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.

Asbestos-induced mesothelial injury and carcinogenesis: Involvement of iron and reactive oxygen species.

Asbestos fibers have been used as an industrial and construction material worldwide due to their high durability and low production cost. Commercial usage of asbestos is currently prohibited in Japan; however, the risk of asbestos-induced malignant mesothelioma (MM) remains. According to epidemiological data, the onset of MM is estimated to occur after a latent period of 30-40 years from initial exposure to asbestos fibers; thus, the continuous increase in MM is a concern. To explore the molecular mechanisms of MM using animal models, iron saccharate with iron chelator-induced sarcomatoid mesothelioma (SM) revealed hallmarks of homozygous deletion of Cdkn2a/2b by aCGH and microRNA-199/214 by expression microarray. Oral treatment of iron chelation by deferasirox decreased the rate of high-grade SM. Moreover, phlebotomy delayed MM development in crocidolite-induced MM in rats. In Divalent metal transporter 1 (Dmt1) transgenic mice, MM development was delayed because of low reactive oxygen species (ROS) production. These results indicate the importance of iron and ROS in mesothelial carcinogenesis. The aims of this review focus on the pathogenesis of elongated mineral particles (EMPs), including asbestos fibers and multiwalled carbon nanotubes (MWCNTs) that share similar rod-like shapes in addition to the molecular mechanisms of MM development.

Differential responses of murine alveolar macrophages to elongate mineral particles of asbestiform and non-asbestiform varieties: Cytotoxicity, cytokine secretion and transcriptional changes.

Human exposures to asbestiform elongate mineral particles (EMP) may lead to diffuse fibrosis, lung cancer, malignant mesothelioma and autoimmune diseases. Cleavage fragments (CF) are chemically identical to asbestiform varieties (or habits) of the parent mineral, but no consensus exists on whether to treat them as asbestos from toxicological and regulatory standpoints. Alveolar macrophages (AM) are the first responders to inhaled particulates, participating in clearance and activating other resident and recruited immunocompetent cells, impacting the long-term outcomes. In this study we address how EMP of asbestiform versus non-asbestiform habit affect AM responses. Max Planck Institute (MPI) cells, a non-transformed mouse line that has an AM phenotype and genotype, were treated with mass-, surface area- (s.a.), and particle number- (p.n.) equivalent concentrations of respirable asbestiform and non-asbestiform riebeckite/tremolite EMP for 24 h. Cytotoxicity, cytokines secretion and transcriptional changes were evaluated. At the equal mass, asbestiform EMP were more cytotoxic, however EMP of both habits induced similar LDH leakage and decrease in viability at s.a. and p.n. equivalent doses. DNA damage assessment and cell cycle analysis revealed differences in the modes of cell death between asbestos and respective CF. There was an increase in chemokines, but not pro-inflammatory cytokines after all EMP treatments. Principal component analysis of the cytokine secretion showed close clustering for the s.a. and p.n. equivalent treatments. There were mineral- and habit-specific patterns of gene expression dysregulation at s.a. equivalent doses. Our study reveals the critical nature of EMP morphometric parameters for exposure assessment and dosing approaches used in toxicity studies.

Occupational risk resulting from exposure to mineral wool when installing insulation in buildings.

Mineral wool is widely used for thermal and sound insulation. The subject of the study is to identify hazards for employees resulting from exposure to mineral wool, when it is used to insulate buildings, and to assess the risk arising from this exposure. When installing mineral wool insulation, respirable mineral fibers, dust, and volatile organic compounds may pose a hazard at workplaces. Based on the results of concentration measurements, it was assessed that the probability of adverse health effects related to the work of insulation installers, resulting from exposure to mineral wool fibers, is low, but for dust associated with exposure, an average health risk was estimated. An additional threat may be the sensitizing effect of substances used as binders and additives improving the utility properties of mineral wool, for example, phenol formaldehyde resins. The paper also contains some information on the labeling of mineral wool; this is very important because the label allows downstream users to recognize mineral wools, the composition and properties of which cause that they are not classified as carcinogens. Int J Occup Med Environ Health. 2020;33(6):757-69.

