Manufactured doubt and the EPA 2020 chrysotile asbestos risk assessment.

While all forms of asbestos have been determined to be carcinogenic to humans by the International Agency for Research on Cancer (IARC) as well as other authoritative bodies, the relative carcinogenic potency of chrysotile continues to be argued, largely in the context of toxic tort litigation. Relatively few epidemiologic studies have investigated only a single form of asbestos; however, one study that included an asbestos textile plant located in Marshville, North Carolina that processed chrysotile asbestos was used by the United States Environmental Protection Agency (EPA) in 2020 to help inform the agency's chrysotile asbestos risk assessment. During the EPA proceedings toxic tort defense consultants submitted comments to the EPA docket and made public presentations asserting that the Marshville plant had processed amphibole asbestos types and should not be used for the chrysotile risk assessment. A detailed evaluation of defense consultant assertions and supporting information and a full assessment of the available information concerning asbestos types used at the Marshville plant was undertaken. The preponderance of evidence continues to support the conclusion that neither amosite nor crocidolite were likely to have been processed in the Marshville textile plant. Defense consultants' assertions about chrysotile use are not supported by the preponderance of evidence and constitute an example of manipulation of information to cast uncertainty and doubt rather than to seek truth and contribute to the body of scientific evidence.

The effect of occupational exposure to welding fumes on trachea, bronchus and lung cancer: A systematic review and meta-analysis from the WHO/ILO Joint Estimates of the Work-related Burden of Disease and Injury.

BACKGROUND: The World Health Organization (WHO) and the International Labour Organization (ILO) are the producers of the WHO/ILO Joint Estimates of the Work-related Burden of Disease and Injury (WHO/ILO Joint Estimates). Welding fumes have been classified as carcinogenic to humans (Group 1) by the WHO International Agency for Research on Cancer (IARC) in IARC Monograph 118; this assessment found sufficient evidence from studies in humans that welding fumes are a cause of lung cancer. In this article, we present a systematic review and meta-analysis of parameters for estimating the number of deaths and disability-adjusted life years from trachea, bronchus, and lung cancer attributable to occupational exposure to welding fumes, to inform the development of WHO/ILO Joint Estimates on this burden of disease (if considered feasible). OBJECTIVES: We aimed to systematically review and meta-analyse estimates of the effect of any (or high) occupational exposure to welding fumes, compared with no (or low) occupational exposure to welding fumes, on trachea, bronchus, and lung cancer (three outcomes: prevalence, incidence, and mortality). DATA SOURCES: We developed and published a protocol, applying the Navigation Guide as an organizing systematic review framework where feasible. We searched electronic databases for potentially relevant records from published and unpublished studies, including Medline, EMBASE, Web of Science, CENTRAL and CISDOC. We also searched grey literature databases, Internet search engines, and organizational websites; hand-searched reference lists of previous systematic reviews; and consulted additional experts. STUDY ELIGIBILITY AND CRITERIA: We included