Systematic review of epidemiological studies evaluating the association between exposure to man-made vitreous fibers and non-malignant respiratory diseases.

This study aimed to systematically review and synthesize epidemiological evidence evaluating the association between occupational man-made vitreous fiber (MMVF) exposure and non-malignant respiratory disease (NMRD). We searched PubMed and Scopus databases to identify epidemiological studies evaluating the association between occupational MMVF exposure (limited to insulation wools) and at least 1 NMRD outcome published prior to January 2023. A total of 23 studies met our inclusion criteria. Studies of NMRD mortality among workers with MMVF exposure (n = 9) predominately reported null findings. Qualitative and quantitative synthesis of evidence from these studies suggests that MMVF exposure is not associated with elevated risk of NMRD mortality. The remaining 14 studies evaluated NMRD morbidity, specifically self-reported respiratory symptoms and/or subclinical measures of respiratory disease. Our review did not identify any consistent or compelling evidence of an association between MMVF exposure and any NMRD morbidity outcome; however, this body of evidence was largely limited by cross-sectional design, self-reported exposure and/or outcome ascertainment, incomplete statistical analysis and reporting, and questionable generalizability given that 13/14 studies were published over 20 years ago. We recommend that future studies aim to overcome the limitations of this literature to more accurately characterize the association between occupational MMVF exposure and NMRD morbidity.

Updated Italian cohort data continues to confirm lack of mesothelioma risk in pooled cohort of international cosmetic talc miners and millers.

OBJECTIVES: To assess potential mesothelioma risk following inhalation of cosmetic talc, we updated previous iterations of a pooled cohort analysis, post-study statistical power analysis, and confidence interval function analysis for a pooled cohort of international cosmetic talc miners/millers given new Italian cohort data. METHODS: Five cohorts of cosmetic talc miners/millers were pooled. Expected numbers of mesotheliomas for each cohort were reported by the original authors. We based our post-study statistical power analysis on an a priori one-sided significance level of 0.05, and exact Poisson and approximate distribution probabilities. To evaluate the confidence interval function for the observed pooled mesothelioma standardized mortality ratios (SMRs), we calculated the probability for the upper 100(1-2α)% confidence limit that equals various SMRs of interest. RESULTS: The pooled cohorts generated a total observation time of 135,524.38 person-years. Overall, 4.14 mesotheliomas were expected (mid-value estimate), though only one case of mesothelioma has been confirmed in the pooled cohort to date. We calculated 71% and 87% post-study power to detect a 2.5-fold or greater and a 3.0-fold or greater increase in mesothelioma, respectively. Our complimentary confidence interval function analysis demonstrated that the probability that the true mesothelioma SMR for the pooled cohort was at or above 2.0 or at or above 3.0 was 0.00235 and 0.00005, respectively. CONCLUSIONS: Based on the updated results of our various analyses, the current epidemiological evidence from cosmetic talc miner/miller cohort studies continues to not support the hypothesis that the inhalation of cosmetic talc is associated with an increased risk of mesothelioma.

A quantitative weight of evidence assessment of Hill's guidelines for causal inference for cosmetic talc as a cause of mesothelioma.

Cosmetic talc has been suggested to cause mesothelioma. To assess a potential causal relationship between cosmetic talc and mesothelioma, a quantitative weight of evidence analysis was performed in accordance with Hill's nine original guidelines for causal inference using a published empirical model to weight each respective guideline. Various epidemiological, toxicological, and exposure studies related to cosmetic talc and risk of mesothelioma were included in an evaluation of each of Hill's guidelines. Probabilities that the guidelines were true were assigned based on expert judgment. We applied a sensitivity analysis to evaluate the variability of our probability estimates. The overall probability of causality for cosmetic talc and mesothelioma was approximately 1.29% (range: 0.73%-3.96%). This low probability of causality supports the conclusion that cosmetic talc is not related to the development of mesothelioma.

Absence of mesothelioma risk maintained in an expanded international cohort of cosmetic talc miners and millers.