Talc and mesothelioma: mineral fiber analysis of 65 cases with clinicopathological correlation.

Malignant mesothelioma is strongly associated with prior asbestos exposure. Recently there has been interest in the role of talc exposure in the pathogenesis of mesothelioma. We have analyzed lung tissue samples from a large series of malignant mesothelioma patients. Asbestos bodies were counted by light microscopy and mineral fiber concentrations for fibers 5 µm or greater in length were determined by scanning electron microscopy equipped with an energy dispersive spectrometer. The values were compared with 20 previously published controls. Among 609 patients with mesothelioma, talc fibers were detected in 375 (62%) and exceeded our control values in 65 (11%). Elevated talc levels were found in 48/524 men (9.2%) and 17/85 women (20%). Parietal pleural plaques were identified in 30/51 informative cases (59%) and asbestosis in 5/62 informative cases (8%). Commercial amphiboles (amosite and/or crocidolite) were elevated in 52/65 (80%) and noncommercial amphiboles (tremolite, actinolite or anthophyllite) in 41/65 (63%). Both were elevated in 34/65 (52%). Asbestos body counts by light microscopy were elevated in 53/64 informative cases (83%). A history of working in industries associated with asbestos exposure and increased mesothelioma risk was identified in 36/48 cases in men, and a history of exposure as household contacts of an occupationally exposed individual was identified in 12/17 cases in women. We conclude that among patients with mesothelioma, the vast majority have talc levels indistinguishable from background. Of the remaining 11% with elevated talc levels, the vast majority (80%) have elevated levels of commercial amphibole fibers.

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.

Chrysotile fibers in tissue adjacent to laryngeal squamous cell carcinoma in cases with a history of occupational asbestos exposure.

Asbestos describes a group of naturally occurring fibrous silicate mineral compounds that have been associated with a number of respiratory maladies, including mesothelioma and lung cancer. In addition, based primarily on epidemiologic studies, asbestos has been implicated as a risk factor for laryngeal and pharyngeal squamous cell carcinoma (SCC). The main objective of this work was to strengthen existing evidence via empirical demonstration of persistent asbestos fibers embedded in the tissue surrounding laryngeal and pharyngeal SCC, thus providing a more definitive biological link between exposure and disease. Six human papillomavirus (HPV)-negative laryngeal (n = 4) and pharyngeal (n = 2) SCC cases with a history working in an asbestos-exposed occupation were selected from a large population-based case-control study of head and neck cancer. A laryngeal SCC case with no history of occupational asbestos exposure was included as a control. Tissue cores were obtained from adjacent nonneoplastic tissue in tumor blocks from the initial primary tumor resection, and mineral fiber analysis was performed using a scanning electron microscope equipped with an energy dispersive X-ray analyzer (EDXA). Chrysotile asbestos fiber bundles were identified in 3/6 of evaluated cases with a history of occupational asbestos exposure. All three cases had tumors originating in the larynx. In addition, a wollastonite fiber of unclear significance was identified one of the HPV-negative pharyngeal SCC cases. No mineral fibers were identified in adjacent tissue of the case without occupational exposure. The presence of asbestos fibers in the epithelial tissue surrounding laryngeal SCC in cases with a history of occupational asbestos exposure adds a key line of physical evidence implicating asbestos as an etiologic factor.

"Nondetected": The Politics of Measurement of Asbestos in Talc, 1971-1976.

The recent lawsuits against Johnson & Johnson have raised the issue of what and when talcum powder manufacturers knew about the presence of asbestos in their products and what they did or did not do to protect the public. Low-level exposure to asbestos in talc is said to result in either mesothelioma or ovarian cancer. Johnson & Johnson has claimed that there was "no detectable asbestos" in their products and that any possible incidental presence was too small to act as a carcinogen. But what exactly does "nondetected" mean? Here, we examine the historical development of the argument that asbestos in talcum powder was "nondetected." We use a unique set of historical documents from the early 1970s, when low-level pollution of talc with asbestos consumed the cosmetics industry. We trace the debate over the Food and Drug Administration's efforts to guarantee that talc was up to 99.99% free of chrysotile and 99.9% free of amphibole asbestos. Cosmetic talc powder manufacturers, through their trade association, pressed for a less stringent methodology and adopted the term "nondetected" rather than "asbestos-free" as a term of art.

