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Background Talc, a hydrous magnesium silicate, often used for genital hygiene purposes, is associated with ovarian carcinoma in case-control studies. Its potential to cause inflammation, injury, and functional changes in cells has been described. A complication of such studies is that talc preparations may be contaminated with other materials. A previous study by (Beck et al. Toxicol Appl Pharmacol 87:222-34, 1987) used a hamster model to study talc and granite dust exposure effects on various biochemical and cellular inflammatory markers. Our current study accessed key materials used in that 1987 study; we re-analyzed the original talc dust with contemporary scanning electron microscopy and energy dispersive x-ray analysis (SEM/EDX) for contaminants. We also examined the original bronchoalveolar lavage (BAL) cells with polarized light microscopy to quantify cell-associated birefringent particles to gain insight into the talc used. Results SEM/EDX analyses showed that asbestos fibers, quartz, and toxic metal particulates were below the limits of detection in the original talc powder. However, fibers with aspect ratios ≥3:1 accounted for 22% of instilled material, mostly as fibrous talc. Talc (based on Mg/Si atomic weight % ratio) was the most abundant chemical signature, and magnesium silicates with various other elements made up the remainder. BAL cell counts confirmed the presence of acute inflammation, which followed intratracheal instillation. Measurements of cell associated birefringent particles phagocytosis revealed significant differences among talc, granite, and control exposures with high initial uptake of talc compared to granite, but over the 14-day experiment, talc phagocytosis by lavaged cells was significantly less than that of granite. Phagocytosis of talc fibers by macrophages was observed, and birefringent particles were found in macrophages, neutrophils, and multinucleate giant cells in lavaged cells from talc-exposed animals. Conclusion Our data support the contention that talc, even without asbestos and other known toxic contaminants, may elicit inflammation and contribute to lung disease. Our findings support the conclusions of (Beck et al. Toxicol Appl Pharmacol 87:222-34, 1987) study. By analyzing particulate exposures with polarized light microscopy and SEM/EDX, fibrous talc was identified and a distinctive pattern of impaired particulate ingestion was demonstrated.

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.

Objective. Talc is widely used in industrial applications. Previous meta-analyses of carcinogenic effects associated with inhaled talc included publications before 2004, with a lack of data in China, the largest talc-producing country. The safety of workers exposed to talc was unclear due to limited evidence. The objective of this study was to reevaluate the association between inhaled talc and lung cancer. Setting, Participants, and Outcome Measures. A meta-analysis was performed to calculate the meta-SMR of lung cancer. We searched the MEDLINE, EMBASE, CNKI, and Wanfang Data databases through March 2017. Data from observational studies were pooled using meta-analysis with random effects models. Results. Fourteen observational cohort studies (13 publications) were located via literature search. The heterogeneity of the included data was high (I-squared = 72.9%). Pooling all the cohorts yielded a meta-SMR of 1.45 (95% CI: 1.22–1.72, p<0.0001) for lung cancer among the study subjects exposed to talc. Subgroup analysis for asbestos contamination showed no significant difference in lung cancer death between subjects exposed to talc with and without asbestos (p=0.8680), indicating that this confounding factor may have no significance. Conclusions. This study provides evidence that nonasbestiform talc might still increase the risk of lung cancer. Further epidemiological studies are required to evaluate the safety of workers with occupational talc exposure.