Objectives: Based on novel information for the Vermont cosmetic talc miner/miller cohort, including a reported case of mesothelioma, we sought to update our prior pooled statistical power analyses of mesothelioma incidence among European cosmetic talc miners/millers. With the inclusion of the Vermont cohort, we expanded our pooled analysis by 17,170 person-years of observation.Methods: Cosmetic talc miner/miller cohort studies conducted in Italy, Norway, France, Austria, and Vermont were pooled. The expected numbers of mesothelioma cases for each cohort as reported in these studies were used. Our statistical power analysis was based on an a priori one-sided significance level of 0.05 and Poisson distribution probabilities.Results: A total of 130,514 person-years of observation was generated across the five cohorts. One case of mesothelioma was observed (in the Vermont cohort), while approximately 3.34 cases (a mid-value estimate) were expected overall. Thus, we found that the pooled cohorts had 59% and 78% power to detect a 2.5-fold or greater and a 3.0-fold or greater increase in mesothelioma, respectively. The work history characteristics of the one mesothelioma case, which included mention of prior asbestos exposure on the case's death certificate, do not support a causal link with cosmetic talc exposure.Conclusions: Despite the recent finding of one case of mesothelioma in the Vermont cohort (a case unlikely related to talc exposure), we continue to conclude that the epidemiological evidence from the cosmetic talc miner/miller cohort studies does not support the hypothesis that cosmetic talc exposures are associated with an increased risk of pleural mesothelioma.

Confidence interval function analysis to evaluate the risk of mesothelioma among an expanded international cohort of cosmetic talc miners and millers.

We used pooled data from international cosmetic talc miner/miller cohorts to determine whether hypothesized increased mesothelioma risks are consistent with the observed data. We evaluated the confidence interval function for the observed pooled mesothelioma SMRs (observed = 1; expected = 3.17, 3.34, or 3.60), and calculated the value of α for the upper 100(1 - 2α)% confidence limit that equals various SMRs of interest (1.5, 2.0, 2.5, 3.0). Using the mid-value estimate of expected number of cases (3.34), the probability (α) that the true mesothelioma SMR is at or above 2.0, or at or above 3.0 is 0.0096 and 0.0005, respectively. Thus, a mesothelioma SMR ≥2.0 is not compatible with the observed pooled data, providing further support for our conclusion that cosmetic talc exposure is not associated with an elevated risk of mesothelioma.

Systematic review and meta-analysis of epidemiological literature evaluating the association between exposure to man-made vitreous fibers and respiratory tract cancers.

We conducted a systematic review and meta-analysis of epidemiological studies that evaluated occupational exposure to man-made vitreous fibers (MMVF) including glass, rock, and slag wools, and respiratory tract cancers (RTC) including cancers of the larynx, trachea, bronchus, and lung. The MEDLINE/PubMed and Web of Science databases were searched in order to identify epidemiological studies that evaluated the association between occupational MMVF exposure and RTCs. We performed random-effects meta-analyses of relevant studies identified by our literature search, and evaluated sources of between-study heterogeneity. The pooled relative risk (RR) of RTC among workers exposed to MMVFs was 1.09 (95% CI = 0.97, 1.22). The RR was closer to 1.0 when limiting the analysis to effect estimates from studies that accounted for the main a priori risk factors for RTC, asbestos exposure and smoking (RR = 1.03, 95% CI = 0.90, 1.18). Overall, our synthesis of the epidemiological literature suggests that occupational MMVF exposure is not associated with risk of RTC.

Occupational exposures to cosmetic talc and risk of mesothelioma: an updated pooled cohort and statistical power analysis with consideration of latency period.

