Rabbit lung after inhalation of manganese chloride: a comparison with the effects of chlorides of nickel, cadmium, cobalt, and copper

Rabbits were exposed to aerosols of MnCl2 (mass median aerodynamic diameter 1 micron) in metal concentrations of 1.1 and 3.9 mg/m3 for 4-6 weeks, 5 days/week, 6 h/day. The effects of alveolar type II cells, phospholipids, alveolar macrophages, and lung structure in general were compared with earlier reported effects of Ni2+, Cd2+, Cu2+, and Co2+. Except for a significant increase in the diameter of the alveolar macrophages after exposure to the higher Mn2+ concentration, no abnormalities were seen. The results of this and earlier studies indicate that these five metal ions have different, specific effects on the alveolar part of the lung.     

Lung morphology and phospholipids after experimental inhalation of soluble cadmium,copper, and cobalt

Rabbits were exposed to chlorides of cadmium, copper, or cobalt, for 4–6 weeks (5 days/week and 6 hr/day) at levels ranging from 0.4 to 0.6 mg metal/m³. After exposure to Cd²⁺ the lungs were enlarged and an interstitial infiltration of neutrophils and lymphocytes as well as intraalveolar accumulations of large, vacuolated macrophages were observed. Morphometrical measurement of volume density of type II cells showed a 2.5-fold increase due to enhancement of cell size as well as cell number. The phospholipid content of lung tissue, determined in the lower left lobe, increased by 40%, mainly due to elevated levels of disaturated phosphatidylcholines. The results indicate that Cd²⁺ induces a reaction pattern similar to that seen following exposure to Ni²⁺, in addition to which Cd²⁺ causes interstitial alveolitis. Exposure to Cu²⁺ and Co²⁺ only affected the type II cells. Exposure to Cu²⁺ resulted in a 1.5-fold increase in volume density, probably due to enhanced number of cells. Following exposure to Co²⁺ the type II cells formed nodules protruding into the alveolar lumen. However, no significant increase in volume density occurred. The possible association between this abnormal growth pattern and early tumor formation deserves further investigation.     

Rabbit alveolar macrophages after inhalation of soluble cadmium,cobalt, and copper: A comparison with the effects of soluble nickel

Rabbits were exposed to aerosols of chlorides of cadmium, copper, and cobalt (0.4–0.6 mg/m³ as metal) for 1 month (5 days/week and 6 hr/day). The effects on alveolar macrophages were compared with earlier reported effects of nickel chloride (0.3 mg/m³ as Ni). Effects of Cd²⁺ exposure resembled those of Ni²⁺ exposure. The number of macrophages in lavage fluid and the variance of cell diameters were thus increased and many cells contained lamellated inclusions. Contrary to macrophages from Ni²⁺-exposed rabbits, the surface of about 50% of the cells had cytoplasmic blebs. However, such cells were rarely seen by scanning electron microscopy. There were significantly more polymorphonucleated neutrophils and small lymphocytes, suggesting lung parenchymal damage. Cells from Cd²⁺-exposed animals, like cells from Ni²⁺-exposed ones, showed an increased oxidative metabolic activity after stimulation with Esherichia coli bacteria. Bactericidal capacity, on the other hand, tended to be enhanced rather than decreased, as in the nickel experiment. After Co²⁺ exposure, the number of macrophages was slightly increased in the lavage fluid and the cells showed an increased metabolic activity both at rest and upon stimulation with bacteria. Cu²⁺ exposure gave a slight increase in lamellated inclusions in the macrophages.     

Lung lesions after combined inhalation of cobalt and nickel

Rabbits inhaled 0.5 mg/m3 Co2+ as CoCl2, a combination of 0.5 mg/m3 Co2+ as CoCl2 and 0.5 mg/m3 of Ni2+ as NiCl2, or filtered air (controls) for 4 months, 5 days/week, 6 hr/day. The pattern of morphological effects on lung tissue and alveolar macrophages after the simultaneous exposure to Co2+ and Ni2+ was a combination of the patterns seen after exposure to Co2+ and Ni2+ alone. However, nickel seemed to potentiate the specific effect of cobalt, i.e., the formation of noduli of type II cells. Further, the increase in phospholipids, especially in 1,2-dipalmitoylphosphatidylcholine, appeared more pronounced after the combined exposure than after the additive combination.     

Mixtures of nickel and cobalt chlorides induce synergistic cytotoxic effects: implications for inhalation exposure modeling.