working-age (≥15 years) workers in the formal and informal economy in any Member State of WHO and/or ILO but excluded children (<15 years) and unpaid domestic workers. We included randomized controlled trials, cohort studies, case-control studies, and other non-randomized intervention studies with an estimate of the effect of any (or high) occupational exposure to welding fumes, compared with occupational exposure to no (or low) welding fumes, on trachea, bronchus, and lung cancer (prevalence, incidence, and mortality). STUDY APPRAISAL AND SYNTHESIS METHODS: At least two review authors independently screened titles and abstracts against the eligibility criteria at a first review stage and full texts of potentially eligible records at a second stage, followed by extraction of data from qualifying studies. If studies reported odds ratios, these were converted to risk ratios (RRs). We combined all RRs using random-effects meta-analysis. Two or more review authors assessed the risk of bias, quality of evidence, and strength of evidence, using the Navigation Guide tools and approaches adapted to this project. Subgroup (e.g., by WHO region and sex) and sensitivity analyses (e.g., studies judged to be of "high"/"probably high" risk of bias compared with "low"/"probably low" risk of bias) were conducted. RESULTS: Forty-one records from 40 studies (29 case control studies and 11 cohort studies) met the inclusion criteria, comprising over 1,265,512 participants (≥22,761 females) in 21 countries in three WHO regions (Region of the Americas, European Region, and Western Pacific Region). The exposure and outcome were generally assessed by job title or self-report, and medical or administrative records, respectively. Across included studies, risk of bias was overall generally probably low/low, with risk judged high or probably high for several studies in the domains for misclassification bias and confounding. Our search identified no evidence on the outcome of having trachea, bronchus, and lung cancer (prevalence). Compared with no (or low) occupational exposure to welding fumes, any (or high) occupational exposure to welding fumes increased the risk of acquiring trachea, bronchus, and lung cancer (incidence) by an estimated 48 % (RR 1.48, 95 % confidence interval [CI] 1.29-1.70, 23 studies, 57,931 participants, I2 24 %; moderate quality of evidence). Compared with no (or low) occupational exposure to welding fumes, any (or high) occupational exposure to welding fumes increased the risk dying from trachea, bronchus, and lung cancer (mortality) by an estimated 27 % (RR 1.27, 95 % CI 1.04-1.56, 3 studies, 8,686 participants, I2 0 %; low quality of evidence). Our subgroup analyses found no evidence for difference by WHO region and sex. Sensitivity analyses supported the main analyses. CONCLUSIONS: Overall, for incidence and mortality of trachea, bronchus, and lung cancer, we judged the existing body of evidence for human data as "sufficient evidence of harmfulness" and "limited evidence of harmfulness", respectively. Occupational exposure to welding fumes increased the risk of acquiring and dying from trachea, bronchus, and lung cancer. Producing estimates for the burden of trachea, bronchus, and lung cancer attributable to any (or high) occupational exposure to welding fumes appears evidence-based, and the pooled effect estimates presented in this systematic review could be used as input data for the WHO/ILO Joint Estimates. PROTOCOL IDENTIFIER: https://doi.org/10.1016/j.envint.2020.106089.