Objectives: We previously published a pooled statistical power analysis of mesothelioma incidence in the Italian, Norwegian, Austrian, and French cosmetic talc miner and miller cohorts. Soon thereafter, updates to the Italian and Norwegian cohorts were published, providing an additional 14,322 person-years of observation. In this study, we provide an updated power analysis using the newly available information. Methods: We pooled the current results regarding pleural cancer/mesothelioma mortality or incidence in four cosmetic talc miner and miller cohorts in Italy, Norway, Austria, and France. We used the expected numbers of cases as reported by the authors and the power analysis was based on an a priori one-sided significance level of 0.05 and Poisson distribution probabilities. Results: There was a pooled total of 113,344 person-years in the cohorts. Although 3.0 pleural cancers/mesotheliomas were expected, there were no reported pleural cancer or mesothelioma cases in any cohort. Our pooled analysis was associated with 79 and 62% power to detect a 3.0-fold and 2.5-fold or greater increase in pleural cancer/mesothelioma, respectively. These favorable power characteristics were effectively maintained when restricting the pooled cohort to workers with a latency period of 30 or more years (observation time from first employment). Conclusions: The epidemiological evidence from the cosmetic talc miner/miller cohort studies does not support the hypothesis that exposure to cosmetic talc is associated with the development of pleural cancer/mesothelioma.

Ethylene oxide and risk of lympho-hematopoietic cancer and breast cancer: a systematic literature review and meta-analysis.

PURPOSE: To conduct a systematic literature review and meta-analysis of studies of lympho-hematopoietic cancers (LHC) and breast cancer risk among persons occupationally exposed to ethylene oxide (EO). METHODS: We performed a literature search for articles available in PubMed and Web of Science databases to identify literature and subsequently systematically searched the reference lists of identified studies, published review papers and meta-analyses, as well as relevant government or regulatory documents. We qualitatively reviewed 30 studies and conducted meta-analyses on 13 studies. Pooled risk estimates were calculated using random effects models, stratifying by occupational group, cancer type and decade of publication. RESULTS: The overall meta-relative risks (meta-RRs) for LHC and breast cancer, respectively, were 1.48 (95% CI 1.07-2.05) and 0.97 (95% CI 0.80-1.18). The meta-RR's for LHC among EO production and EO sterilization workers were 1.46 (95% CI 0.85-2.50) and 1.07 (95% CI 0.87-1.30), respectively. We observed higher risks of LHC in the earlier published studies, compared to the later studies, and the meta-RR's for the 1980s, 1990s, 2000s, and the 2010s, respectively, were 3.87 (95% CI 1.87-8.01), 1.38 (95% CI 0.85-2.25), 1.05 (95% CI 0.84-1.31), and 1.19 (95% CI 0.80-1.77). CONCLUSIONS: The most informative epidemiology studies, which were published in the 2000s and 2010s, do not support the conclusion that exposure to EO is associated with an increased risk of LHC or breast cancer.

Considerations for refining the risk assessment process for formaldehyde: Results from an interdisciplinary workshop.

Anticipating the need to evaluate and integrate scientific evidence to inform new risk assessments or to update existing risk assessments, the Formaldehyde Panel of the American Chemistry Council (ACC), in collaboration with the University of North Carolina, convened a workshop: "Understanding Potential Human Health Cancer Risk - From Data Integration to Risk Evaluation" in October 2017. Twenty-four (24) invited-experts participated with expertise in epidemiology, toxicology, science integration and risk evaluation. Including members of the organizing committee, there were 29 participants. The meeting included eleven presentations encompassing an introduction and three sessions: (1) "integrating the formaldehyde science on nasal/nasopharyngeal carcinogenicity and potential for causality"; (2) "integrating the formaldehyde science on lymphohematopoietic cancer and potential for causality; and, (3) "formaldehyde research-data suitable for risk assessment". Here we describe key points from the presentations on epidemiology, toxicology and mechanistic studies that should inform decisions about the potential carcinogenicity of formaldehyde in humans and the discussions about approaches for structuring an integrated, comprehensive risk assessment for formaldehyde. We also note challenges expected when attempting to reconcile divergent results observed from research conducted within and across different scientific disciplines - especially toxicology and epidemiology - and in integrating diverse, multi-disciplinary mechanistic evidence.

Mortality among United States aerospace materials manufacturing workers.

