Carcinogenicity of Poorly Soluble Low Toxicity Particles: Commentary on Epidemiology as a Risk Assessment "Reality Check".

Inhaled particles that are poorly soluble or insoluble and of low toxicity ("poorly soluble low toxicity" or "PSLT" particles), can accumulate in the lung and at lung overload levels induce lung cancers in rats. The question of whether PSLT particles increase lung cancer risk in humans is complicated by large differences between rats and humans and the relatively large particle doses administered in animal studies even when compared with heavy human occupational exposures. We review the findings of epidemiological studies on occupational exposure to each of three different PSLT particles (carbon black, talc and taconite). The epidemiological evidence indicates that at even very high occupational exposure levels at which non-malignant respiratory diseases including pneumoconiosis and even talcosis are observed, lung cancer risks appear not to be elevated. Although positive human cancer risks might be predicted based on extrapolation from overload doses in rats to relevant exposures in humans, the epidemiological "reality check" based on the three examples indicates that these PSLT particles are unlikely to increase lung cancer risk in humans even at high occupational levels of exposure. Therefore, we propose that careful evaluation of the epidemiological evidence can serve as a "reality check" for human risk assessment and help balance the risk evaluation process.

Does Sericin, as a Novel Pleurodesis Agent, Have Higher Effectiveness Compared to Talcum Powder, Doxycycline, and Silver Nitrate Pleurodesis?

INTRODUCTION: The usefulness of sericin as pleurodesis agent has previously been described. Present study aims to compare sericin pleurodesis regarding success, effectiveness, tolerability, and side-effects. METHODS: Adult, 12-week-old Wistar-albino rats (n=60), divided to five groups as sericin, talcum-powder, doxycycline, silver-nitrate and control. Agents were administrated through left thoracotomy, rats sacrificed twelve-days after. RESULTS: Highest ratio of collagen fibers was observed in sericin group, and the intensity was higher than talcum-powder group (p<0.05). Compared to silver nitrate, sericin group displayed better mesothelial reaction, and multi-layer mesothelium was also better (p<0.05). Foreign body reaction and emphysema were less frequent in sericin group (p<0.05). The presence of biological tissue in parenchyma was less prominent in sericin group (p<0.05). Foreign body reaction on thoracic wall was less common in sericin group (p<0.05). Presence of biological tissue glue in thoracic wall was less prominent in sericin group (p<0.05). Glomerular degeneration was lower in sericin group compared to the silver nitrate group (p<0.05), and tubular degeneration was less common in sericin group than talcum group (p<0.05). Pericarditis was less common in sericin group compared to the other groups (p<0.05). CONCLUSION: As an intrinsic, natural glue protein, sericin protects the lung parenchyma and tissues, and its glue-like characteristics enable pleurodesis. The success of sericin in pleurodesis was demonstrated in the present study based on investigations of the pleurae. Being cost-effective and better tolerated agent associated with a low potential of side effects, sericin is more effective, less expensive and provides more lung parenchyma protection.

Assessment of Health Risk from Historical Use of Cosmetic Talcum Powder.

This study's objective is to assess the risk of asbestos-related disease being contracted by past users of cosmetic talcum powder.  To our knowledge, no risk assessment studies using exposure data from historical exposures or chamber simulations have been published. We conducted activity-based sampling with cosmetic talcum powder samples from five opened and previously used containers that are believed to have been first manufactured and sold in the 1960s and 1970s.  These samples had been subject to conflicting claims of asbestos content; samples with the highest claimed asbestos content were tested.  The tests were conducted in simulated-bathroom controlled chambers with volunteers who were talc users.  Air sampling filters were prepared by direct preparation techniques and analyzed by phase contrast microscopy (PCM), transmission electron microscopy (TEM) with energy-dispersive x-ray (EDX) spectra, and selective area diffraction (SAED).  TEM analysis for asbestos resulted in no confirmed asbestos fibers and only a single fiber classified as "ambiguous."  Hypothetical treatment of this fiber as if it were asbestos yields a risk of 9.6 × 10-7 (under one in one million) for a lifetime user of this cosmetic talcum powder.  The exposure levels associated with these results range from zero to levels far below those identified in the epidemiology literature as posing a risk for asbestos-related disease, and substantially below published historical environmental background levels.  The approaches used for this study have potential application to exposure evaluations of other talc or asbestos-containing materials and consumer products.