Respiratory effects of road pollution in recreational cyclists: a pilot study.

We sought to measure bicyclists' roadway exposures to particulate matter and assess whether those exposures are associated with reduced pulmonary function. Thirty-one (31) volunteer participants riding bicycles on selected routes were tracked using the Global Positioning System. Personal exposures to particulate matter (PM-10) were measured during the rides and pulmonary function tests were administered at baseline, immediately after the ride, and 2 and 6-24 hours later. Post-ride decrements in pulmonary function were observed for several outcome measures, with the largest differences immediately post-ride. Statistically-significant declines in FEV1 (-38.42, 95% Confidence Interval (CI), -63.79 to -13.05 ml), FVC (-36.89, 95% CI, -62.96, -10.84 ml), and PEFR (-162, 95% CI -316.02 to -9.49 ml/sec) were observed for each increase in decile of peak exposure. PM-10 exposures encountered on roadways may put bicyclists at risk for pulmonary deficits.

Agricultural Injuries among Farmers and Ranchers in the Central United States during 2011-2015.

The high risk of occupational fatalities in agriculture is well documented, but information on non-fatal injuries is lacking due to challenges in injury surveillance. This surveillance study explored the frequency, characteristics, and risk factors for non-fatal injuries among farmers and ranchers in the central United States. The Central States Center for Agricultural Safety and Health (CS-CASH), in collaboration with the USDA National Agricultural Statistics Service (NASS), conducted annual surveys (n = 34,777 sent) during 2011-2015 covering a seven-state region (Iowa, Kansas, Minnesota, Missouri, North Dakota, Nebraska, and South Dakota). The average response rate was 32% in the five consecutive annual surveys. The average injury incidence rate was 7.0 injuries/100 operators per year. Most injuries (89%) occurred during agricultural work. The most frequent sources of injury were livestock (22%), machinery (13%), and hand tools (12%). Risk factors for injury included: male gender, younger age (vs. 65+ years), farming as the primary occupation, greater work time, greater land area, ranch (vs. farm), organic farming, internet access, and production of several types of crops and animals. Most injuries (56%) required a doctor visit, and 12% required hospitalization. The average medical costs were $1,936 out of pocket and $8,043 paid by insurance. The combined average costs for most serious injuries were $7,858. Most injuries (66%) resulted in some lost time from agricultural work, and 13% were serious, resulting in more than 30 days of lost work time. The non-fatal injury rate for self-employed farmers and ranchers was higher than that of hired agricultural workers reported by the Bureau of Labor Statistics. This result reaffirms farming/ranching as a dangerous occupation and emphasizes the need for efforts to prevent agricultural injuries, especially those associated with identified injury sources and risk factors.

The effect of occupational exposure to welding fumes on trachea, bronchus and lung cancer: A protocol for a systematic review and meta-analysis from the WHO/ILO Joint Estimates of the Work-related Burden of Disease and Injury.

BACKGROUND: The World Health Organization (WHO) and the International Labour Organization (ILO) are developing joint estimates of the work-related burden of disease and injury (WHO/ILO Joint Estimates), with contributions from a large network of experts. Welding fumes have been classified as carcinogenic to humans (Group 1) by the International Agency for Research on Cancer (IARC); this assessment found sufficient evidence from studies in humans that welding fumes are a cause of lung cancer. In this article, we present the protocol for a systematic review of parameters for estimating the number of deaths and disability-adjusted life years from trachea, bronchus and lung cancer attributable to occupational exposure to welding fumes, to inform the development of the WHO/ILO Joint Estimates. OBJECTIVES: We aim to systematically review and meta-analyse estimates of the effect of occupational exposure to welding fumes on trachea, bronchus and lung cancer, applying the Navigation Guide systematic review methodology as an organizing framework. DATA SOURCES: We will search electronic bibliographic databases for potentially relevant records from published and unpublished studies, including Medline, EMBASE, Web of Science, and CISDOC. We will also search electronic grey literature databases, Internet search engines and organizational websites; hand search reference list of previous systematic reviews and included study records; and consult additional experts. STUDY ELIGIBILITY AND CRITERIA: We will include working-age (≥15 years) workers in the formal and informal economy in any Member State of WHO and/or ILO but exclude children (<15 years) and unpaid domestic workers. The eligible risk factor will be occupational exposure to welding fumes, measured directly or indirectly (i.e., through proxy of relevant occupation, work task, job-exposure matrix, expert judgment or self-report). The eligible outcomes will be trachea, bronchus and lung cancer. We will include randomized controlled trials, cohort studies, case-control studies and other non-randomized intervention studies with an estimate of the relative effect of any occupational exposure to welding fumes on the prevalence of, incidence of or mortality from trachea, bronchus and lung cancer, compared with the theoretical minimum risk exposure level of no occupational exposure to welding fumes. STUDY APPRAISAL AND SYNTHESIS METHODS: At least two review authors will independently screen titles and abstracts against the eligibility criteria at a first stage and full texts of potentially eligible records at a second stage, followed by extraction of data from qualifying studies. Two or more review authors will assess risk of bias and the quality of evidence, using the Navigation Guide tool or approach. If feasible, we will combine relative risks using meta-analysis. We will report results using the preferred reporting items for systematic reviews and meta-analyses guidelines (PRISMA).

Quantitative relationships of exposure to chrysotile asbestos and mesothelioma mortality.

