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Biomedical subjects

F Serita

Publications and source records attributed to F Serita.

12 recordsLinked to original sources

Acute biological effects of intratracheally instilled titanium dioxide whiskers compared with nonfibrous titanium dioxide and amosite in rats.

The dimensions of man-made mineral fiber whiskers are similar to those of some kinds of asbestos. Thus these mineral fibers raise the concern for potential health hazard for workers exposed in the occupational environments. This study was designed to define acute biological effects of intratracheally administered titanium dioxide whiskers (TO1) compared with nonfibrous titanium dioxide (TOP) and UICC amosite (Ams), and their relations to acute lung inflammation in rats. The observed geometric mean length (microm) and width (microm) and geometric standard deviation are: TO1(2.1[2.0], 0.14[1. 53]); Ams (4.3[3.3], 0.31[1.9]); and TOP (50 nm, 1-2 microm aggregates). Ten-week-old Wistar-Jcl male rats received a single tracheal injection of test materials at doses between 0.05 and 1.0 mg/rat. Control animals were injected with the same volume of saline. Lung tissue and bronchoalveolar lavage (BAL) fluid were collected from rats on days 1, 3, and 7 after administration. In the group injected with TO1, total protein, cytokine-induced neutrophil chemoattractant (CINC)/growth-regulated gene product (GRO), interleukin (IL) 1beta, and tumor necrosis factor (TNF) alpha increased on day 1. Subsequently, total elastolytic activity and fucose levels in BAL increased by day 3. All parameters, except for fucose in BAL, recovered to the normal levels. Animals in the Ams group showed increased total protein and CINC/GRO and decreased total elastolytic activity in a dose-dependent manner on day 1. The fucose level increased on day 3 in the Ams group. All parameters returned to their control levels on day 7. Animals in the TOP group did not show significant changes any of parameters during the experimental period. Gene expression of TNF-alpha and monocyte chemoattractant protein (MCP) 3 in the lung increased dose-dependently in the animals treated with the three materials. The mRNAs for eotaxin and MIP-1alpha were overexpressed in the lung of animals treated with Ams and TO1, while RANTES mRNA was overexpressed dose-dependently in the lung of animals treated with Ams on day 1. Onset of inflammatory response was more rapid in the Ams group than the TO1 group. Recovery of the fucose level in BAL was slower in the TO1 group than in the Ams group, though we observed similar histopathological changes in the lung of animals with TO1 or Ams. We conclude that whisker-induced acute biological effects in the lung may be related to the shape of the whiskers and not to their chemical composition or surface crystal structure, showing biological effects similar to those of UICC amosite.

Administration, Inhalation↗

Pulmonary clearance and lesions in rats after a single inhalation of ultrafine metallic nickel at dose levels comparable to the threshold limit value.

This study aimed to (1) determine the deposition and clearance rates of ultrafine metallic nickel (Uf-Ni) in rats after a 5 hours single inhalation exposure, and (2) to histopathologically examine the pulmonary lesions induced at dose levels comparable to the Occupational Exposure Limit recommended in Japan (OEL). The exposure concentrations of Uf-Ni for the 3 groups were 0.15 (Low), 1.14 (Medium), and 2.54 (High) mg/m3. Five rats/group were sacrificed at 0 h and 1, 3, 7, 14, and 21 days post exposure. The amount of Ni in the lung accumulated dose-dependently. The half-times for Ni in the lung were estimated as 32 days on average, and were similar to each other regardless of the initial dosage. The histopathologically observed pulmonary lesions induced by a single inhalation of Uf-Ni were, (1) a significant increase in lung weight in the High and Medium groups with time, (2) accumulation of foamy alveolar macrophages (AM), (3) degenerated AM indicating alveolar lipoproteinosis which was aggravated for up to 4 weeks in the High group and (4) acute calcification of the degenerated AM was remarkable. The present results suggest that even a single inhalation of Uf-Ni induces potency of lung lesions at dose levels comparable to the OEL (1 mg/m3 as Ni), or the TWA of ACGIH (1.5 mg/m3 for elemental/metal).

Animals↗

A new model rat with acute bronchiolitis and its application to research on the toxicology of inhaled particulate matter.