A comparison of asbestos fiber potency and elongate mineral particle (EMP) potency for mesothelioma in humans.

Dr. Garabrant presented a paper concerning a comparison of asbestos fiber potency and elongate mineral particle (EMP) potency for mesothelioma in humans at the Elongate Mineral Particles Conference in Charlottesville, Virginia in 2017. I was a participant at the Conference. Following Dr. Garabrant's talk, I rose in question period to point out that he had not considered information about the occurrence of mesothelioma in several cohorts that was published after the studies that he cited. These additional data were still not addressed in the paper published in your Journal. I believe that your readers would be interested in these, so this letter is written to draw the additional data to their attention.

Measurement of Lung Cancer Tumor Markers in a Glass Wool Company Workers Exposed to Respirable Synthetic Vitreous Fiber and Dust.

BACKGROUND: Occupational exposures to respirable synthetic vitreous fiber (SVF) and dust are associated with many lung diseases including lung cancer. Low-dose computed tomography is used for screening patients who are highly suspicious of having lung carcinoma. However, it seems not to be cost-effective. Serum biomarkers could be a useful tool for the surveillance of occupational exposure, by providing the possibility of diagnosing lung cancer in its early stages. OBJECTIVE: To determine if serum carcinoembryonic antigen (CEA) and cytokeratin fragment (CYFRA) 21-1 levels in workers exposed more than normal population to respirable SVF and dust may be used as indicators of progression towards lung cancer. METHODS: An analytic cross-sectional study, including 145 personnel of a glass wool company, along with 25 age-matched healthy individuals, was conducted to investigate the relationship between occupational exposure to respirable SVFs and dust and serum levels of two lung/pleura serum tumor markers, CEA and CYFRA 21-1, measured by ELISA. RESULTS: Individuals exposed to higher than the recommended levels of respirable SVF had higher serum concentrations of CEA and CYFRA 21-1, compared to controls (p=0.008 and 0.040, respectively), as well as in comparison to those exposed to lower than recommended OSHA levels (p=0.046 and 0.033, respectively). Workers with >9 years work experience, had significantly (p=0.045) higher levels of serum CYFRA 21-1 than those with ≤9 years of experience. CONCLUSION: It seems that working for >9 years in sites with detectable levels of respirable SVF and dust would increase the levels of known lung cancer serum tumor markers. Transferring these workers to sites with respirable SVF concentrations lower than the limit of detection in the air is recommended.

Prevalence of anti-nuclear autoantibodies in subjects exposed to natural asbestiform fibers: a cross-sectional study.

Fluoro-edenite (FE) is an asbestiform mineral fiber spotted in the lava rocks excavated from a stone quarry in Biancavilla (Italy). The derived material had been employed locally for building purposes. Previous studies found evidence that exposure to asbestos may induce autoimmunity, with frequency of anti-nuclear autoantibodies (ANA). The aim of this study was to explore the relationship between FE exposure and autoimmune responses in an exposed population. For the study, 60 subjects living in the area of Biancavilla and 60 subjects as control group were randomly invited to participate. A free medical check, including spirometry and a high-resolution computer tomography chest scan, was given to all participants. ANA were determined by indirect immunofluorescence. On medical check, no subject showed any sign and/or symptoms of illness. Prevalence for samples positive to ANA were 70% (n = 42) and 25% (n = 15), respectively, for exposed and non-exposed subjects (p < 0.05). The presence of pleural plaques (PP) was found in 21 (30%) of the exposed subjects and in 2 (3%) of the non-exposed participants. PP subjects were always ANAs positive. In conclusion, as already it was observed with exposure to asbestos fibers, levels of ANA seemed to significantly increase in subjects who had been exposed to FE. Furthermore, all subjects showing PP were also ANA-positive. This first finding in subjects exposed to FE should encourage researchers to further investigate associations between autoimmune unbalance and environmental exposure to asbestiform fibers.