Human mesothelial cells (LP9/TERT-1) were exposed to low and high (15 and 75 microm(2)/cm(2) dish) equal surface area concentrations of crocidolite asbestos, nonfibrous talc, fine titanium dioxide (TiO2), or glass beads for 8 or 24 hours. RNA was then isolated for Affymetrix microarrays, GeneSifter analysis and QRT-PCR. Gene changes by asbestos were concentration- and time-dependent. At low nontoxic concentrations, asbestos caused significant changes in mRNA expression of 29 genes at 8 hours and of 205 genes at 24 hours, whereas changes in mRNA levels of 236 genes occurred in cells exposed to high concentrations of asbestos for 8 hours. Human primary pleural mesothelial cells also showed the same patterns of increased gene expression by asbestos. Nonfibrous talc at low concentrations in LP9/TERT-1 mesothelial cells caused increased expression of 1 gene Activating Transcription Factor 3 (ATF3) at 8 hours and no changes at 24 hours, whereas expression levels of 30 genes were elevated at 8 hours at high talc concentrations. Fine TiO2 or glass beads caused no changes in gene expression. In human ovarian epithelial (IOSE) cells, asbestos at high concentrations elevated expression of two genes (NR4A2, MIP2) at 8 hours and 16 genes at 24 hours that were distinct from those elevated in mesothelial cells. Since ATF3 was the most highly expressed gene by asbestos, its functional importance in cytokine production by LP9/TERT-1 cells was assessed using siRNA approaches. Results reveal that ATF3 modulates production of inflammatory cytokines (IL-1 beta, IL-13, G-CSF) and growth factors (VEGF and PDGF-BB) in human mesothelial cells.

Purpose Use of talcum powder in the perineal area has been associated with an increased risk of ovarian cancer, and a recent cohort study found a positive association with endometrial cancer. We sought to confirm this association using data from the Australian National Endometrial Cancer Study (ANECS). Methods ANECS was a population-based case-control study conducted from 2005 to 2007, in which 1,399 women with newly diagnosed histologically confirmed primary endometrial cancer and 740 control women provided risk factor information via telephone interview. Unconditional logistic regression was used to estimate odds ratios adjusting for potential confounders. Results We found no significant association between ever use of talc in the perineal area (OR 0.88, 95% CI: 0.68-1.14) or upper body area (OR 0.90, 95% CI: 0.71-1.14) and risk of endometrial cancer. The results were similar when stratified by subtype. Composite variables combining frequency and duration of talc use were also not significantly associated with risk (any perineal area use p = 0.07 and any upper body use p = 0.49). Conclusions The absence of any increase in risk and the similarity of our results for talc use on the upper body and in the perineal area do not support the hypothesis that use of talc in the perineal area is associated with an increased risk of endometrial cancer. Our data do not confirm the positive association between perineal talc use and endometrial cancer observed in the only previous study.

The mechanisms of chemical pleurodesis are still not fully explained. We aimed to evaluate the feasibility of using primary biopsy‐derived human mesothelial cells to establish an in vitro culture and to assess the response of pleural mesothelial cells to different sclerosing agents. Talc, povidone‐iodine, doxycycline, and TGF‐β were used at different doses to stimulate pleural mesothelial cells. After 6 and 24 h, mRNA expression of interleukin (IL)‐1β, IL‐6, IL‐8, TGF‐β, MCP‐1, IL‐17A, and MMP9 was measured in cultured cells, and the protein level of IL‐1β, IL‐6, and IL‐8 was measured in the culture supernatant. The most pronounced response was observed after talc exposure. It was expressed as an increase in IL‐1β concentration in culture supernatant after 24 h of higher talc dose stimulation compared to 6 h of stimulation (17.14 pg/ml [11.96–33.32 pg/ml] vs. 1.84 pg/ml [1.81–1.90 pg/ml], p = 0.02). We showed that culture pleural mesothelial cells isolated from pleura biopsy specimens is feasible. Inflammatory responses of mesothelial cells to different sclerosants were highly variable with no consistent pattern of mesothelium reaction neither in terms of different sclerosing agents nor in the time of the most significant reaction. We demonstrated that pro‐inflammatory mesothelial response includes an increase in IL‐1β mRNA expression and protein production. This may suggest the role of IL‐1β in the formation and maintenance of the inflammatory response during pleurodesis. We performed the prospective study using primary, biopsy‐derived human mesothelial cells to establish an in vitro culture and to assess the response of pleural mesothelial cells to four different sclerosing agents (talc, povidone‐iodine, doxycycline, and transforming growth factor β) in different doses. Our study shows, that it is feasible to culture pleural mesothelial cells isolated from pleura biopsy specimens, that can be used for research on pleurodesis mechanisms. We found that pro‐inflammatory mesothelial response includes an increase in interleukin (IL)‐1β mRNA expression and protein production, which suggests the role of IL‐1β in the formation and maintenance of the inflammatory response during pleurodesis. ​