OBJECTIVES: To evaluate long-term mortality rates among aerospace material manufacturing workers as follow-up to an earlier observed excess of nephritis/nephrosis. METHODS: Subjects were 2020 workers ever employed in the facility during 1963-2014. Vital status through 2014 was determined for all subjects and cause of death for 99.2% of 492 deaths. We computed standard mortality ratios (SMR) and internal relative risks. RESULTS: SMRs for nephritis/nephrosis were unremarkable. We observed statistically significant elevated SMRs for kidney cancer among all workers and for the category "other lymphatic hematopoietic tissue cancer" (4/5 deaths from multiple myeloma) among long-term workers with potential plant exposure. CONCLUSIONS: We found no evidence of elevated mortality rates for nephritis/nephrosis. Study limitations precluded robust evaluation of whether the elevated rates for kidney cancer and other lymphatic hematopoietic tissue cancer were related to occupational factors at the study site. Our findings for these two cancers warrant continued mortality follow-up.

The influence of demographic, physical, behavioral, and dietary factors on hemoglobin adduct levels of acrylamide and glycidamide in the general U.S. population.

PURPOSE: This study aims to better understand the individual characteristics and dietary factors that affect the relationship between estimated consumption of acrylamide and measured acrylamide hemoglobin adduct levels (HbAA) and glycidamide hemoglobin adduct levels (HbGA). METHODS: Acrylamide levels in individual food items, estimated by the U.S. Food and Drug Administration, were linked to data collected in the 2003-2004 National Health and Nutrition Examination Survey. Multivariable linear regression was used to evaluate the relationship between estimated consumption of acrylamide and HbAA. RESULTS: A significant association between acrylamide intake and HbAA was observed, after adjustment for gender, race/ethnicity, smoking status, age, and BMI (R2 = 0.34). Across quartiles of acrylamide consumption, HbAA and HbGA levels increased monotonically. Among nonsmokers, an evaluation of three heavily consumed, high AA concentration foods showed a positive trend between the consumed amount of fried potatoes and HbAA in children, adolescents, and adults. A significant positive trend between the consumed amount of potato chips or coffee was indicated in adolescents, adults, and seniors. CONCLUSIONS: Consumption of some individual foods affects HbAA concentrations more strongly and in an age-dependent manner. Our results suggest that effective dietary guidelines for controlling acrylamide intake should be subpopulation specific.

Systemic inflammatory markers associated with cardiovascular disease and acute and chronic exposure to fine particulate matter air pollution (PM2.5) among US NHANES adults with metabolic syndrome.

BACKGROUND: There has been no investigation to date of adults with metabolic syndrome examining the association of short and long-term exposure to fine particulate matter (PM2.5) air pollution with cardiovascular-disease related inflammatory marker (WBC and CRP) levels in a nationally representative sample. The goal of this study is to assess the susceptibility of adults with metabolic syndrome to PM2.5 exposure as suggested by increased cardiovascular-disease related inflammatory marker levels. METHODS: A cross sectional analysis of adult National Health and Nutrition Examination Survey (NHANES) participants (2000-2008) was carried out with linkage of CDC WONDER meteorological data and downscaler modeled USEPA air pollution data for census tracts in the continental United States. Participants were non-pregnant NHANES adults (2000-2008) with complete data for evaluating presence of metabolic syndrome and laboratory data on WBC and CRP. Exposures studied included short (lags 0-3 days and their averages), long-term (30 and 60 day moving and annual averages) PM2.5 exposure levels at the census tract level in the continental United States. The main outcomes included CRP and WBC levels the day of NHANES study visit analyzed using multiple linear regression, adjusting for age, gender, race, education, smoking status, history of any cardiovascular disease, maximum apparent temperature and ozone level, for participants with and without metabolic syndrome. RESULTS: A total of 7134 NHANES participants (35% with metabolic syndrome) met the inclusion criteria. After adjusting for confounders, we observed a significant effect of PM2.5 acutely at lag day 0 on CRP level; a 10µg/m3 rise in lag day 0 PM2.5 level was associated with a 10.1% increase (95% CI: 2.2-18.6%) in CRP levels for participants with metabolic syndrome. For those without metabolic syndrome, the change in CRP was -1.3% (95% CI -8.8%, 6.8%). There were no significant associations for WBC count. In this first national study of the effect of PM2.5 air pollution on levels of cardiovascular-disease related inflammatory markers in adults with metabolic syndrome, CRP levels were found to be significantly increased in those with this condition with increased fine particulate matter levels at lag day 0. With one third of US adults with metabolic syndrome, the health impact of PM2.5 in this sensitive population may be significant.

