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PubMedDate not supplied

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.

Administration, Inhalation↗
PubMed1989

Dust inhalation exposures from the handling of small volumes of powders.

Worker exposure to airborne particulates was stimulated in a laboratory under controlled conditions. Small volumes, 3.8 L (1 gal.), of finely divided powders were transferred at 1-min intervals to 23-L (6-gal.) containers over 30-min time intervals. A high-volume filter array in the exit vent of the specially designed exposure laboratory was used both to control the ventilation rate and to determine the emission factor of the pouring operation. The room ventilation rate, method of transfer, and drop height were varied, and the resulting particulate concentrations were monitored by personal and area samplers. The four powders studied were talc, sodium chloride, Portland cement, and Direct Yellow 4 dye. Based on this study, a model was developed to predict potential worker exposure from the pouring of small volumes of powders. The model is based on the following major conclusions. First, the space- and time-averaged concentration of suspended particulate matter at breathing height agrees well with the mean concentration of suspended particulate matter in the room air effluent. Second, material-specific suspended particulate emission factors vary approximately in direct proportion to the drop height. Third, emission factors for scooping/dumping operations agree well with factors for pouring operations for a given drop height. Fourth, emission factors compare well with dustiness indexes that were determined using a bench-scale dustiness test chamber described in a companion paper. Parameters of the exposure model include dustiness index, drop height of the pouring operation, total quantity of material poured, averaging time, and the fraction of respirable material. For the validation of the model, additional data would be necessary.

Air Pollutants, Occupational↗
PubMedDate not supplied

Laboratory and field testing of particle size-selective sampling methods for mineral dusts.

The performances of eight sampling devices were tested with mineral dusts in the laboratory and in a talc production plant. The IOM sampler was chosen as the reference method for inhalable dust, and the IOM samplers provided with the porous plastic foam media were used as the reference methods for both the thoracic and respirable aerosols. The other size-selective instruments tested included the Respicon virtual impactor, the optical GRIMM aerosol monitor, and a two-stage cascade impactor with cut points of 10 and 4 microm. The 37-mm cassettes were also included both as open- and closed-face versions. The study confirmed the usability of the IOM samplers for mineral dust, not only in its original version for the inhalable fraction but also its modified versions for the thoracic and respirable fractions. A high correlation with the two-stage impactor results is an indication of good reproducibility. The results increased the evidence that the 37-mm cassette is a poor indicator of inhalable aerosol. The concentrations obtained with both cassette methods were not only systematically too low but also showed large collection efficiency variability. Therefore, the results cannot be corrected by using correction factors. The concentrations of inhalable aerosol measured with the Respicon were generally low, but its performances for the thoracic and respirable fractions were closer to those for the reference samplers. The results also indicate that the GRIMM monitor is well-suited for such mineral dust determinations when very good accuracy is not required, but the immediate availability of the result is more important.

Air Pollutants, Occupational↗
PubMed1981

Infantile pulmonary hypertension associated with foreign body vasculitis.

An infant dying with pulmonary hypertension had a pulmonary vessel foreign body vasculitis as identified by light microscopy and characterized ultrastructurally by scanning electron microscopy and energy-dispersive x-ray analysis. The inclusions were of two distinct types: those containing silicon and titanium, and others consisting of talc. The possible sources of these inclusions and the importance of considering foreign body vasculitis in the pathogenesis of clinically idiopathic pulmonary hypertension are discussed.

Humans↗
PubMed2001

Risk factors for uterine leiomyoma: a practice-based case-control study. II. Atherogenic risk factors and potential sources of uterine irritation.