Fibrous nanocellulose, crystalline nanocellulose, carbon nanotubes, and crocidolite asbestos elicit disparate immune responses upon pharyngeal aspiration in mice.

With the rapid development of synthetic alternatives to mineral fibers, their possible effects on the environment and human health have become recognized as important issues worldwide. This study investigated effects of four fibrous materials, i.e. nanofibrillar/nanocrystalline celluloses (NCF and CNC), single-walled carbon nanotubes (CNTs), and crocidolite asbestos (ASB), on pulmonary inflammation and immune responses found in the lungs, as well as the effects on spleen and peripheral blood immune cell subsets. BALB/c mice were given NCF, CNC, CNT, and ASB on Day 1 by oropharyngeal aspiration. At 14 days post-exposure, the animals were evaluated. Total cell number, mononuclear phagocytes, polymorphonuclear leukocytes, lymphocytes, and LDH levels were significantly increased in ASB and CNT-exposed mice. Expression of cytokines and chemokines in bronchoalveolar lavage (BAL) was quite different in mice exposed to four particle types, as well as expression of antigen presentation-related surface proteins on BAL cells. The results revealed that pulmonary exposure to fibrous materials led to discrete local immune cell polarization patterns with a TH2-like response caused by ASB and TH1-like immune reaction to NCF, while CNT and CNC caused non-classical or non-uniform responses. These alterations in immune response following pulmonary exposure should be taken into account when testing the applicability of new nanosized materials with fibrous morphology.

New insights on the biomineralisation process developing in human lungs around inhaled asbestos fibres.

Once penetrated into the lungs of exposed people, asbestos induces an in vivo biomineralisation process that leads to the formation of a ferruginous coating embedding the fibres. The ensemble of the fibre and the coating is referred to as asbestos body and is believed to be responsible for the high toxicological outcome of asbestos. Lung tissue of two individuals subjected to prolonged occupational exposure to crocidolite asbestos was investigated using synchrotron radiation micro-probe tools. The distribution of K and of elements heavier than Fe (Zn, Cu, As, and Ba) in the asbestos bodies was observed for the first time. Elemental quantification, also reported for the first time, confirmed that the coating is highly enriched in Fe (~20% w/w), and x-ray absorption spectroscopy indicated that Fe is in the 3+ oxidation state and that it is present in the form of ferritin or hemosiderin. Comparison of the results obtained studying the asbestos bodies upon removing the biological tissue by chemical digestion and those embedded in histological sections, allowed unambiguously distinguishing the composition of the asbestos bodies, and understanding to what extent the digestion procedure altered their chemical composition. A speculative model is proposed to explain the observed distribution of Fe.

Asbestos ingestion and gastrointestinal cancer: a possible underestimated hazard.

INTRODUCTION: The presence of asbestos fibres (AFs) in drinking water could be linked with gastrointestinal cancers. However, it is not regulated in several countries due to conflicting evidence. Areas covered: Some reports mainly associated AF ingestion with gastric and colorectal cancer. Experimental evidence suggested a role for timing and extent of exposure, and showed that ingested AFs induce toxic effects on the stomach, ileum and colon, histological alterations and negative effects at a molecular level, cross the placenta and enter foetal organs (including the liver), and seem able to act as a co-carcinogen agent. Occupational studies suggest associations between asbestos exposure and intrahepatic cholangiocarcinoma, and observations exist indicating the possibility that AFs could enter the liver and bile through enteric absorption. Expert commentary: A risk threshold (AF concentration in drinking water) for digestive cancers has not been convincingly identified so far and regulations, where adopted, have weak scientific basis and may not be adequate. With further and more definitive studies, evidence might become sufficient to justify monitoring plans, persuade countries with no current limits to set a maximum level of AFs in drinking water and might induce a revision of the existing legislations, pointing to efficient primary prevention policies.