Complex antioxidants in a randomized single-blinded study of memory in seniors.

INTRODUCTION: Oxidative injury to the brain and aging are theoretical co-causes of Alzheimer's Disease (AD). Amyloid plaques and tangles are then secondary phenomenon. The preclinical state would then be 'normal' elderly. METHODS: A potent complex antioxidant (antiOx) was tested against a popular one-a-day multivitamin (mV) in a randomized single blind design in 'normal' senior subjects over 6 months. Memory testing was done at baseline, 1, 3, and 6 months. The generalized estimating equation (GEE) approach was used to compare the change score of NLT100 and 20WR between two groups over time. RESULTS: Analysis of the antiOx group (30 subjects) demonstrated significant improvement in declarative memory (change score for NLT100 at month 6 = 6.36 p < 0.0001) and working memory (change score for 20WR at month 6 = 3.23, p < 0.0001). A change-score analysis over 6 months suggests possible neurogenesis in the antiOx group. The mV group (33 subjects) had a change score of the NLT100 and 20WR on the sixth month of 2.20 and 0.32 (p = 0.07, 0.35). CONCLUSIONS: A complex antioxidant blend, sold as an over-the-counter (OTC) supplement, can improve memory in elder subjects. Antioxidants may be beneficial in AD and other neurodegerative diseases.

Non-occupational exposure to asbestos and risk of pleural mesothelioma: review and meta-analysis.

OBJECTIVE: To conduct an updated literature review and meta-analysis of studies of pleural malignant mesothelioma (PMM) risk among persons exposed to asbestos non-occupationally (household and neighbourhood). METHODS: We performed a literature search for articles available in the National Center for Biotechnology Information's PubMed database published between 1967 and 2016. Meta-analyses were conducted to calculate pooled PMM risk estimates, stratifying for household or neighbourhood exposure to asbestos and/or predominant asbestos fibre type (chrysotile, amphibole or mixed). RESULTS: Eighteen studies in 12 countries comprising 665 cases met the meta-analysis inclusion criteria. We identified 13 estimates of PMM risk from neighbourhood exposures, 10 from household and one from mixed exposure, and combined the estimates using random-effects models. The overall meta-relative risk (meta-RR) was 5.9 (95% CI 4.4 to 8.7). The meta-RRs for household and neighbourhood exposures were 5.4 (95% CI 2.6 to 11.2) and 6.9 (95% CI 4.2 to 11.4), respectively. We observed trends in risk in relation to fibre type for both household and neighbourhood studies. For chrysotile, mixed and amphibole fibres, respectively, meta-RRs for neighbourhood studies were 3.8 (95% CI 0.4 to 38.4), 8.4 (95% CI 4.7 to 14.9) and 21.1 (95% CI 5.3 to 84.5) and meta-RRs for household studies were 4.0 (95% CI 0.8 to 18.8), 5.3 (95% CI 1.9 to 15.0) and 21.1 (95% CI 2.8 to 156.0). CONCLUSIONS: PMM risks from non-occupational asbestos exposure are consistent with the fibre-type potency response observed in occupational settings. By relating our findings to knowledge of exposure-response relationships in occupational settings, we can better evaluate PMM risks in communities with ambient asbestos exposures from industrial or other sources.

Cosmetic talc as a risk factor for pleural mesothelioma: a weight of evidence evaluation of the epidemiology.

