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LETTERS TO THE EDITOR

Authors’ Response to “Evidence Does Not Support Exposure to Cosmetic Talc as a Cause of Malignant Mesothelioma”

Moline, Jacqueline MD; Bevilacqua, Kristin MPH; Gordon, Ronald E. PhD

Editor(s): information., Readers are invited to submit letters for publication in this department. Submit letters online at http://joem.edmgr.com. Choose “Submit New Manuscript.” A signed copyright assignment and financial disclosure form must be submitted with the letter. Form available at www.joem.org under Author and Reviewer

Author Information
Journal of Occupational and Environmental Medicine: February 2020 - Volume 62 - Issue 2 - p e85-e86
doi: 10.1097/JOM.0000000000001790
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Readers are invited to submit letters for publication in this department. Submit letters online at http://joem.edmgr.com. Choose “Submit New Manuscript.” A signed copyright assignment and financial disclosure form must be submitted with the letter. Form available at www.joem.org under Author and Reviewer information.

Reply:

We appreciate the opportunity to reply to Dr. Geyer letter.

Dr. Geyer's has commented on the section in our paper1 related to “standard methodology.” While it is true that there is no uniform method that is followed by every scientist, standard methodology for analysis of human tissue is based on being able to identify and define the asbestos and other particles that are present in patient tissues and isolated during an asbestos fiber burden analysis. All laboratories use similar methods that can be defined as “standard” to digest the tissue, clean the remaining inorganic material and to observe it by transmission electron microscopy. Slight differences in the preparation procedures might vary from laboratory to laboratory and these differences have been published.2,3 For example, some investigators use hypochlorous acid, Chlorox, while others use potassium hydroxide (KOH). Both work equally to digest away the organic material of the tissue. The other major difference is once the inorganic material is cleaned of the Chlorox/KOH, it is either filtered onto a filter or directly dropped onto a Formvar or carbon coated electron microscopy grid. This first technique allows for the direct observation of the coated grid under the microscope whereas in the second technique the filter has to be collapsed using an appropriate solvent so it will be possible to get an electron beam through the open areas of the filter. Despite potential procedural differences, analyses across procedures are comparable.

Standard and acceptable means of identifying and defining asbestos type by transmission electron microscopy (TEM) are to determine the morphologic appearance of the structure, to determine the elemental analysis of that structure, energy-dispersive X-ray spectroscopy (EDS), and then to determine the crystalline structure using selected area electron diffraction (SAED). These are the criteria that have been set by government standards. However, Scanning Electron Microscopy, SEM, lacks the resolution a TEM has, and the acceleration voltage may not be adequate to get an accurate EDS spectra. It is impossible to acquire an SAED image to confirm the crystalline structure or identify the specific type of asbestos. With respect to sensitivity of the findings, one might have to look at more grid openings for a comprehensive analysis.

Dr. Geyer also indicated that, in the past, the identification of the asbestos was questioned by a single laboratory as a basis for criticism. For this paper, Dr. Gordon employed the basic methodology of morphology, chemistry, and crystalline structure as defined by all governmental agencies. Similar criticisms have been raised in response to prior work, and a response to the earlier criticism is referenced below.3

Dr. Geyer also indicated that Dr. Gordon could not confirm that the asbestos was a result of the talcum powder usage. His question presupposes that there is a unique marker on asbestos contained in cosmetic talcum powder that would allow for its identification. This defies logic. It is almost impossible to confirm exactly where any asbestos fiber could have come from in a human tissue sampling taken many years after exposure. This article notes that the type of fibers found in the tissues of these individuals were the same type as are consistently found in cosmetic talcum powder.4

Dr. Geyer indicated that Dr. Gordon's controls showed asbestos fibers in a very small minority of the cases tested, and that the length of those fibers was less than 1 μm in length. These are laboratory controls that had been prepared years before this current study was completed. Findings from the tissue of the mesothelioma patients in these six cases were performed, and reported in this study. Only fibers greater than 5 μm were counted. For the historical controls, Dr. Gordon described all fibers found, including shorter fibers, to illustrate what might be seen in the general population.

This case series provides the first compilation of a number of cosmetic talc users, rather than talc miners and millers, who might have had different dust exposures than users of a fully milled product. As Gordon et al2 noted, air sampling during simulated exposure to commercial cosmetic talc led to an exposure of 1.9 f/cc, a level well above background exposure to asbestos. Coggiola et al,5 described that dust suppression within the mines decreased the miners exposures to dust. No such dust suppression is readily available for consumers of cosmetic talc in their homes. In addition, a study of Vermont talc miners had an inadequate latency period to determine whether any mesotheliomas were present in the small cohort.6