In this case-control study, the authors analyzed associations of uterine leiomyoma with atherogenic risk factors and potential sources of uterine irritation. The study included 318 case women with uterine leiomyoma that was first confirmed between 1990 and 1993 in the Baltimore, Maryland, area and 394 controls selected from women visiting the same gynecologists' offices for routine reasons. Telephone interviews were conducted with 77.8% of eligible cases and 78.0% of eligible controls. Compared with participants with no hypertension history, increased risks were observed among participants with any history of hypertension (odds ratio (OR) = 1.7; 95% confidence interval (CI): 1.0, 2.8), hypertension requiring medication (OR = 2.1; 95% CI: 1.1, 4.1), hypertension diagnosed at ages less than 35 years (for hypertension requiring medication, OR = 2.7; 95% CI: 1.0, 7.6), and hypertension of 5 or more years' duration (for hypertension requiring medication, OR = 3.1; 95% CI: 1.2, 8.2). Estimates of associations with diabetes history were very imprecise but followed similar patterns. Adjusted associations were observed with pelvic inflammatory disease (three or more episodes vs. none: OR = 3.7; 95% CI: 0.9, 15.9), chlamydial infection (history vs. no history: OR = 3.2; 95% CI: 0.8, 13.7), and use of an intrauterine device when it caused infectious complications (use vs. no use: OR = 5.3; 95% CI: 1.8, 16.3). Risk of uterine leiomyoma was also associated in a graded fashion with frequency of perineal talc use (daily use vs. no use: OR = 2.2; 95% CI: 1.4, 3.1). The authors conclude that nonhormonal factors may influence risk of uterine leiomyoma.

Adolescent↗
PubMed1999

Possible role of ovarian epithelial inflammation in ovarian cancer.

Ovarian cancer is a commonly fatal disease for which prevention strategies have been limited, in part because of a lack of understanding of the underlying biology. This paper reviews the epidemiologic literature in the English language on risk factors and protective factors for ovarian cancer and proposes a novel hypothesis that a common mechanism underlying this disease is inflammation. Previous hypotheses about the causes of ovarian cancer have attributed risk to an excess number of lifetime ovulations or to elevations in steroid hormones. Inflammation may underlie ovulatory events because an inflammatory reaction is induced during the process of ovulation. Additional risk factors for ovarian cancer, including asbestos and talc exposure, endometriosis (i.e., ectopic implantation of uterine lining tissue), and pelvic inflammatory disease, cannot be directly linked to ovulation or to hormones but do cause local pelvic inflammation. On the other hand, tubal ligation and hysterectomy act as protective factors, perhaps by diminishing the likelihood that the ovarian epithelium will be exposed to environmental initiators of inflammation. Inflammation entails cell damage, oxidative stress, and elevations of cytokines and prostaglandins, all of which may be mutagenic. The possibility that inflammation is a pathophysiologic contributor to the development of ovarian cancer suggests a directed approach to future research

Asbestos↗
PubMed1988

Analysis of excess lung cancer risk in short-term employees.

An excess of lung cancer found in a cohort of 741 New York State tremolitic talc workers observed from 1947 through 1978 has been shown paradoxically to be concentrated in short-term workers. Review of past work histories suggests that the excess of lung cancer in these short-term workers may be accounted for by prior exposures rather than by exposures at the employment under investigation. This finding has significant implications in view of the developing practice of including short-term workers in occupational cohort studies in contrast to the more traditional practice of excluding short-term workers. The traditional practice was based on the assumption that the inclusion of short-term workers with little exposure, and thus little risk, might dilute an otherwise apparent association between mortality and exposure. This study suggests that in certain instances the inclusion of short-term workers may magnify rather than dilute the estimation of risk, reflecting the presence of confounding variables.

Adult↗
PubMed1981

Complications of knee joint arthroscopy.

Two iatragenic complications, granuloma formation in the fat pad, and fat pad herniation through the extensor fascia, occurred in a 20-year-old woman and a 50-year-old man. Granuloma formation may be induced by deposits of talc in the fat pad. Fat pad excisional surgery and repair of the hernia are generally effective.

Adult↗
PubMed1993

Precocious emphysema in intravenous drug abusers.

It is becoming increasingly clear that obstructive airway disease and early emphysema occur in some drug addicts who intravenously abuse drugs intended for oral use. We report four patients with such a history who had clinical, pathophysiologic, and radiologic evidence of severe obstructive airway disease with hyperinflation. Three patients had bullae. All had radiologic changes of intravenous talc granulomatosis. One patient had moderately severe emphysema at autopsy. The pathogenesis of this disease is uncertain but may involve synergism with cigarette smoke, direct toxic effects of the drug, or induced intravascular leukocyte sequestration causing proteolytic pulmonary injury.