OBJECTIVE: Due to some historical (and inaccurate) reports that asbestos might be present in some cosmetic talc products, questions are occasionally raised regarding the potential pleural mesothelioma risks associated with cosmetic talc products. Our objective was to determine the incidence of pleural mesothelioma of individuals exposed to cosmetic talc. MATERIALS AND METHODS: We conducted a systematic review of the epidemiological literature for cosmetic talc miners and millers and found three occupational cohort studies that evaluated pleural mesothelioma incidence in workers in Italy, Norway, France, and Austria. We conducted a second literature review to evaluate the incidence and mortality of pleural mesothelioma among patients who received talc pleurodesis treatments before 1965 and found retrospective clinical studies including over 300 patients with follow-up ranging from 14 to 40 years. RESULTS: There were no mesotheliomas reported in any of the cosmetic talc miner and miller cohorts. A pooled analysis of data from the cohort mortality studies indicated that four mesothelioma deaths would have been expected from the 90,022 person-years of observation, and this was associated with 84% and 67% statistical power to observe a 3-fold or 2.5-fold increase in pleural mesothelioma mortality, respectively. None of the patients who received talc pleurodesis treatments developed mesothelioma. CONCLUSION: We conclude that there is no epidemiological evidence to support the hypothesis that exposure to cosmetic talc is associated with the development of pleural mesothelioma.

Patterns and trends in accidental poisoning death rates in the US, 1979-2014.

OBJECTIVES: The purpose of this study was to examine US accidental poisoning death rates by demographic and geographic factors from 1979 to 2014, including High Intensity Drug Trafficking Areas. METHODS: Crude and age-adjusted death rates were formed for age group, race, sex, and county for accidental poisonings (ICD 9th revision: E850-E869; ICD 10th revision: X40-X49) from 1979 to 2014 using the Mortality and Population Data System housed at the University of Pittsburgh. Rate ratios were calculated comparing rates from 2014 to 1979, overall, by sex, age group, race, and county. Joinpoint regression detected changes in trends and calculated the average annual percentage change (AAPC) as a summary measure of trend. RESULTS: Drug poisoning mortality rates have risen an average of 6% per year since 1979. Increases are occurring in all ages 15+, and in all race-sex groups. HIDTA counties with the highest mortality rates were in Appalachia and New Mexico. Many of the HIDTA border counties had lower rates of mortality. CONCLUSIONS: The drug poisoning mortality epidemic is continuing to grow. While HIDTA resources are appropriately targeted at many areas in the US most affected, rates are also rapidly rising in some non-HIDTA areas.

Using spatio-temporal modeling for exposure assessment in an investigation of fine particulate air pollution and cardiovascular mortality.

BACKGROUND: U.S. urban air quality has improved dramatically over the past decades. We evaluated acute effects of fine particulate matter (PM2.5) on cardiovascular (CVD) mortality among residents of Allegheny County in SW Pennsylvania (1999-2011) using spatio-temporal modeling of air pollutants (AP) to reduce misclassification error in exposure assessment. METHODS: Spatio-temporal kriging of daily PM2.5 and ozone (O3) was used to produce daily exposure estimates at the residence ZIP code. Time-stratified case-crossover analysis was conducted to examine short-term effects of PM2.5 on CVD mortality, adjusting for O3 and apparent mean temperature. We studied both single and distributed lags for days 0-5. All CVD mortality and subcategories of ischemic heart disease (IHD), acute myocardial infarction, cerebrovascular disease, peripheral vascular disease (PVD), heart failure and cardiac arrhythmia were examined. RESULTS: A total of 62,135 deaths were identified. We found significant associations of PM2.5 with IHD and PVD mortality at lag day 5: (2.1% (95% CI, 0.2-4.1%) and (7.6%, 95% CI, 0.05-15.7%) per 10µg/m3 increase of PM2.5 in single lag models and for IHD in distributed lag models. There were no statistically significant associations with PM2.5 for any of the other outcomes. CONCLUSIONS: The application of finer scale geographically resolved AP exposures made it possible to study acute effects of PM2.5 on CVD mortality in a large metropolitan area. Our study results demonstrated the continued presence of a dose response relationship of increased risk of CVD mortality within this lower range of PM2.5 exposure.