.2 (Pb/Cd/Hg/As). Race/ethnicity was significant for Pb/Cd/Hg/As. Among women of reproductive age, frequency of oHg/iAs/met-iAS and oHg/met-iAs was 22.9 and 40.3%, respectively. These findings may help prioritize efforts to assess joint toxicities and their impact on public health.

Comparison of blood volatile organic compound levels in residents of Calcasieu and Lafayette Parishes, LA, with US reference ranges.

Agency for Toxic Substances and Disease Registry conducted a study to evaluate body burden levels of volatile organic compounds (VOCs) among residents of highly industrialized Calcasieu Parish, LA, USA, in 2002. Blood VOC levels in a representative sample of participants in Calcasieu Parish were compared with a similar group of participants in the less-industrialized Lafayette Parish. Participants’ ages ranged from 15 to 91 years, 46% were men, and 89% were Caucasian. VOC levels in these two populations were also compared at the national levels. Solid-phase microextraction coupled with gas chromatography mass spectrometry was used to measure levels of 30 VOCs in blood samples collected from 283 self-described non-smoking study participants. Of the 30 VOCs, 6 had quantifiable levels in at least 25% of the blood samples analyzed. The frequency of detection was >95% for benzene and m-/p-xylene, >60% for 1,4-dichlorbenzene and toluene, 27% for ethylbenzene, and 39% for styrene. Calcasieu and Lafayette Parish participants had similar distributions for six VOCs in key percentiles and geometric means. When compared with a representative sampling of the 1999–2000 US general population, no significant differences were found between the parish data and the US general population.

Lessons from the 2006 Louisiana health and population survey.

The 2005 hurricane season caused extensive damage and induced a mass migration of approximately 1.1 million people from southern Louisiana in the United States. Current and accurate estimates of population size and demographics and an assessment of the critical needs for public services were required to guide recovery efforts. Since forecasts using pre-hurricane data may produce inaccurate estimates of the post-hurricane population, a household survey in 18 hurricane-affected parishes was conducted to provide timely and credible information on the size of these populations, their demographics and their condition. This paper describes the methods used, the challenges encountered, and the key factors for successful implementation. This post-disaster survey was unique because it identified the needs of the people in the affected parishes and quantified the number of people with these needs. Consequently, this survey established new population and health indicator baselines that otherwise would have not been available to guide the relief and recovery efforts in southern Louisiana.