Safety Assessment of Talc as Used in Cosmetics.

The Cosmetic Ingredient Review Expert Panel (Panel) assessed the safety of talc for use in cosmetics. The safety of talc has been the subject of much debate through the years, partly because the relationship between talc and asbestos is commonly misunderstood. Industry specifications state that cosmetic-grade talc must contain no detectable fibrous, asbestos minerals. Therefore, the large amount of available animal and clinical data the Panel relied on in assessing the safety of talc only included those studies on talc that did not contain asbestos. The Panel concluded that talc is safe for use in cosmetics in the present practices of use and concentration (some cosmetic products are entirely composed of talc). Talc should not be applied to the skin when the epidermal barrier is missing or significantly disrupted.

Lucigenin chemiluminescence assay as an adjunctive tool for assessment of various stages of inflammation: a study of quiescent inflammatory cells.

A simple, fast, precise and biologically relevant toxicity assay for screening cytotoxicity of minerals would have distinct advantages due to its cost benefits and relative savings in time. Furthermore, a bioassay to differentiate acute and chronic in vivo pulmonary reactions could have potential value as predictors of fibrogenicity and pathogenicity. In this study we examined the potential use of lucigenin as a probe to evaluate the correlation between chemiluminescence (CL) generated by alveolar macrophages with the known cytotoxicity and patho genicity by conventional bioassays. In this study, we used small doses of dust (20 microg) to minimize cellular overload and to maintain homeostasis. Crystalline silica a highly fibrogenic dust was used as positive control and results are compared with those for bentonite, kaolin and talc. Among the three minerals compared with silica, bentonite was more reactive (27%) in CL assay and declined sharply compared to other minerals. This sudden decline in bentonite CL is caused by cytotoxicity leading to cell death. CL-induced by talc was comparable to silica and declines slowly. Kaolin on the other hand produced relatively a weaker (25%) CL compared to silica. Our data using relatively low doses of dust suggest that the CL assay may have a better predictive value in cytotoxicity evaluations compared to conventional toxicity assays.

The relevance of the rat lung response to particle overload for human risk assessment: a workshop consensus report.

On 23-24 March 1998, the International Life Sciences Institute (ILSI) Risk Science Institute convened a workshop entitled "Relevance of the Rat Lung Response to Particle Overload for Human Risk Assessment." The workshop addressed the numerous study reports of lung tumors in rats resulting from chronic inhalation exposures to poorly soluble, nonfibrous particles of low acute toxicity and not directly genotoxic. These poorly soluble particles, indicated by the acronym PSPs (e.g., carbon black, coal dust, diesel soot, nonasbestiform talc, and titanium dioxide), elicit tumors in rats when deposition overwhelms the clearance mechanisms of the lung resulting in a condition referred to as "overload." These PSPs have been shown not to induce tumors in mice and hamsters, and the available data in humans are consistently negative. The objectives were twofold: (1) to provide guidance for risk assessment on the interpretation of neoplastic and nonneoplastic responses of the rat lung to PSPs; and (2) to identify important data gaps in our understanding of the lung responses of rats and other species to PSPs. Utilizing the five critical reviews of relevant literature that follow herein and the combined expertise and experience of the 30 workshop participants, a number of questions were addressed. The consensus views of the workshop participants are presented in this report. Because it is still not known with certainty whether high lung burdens of PSPs can lead to lung cancer in humans via mechanisms similar to those of the rat, in the absence of mechanistic data to the contrary it must be assumed that the rat model can identify potential carcinogenic hazards to humans. Since the apparent responsiveness of the rat model at overload is dependent on coexistent chronic active inflammation and cell proliferation, at lower lung doses where chronic active inflammation and cell proliferation are not present, no lung cancer hazard is anticipated.