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The characteristics of powders used in additive manufacturing can have significant effects on process efficiencies and the quality of the final products. Powder sizes and morphologies need to be optimised for a particular process, and this requires the facilities to perform these measurements as well as provide a quality check on powder batches that are purchased. The establishment of a national powder characterisation facility has been identified by the Titanium Centre of Competence (a DST-funded initiative) as a critical form of support for the development of a South African titanium metal industry. This paper discusses what effect the different powder characteristics can have on the selective laser sintering processes, as well as the state of development of this national facility. [ABSTRACT FROM AUTHOR]

Due to the severe adverse effects that can accompany conventional therapies for Crohn's disease, the search for natural complementary therapies has increased dramatically in recent years. Indole-3-carbinol (I3C), a constituent of cruciferous vegetables, possesses anti-inflammatory properties; however, its effects on intestinal inflammation have yet to be evaluated. To test the hypothesis that I3C dampens intestinal inflammation, C57B1/6 mice were treated with I3C and exposed to 2,4,6-trinitrobenzenesulfonic acid (TNBS) to induce colitis. Several parameters of disease severity and inflammation were subsequently evaluated. I3C dampened the disease severity, as indicated by decreased body weight loss and decreased severity of clinical signs. Interestingly, this effect was observed in female but not male mice, which displayed a trend towards exacerbated colitis. Differential effects were observed in the profiles of cytokine production, as the production of pro-inflammatory cytokines was increased in males. The sex-specific effect of I3C in TNBS-induced colitis is a novel finding and warrants further investigation since this is a common dietary compound and is also available commercially. [ABSTRACT FROM AUTHOR]

There is growing epidemiological evidence for statistical associations between increases in air pollution, especially particulate matter, and increases in cardiovascular morbidity and mortality. Laboratory studies have shown that transition metals contribute strongly to the effects of high lung doses of model particles on changes in the electrocardiograms of animals. The present study evaluated the effects of short-term inhalation exposure to respirable particles of specific oxide and sulfate forms of transition metals on heart rate and the electrocardiogram of old dogs having preexisting cardiac abnormalities. Conscious beagle dogs were exposed by oral inhalation for 3 h on each of 3 successive days to aerosols of manganese, nickel, vanadium, iron, and copper oxides, and nickel and vanadium sulfates as single compounds at concentrations of 0.05 mg/m 3 . Electrocardiograms were recorded and evaluated for exposure-related changes in heart rate, heart rate variability, and abnormalities of waveforms. Although the electrocardiograms of this population of dogs having potential age and cardiovascular susceptibility factors reflected their underlying clinical abnormalities, no significant effect of exposure to the transition metal aerosols was observed. [ABSTRACT FROM AUTHOR]

Carbon tetrachloride is hepatotoxic in rats, mice, and hamsters. However, rats are less sensitive to the hepatotoxic effects of CCl4 than the other two species. The purpose of this study was to compare the uptake, tissue distribution, and elimination of CCl[sub 4] by these three rodent species. Groups of 20 F344/Crl BR rats, B6C3F[sub 1] mice, and Syrian hamsters were exposed by nose-only inhalation for 4 h to 20 ppm [sup 14]C-labeled CCl[sub 4]. The fate of [sup 14]C was followed in tissues, excreta, and exhaled breath for 48 h after the exposure. At the end of the exposure, concentrations of CCl[sub 4] equivalents (CE) in tissue were highest in liver of rats and mice, but highest in fat for rats. The liver received the highest dose of CCl[sub 4] equivalents with the following species ranking: mouse > hamster > rat. Patterns of CE elimination were species and tissue dependent, with the majority of elimination occurring within 48 h after exposure. Rats eliminated less radioactivity associated with metabolism ([sup 14]CO[sub 2], urine and feces) and more radioactivity associated with parent compound (exhaled activity trapped on charcoal) than did mice or hamsters. The results indicate that ranking of species sensitivity to the hepatotoxic effects of inhaled CCl[sub 4] correlates with CE dose to liver and with the ability to metabolize CCl[sub 4]. [ABSTRACT FROM AUTHOR]

