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The presentations in this session of the Monticello II conference were aimed at summarizing what is known about asbestiform and non-asbestiform elongate mineral particles (EMPs) and mesothelioma risks based on evidence from experimental and epidemiology studies. Dr. Case discussed case reports of mesothelioma over the last several decades. Dr. Taioli indicated that the epidemiology evidence concerning non-asbestiform EMPs is weak or lacking, and that progress would be limited unless mesothelioma registries are established. One exception discussed is that of taconite miners, who are exposed to grunerite. Drs. Mandel and Odo noted that studies of taconite miners in Minnesota have revealed an excess rate of mesothelioma, but the role of non-asbestiform EMPs in this excess incidence of mesothelioma is unclear. Dr. Becich discussed the National Mesothelioma Virtual Bank (NMVB), a virtual mesothelioma patient registry that includes mesothelioma patients' lifetime work histories, exposure histories, biospecimens, proteogenomic information, and imaging data that can be used in epidemiology research on mesothelioma. Dr. Bernstein indicated that there is a strong consensus that long, highly durable respirable asbestiform EMPs have the potential to cause mesothelioma, but there is continued debate concerning the biodurability required, and the dimensions (both length and diameter), the shape, and the dose associated with mesothelioma risk. Finally, Dr. Nel discussed how experimental studies of High Aspect Ratio Engineered Nanomaterials have clarified dimensional and durability features that impact disease risk, the impact of inflammation and oxidative stress on the epigenetic regulation of tumor suppressor genes, and the generation of immune suppressive effects in the mesothelioma tumor microenvironment. The session ended with a discussion of future research needs., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:JG, SS, BC, DB, AN, and GG have served as experts in asbestos and/or talc litigation. JG and GG are members of the Scientific Advisory Board of NSSGA and received a honorarium for time spent on organizing the conference. They, and most other participants, are grateful to NSSGA for covering travel and accommodation costs. The time spent by the authors in the preparation of this manuscript was at their own expense or of their employers. The National Mesothelioma Virtual Bank (NMVB) section of this workshop summary is funded and supported by the Centers for Disease Control and Prevention (CDC) in association with the National Institute for Occupational Safety and Health (NIOSH) Grant U24OH009077., (Copyright © 2022 Gradco LLC dba Gradient. Published by Elsevier Inc. All rights reserved.)

Exposure-response relationships between the relative risk of lung cancer and quantitative measures of exposure to asbestos are available from a number of epidemiological studies. Meta-analyses of these relationships have been published by Lash et al. (1997) [Lash, T.L., Crouch, E.A.C., Green, L.C., 1997. A meta-analysis of the relation between cumulative exposure to asbestos and relative risk of lung cancer. Occup. Environ. Med. 54, 254-263] and Hodgson and Darnton (2000) [Hodgson, J.T., Darnton, A., 2000. The quantitative risks of mesothelioma and lung cancer in relation to asbestos exposure. Ann. Occup. Hyg. 44, 565-601]. In this paper, the risks derived in these meta-analyses have been compared. Lash et al., concentrated on process and found that the risk of lung cancer increased as the asbestos is refined by processing. Hodgson and Darnton concentrated on fibre type and found that the risk was highest for exposure to amphibole asbestos (crocidolite and amosite), lowest for chrysotile and intermediate for mixed exposure. Some of the differences between the conclusions from the two meta-analyses are a consequence of the choice of studies included. The range of asbestos types included in the studies in the analysis of Hodgson and Darnton was wider than that in Lash et al., enabling differences between fibre types to be analyzed more readily. There are situations where occupational exposure to chrysotile asbestos has shown no detectable increase in risk of lung cancer. Taconite miners have shown no increased risk of mortality due to lung cancer.

The current state of knowledge concerning mesothelioma risk estimates is reviewed. Estimates of the risk of mesothelioma exist for the commercial asbestos fiber types chrysotile, amosite and crocidolite. Data also exist on which to assess risks for winchite (sodic tremolite) and anthophyllite asbestos. Uncertainty in estimates is primarily related to limitations in measurements of exposure. Differences in the dimensions of the various fiber types and of the same fiber types at different stages of processing add a further complication. Never-the-less, in practical terms, crocidolite presents the highest asbestos related mesothelioma risk. The risk associated with sodic tremolite (winchite) appears to be similar. In chrysotile miners and millers, the mesothelioma risk has been linked with exposure to asbestiform tremolite. Exposure to chrysotile in a pure form seems likely to present a very low if any risk of mesothelioma. While the majority of mesothelial tumors result from exposure to the asbestos minerals, there are other well established and suspected etiological agents. While a practical threshold seems to exist for exposure to chrysotile, it is unlikely to exist for the amphibole asbestos minerals, especially for crocidolite. To date there is no indication of an increased risk of mesothelioma resulting from non-commercial fiber exposure in the taconite industry.