BACKGROUND: While asbestos has long been known to cause mesothelioma, quantitative exposure-response data on the relation of mesothelioma risk and exposure to chrysotile asbestos are sparse. METHODS: Quantitative relationships of mortality from mesothelioma and pleural cancer were investigated in an established cohort of 5397 asbestos textile manufacturing workers in North Carolina, USA. Eligible workers were those employed between 1950 and 1973 with mortality follow-up through 2003. Individual exposure to chrysotile fibres was estimated on the basis of 3420 air samples covering the entire study period linked to work history records. Exposure coefficients adjusted for age, race, and time-related covariates were estimated by Poisson regression. RESULTS: Positive, statistically significant associations were observed between mortality from all pleural cancer (including mesothelioma) and time since first exposure (TSFE) to asbestos (rate ratio [RR], 1.19; 95% confidence interval [CI], 1.06-1.34 per year), duration of exposure, and cumulative asbestos fibre exposure (RR, 1.15; 95% CI, 1.04-1.28 per 100 f-years/mL; 10-year lag). Analyses of the shape of exposure-response functions suggested a linear relationship with TSFE and a less-than-linear relationship with cumulative exposure. Restricting the analysis to years when mesothelioma was coded as a unique cause of death yielded stronger but less precise associations. CONCLUSIONS: These observations support with quantitative data the conclusion that chrysotile causes mesothelioma and encourage exposure-response analyses of mesothelioma in other cohorts exposed to chrysotile.

Welding fumes and lung cancer: a meta-analysis of case-control and cohort studies.

BACKGROUND: An estimated 110 million workers are exposed to welding fumes worldwide. Welding fumes are classified by the International Agency for Research on Cancer as carcinogenic to humans (group 1), based on sufficient evidence of lung cancer from epidemiological studies. OBJECTIVE: To conduct a meta-analysis of case-control and cohort studies on welding or exposure to welding fumes and risk of lung cancer, accounting for confounding by exposure to asbestos and tobacco smoking. METHODS: The literature was searched comprehensively in PubMed, reference lists of relevant publications and additional databases. Overlapping populations were removed. Meta-relative risks (mRRs) were calculated using random effects models. Publication bias was assessed using funnel plot, Eggers's test and Begg's test. RESULTS: Forty-five studies met the inclusion criteria (20 case-control, 25 cohort/nested case-control), which reduced to 37 when overlapping study populations were removed. For 'ever' compared with 'never' being a welder or exposed to welding fumes, mRRs and 95% CIs were 1.29 (1.20 to 1.39; I2=26.4%; 22 studies) for cohort studies, 1.87 (1.53 to 2.29; I2=44.1%; 15 studies) for case-control studies and 1.17 (1.04 to 1.38; I2=41.2%) for 8 case-control studies that adjusted for smoking and asbestos exposure. The mRRs were 1.32 (95% CI 1.20 to 1.45; I2=6.3%; 15 studies) among 'shipyard welders', 1.44 (95% CI 1.07 to 1.95; I2=35.8%; 3 studies) for 'mild steel welders' and 1.38 (95% CI 0.89 to 2.13; I2=68.1%; 5 studies) among 'stainless steel welders'. Increased risks persisted regardless of time period, geographic location, study design, occupational setting, exposure assessment method and histological subtype. CONCLUSIONS: These results support the conclusion that exposure to welding fumes increases the risk of lung cancer, regardless of the type of steel welded, the welding method (arc vs gas welding) and independent of exposure to asbestos or tobacco smoking.

Cancer mortality in an international cohort of reinforced plastics workers exposed to styrene: a reanalysis.