No study has comprehensively compared the rate of metabolism of carbon tetrachloride (CCl[sub 4]) across species. Therefore, the in vivo metabolism of CCl[sub 4] was evaluated using groups of male animals (F344 rats, B6C3F[sub 1] mice, and Syrian hamsters) exposed to 40-1800 ppm CCl[sub 4] in a closed, recirculating gas-uptake system. For each species, an optimal fit of the family of uptake curves was obtained by adjusting Michaelis-Menten metabolic constants K [sub m] (affinity) and V [sub max] (capacity) using a physiologically based pharmacokinetic (PBPK) model. The results show that the mouse has a slightly higher capacity and lower affinity for metabolizing CCl[sub 4] compared to the rat, while the hamster has a higher capacity and lower affinity than either rat or mouse. A comparison of the V [sub max] to K [sub m] ratio, normalized for milligrams of liver protein (L/ h/ mg) across species, indicates that hamsters metabolize more CCl[sub 4] than either rats or mice, and should be more susceptible to CCl[sub 4]-induced hepatotoxicity. These species comparisons were evaluated against toxicokinetic studies conducted in animals exposed by nose-only inhalation to 20 ppm 14C-labeled CCl[sub 4] for 4 h. The toxicokinetic study results are consistent with the in vivo rates of metabolism, with rats eliminating less radioactivity associated with metabolism ( 14CO [sub 2] and urine/ feces) and more radioactivity associated with the parent compound (radioactivity trapped on charcoal) compared to either hamsters or mice. The in vivo metabolic constants determined here, together with in vitro constants determined using rat, mouse, hamster, and human liver microsomes, were used to estimate human in vivo metabolic rates of 1.49 mg/ h/ kg body weight and 0.25 mg/ L for V [sub max] and K [sub m], respectively. Normalizing the rate of metabolism ( V [sub ma] / K [sub m]) by milligrams liver protein, the rate of metabolism of CCl[sub 4] differs across species, with[sup x]hamster > mouse > rat > human. [ABSTRACT FROM AUTHOR]

Beryllium/copper (BeCu) alloys are commonly used in the electronics, automotive, consumer, defense, and aerospace industries. Some individuals exposed occupationally to BeCu alloys have developed chronic beryllium disease. However, little is known of the toxicity and fate of BeCu alloys in the respiratory tract. To begin to address this question, we investigated the pulmonary toxicity and clearance of BeCu alloy (2% Be; 98% Cu) in mice. Groups of 40 female C3H/HeJ mice were administered 12.5, 25, and 100 µg BeCu alloy or 2 and 8 µg Be metal by intratracheal instillation. Mice were sacrificed at 1h and 1, 7, 14, and 28 days postinstillation. Left lungs were evaluated for histopathological change. Right lungs were analyzed for Be and Cu content. Twentyfive percent of the high-dose BeCu mice and 7.5% of the mid-dose BeCu mice died within 24h of dosing. Acute pulmonary lesions included acute alveolitis and interstitial inflammation. Type II epithelial cell hyperplasia and centriacinar fibrosis were present by 7 days after dosing. Lesions persisted through 28 days after instillation. No lesions attributable to alloy exposure were present in liver or kidney. Be metal instillation caused no deaths and minimal pulmonary changes over the time studied, indicating that the pulmonary lesions were due to Cu rather than Be. Cu cleared the lung with a half-time of 0.5-2 days. Be cleared with a half-time of several weeks or longer. Results of this study suggest that exposure to BeCu alloy is more acutely toxic to lung than Be metal. The results of tissue analyses also indicate that, while the Cu component of the alloy clears the lung rapidly, Be is retained and may accumulate upon repeated exposure. [ABSTRACT FROM AUTHOR]

Reports the opinion of United States voters on issues related to health care, including health care as an election issue and Medicare. Data and methods; Results; Conclusions.

Butadiene diepoxide (BDO2), a metabolite of 1,3-butadiene (BD) and potent mutagen, is suspected to be a proximate carcinogen in the multisite tumorigenesis in B6C3F1 mice exposed to BD. Rats, in contrast to mice, do not form much BDO2 when exposed to BD, and they do not form cancers after exposure to the low levels of BD at which mice develop lung and heart tumors. Tests were planned to determine the direct carcinogenic potential of BDO2 in similarly exposed rats and mice, to see if they would develop tumors of the lung (the most sensitive target organ in BD-exposed mice) or other target tissues. The objective of the current series of studies was to assess the acute toxicity and dosimetry to blood and lung of BDO2 administered by various routes to B6C3F1 mice and Sprague-Dawley rats. The studies were needed to aid in the design of the carcinogenesis study. Initial studies using intraperitoneal injection of BDO2 were designed to determine the rate at which each of the species cleared the compound from the body; the clearance was equally fast in both species. A second study was designed to determine if the highly reactive BDO2, when deposited in the lung, would enter the bloodstream from the lung; intratracheally instilled BDO2 did enter the bloodstream, indicating that exposure via the lungs would result in BDO2 reaching other organs of the body. In a third study, rats and mice were exposed by inhalation for 6 h to 12 ppm BDO2 to determine blood and lung levels of the compound. Concentrations of BDO2 in the lung immediately after the exposure were 2 to 3 times higher than in the blood in both species (approximately 500 and 1000 pmol/g blood in the rat and mouse, respectively). As expected, mice received a higher dose/g tissue than did rats, consistent with the higher minute volume/kg body weight of the mice. The inhalation dosimetry study was followed by a histopathology study to determine the acute toxicity to rodents following a single, 6-h exposure to 18 ppm BDO2. No clinical signs of toxicity were observed; lesions were confined to the olfactory epithelium where areas of necrosis were observed. Analysis of bronchoalveolar lavage fluid did not indicate pulmonary inflammation. Based on these findings, an attempt was made to expose rats and mice repeatedly (for 7 days) to 10 and 20 ppm BDO2, but these exposure concentrations proved too toxic, due to inflammation of the nasal mucosa and occlusion of the nasal airway, a lesion that cannot be tolerated by obligate nose breathers. Finally, the toxicity of rats and mice exposed 6 h/day for 5 days to 0. 2.5, or 5.0 ppm BDO2 was determined. The repeated exposures caused no clinical signs of toxicity, nor were any lesions observed in the respiratory tract or other major organs. Therefore, the final design selected for the carcinogenesis study comprised exposing the rats and mice for 6 h/day, 5 days/week for 6 weeks to 0, 2.5, or 5.0 ppm BDO2. [ABSTRACT FROM PUBLISHER]