Malignant Mesothelioma Mortality - United States, 1999-2015.

Malignant mesothelioma is a neoplasm associated with occupational and environmental inhalation exposure to asbestos* fibers and other elongate mineral particles (EMPs) (1-3). Patients have a median survival of approximately 1 year from the time of diagnosis (1). The latency period from first causative exposure to malignant mesothelioma development typically ranges from 20 to 40 years but can be as long as 71 years (2,3). Hazardous occupational exposures to asbestos fibers and other EMPs have occurred in a variety of industrial operations, including mining and milling, manufacturing, shipbuilding and repair, and construction (3). Current exposures to commercial asbestos in the United States occur predominantly during maintenance operations and remediation of older buildings containing asbestos (3,4). To update information on malignant mesothelioma mortality (5), CDC analyzed annual multiple cause-of-death records† for 1999-2015, the most recent years for which complete data are available. During 1999-2015, a total of 45,221 deaths with malignant mesothelioma mentioned on the death certificate as the underlying or contributing cause of death were reported in the United States, increasing from 2,479 deaths in 1999 to 2,597 in 2015 (in the same time period the age-adjusted death rates§ decreased from 13.96 per million in 1999 to 10.93 in 2015). Malignant mesothelioma deaths increased for persons aged ≥85 years, both sexes, persons of white, black, and Asian or Pacific Islander race, and all ethnic groups. Despite regulatory actions and the decline in use of asbestos the annual number of malignant mesothelioma deaths remains substantial. The continuing occurrence of malignant mesothelioma deaths underscores the need for maintaining measures to prevent exposure to asbestos fibers and other causative EMPs and for ongoing surveillance to monitor temporal trends.

[Possible health risks from asbestos in drinking water]. / Rischio clinico da ingestione di fibre di amianto in acqua potabile.

The recent finding of asbestos fibres in drinking water (up to 700.000 fibres/litres) in Tuscany (Central Italy) leads to concerns about health risks in exposed communities. Exposure to asbestos has been linked with cancer at several levels of the gastrointestinal tract, and it has been documented, in an animal model, a direct cytotoxic effect of asbestos fibres on the ileum. It has been recently described a possible link between asbestos and intrahepatic cholangiocarcinoma, and asbestos fibres have been detected in humans in histological samples from colon cancer and in gallbladder bile. Taken together, these findings suggest the possibility of an enterohepatic translocation of asbestos fibres, alternative to lymphatic translocation from lungs. In animal models, asbestos fibres ingested with drinking water act as a co-carcinogen in the presence of benzo(a) pyrene and, according to the International Agency for Research on Cancer (IARC ), there is evidence pointing to a causal effect of ingested asbestos on gastric and colorectal cancer. The risk seems to be proportional to the concentration of ingested fibres, to the extent of individual water consumption, to exposure timing, and to the possible exposure to other toxics (i.e., benzo(a)pyrene). Furthermore, the exposure to asbestos by ingestion could explain the epidemiological finding of mesothelioma in subjects certainly unexposed by inhalation. In conclusion, several findings suggest that health risks from asbestos could not exclusively derive from inhalation of fibres. Health hazards might also be present after ingestion, mainly after daily ingestion of drinking water for long periods. In Italy, a systemic assessment of the presence of asbestos fibres in drinking water is still lacking, although asbestos-coated pipelines are widely diffused and still operating. Despite the fact that the existence of a threshold level for health risks linked to the presence of asbestos in drinking water is still under debate, the precautionary principle should impose all possible efforts in order to revise health policies concerning this topic, and a systematic monitoring of drinking water to quantify the presence of asbestos is certainly needed in all regions. Further epidemiological studies aimed to the identification of exposed communities and to an adequate health risk assessment in their specific geographical areas are urgently needed.