Workers are often simultaneously exposed to two or more chemicals, yet little is known about the toxicity of most chemical mixtures. The traditional assumption, in the absence of further information, has been that the chemical components of a mixture have mutually independent effects, and the toxic response to multiple chemicals is additive. The data presented here show that mixtures of NiCl(2) and CoCl(2) induce a synergistic (that is, greater than additive) toxic response in cell culture. Immortalized alveolar epithelial type II cells were incubated for 4 h with various concentrations of either NiCl(2), CoCl(2), or NiCl(2) and CoCl(2) together, and cell viability assessed 24 h later. The LD(50) for NiCl(2) was 5.7 mM. CoCl(2), with an LD(50) of 1.1 mM, was about five times more potent than NiCl(2). Mixtures of NiCl(2) and CoCl(2) decreased cell viability synergistically. For example, a mixture of 750 microM NiCl(2) and 750 microM CoCl(2) reduced cell viability by more than three times the value predicted by the additive approach. We used concentration-response data from these studies in a mathematical model; this model describes the equivalent inhalation exposure to an aerosol composed of a mixture of chemicals with different toxicities and also accounts for synergistic responses to these chemicals. Our results along with previous studies using an animal model suggest that these synergisms should be taken into account when conducting future exposure assessments.     

Lysozyme activity in ultrastructurally defined fractions of alveolar macrophages after inhalation exposure to nickel

Rabbits were exposed to 0.6 mg/m3 of nickel as NiCl2 for about one month. After exposure, alveolar macrophages were lavaged from the lung and divided into three fractions by elutriation. Laminated structures in the macrophages were related to fraction number so that the fractions with the largest cells contained the highest number of structures. The lysozyme activity decreased in unfractionated as well as in fractionated macrophages from nickel exposed rabbits. The decrease was most pronounced in the fraction with the smallest macrophages and smallest number of laminated structures. Therefore the pronounced decrease in lysozyme activity seen in this and earlier studies is not caused by the increased amount of surfactant material. Increased amount of surfactant is a hallmark of nickel inhalation exposure and the surfactant material is responsible for the morphological and metabolic effects of the macrophages. The decreased lysozyme activity is probably a direct effect of nickel on the macrophages.     

Lysozyme activity in ultrastructurally defined fractions of alveolar macrophages after inhalation exposure to nickel.

Rabbits were exposed to 0.6 mg/m3 of nickel as NiCl2 for about one month. After exposure, alveolar macrophages were lavaged from the lung and divided into three fractions by elutriation. Laminated structures in the macrophages were related to fraction number so that the fractions with the largest cells contained the highest number of structures. The lysozyme activity decreased in unfractionated as well as in fractionated macrophages from nickel exposed rabbits. The decrease was most pronounced in the fraction with the smallest macrophages and smallest number of laminated structures. Therefore the pronounced decrease in lysozyme activity seen in this and earlier studies is not caused by the increased amount of surfactant material. Increased amount of surfactant is a hallmark of nickel inhalation exposure and the surfactant material is responsible for the morphological and metabolic effects of the macrophages. The decreased lysozyme activity is probably a direct effect of nickel on the macrophages.     

Lead, cadmium, manganese, cobalt, zinc and copper levels in whole blood of urban teenagers with non-toxic diffuse goiter

The amount of lead (Pb), cadmium (Cd), manganese (Mn), cobalt (Co), zinc (Zn), and copper (Cu) present in whole blood of 118 teenagers were determined by atomic absorption spectrometry. The blood samples of 23 healthy teenagers were compared with the blood samples of 95 adolescents who were diagnosed with non-toxic diffuse goiter (NTDG). The study was aimed at examining whether in addition to mild iodine deficiency other trace elements could contribute to the development of non-toxic diffuse goiter. The results indicated that the levels of Pb, Cd and Mn in the blood samples of teenagers diagnosed with NTDG were higher than that in healthy children. Also, the results indicated that higher levels of metals were present in the blood samples with NTDG in adolescent patients who lived in areas with a higher amount of pollution.     

Rabbit lung after inhalation of soluble nickel: II. Effects on lung tissue and phospholipids

Rabbits were exposed to soluble nickel chloride, about 0.3 mg/m³ as nickel, for about 1 month (5 days/week, 6 hr/day). The upper lobe in the left lung was examined with light microscopy and samples from the left lower lobe with electron microscopy. Nodular accumulation of macrophages and laminated structures occurred in alveoli of all exposed rabbits, but otherwise no inflammatory reactions. Volume density of the alveolar epithelial type II cells was doubled due to increased cell number as well as cell volume. The tissue content of phospholipids, determined in the lower lobe of the left lung, had increased by about 40%, mainly due to elevated disaturated phosphatidylcholines. The effect pattern was almost identical to that seen earlier in inhalation experiments with metallic nickel dust, strongly indicating that nickel ions are responsible also for the changes seen after exposure to metallic nickel. This suggests that all nickel compounds may produce the pathological condition, which is similar to that seen in the disease pulmonary alveolar proteinosis.     