Ferrocene (dicyclopentadienyl iron; CAS No. 102-54-5) is a relatively volatile compound used as a chemical intermediate, a catalyst, and an antiknock additive in gasoline. This organometallic chemical is of particular interest because of its structural similarities to other metallocenes, some of which are carcinogenic. F344/N rats and B6C3F mice were exposed to 0, 3.0, 10, and 30 mg ferrocene vapor/m, 6 hr/day, 5 days/week, for 13 weeks. During these exposures, no rats or mice died, nor were any clinical signs of ferrocene-related toxicity observed. At the end of the exposures, male rats exposed to the lowest and highest level of ferrocene had decreased body weight gains compared to filtered-air-exposed control male rats, while body weight gains for all groups of both ferrocene- and filtered-air-exposed female rats were similar. Male mice exposed to ferrocene had no differences in body weight gains, compared to controls, but female mice had decreases in body weight gains at the 10 and 30 mg/m exposure levels. There were exposure concentration- and exposure-time-related increases in lung burdens of iron. The mean iron lung burden in rats exposed to 30 mg ferrocene vapor/m for 90 days was four times greater than the burden in control rats. No exposure-related changes in respiratory function, lung biochemistry, bronchoalveolar lavage cytology, total lung collagen, clinical chemistry, and hematology parameters were observed. This suggests that the accumulations of iron in lung did not cause an inflammatory response nor any functional impairment of the lung. There were no indications of developing pulmonary fibrosis nor of any hematologic toxicity. No exposure-related gross lesions were seen in any of the rats or mice at necropsy. Exposure-related histopathologic alterations, primarily pigment accumulations, were observed in the nose, larynx, trachea, lung, and liver of both species, and in the kidneys of mice. Lesions were most severe in the nasal olfactory epithelium where pigment accumulation, necrotizing inflammation, metaplasia, and epithelial regeneration occurred. Nasal lesions were observed in all ferrocene-exposed animals and differed only in severity, which was dependent on the exposure concentration. Histochernical stains of these target tissues showed the presence of iron ions. The results suggest that the mechanism of ferrocene toxicity may be the intracellular release of ferrous ion through ferrocene metabolism, followed by either iron-catalyzed lipid peroxidation of cellular membranes or the iron-catalyzed Fenton reaction to form hydroxyl radicals that directly react with other key cellular components, such as protein or DNA. [ABSTRACT FROM PUBLISHER]

Lung Toxicity after 13-Week Inhalation Exposure to Nickel Oxide, Nickel Subsulfide, or Nickel Sulfate Hexahydrate in F344/N Rats and B6C3F Mice. DUNNICK, J. K., ELWELL, M. BENSON, J. M., HOBBS, C. H., HAHN, F. F., HALY, P. J., CHENG, Y. S., AND EIDSON, A. F. (1989). . 12, 584–594. The relative toxicity of nickel oxide (NiO), nickel sulfate hexahydrate (NiSO6HO) and nickel subsulfide (NiS) was studied in F344/N rats and B6C3F mice after inhalation exposure for 6 hr/day, 5 days/week, for 13 weeks. Exposure concentrations used (as mg Ni/m were 0.4–7.9 for NiO, 0.02–0.4 for NiSO 6HO and 0.11–1.8 for NiS. No exposure-related effects on mortality and only minor effects on body weight gain were seen in rats or mice. The most sensitive parameter for nickel toxicity was histopatho logic change in the lungs of exposed animals where chronic active inflammation, fibrosis, and alveolar macrophage hyperplasia werez associated with nickel exposure. There was an exposure- related increase in lung weight in rats and mice. Equilibrium levels of nickel in the lung were reached by 13 weeks of nickel sulfate and nickel subsulfide exposure, whereas lung levels of nickel continued to increase throughout exposure to nickel oxide. Additional exposure-related histopathologic lesions in treated animals included atrophy of the olfactory epithelium after nickel sulfate and nickel subsulfide exposure. No nasal lesions were seen after nickel oxide expo sure. Lymphoid hyperplasia of the bronchial lymph nodes developed in animals exposed to all three nickel compounds. The order oftoxicity corresponded to the water solubility of the nickel compounds, with nickel sulfate being most toxic, followed by nickel subsulfide and nickel oxide. [ABSTRACT FROM PUBLISHER]