The aim of the present study was to establish a useful animal model that simulates humans sensitive to inhaled particulate matter (PM). We have developed a new rat model of acute bronchiolitis (Br) by exposing animals to NiCl2 (Ni) aerosols for five days. Three days following the Ni exposure, the animals developed signs of tachypnea, mucous hypersecretion, and bronchiolar inflammation which seemed to progress quickly during the fourth to fifth day. They recovered from lesions after four weeks in clean air. To assess the sensitivity of the Br rats to inhaled particles, two kinds of PM of respirable size were tested with doses similar to or a little higher to the recommended threshold limit values (TLVs) for the working environment in Japan. Titanium dioxide (TiO2 = Ti) was chosen as an inert and insoluble particles and vanadium pentoxide (V2O5 = V), as a representative soluble and toxic airborne material. The Br rats exposed to either Ti or V were compared the pathological changes in the lungs and the clearance of particles to those in normal control or Br rats kept in clean air. The following significant differences were observed in Br rats: 1. delayed recovery from pre-existing lesions or exacerbated inflammation, 2. reductions in deposition and clearance rate of inhaled particles with the progress of lesions. The present results suggest that Br rats are more susceptible to inhaled particles than control rats. Therefore, concentrations of particulate matter lower than the TLVs for Japan, which have no harmful effects on normal lungs, may not always be safe in the case of pre-existing lung inflammation.

Acute Disease↗

An animal exposure system using ultrasonic nebulizer that generates well controlled aerosols from liquids.

Various aerosol generators have been developed for animal inhalation experiments and the performance tests of measuring instruments and respirators. It has been, however, difficult to generate aerosols from an aqueous solution or suspension keeping the concentration and particle size distribution constant for a long time. Resolving such difficulties, the present study developed an animal exposure system that generates well-controlled and stable aerosols from liquids. The exposure system consists of an aerosol generator using ultrasonic nebulizer, a mixing chamber and an exposure chamber. The validity of this system was confirmed in the generation of NiCl2 and TiO2 aerosol from solution and suspension, respectively. The concentration levels of NiCl2 aerosol were kept at 3.2 mg/m3 and 0.89 mg/m3 for 5 hours with good coefficients of variation (CVs) of 2.5% and 1.7%, respectively. For TiO2 aerosol, the concentration levels of 1.59 mg/m3 and 0.90 mg/m3 were kept for 5 hours with small CVs of 1.3% and 2.0%, respectively. This exposure system could be sufficiently used for inhalation experiments with even high toxic aerosols such as NiCl2 because a momentary high concentration possibly affects results and an extremely stable concentration is required.

Administration, Inhalation↗

Development of a new aerosol generating cell with an ultrasonic nebulizer.

A new efficient cell was developed to generate a large quantity of aerosol using an ultrasonic nebulizer. The currently used conventional pail-type cell cannot generate such a large quantity of aerosol because a large portion of the mist is lost by agglomeration and subsequent liquefaction onto the cell wall and liquid surface. The newly developed cell is a chimney-type cell characterized by the attachment of a vertical cylinder at its center and a partition to separate the cell into upper and lower compartments, each of which is supplied with a carrier air flow. The mist emanating from the fluid surface is carried upward through the vertical cylinder by a laminar primary airflow. The secondary airflow served to sheath the primary airflow containing the mist and to prevent the impact and adhesion of the mist on the surrounding wall. The nebulizing rate of TiO2 suspension was found to be three times higher with the chimney-type than with the pail-type. No differences were found between the two types in terms of particle diameters, particle size distribution, and the electron microscopic images of the aerosol. It was concluded that a commercially available ultrasonic nebulizer equipped with the chimney-type cell allowed generation of a large quantity of aerosol for use in inhalation animal experiments.

Aerosols↗

Lung lesions induced by intratracheal instillation of nickel fumes and nickeloxide powder in rats.

