In Reply to “Malignant Mesothelioma and Its Nonasbestos Causes”

In recent years, coinciding with cosmetic talc litigation, Dr Finkelstein has written a number of correspondence letters regarding peer-reviewed scientific literature in which he espouses various claims regarding cosmetic talcum powder, asbestos exposure, and mesothelioma.1–3 In each case, the authors of those publications have respectfully disagreed with Dr Finkelstein's assertions, although he has since repeated the same claims.4–6 We now would like to respond to his commentary that addresses statements we made in our publication regarding spontaneous mesothelioma in North American women.7,8Dr Finkelstein questions 2 statements in our article, both in reference to spontaneous mesothelioma. First, that most mesotheliomas not clearly attributable to asbestos are spontaneous. Second, that in North America few mesotheliomas in women at any site are attributable to asbestos. We made clear our scientific methodology and peer-reviewed reliance literature, which enabled us to conclude in the manner we did.Dr Finkelstein argues that there is common occult asbestos exposure arising from use of some talcum powders, something that we did not discuss, and therefore it was inappropriate to conclude in the manner we did. That being so, one would expect that Dr Finkelstein would set out the contrary scientific basis with literature supporting his assertion that consumer usage of cosmetic talc, even if contaminated by amphibole minerals (asbestiform or non-asbestiform), poses any risk of malignant mesothelioma.Dr Finkelstein actually provides no contrary peer-reviewed scientific literature that challenges our 2 statements. Instead, he relies first, on data from Statista, a German market research company, for US purchasing patterns of body and baby powder use between 2011 and 2017,9 and second, on a misrepresentation of a fiber burden database obtained without permission through litigation and published without consent from one of us. Dr Finkelstein is unable to draw any conclusion beyond a commentary on present-day consumer usage of body and baby powder, which as Keeton et al6 highlight, is not specific to products containing talcum powder.We disagree with Dr Finkelstein because he ignores basic scientific principles of interpreting fiber burden analyses when seeking to attribute significance to an exposure in the causation of disease, because he relies on incorrect and irrelevant data sources, and because he ignores the wider scientific evidence that consistently concludes that cosmetic talc is not a cause for malignant mesothelioma.First, with respect to interpreting fiber burden analyses, it is widely accepted that asbestos, as a collective group, is one among many minerals that are ubiquitous in the ambient atmosphere and that there is no evidence that these exposures have any significance with respect to the development of any disease. The scientific evidence correlating cumulative asbestos exposure with disease has been extensively established in occupational settings that are many orders of magnitude above background ambient exposure levels.10–12 Numerous analytic laboratories have made correlations between retained amphibole asbestos fiber concentrations in lungs of asbestos-exposed workers and asbestos-related disease. Control reference ranges should be established within laboratories performing fiber burden analyses, and the significance of an individual exposure may then be determined by benchmarking the case to the established laboratory control population.13,14 The control population represents, most closely, only subjects with ambient exposure and no increased risk of asbestos-related disease.An important rule in evaluating fiber burden studies is that, at a minimum, an elevation above background is required before considering whether a given case might represent an asbestos-related disease. Another fundamental principle of interpreting fiber burden analyses, ignored by Dr Finkelstein, is that absent contamination, the mere detection of a mineral confers no more significance than prior exposure. It is not possible to infer the specific source or timing of exposure (unless this correlates closely with a clear exposure history) or any etiologic significance absent a comparison with the laboratory control reference population, and preferably a comparison with established disease-specific ranges for that laboratory.Dr Finkelstein makes no attempt to correlate fiber detection with any causal significance. However, Roggli (in Srebro et al15) has previously published his laboratory controls so such comparisons could have been undertaken. In fact, as Roggli points out (in Kraynie et al16), many of the female subjects with malignant mesothelioma have asbestos fiber burdens and asbestos body counts that fall within his laboratory control reference population. Thereby, there is no mineralogic evidence of significant above-background exposure and no evidence for any increased mesothelioma risk from mineral fibers in these North American women with malignant mesothelioma as determined by the fiber burden database cited by Dr Finkelstein. Although we did not use the fiber burden database in our article, these results support our original proposition, which was based on published literature review stating that “in North America few mesotheliomas in women at any