Dr. Geyer states that we did not discuss the sparse literature related to long-term sequelae of talc pleurodesis. The studies have small sample sizes and have, at least in the case of one study,7 a relatively short follow-up period for over half of the patients in the study. Furthermore, it has been noted that talc should not be used for nonmalignant conditions because of potential health risks.8 This study was designed as a case series, not a comprehensive review of the other health effects related to talc exposure such as talcosis.9

Our study is a descriptive study of 33 cases, with six cases presented in depth, and included tissue digestion studies of these six cases. The detailed case histories, including the tissue digestion, provided information to the journal readers of findings of asbestos within the tissue consistent with the types of asbestos seen in cosmetic talc. The fiber studies were all performed in the same laboratory, to provide consistency in methodology and microscopist. Tissue digestions are not required for the attribution of disease in mesothelioma, but when present, can provide additional information.10

In discussing the importance of case series in the scientific literature, Carey writes that case reports “represent a relevant, timely, and important study design in advancing medical scientific knowledge, especially of rare diseases.”11 It is true that, to our knowledge, no prior publications have described the health effects of cosmetic talc on users of these products. However, a dearth of literature is reason for further exploration, not the end of scientific inquiry. Dr. Geyer rightfully points out that there is no control population in our case series, and as a result, no incidence rates for mesothelioma were calculated. Citing Bradford Hill criteria of causation, Dr. Geyer misrepresents the purpose of a case series by placing the wrong emphasis, noted in boldface type, on our assertion that asbestos-contaminated talcum powder can cause [emphasis his] mesothelioma. As Checkoway et al12 pointed out, in the setting of a known causal link between an exposure and disease, especially one with as close a link as exists between asbestos and malignant mesothelioma, a case series can establish that a particular set of asbestos exposure conditions can cause mesothelioma. In this way, our case series suggests that asbestos-contaminated talcum powder can [emphasis ours] cause mesothelioma or, as Bradford Hill might say, based on the scientific knowledge of our day, it is plausible that talcum powder contaminated with asbestos can cause mesothelioma and thus, further inquiry is necessary. As Albrecht et al,13 stated, case reports and case series can have significant influence on subsequent literature and possibly on clinical practice. In this way, though our case series should be considered within the context of its limitations, the implications for comprehensive exposure assessment are undeniably important.

As explicitly stated in our paper, our goal was to alert clinicians of a potential source of asbestos exposure that could lead to disease, and to stress the importance of taking a comprehensive exposure history. The finding of 33 individuals with malignant mesothelioma who have exposure only to cosmetic talc, is notable. Based on the exposure information, with identification of no other known source of asbestos, we believe that this case series provides evidence that exposure to asbestos contaminated cosmetic talc should be considered as a cause of mesothelioma. Future studies of users of commercial cosmetic talc should be undertaken.

REFERENCES

1. Moline J, Bevilacqua K, Alexandri M, Gordon RE. Mesothelioma associated with the use of cosmetic talc. J Occup Environ Med 2019; doi:10.1097/JOM.0000000000001723. [Epub ahead of print].
2. Gordon RE, Fitzgerald S, Millette J. Asbestos in commercial cosmetic talcum powder as a cause of mesothelioma in women. Int J Occup Environ Health 2014; 20:318–332.
3. Gordon RE. Response to second letter by Lee et al. of 2016. Int J Occup Environ Health 2017; 23:177–180.
4. Rohl AN, Langer AM. Identification and quantitation of asbestos in talc. Environ Health Perspect 1974; 9:95–109.
5. Coggiola M, Bosio D, Pira E, et al. An update of a mortality study of talc miners and millers in Italy. Am J Ind Med 2003; 44:63–69.
6. Selevan S, Dement J, Wagoner J, Froines J. Mortality patterns among miners and millers of non-asbestiform talc: preliminary report. J Environ Pathol Toxicol 1979; 2:273–284.
7. Unit TMRCP. Research Committee of the British Thoracic Association. A survey of the long-term effects of talc and kaolin pleurodesis. Br J Dis Chest 1979; 73:285–288.
8. Ghio AJ, Roggli V, Light RW. Talc should not be used for pleurodesis in patients with nonmalignant pleural effusions. Am J Respir Crit Care Med 2001; 164:1741.
9. Kleinfeld M, Messite J, Tabershaw I. Talc pneumoconiosis. AMA Arch Ind Health 1955; 12:66–72.
10. Tossavainen A. Asbestos, asbestosis, and cancer: the Helsinki criteria for diagnosis and attribution. Scand J Work Environ Health 1997; 23:311–316.
11. Carey JC. The importance of case reports in advancing scientific knowledge of rare diseases. Adv Exp Med Biol 2010; 686:77–86.
12. Checkoway H, Pearce N, Kriebel D. Research methods in occupational epidemiology. Monogra Epidemiol 2004; 34:12–13.
13. Albrecht J, Meves A, Bigby M. Case reports and case series from Lancet had significant impact on medical literature. J Clin Epidemiol 2005; 58:1227–1232.
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