The mechanism for biological effects after exposure to particles is incompletely understood. One postulate proposed to explain biological effects after exposure to particles involves altered iron homeostasis in the host. The fibro-inflammatory properties of mineral oxide particles are exploited therapeutically with the instillation of massive quantities of talc into the pleural space, to provide sclerosis. We tested the postulates that (1) in vitro exposure to talc induces a disruption in iron homeostasis, oxidative stress, and a biological effect, and (2) talc pleurodesis in humans alters iron homeostasis. In vitro exposures of both mesothelial and airway epithelial cells to 100 μg/ml talc significantly increased iron importation and concentrations of the storage protein ferritin. Using dichlorodihydrofluorescein, exposure to talc was associated with a time-dependent and concentration-dependent generation of oxidants in both cell types. The expression of proinflammatory mediators was also increased after in vitro exposures of mesothelial and airway epithelial cells to talc. Relative to control lung tissue, lung tissue from patients treated with sclerodesis demonstrated an accumulation of iron and increased expression of iron-related proteins, including ferritin, the importer divalent metal transport-1 and the exporter ferroportin-1. Talc was also observed to translocate to the parenchyma, and changes in iron homeostasis were focally distributed to sites of retention. We conclude that exposure to talc disrupts iron homeostasis, is associated with oxidative stress, and results in a biological effect (i.e., a fibro-inflammatory response). Talc pleurodesis can function as a model of the human response to mineral oxide particle exposure, albeit a massive one.

Cases of acute respiratory failure reported after talc pleurodesis have raised concerns about its safety. It has been speculated that this pulmonary inflammatory syndrome is secondary to the extrapleural dissemination of the talc particles. To test the hypothesis that particle size influences extrapleural talc deposition and pleural inflammation after talc slurry pleurodesis. Thirty rabbits underwent pleurodesis as follows: 10 rabbits received 200 mg/kg of the talc used for human pleurodesis, normal talc (NT); 10 rabbits received 200 mg/kg of talc with particles of larger size, large talc (LT); and 10 rabbits received saline solution. Samples from the ipsilateral lung, chest wall, diaphragm, mediastinal pleura, heart, liver, spleen, and right kidney were obtained at 24 h and 7 days and processed for optic and electron microscopy and energy-dispersive x-ray analysis. Visceral pleural thickening was greater with NT than with LT, but no differences were observed in the macroscopic score of adhesions. There was more talc in the lungs of the rabbits that received NT than in those that received LT. Talc particles were detected in mediastinum (100%) and pericardium (20%), irrespective of the talc used. Three animals, all receiving NT, had talc particles in the liver. Our study shows that while both talcs were equally effective in achieving pleurodesis, the intrapleural injection of NT elicits greater pulmonary and systemic talc particle deposition than LT. Moreover, pleural inflammation was greater with NT than with LT.

Intrapleural talc is used to produce pleurodesis in malignant pleural effusions. Prior in vivo studies have documented an acute inflammatory response to talc in the pleural space but the cellular source of cytokines has not been identified. The aim of this study was to investigate the acute response of rabbit pleural mesothelial cells challenged with talc used for pleurodesis and compare it to prior studies of the response to talc in the rabbit pleural space. Cultured rabbit pleural mesothelial cells (PMC) were exposed to talc (25 mug/cm(2)) for 6, 24, or 48 h and assessed for viability, necrosis, and apoptosis by flow cytometry, Trypan Blue exclusion, and immunocytochemistry, and for the production of interleukin-8 (IL-8), vascular endothelial growth factor (VEGF), and transforming growth factor-beta(1) (TGF-beta(1)) by ELISA. More than 50% of the PMC remained viable 48 h after talc stimulation. The PMC that were nonviable were identified as either apoptotic or necrotic, with roughly 20% in each category over the 48 h. At 6 h, the IL-8, VEGF, and TGF-beta(1) levels produced by talc-exposed PMC increased significantly and remained elevated for up to 48 h. These cytokine levels rose at similar times and at the same or higher levels than have been measured in the rabbit pleural space in prior studies. We report that viable, talc-exposed, pleural mesothelial cells may actively mediate the primary inflammatory pleural response in talc-induced pleurodesis.