OBJECTIVE: To investigate the carcinogenicity of styrene by reanalysing data from a previous international cohort study of workers in the reinforced plastics industry. METHODS: Mortality from cancers of prior interest was analysed with more detailed consideration of exposure-response relations and an updated classification of leukaemias and lymphomas in data from a previous international cohort study of 37 021 reinforced plastics workers exposed to airborne styrene. RESULTS: Increased mortality from non-Hodgkin's lymphoma (NHL) was associated with the mean level of exposure to styrene in air (relative risk (RR) 2.31, 95% CI 1.29 to 4.12 per 100 ppm), but not with cumulative styrene exposure. Similar associations with mean exposure were observed for the oesophagus (RR 2.44, 95% CI 1.11 to 5.36 per 100 ppm) and pancreas (RR 1.89, 95% CI 1.17 to 3.09). Oesophageal cancer mortality was also associated with cumulative styrene exposure lagged 20 years (RR 1.16, 95% CI 1.03 to 1.31). No other cancer, including lung cancer, was associated with any indicator of styrene exposure. CONCLUSION: This reanalysis does not substantially change the conclusions of the original study with respect to NHL or lung cancer but new evidence concerning cancers of the oesophagus and pancreas merits further investigation.

The fraction of lung cancer incidence attributable to fine particulate air pollution in France: Impact of spatial resolution of air pollution models.

Outdoor air pollution is a leading environmental cause of death and cancer incidence in humans. We aimed to estimate the fraction of lung cancer incidence attributable to fine particulate matter (PM2.5) exposure in France, and secondarily to illustrate the influence of the input data and the spatial resolution of information on air pollution levels on this estimate. The population attributable fraction (PAF) was estimated using a nationwide spatially refined chemistry-transport model with a 2-km spatial resolution, neighbourhood-scale population density data, and a relative risk from a published meta-analysis. We used the WHO guideline value for PM2.5 exposure (10 µg/m3) as reference. Sensitivity analyses consisted in attributing the nation-wide median exposure to all areas and using alternative input data such as reference of PM2.5 exposure level and relative risk. Population-weighted median PM2.5 level in 2005 was 13.8 µg/m3; 87% of the population was exposed above the guideline value. The burden of lung cancer attributable to PM2.5 exposure corresponded to 1466 cases, or 3.6% of all cases diagnosed in 2015. Sensitivity analyses showed that the use of a national median of PM2.5 exposure would have led to an underestimation of the PAF by 11% (population-weighted median) and by 72% (median of raw concentration), suggesting that our estimates would have been higher with even more finely spatially-resolved models. When the PM2.5 reference level was replaced by the 5th percentile of country-scale exposure (4.9 µg/m3), PAF increased to 7.6%. Other sensitivity analyses resulted in even higher PAFs. Improvements in air pollution are crucial for quantitative health impacts assessment studies. Actions to reduce PM2.5 levels could substantially reduce the burden of lung cancer in France.

Software Tools to Facilitate Systematic Review Used for Cancer Hazard Identification.

Objective and systematic methods to search, review, and synthesize published studies are a fundamental aspect of carcinogen hazard classification. Systematic review is a historical strength of the International Agency for Research on Cancer (IARC) Monographs Program and the United States National Toxicology Program (NTP) Office of the Report on Carcinogens (RoC). Both organizations are tasked with evaluating peer-reviewed, published evidence to determine whether specific substances, exposure scenarios, or mixtures pose a cancer hazard to humans. This evidence synthesis is based on objective, transparent, published methods that call for extracting and interpreting data in a systematic manner from multiple domains, including a) human exposure, b) epidemiological evidence, c) evidence from experimental animals, and d) mechanistic evidence. The process involves multiple collaborators and requires an extensive literature search, review, and synthesis of the evidence. Several online tools have been implemented to facilitate these collaborative systematic review processes. Specifically, Health Assessment Workplace Collaborative (HAWC) and Table Builder are custom solutions designed to record and share the results of the systematic literature search, data extraction, and analyses. In addition, a content management system for web-based project management and document submission has been adopted to enable access to submitted drafts simultaneously by multiple co-authors and to facilitate their peer review and revision. These advancements in cancer hazard classification have applicability in multiple systematic review efforts. https://doi.org/10.1289/EHP4224.

Identifying occupational carcinogens: an update from the IARC Monographs.