Response of Rodents to Inhaled Diluted Diesel Exhaust: Biochemical and Cytological Changes in Bronchoalveolar Lavage Fluid and in Lung Tissue. HENDERSON, R. F., PICKRELL, J. A., JONES, R. K., SUN, J. D., BENSON, J. M., MAUDERLY, J. L., AND MCCLELLAN, R. O. (1988). . 11, 546-567. The effect of long-term (24 months) inhalation of diesel exhaust on the bronchoalveolar region of the respiratory tract of rodents was assessed by serial (every 6 months) analysis of bronchoalveolar lavage fluid (BALF) and of lung tissue from F344/Crl rats and CD-I mice (both sexes) exposed to diesel exhaust diluted to contain 0, 0.35, 3.5, or 7.0 mg soot/m. The purpose of the study was twofold. One was to assess the potential health effects of inhaling diluted exhaust from light-duty diesel engines. The second was to determine the usefulness of BALF analysis in detecting the early stages in the development ofnonon-cogenic lung disease and differentiating them from the normal repair processes. No biochemical or cytological changes in BALF or in lung tissue were noted in either species exposed to the lowest, and most environmentally relevant, concentration of diesel exhaust. In the two higher levels of exposure, a chronic inflammatory response was measured in both species by dose-dependent increases in inflammatory cells, cytoplasmic and lysosomal enzymes, and protein in BALF. Histologically, after 1 year of exposure, the rats had developed focal areas of fibrosis associated with the deposits of soot, while the mice, despite a higher lung burden of soot than the rats, had only a fine fibrillar thickening of an occasional alveolar septa in the high-level exposure group. Higher increases in BALF β-glucuronidase activity and in hydroxyproline content accompanied the greater degree of fibrosis in the rat BALF levels of glutathione (GSH) and glutathione reductase activity increased in a dose-dependent fashion and were higher in mice than in rats. Lung tissue GSH was depleted in a dose-dependent fashion in rats but was slightly increased in mice. This depletion may have played a role in the greater fibrogenic response observed in rats. Other tissue changes in enzymatic activity were small compared to changes observed in BALF. The exposure did not increase the cytochrome P-450 content of the lung in either species. The results suggest that, for the noncarcinogenic health effects reported in this paper, there is a threshold of exposure below which adverse effects were not observed. This threshold was well above environmentally relevant levels of diesel exhaust but may be in the range of some occupational exposures. The analysis of BALF proved a useful adjunct to the chronic toxicity study to quantitate the inflammatory changes accompanying the development of pulmonary disease. [ABSTRACT FROM PUBLISHER]

New Approaches for the Evaluation of Pulmonary Toxicity: Bronchoalveolar Lavage Fluid Analysis. Henderson, R. F., BENSON, J. M., HAHN, F. F., HOBBS, C. H., JONES, R. K., MAUDERLY, J. L., MCCLELLAN, R. O., AND PICKRELL, J. A., (1985). . 5, 451–458. Analysis of bronchoalveolar lavage fluid (BAL) is an effective method of detecting an inflammatory response in the lungs of animals in toxicological studies. Alterations in BAL that are the most sensitive indications of an inflammatory response are an increased content of serum proteins and an influx of neutrophils (PMNs). Elevation of the cytoplasmic enzyme lactate dehydrogenase (LDH) is a useful indicator of cytotoxicity. The pulmonary inflammatory response to particles (either mineral dusts or soot) in the lung includes greatly increased activities of such lysosomal enzymes as β-glucuronidase and β--acetylglucosaminidase in BAL. Examination of alterations in BAL in rats and mice during chronic exposure to high levels of diluted diesel exhaust revealed that steadily increasing levels of LDH, β-glucuronidase, and hydroxyproline in BAL correlated better with the development of pulmonary fibrosis than did measures of an inflammatory response (protein, PMNs). Analysis of BAL has proven useful, both for detection of lung injury in toxicological screening tests and for determination of the mechanisms of developing chronic lung disease. Future work shows promise of developing assays for BAL analysis to identify the specific site or type of pulmonary injury present [ABSTRACT FROM PUBLISHER]