Amphiboles are hydrated mineral silicates five of which occur in asbestiform habits as asbestos grunerite (amosite) asbestos, riebeckite (crocidolite) asbestos, anthophyllite asbestos, tremolite asbestos and actinolite asbestos] and non-asbestiform habits (grunerite, riebeckite, anthophyllite, tremolite and actinolite). The asbestiform varieties are characterized by long, thin fibers while non-asbestiform varieties such as cleavage fragments form short fibers with larger widths. The U.S. regulatory method for counting asbestos fibers (aspect ratio > or = 3:1, length > or = 5 microm) does not distinguish between asbestos and cleavage fragments. The method biases toward increased counts of non-asbestiform cleavage fragments compared to long, thin asbestos fibers. One consequence of this regulatory approach is that workers can be erroneously classified as exposed to concentrations of asbestos (asbestiform amphiboles) above the U.S. 0.1 f/mL exposure standard when in fact they are not exposed to asbestos at all but non-asbestiform amphibole cleavage fragments. Another consequence is that the known carcinogenic effects of asbestos may be falsely attributed to non-asbestiform amphibole cleavage fragments of the same mineral. The purpose of this review is to assess whether amphibole cleavage fragments pose the same risk of lung cancer and mesothelioma characteristic of amphibole asbestos fibers. We identified three groups of workers exposed to non-asbestiform amphiboles: two groups exposed to grunerite (Homestake gold miners and taconite miners) and one group exposed to industrial talc containing non-asbestiform tremolite and anthophyllite in St. Lawrence County, NY. In addition to assessing strength of association and exposure-response trends in the non-asbestiform amphibole cohorts, comparisons were also made with cohorts exposed to the asbestiform counterpart (positive control) and cohorts exposed to the mineral (e.g. talc) that does not contain amphiboles (negative controls). The cohorts exposed to non-asbestiform amphiboles had no excesses of lung cancer or mesothelioma. Similar results were observed in the negative control groups, in stark contrast to the excess risks of asbestos-related disease found in the asbestos cohorts. The only possible exception is the twofold increased risk of lung cancer where exposure was to industrial talc containing cleavage fragments of tremolite and anthophyllite. However, this risk is not considered attributable to the talc or amphibole cleavage fragments for several reasons. A similar increased risk of lung cancer was found in Vermont talc workers, studied in the same time period. Their exposure was to relatively pure talc. There was no relationship between lung cancer mortality and exposure measured as mg/m(3)years and years worked. A case-control study reported that all the lung cancer cases were smokers (or former smokers) and attributed the excess to smoking. There were two mesothelioma cases among the NY State talc workers exposed to cleavage fragments of tremolite and anthophyllite, but talc is not a plausible cause because of too short latency and potential for previous asbestos exposure. The positive controls of tremolite asbestos and anthophyllite asbestos exposed workers showed excess risks of both lung cancer and mesothelioma and positive exposure-response trends. St. Lawrence, NY talc does not produce mesotheliomas in animals while amphibole asbestos does. In sum, the weight of evidence fully supports a conclusion that non-asbestiform amphiboles do not increase the risk of lung cancer or mesothelioma.

The presentations in this session of the Monticello II conference were aimed at summarizing what is known about asbestiform and non-asbestiform elongate mineral particles (EMPs) and mesothelioma risks based on evidence from experimental and epidemiology studies. Dr. Case discussed case reports of mesothelioma over the last several decades. Dr. Taioli indicated that the epidemiology evidence concerning non-asbestiform EMPs is weak or lacking, and that progress would be limited unless mesothelioma registries are established. One exception discussed is that of taconite miners, who are exposed to grunerite. Drs. Mandel and Odo noted that studies of taconite miners in Minnesota have revealed an excess rate of mesothelioma, but the role of non-asbestiform EMPs in this excess incidence of mesothelioma is unclear. Dr. Becich discussed the National Mesothelioma Virtual Bank (NMVB), a virtual mesothelioma patient registry that includes mesothelioma patients' lifetime work histories, exposure histories, biospecimens, proteogenomic information, and imaging data that can be used in epidemiology research on mesothelioma. Dr. Bernstein indicated that there is a strong consensus that long, highly durable respirable asbestiform EMPs have the potential to cause mesothelioma, but there is continued debate concerning the biodurability required, and the dimensions (both length and diameter), the shape, and the dose associated with mesothelioma risk. Finally, Dr. Nel discussed how experimental studies of High Aspect Ratio Engineered Nanomaterials have clarified dimensional and durability features that impact disease risk, the impact of inflammation and oxidative stress on the epigenetic regulation of tumor suppressor genes, and the generation of immune suppressive effects in the mesothelioma tumor microenvironment. The session ended with a discussion of future research needs.