The recognition of occupational carcinogens is important for primary prevention, compensation and surveillance of exposed workers, as well as identifying causes of cancer in the general population. This study updates previously published lists of known occupational carcinogens while providing additional information on cancer type, exposure scenarios and routes, and discussing trends in the identification of carcinogens over time. Data were extracted from International Agency for Research on Cancer (IARC) Monographs covering the years 1971-2017, using specific criteria to ensure occupational relevance and provide high confidence in the causality of observed exposure-disease associations. Selected agents were substances, mixtures or types of radiation classified in IARC Group 1 with 'sufficient evidence of carcinogenicity' in humans from studies of exposed workers and evidence of occupational exposure documented in the pertinent monograph. The number of known occupational carcinogens has increased over time: 47 agents were identified as known occupational carcinogens in 2017 compared with 28 in 2004. These estimates are conservative and likely underestimate the number of carcinogenic agents present in workplaces. Exposure to these agents causes a wide range of cancers; cancers of the lung and other respiratory sites, followed by skin, account for the largest proportion. The dominant routes of exposure are inhalation and dermal contact. Important progress has been made in identifying occupational carcinogens; nevertheless, there is an ongoing need for research on the causes of work-related cancer. Most workplace exposures have not been evaluated for their carcinogenic potential due to inadequate epidemiologic evidence and a paucity of quantitative exposure data.

Lung Cancer Risk Associated with Regulated and Unregulated Chrysotile Asbestos Fibers.

BACKGROUND: Regulation of asbestos fibers in the workplace is partly determined by which fibers can be visually counted. However, a majority of fibers are too short and thin to count this way and are, consequently, not subject to regulation. METHODS: We estimate lung cancer risk associated with asbestos fibers of varying length and width. We apply an order-constrained prior both to leverage external information from toxicological studies of asbestos health effects. This prior assumes that risk from asbestos fibers increases with increasing length and decreases with increasing width. RESULTS: When we apply a shared mean for the effect of all asbestos fiber exposure groups, the rate ratios for each fiber group per unit exposure appear mostly equal. Rate ratio estimates for fibers of diameter <0.25 µm and length <1.5 and 1.5-5.0 µm are the most precise. When applying an order-constrained prior, we find that estimates of lung cancer rate ratio per unit of exposure to unregulated fibers 20-40 and >40 µm in the thinnest fiber group are similar in magnitude to estimates of risk associated with long fibers in the regulated fraction of airborne asbestos fibers. Rate ratio estimates for longer fibers are larger than those for shorter fibers, but thicker and thinner fibers do not differ as the toxicologically derived prior had expected. CONCLUSION: Credible intervals for fiber size-specific risk estimates overlap; thus, we cannot conclude that there are substantial differences in effect by fiber size. Nonetheless, our results suggest that some unregulated asbestos fibers may be associated with increased incidence of lung cancer.

Cancer Registration in India - Current Scenario and Future Perspectives.

Cancer registration, an important component of cancer surveillance, is essential to a uni ed, scienti c and public health approach to cancer prevention and control. India has one of the highest cancer incidence and mortality rates in the world. A good surveillance system in the form of cancer registries is important for planning and evaluating cancer-control activities. Cancer registration in India was initiated in 1964 and expanded since 1982, through initiation of the National Cancer Registry Program (NCRP) by the Indian Council of Medical Research. NCRP currently has twenty-six population based registries and seven hospital based registries. Yet, Indian cancer registries, mostly in urban areas, cover less than 15% of the population. Other potential concerns about some Indian registries include accuracy and detail of information on cancer diagnosis, and timeliness in updating the registry databases. It is also important that necessary data collection related quality assurance measures be undertaken rigorously by the registries to ensure reliable and valid information availability. This paper reviews the current status of cancer registration in India and discusses some of the important pitfalls and issues related to cancer registration. Cancer registration in India should be complemented with a nationwide effort to foster systematic investigations of cancer patterns and trends by states, regions and sub populations and allow a continuous cycle of measurement, communication and action.