Adult↗
PubMed2001

Epidemiology of ovarian cancer: a summary review.

Ovarian cancer is among the five leading sites for cancer incidence and mortality in women from developed countries. Its incidence and mortality rates have, however, been declining over the last few decades following the introduction of oral contraceptives, which - together with parity - are the best recognized protective factor for the disease. Late menopause and irregular menstrual cycles may also reduce the risk, while the role of hormone replacement therapy in menopause and fertility treatments is still unclear. Cosmetic talc use and some aspect of diet (i.e. saturated fats, refined carbohydrates) have been associated with increased risk, in some--though not all--studies), while vegetable consumption appears to be inversely related to risk. These issues remain open to debate. Women with a family history of ovarian and breast cancer in first-degree relatives are also at increased risk, but family history accounts for only 4-5% of cases. Most ovarian cancers are therefore environmental in origin and consequently, at least in principle, avoidable.

Adult↗
PubMed1996

Uncommon causes of occupational interstitial lung diseases.

Uncommon causes of occupational interstitial lung disease, or pneumoconiosis, are being increasingly recognized and diagnosed. The fibrogenic potential of numerous types of respirable inorganic particles remains poorly understood but is significantly determined by lung deposition and clearance, the agent's size and solubility, host susceptibility, and other factors. Microanalytic techniques have improved the identification of uncommon or unusual biopersistent particles or elements in fibrotic lung tissue. Recent findings in workers exposed to manmade vitreous fibers, silicon carbide, talc, titanium, cerium, and polyvinyl chloride provide new clinical insights into not only their specific fibrogenic capabilities but also in the broader appreciation that many cases of unexplained interstitial lung disease may be caused by occupational exposures to one or more uncommon airborne substances.

Air Pollutants, Occupational↗
PubMed2004

Pneumothorax.

Spontaneous pneumothoraces can occur without obvious underlying lung disease (primary) or in patients with known underlying lung disease (secondary). Management guidelines for spontaneous pneumothorax have been published by major professional organizations, but awareness and application among clinicians seems poor. First episodes of primary spontaneous pneumothorax can be managed with observation if the pneumothorax is small. If the pneumothorax is large or if the patient is symptomatic, manual aspiration via a small catheter or insertion of a small-bore catheter coupled to a Heimlich valve or water-seal device, should be performed. In general, definitive measures to prevent recurrence are recommended after the first recurrence of the pneumothorax, and can be achieved by medical (e.g. talc) or surgical (video-assisted thoracic surgery) pleurodesis. Secondary pneumothoraces should be treated with chest tube drainage followed by pleurodesis after the first episode to minimize any risk of recurrence. Traumatic pneumothoraces may be occult (not seen on an initial CXR) or non-occult. The majority are treated by placement of a chest tube. Selected patients may be treated conservatively, with approximately 10% of these patients eventually requiring chest tube placement. Iatrogenic pneumothoraces have a myriad of causes with transthoracic lung needle biopsy being most common. Transthoracic needle biopsy-related pneumothoraces have CT findings that can predict their occurrence and the need for chest tube placement. Iatrogenic pneumothoraces, regardless of cause, may be managed by observation or small bore chest tube placement, depending upon patient stability and the size of the pneumothorax.

Algorithms↗
PubMed1993

Thoracoscopy: a useful diagnostic and therapeutic procedure.

This study was performed to review the place of thoracoscopy in the diagnosis and treatment of intrathoracic disorders. A combined retrospective and prospective review was undertaken of the first 50 patients who underwent diagnostic or therapeutic thoracoscopy in Ballarat. Recurrent pleural effusions (29), pneumothoraces (7), or diffuse or localized lung disease (14) were the main indications. Thoracoscopy was performed in conjunction with pleural or lung biopsy, excision of cysts, or pleurodesis. Patient tolerance of the procedure was excellent with minimal postoperative pain. Operative morbidity rates were very low (< 4%). The low mortality rate was related to underlying disease processes. Hospital stay was short. The long-term results were excellent. Adequate tissue was obtained on biopsy in most cases, cure achieved for pneumothoraces, and permanent palliation after talc pleurodesis for malignant effusions approached 80%.