Acute and subacute lung toxicity of nickel fumes was examined by single and repeated intratracheal instillation of nickel fumes and Ni2O3 and NiO powders in the rat. LD50 of nickel fumes was estimated as 38.2 mg/kg body weight (b.w.) according to the method of Litchfield and Wilcoxon. Body weight gain was retarded as in the order of a single dose of 13.0 mg Ni2O3/kg > 14.3 mg nickel fumes/kg > 1.4 mg Ni2O3/kg > 13.0 mg NiO/kg b.w. compared to controls. The histopathological changes in the lungs of the 14.3 mg nickel fumes/kg-dosed rats were milder than those induced by administration of 13.0 mg Ni2O3/kg but severer than those induced by administration of 1.4 mg Ni2O3/kg b.w. A single administration of NiO powder did not produce any histopathological effects on the lungs. The repeated administration of nickel fumes produced persistent edema and proteinosis in the alveoli. The nickel fumes, which were chemically composed of 97% of NiO and 3% of Ni2O3, were very fine particles about 5-10 nm in diameter, partly aggregated into larger particles and spherical particles about 0.6 micron in diameter. Solubility in distilled water and saline was in the order of nickel fumes > Ni2O3 powder > > NiO powder. It was suggested that a toxic Ni2O3 component and very fine particles of nickel fumes are involved in the acute lung toxicity of nickel fumes. The epithelial injury induced by reactive oxygen and hydroxy radicals, which would be produced during the process of conversion of Ni(III) to Ni(II) and phagocytosis of nickel fumes by macrophages and polymorphonuclear cells, are presumed to be involved in the pathogenesis of nickel fumes-induced lung lesion.

Aerosols↗

Changes in breathing pattern at loads near perceptual threshold at different work levels.

Five subjects were tested to determine the threshold for detection of an added resistance to inspiration in three tests, one at rest and two with exercise (mild = 50 W; moderate = 100 W) on a cycle ergometer. Changes in the breathing pattern were examined at added resistances near the perceptual threshold. Added inspiratory resistances with a 50% probability of detection were very variable at rest; they decreased significantly from rest (250 Pa.l-1.s-1) to moderate exercise (98 Pa.l-1.s-1) in four subjects. It is suggested that physical exercise may cause discomfort even when workers wearing a respirator do not have any abnormal sensation during sedentary work. Breathing patterns were compared between resistance loaded and unloaded breathing during each test. Decreases in inspiratory peak flow and acceleration of flow early in inspiration were found in resistance loaded breathing in almost all tests and a tendency for tidal volume to decrease was found during moderate exercise only. The ratios of resistance loaded to unloaded breathing for inspiratory time (ti) and total time (tt) tended to be greater in the detected than in the undetected responses at rest and during mild exercise but not during moderate exercise. This would imply that further prolongation of ti and tt in the detected responses was attributable to conscious or subconscious aspects of the resistance leading responses: however, these adjustments in breathing, which reduce frequency, would be less likely to occur as the work rate increases.

Adult↗

Development of an inhalation system of high melting point metal fumes and its use for exposure of rats to chromium and nickel fumes.

An experimental inhalation system was developed for fumes generated from powders of high melting point metals such as chromium, nickel, manganese and iron. The system consisted of a plasma flame metal sprayer as a fume generator, a granular bed type fume collector, a fluidized bed aerosol generator, an exposure and a control chamber of a horizontal-flow type and inhalant monitoring and controlling units. Performance of the chambers was ensured by a distribution test using flyash as a test aerosol. Using this system, rats were exposed to chromium fumes for one week or to nickel fumes for two months. The exposure concentrations of the chromium and nickel fumes were 1.85 +/- 0.55 mg/m3 and 0.51 +/- 0.15 mg/m3 (mean +/- SD), near the target levels of 2 mg/m3 and 0.5 mg/m3, respectively. The mass median aerodynamic diameter and the geometric standard deviation of the chromium fumes were 2.1 microns and 2.00, respectively. Those of the nickel fumes were 3.7 microns and 1.74, respectively. Species analysis of these fume particles revealed that 26.4% of the total chromium was hexavalent and the residue was trivalent and that 1-3% of the total nickel was nickel(III) and the residue was nickel(II). Inhaled-metal concentrations in the lungs showed steady increases with the exposure periods and were within the normal range of variation. On the basis of these results, it is concluded that this system is useful for long-term inhalation experiments using high melting point metal fumes.

Administration, Inhalation↗