site are attributable to asbestos.”Additionally, it is recognized that various elongate mineral particles can be detected in human lung samples by electron microscopic analysis with energy-dispersive x-ray spectrometry. Although potentially satisfying the definition for a fiber (an elongate mineral particle with an aspect ratio of at least 3:1 and roughly parallel sides), it has been suggested that a minimum 10:1 or preferably 20:1 aspect ratio be used as one criterion for determining asbestiform fibers from elongate particulates of non-asbestiform cleavage fragments.17,18 This has biologic significance, as cleavage fragments of non-asbestiform minerals have not been associated with asbestos-related disease nor are they regulated as asbestos by the Occupational Safety and Health Administration. As Roggli et al19 noted for persons with asbestos-related disease, lung fiber burdens of commercial amphibole forms of asbestos (amosite and crocidolite) show that almost all are greater than 10 μm and their diameter is nearly always less than 1 μm. This contrasts with the noncommercial amphibole minerals (tremolite, actinolite, and anthophyllite) whose aspect ratio is lower, with wider fiber diameters and shorter fiber lengths corresponding to the presence of the more commonly detected cleavage fragments rather than the rarer asbestiform habits of the amphibole minerals.We recognize that there exists scientific debate regarding the precise nature of accessory minerals in cosmetic talcum products. This was discussed in detail by Keeton et al6 in response to precisely the same commentary made by Dr Finkelstein. We do not consider there is any purpose in simply rehearsing the same discussions.Dr Finkelstein seeks to attempt to develop a conclusion from his re-analysis of Roggli's fiber burden database, namely, that in women, talc and noncommercial amphiboles are detected more frequently than in men, to support his proposition that the consumer usage of cosmetic talc was more common in women and exposed women to noncommercial amphibole minerals. Even if talc is detected on mineral analysis, Dr Finkelstein cannot conclude by his methodology that the talc is from a cosmetic talc source or that talc was the source of any codetected noncommercial amphibole minerals. Talc was the most common non-asbestos mineral fiber that was identified in the reference population.20An understanding of gender differences observed in fiber burdens, fiber counting protocols, and limits of detection in analyzing cases provides a clear explanation for this observation, which Dr Finkelstein ignores. In general, fiber burden studies undertaken on lung digests from men with asbestos-related disease reflect prior occupational exposures to commercial forms of amphibole asbestos, predominantly amosite. The exposures to asbestos in men are very typically heavier than the exposures observed in women. This fact impacts upon fiber burden detection limits of minerals analyzed. In asbestos-related disease, because of fiber-counting protocols, in heavier exposures (more often reflected in men, following occupational settings) the fiber burdens will be dominated by commercial amphibole asbestos. At low exposures (more typically observed in women), commercial forms of amphibole asbestos are less frequently detected and noncommercial amphiboles and non-asbestos minerals are disproportionately represented. Most importantly, it provides no evidence for the timing or significance of such exposure.We did not introduce discussions regarding talc (industrial or cosmetic/pharmaceutic grade), its mineralogy, or its biologic significance or any accessory minerals, even if present, or their role, if any, in the development of malignant mesothelioma. This was because we did not consider it as relevant to the scope of our review.However, as this has been raised by Dr Finkelstein, we will now address the issue. First, it is worth noting that there has never been a single confirmed case of malignant mesothelioma in any of the epidemiologic studies of cosmetic talc mine and mill workers conducted in Europe or North America, a finding that is consistent with the fact that these mines did not contain asbestiform amphiboles.21–28 Second, published reviews of subjects undergoing pleurodesis with cosmetic/pharmaceutical-grade talc for various benign pleuropulmonary conditions, which investigated the potential development of mesothelioma, identified no mesotheliomas in any of the more than 300 patients with follow-up ranging from 14 to 40 years.29–31 A weight of evidence review concluded that talc pleurodesis was safe for use with no long-term effects.32 Finally, toxicologic studies of rats exposed to high levels of Italian cosmetic-grade talc showed no asbestos-related effects and no mesotheliomas after either intrapleural injection or inhalation.33,34 Additionally, Syrian golden hamsters showed no mesotheliomas after exposure to Vermont talc.35,36In the final analysis we are unable to identify any evidence that supports Dr Finkelstein's propositions regarding our statements about spontaneous mesotheliomas, or cases of malignant mesothelioma arising in US women. We identify no evidence for any causative role of cosmetic talc in malignant mesothelioma.We thank Dr Finkelstein for his comments but respectfully do not agree with them.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.