Adult↗
PubMed1980

Influence of the sterilization method and of magnesium oxide on the tissue responses in the rat to modified starch glove powders.

The tissue response to samples of a surgical glove powder was assessed from counts of the adhesions and granulomas found 7 and 14 days after introduction into the peritoneal cavity of rats, and by a histological study of affected tissues. Negative control groups treated with no powder and positive controls treated with talc were included. Various sample treatments were implemented to examine the effect of the sterilization method on the tissue response and the influence of magnesium oxide, normally added as a dispersing agent. The glove powder produced less reaction when steam-sterilized than when gamma-irradiated and the presence of magnesium oxide at 2% concentration made no detectable difference.

Animals↗
PubMed1985

Stress crack resistance of some pigmented and unpigmented tablet film coating systems.

Stress crack resistance parameters--tensile strength: Young's modulus ratio, relative surface energy, and toughness index--have been examined for unpigmented free films of hydroxypropyl methylcellulose containing polyvinyl alcohol, and polyethylene glycols 400 and 1000, as well as similar film systems pigmented with either talc or titanium dioxide. Incorporation of either polyvinyl alcohol or polyethylene glycols 400 and 1000 in hydroxypropyl methylcellulose film coatings eliminated the incidence of edge splitting in the coated tablets. Increase in pigment concentration generally led to a decrease in the crack resistance of pigmented films. There was a relation between the stress crack resistance of pigmented free films and the incidence of edge splitting of corresponding film coatings applied to aspirin tablets--generally, the higher the crack resistance the lower the incidence of edge splitting. A similar relationship applied to the unpigmented films only when the tensile strength: Young's modulus ratio was considered.

Aspirin↗
PubMed1985

Tensile anisotropy of some pigmented tablet film coating systems.

The tensile properties of representative tablet film coating systems, containing hydroxypropyl methylcellulose alone and in combination with either polyvinyl alcohol, polyethylene glycol 400 and polyethylene glycol 1000 and pigmented with either talc or titanium dioxide, have been investigated. Tensile anisotropy was observed between film samples cut parallel to, and perpendicular to, the direction of rotation of the casting substrate and factors accounting for this phenomenon are presented.

Chemistry, Pharmaceutical↗
PubMed1998

Resistance to densification, tensile strength and capsule-filling performance of some pharmaceutical diluents.

The purpose of this study was to compare some indicators of capsule-filling performance, as measured by tapped density under different conditions, and elucidate possible quantitative relationships between variation of capsule fill-weight (%CV) and gravitational and inter-particle forces (attractive or frictional) derived from measurements of particle size, true density, low compression and tensile strength. Five common pharmaceutical diluents (lactose, maize starch, talc, Emcocel and Avicel) were investigated and two capsule-filling methods (pouring powder and dosator nozzle) were employed. It was found that for the pouring-type method the appropriateness of Hausner's ratio (HR), Carr's compressibility index (CC%) and Kawakita's constant (alpha) as indicators of capsule fill-weight variation decreases in the order alpha > CC% > HR; the appropriateness of these indicators also decreases with increasing cylinder size and with impact velocity during tapping. For the dosator-type method the appropriateness of the indicators decreases in the order HR > CC% > alpha, the opposite of that for the pouring-type method; the appropriateness of the indicators increases with decreasing cylinder size and impact velocity. The relationship between %CV and the ratio of inter-particle attractive to gravitational forces calculated from measurements of particle size and true density (Fvdw/Wp) was more significant for the pouring-type capsule-filling method. For the dosator-type method a significant relationship (1% level) was found between %CV and the product of Fvdw/Wp and a function expressing the increase, with packing density (p(f)), in the ratio of frictional to attractive inter-particle forces derived from compression (P) and tensile-strength (T) testing, d(log(P/T))/d(p(f)). The value of tapped density in predictions of capsule-filling performance is affected by the testing conditions in a manner depending on the filling method applied. For the pouring-type method predictions can be based on the ratio of attractive (inter-particle) to gravitational forces, whereas for the dosator-type method the contribution of frictional and attractive forces should, because of packing density change, also be taken into account.

Capsules↗