Effects of cadmium,cobalt, copper,and nickel on growth of the green alga Chlamydomonas reinhardtii: The influences of the cell wall and pH

Comparative studies of the toxicity of Cd, Co, Cu, and Ni to walled (UTCC 11) and wall-less (UTCC 12) strains of Chlamydomonas reinhardtii were made in order to test the hypothesis that the cell wall affords some protection against metal toxicity. The wall-less strain was consistently more sensitive than the walled strain to all four metals, indicating that the cell wall plays a role in conferring metal tolerance. Between-strain differences were most striking for Cu and for Co. The effect of hydrogen ion concentration (pH 5 and 6.8) on metal toxicity was also determined for the two strains. Having established that both strains grew equally well at pH 5 or 7 in the absence of added metal, it was necessary to correct for the changes in metal speciation due to pH in the medium used for the tests. Speciation of each metal at each pH was determined by mathematical (GEOCHEM) modeling of the medium and the calculated free (ionic) metal concentration was used to express toxicity. In addition, the concentration of ionic metal that reduced final cell density to 30% of that in control solution (EC₃₀) was used as an indicator of relative metal toxicity. For both strains, all metals were less toxic at pH 5 than at pH 7, supporting previous observations. The results are discussed in terms of the possible mechanisms by which the cell wall could protect the cell from metal toxicity, and the relevance of the results to more general considerations of metal tolerance mechanisms in plants.     

Rabbit lung after inhalation of soluble nickel: I. Effects on alveolar macrophages

Alveolar macrophages from eight rabbits, exposed for about 1 month (5 days/week, 6 hr/day) to an aerosol of nickel chloride, 0.3 mg/m³ (as Ni), were studied. The number of macrophages in the lavage fluid and the variance of the cell diameter increased. The macrophages contained laminated structures and most cells had an active cell surface. A few macrophages had a large number of laminated structures and a smooth cell surface. The capacity of the macrophages to reduce nitroblue tetrazolium (NBT) tended to be increased at rest and was significantly increased after stimulation with Escherichia coli. The bactericidal capacity of the macrophages was decreased. The effects were similar to those earlier described after exposure of rabbits for 1 month to about 1 mg/m³ of metallic nickel dust. After exposure both to metallic and soluble nickel the effects are probably caused by an increased amount of surfactant produced by the type II cells in response to nickel ions.     

Reduction of mercury,copper, nickel,cadmium, and zinc levels in solution by competitive adsorption onto peanut hulls,and raw and aged bark

Summary The competitive adsorption of common heavy metal ions by peanut hulls, raw bark, and composted bark was studied. These solid wastes were found to adsorb significant amounts of one or more of the heavy metals (Hg, Cu, Ni, Cd, Zn) commonly found in municipal sludge and wastewater.     

电感耦合等离子体质谱测定尿样中的铍、钴、镉、镍、铊

%,标准物质的元素测定值均在标准值范围之内.结论 本方法可同时测定尿中的Be、Co、Cd、Ni、Tl.     

Distribution of blood lead, blood cadmium, urinary cadmium, and urinary arsenic levels in employees of a copper smelter

A cross-sectional medical examination of a copper smelter work force included determination of blood lead (Pb-B), zinc protoporphyrin (ZPP), blood cadmium (Cd-B), urinary cadmium (Cd-U), and urinary arsenic (As-U), since it was known that such metal impurities were present in the copper concentrate. A total of 776 copper smelter employees (680 active and 96 retirees and ex-employees) were examined. Another 144 men, never employed in the smelter, but who had worked in copper mines (and sometimes in gold mines) were also examined. Mean Pb-B, ZPP, Cd-B, and As-U were significantly higher in active copper smelter employees than in retirees or miners, indicating exposure and absorption in the copper smelter. Significant correlations between Pb-B and Cd-B, and Cd-U and As-U were present, confirming the common source of absorption. Although there was evidence for an increased lead absorption, this was very moderate, with practically no Pb-B levels in excess of 60 micrograms/dl. A marked effect of smoking on blood cadmium levels was present; nevertheless, for all smoking categories Cd-B levels were significantly higher in active employees, indicating the independent contribution of exposure to cadmium in the smelter. Cd-U did not exceed 10 micrograms/g creatinine, the generally accepted "critical" level for the kidney, but was higher than 2 micrograms/g creatinine, a level very rarely exceeded in the general population, in a sizable proportion of those examined. The highest Cd-U levels were found in retired copper smelter employees; age might have been a contributing factor, besides a longer duration of exposure in the smelter.     

Fibronectin concentrations in lung lavage fluid after inhalation exposure to low levels of metals

Groups of rabbits were exposed by inhalation to chlorides of cobalt, nickel, and manganese as well as to tri- and hexavalent chromium at metal concentrations ranging from 0.4 to 3.9 mg/m3 for 1-4 months (5 days/week, 6 hr/day). Fibronectin content and lysozyme (muramidase) activity in lavage fluid were measured after all treatments and in alveolar macrophages after treatment with nickel chloride. In the lavage fluid no marked changes were seen in fibronectin content and lysozyme activity after exposure to tri- or hexavalent chromium or manganese. Nickel exposure significantly decreased the lysozyme activity in the lavage fluid and in the macrophages whereas the fibronectin content was unchanged in the lavage fluid and significantly increased in the macrophages. Both fibronectin content and lysozyme activity were increased markedly in the lavage fluid after cobalt exposure.