Size- and type-specific exposure assessment of an asbestos products factory in China.

This study describes fibre size and type-specific airborne asbestos exposures in an asbestos product factory. Forty-four membrane filter samples were analysed by scanning electron microscopy to determine the size distribution of asbestos fibres, by workshop. Fibre frequencies of bivariate (length by width) categories were calculated and differences between workshops were tested by analysis of variance. Data were recorded for 13,435 chrysotile and 1075 tremolite fibres. The proportions between size metrics traditionally measured and potentially biologically important size metrics were found to vary in this study from proportions reported in other cohort studies. One, common size distribution was generated for each asbestos type over the entire factory because statistically significant differences in frequency between workshops were not detected. This study provides new information on asbestos fibre size and type distributions in an asbestos factory. The extent to which biologically relevant fibre size indices were captured or overlooked between studies can potentially reconcile currently unexplained differences in asbestos-related disease (ARD) risk between cohorts. The fibre distributions presented here, when combined with similar data from other sites, will contribute to the development of quantitative models for predicting risk and our understanding of the effects of fibre characteristics in the development of ARD.

Pleural mesothelioma and lung cancer risks in relation to occupational history and asbestos lung burden.

BACKGROUND: We have conducted a population-based study of pleural mesothelioma patients with occupational histories and measured asbestos lung burdens in occupationally exposed workers and in the general population. The relationship between lung burden and risk, particularly at environmental exposure levels, will enable future mesothelioma rates in people born after 1965 who never installed asbestos to be predicted from their asbestos lung burdens. METHODS: Following personal interview asbestos fibres longer than 5 µm were counted by transmission electron microscopy in lung samples obtained from 133 patients with mesothelioma and 262 patients with lung cancer. ORs for mesothelioma were converted to lifetime risks. RESULTS: Lifetime mesothelioma risk is approximately 0.02% per 1000 amphibole fibres per gram of dry lung tissue over a more than 100-fold range, from 1 to 4 in the most heavily exposed building workers to less than 1 in 500 in most of the population. The asbestos fibres counted were amosite (75%), crocidolite (18%), other amphiboles (5%) and chrysotile (2%). CONCLUSIONS: The approximate linearity of the dose-response together with lung burden measurements in younger people will provide reasonably reliable predictions of future mesothelioma rates in those born since 1965 whose risks cannot yet be seen in national rates. Burdens in those born more recently will indicate the continuing occupational and environmental hazards under current asbestos control regulations. Our results confirm the major contribution of amosite to UK mesothelioma incidence and the substantial contribution of non-occupational exposure, particularly in women.

The So-called Short-Fiber Controversy: Literature Review and Critical Analysis.

CONTEXT: Numerous articles in the scientific literature indicate that pathogenic fibers with respect to asbestos-related diseases are those that exceed 5 µm in length. Nonetheless, some authors have expressed concerns regarding pathogenicity of shorter fibers. OBJECTIVE: To review the scientific evidence regarding pathogenicity (or lack thereof) of fibers less than or equal to 5 µm in length, with particular attention to publications indicating that such fibers might be hazardous. DATA SOURCES: The scientific literature was reviewed for experimental animal studies and human studies that address the role of fiber size in causation of disease. Sources included original studies, as well as review articles related to the topic. CONCLUSIONS: Experimental animal studies involving inhalation of fibers have demonstrated that fibers greater than 5 µm in length are associated with both pulmonary fibrosis (ie, asbestosis) and malignancies (carcinoma of the lung and mesothelioma). There is no convincing evidence for a pathogenic effect for fibers that are 5 µm or less in length. Fiber analyses of human lung tissue samples provide further support for pathogenicity of long fibers, particularly the more biopersistent amphibole fibers. Similar observations have been reported for nonasbestos mineral fibers. Concerns expressed by some authors (eg, the greater abundance of short fibers) do not alter these conclusions. Similarly, in vitro studies demonstrating biological activity of short fibers do not override inhalational studies of whole animals or the epidemiological findings in humans.