Biopersistence of inhaled nickel oxide nanoparticles in rat lung.

In order to investigate whether or not airborne nanoparticles with a minimum agglomeration could be used for exposure tests on animals, we developed a nanoparticle generation system and examined the biological effects of the particles in an inhalation study. The generation system was composed of an ultrasonic nebulizer and diffusion dryers, and 30 Wistar male rats were exposed to nickel oxide (NiO) nanoparticles for 4 wk (6 h/day). The geometric mean diameter of the particles and the daily average exposure concentration determined by a combination of a differential mobility analyzer and a condensation nucleus counter in the exposure chamber were 139 +/- 12 nm and 1.0 +/- 0.5 x 10(5) particles/cm3, respectively. At 4 days and 1 and 3 mo after the inhalation, each group of 10 rats were sacrificed and NiO nanoparticles deposited in the lung were determined by chemical analysis and the biopersistence (biological half time) was calculated. The deposited amount of NiO nanoparticles in the rat lungs at 4 days after the inhalation was 29 +/- 4 microg. The retained particle amount in the rat lungs after the inhalation exponentially decreased and the calculated biological half time was 62 days. The histopathological change was not severe just after the inhalation nor throughout the observation time. We concluded that nanoparticles with a minimum agglomeration were dispersed stably in the chamber and exposed to rats for 4 wk and that deposited amounts in the rat lungs and the biopersistence of the particles and the biological response in lung were detected.

Comparison of gene expression of cytokines mRNA in lungs of rats induced by intratracheal instillation and inhalation of mineral fibers.

To investigate whether the results of intratracheal instillation studies on mineral fibers reflect the findings obtained by long-term inhalation data on mineral fibers, we have examined gene expression of cytokines and pathological features in lungs induced by intratracheal instillation and inhalation of mineral fibers. Male Wistar rats were given a single intratracheal instillation of 2 mg alumina silicate refractory fiber (RF1) or potassium octatitanate whisker (PT1), and were sacrificed 4 wk after the fiber instillation. Long-term inhalation studies were also performed. In these, animals were exposed to fiber aerosol of RF1 or PT1 for 5 days/wk for 1 yr, and sacrificed after 1 yr of inhalation. Expression of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and transforming growth factor-beta1 (TGF-beta1) from lungs was observed by reverse-transcription polymerase chain reaction (RT-PCR). The expression of TNF-alpha, IL-6, and TGF-beta1 mRNA in PT1-exposed lung was significantly higher than for those exposed to RF1 in both intratracheal instillation and inhalation studies. Pathological findings revealed that mild pulmonary fibrosis was seen in the lungs after intratracheal instillation and inhalation of PT1 but not RF1. Similarities were observed not only in gene expression of cytokines but in pathological features between both studies. These data suggested that the results of intratracheal instillation reflect the findings obtained from long-term inhalation data.

Biopersistence of man-made fibers by animal inhalation experiments in recent reports.

Biopersistence of man-made fibers by animal inhalation experiments was mainly reviewed. This report showed that the biopersistence and maximum tolerated dose are significantly important factors for hazard assessment for man-made fibers as well as fiber size (diameter/length), chemical compositions and surface properties.

Short term effect of silicon carbide whisker to the rat lung.

We studied the short-term effect of silicon carbide whisker (SiCW) in vivo by instillation and inhalation to the rat lung. SiCW was instilled low dose (2 mg/0.5 ml saline) or high dose (10 mg/ 0.5 ml) intratracheally into the lungs of 25 rats. SiCW was also inhaled to another 25 rats at the average concentration of 10.4 mg/m3 for 1 month. In instillation study, the lung had focal alveolitis with the destruction of alveolar wall especially at 3 days after the instillation, and the lesion remained as an aggregated foci of SiCW at 6 months. The 'inflammation-score' of the instilled group by point counting method of the specimen correspondingly decreased gradually. In inhalation group, a minimum inflammatory change was observed. Collagen deposition in the aggregated foci of SiCW with accumulated alveolar macrophages and neutrophils was not progressive during the observed period. These findings suggest that SiCW may cause a minor effect to the rat lung in 6 months after exposure.

A new digestion method for recovery of MMMFs from lungs.

A new tissue digestion method is proposed to recover man-made mineral fibers (MMMFs) from lungs, which is an improved Kjeldahl method using microwaves. Tissue digestion is carried out under five different conditions in this experiment, and the most suitable condition is found as follows; dried rat lung (0.5 g of wet weight) is put into a flask with 0.1 ml of H2SO4 and 2.0 ml of HNO3, and treated by microwaves for 5 min. After the treatment, 1.0 ml of H2O2 is added immediately and the sample is treated again under the same condition. Pure samples of glass fibers and refractory ceramic fibers are treated by this proposed method. Numbers and sizes of the fibers are measured before and after the treatment on enlarged photos taking by a scanning electron microscope. As no significant changes are observed in fiber dimensions and numbers, the proposed method is shown to be applicable to recover these MMMFs from lungs.

A clearance model of inhaled man-made fibers in rat lungs.

A clearance model of inhaled man-made fibers (MMFs) was developed, and the calculated fiber numbers and dimensions were compared with the experimental ones using a glass fiber (GF), ceramic fiber (RF1) and two potassium octatitanate whiskers (PT1, TW). If the translocation rate by macrophages is constant and the effect of dissolution and disintegration can be ignored, the fiber number is expected to decrease exponentially with time. In the experimental study, however, the fiber number did not always decrease exponentially. In the case of RF1, the fiber number decreased almost exponentially and the diameter decreased linearly with the time. The clearance rate constant of GF during 3 to 6 months after the end of one-month exposure was greater than that during 1 to 3 months. On the contrary, the clearance rate constants of PT1 and TW during 1 to 6 months were greater than next six months. The diameter and the length of GF did not change significantly. The fiber length of PT1 tends to become longer with time although the diameter did not change significantly. Our theoretical model gives a satisfactory fit to these experimental results.

Pulmonary deposition and clearance of glass fiber in rat lungs after long-term inhalation.

In this study Wistar male rats were exposed to glass fiber obtained by the disintegration of a binderless glass fiber filter, for 6 hr/day, 5 days/week for 12 months. The mass median aerodynamic diameter (MMAD) of the fiber, determined with an Andersen sampler, was 2.6 microns. The count median diameter and length of the fibers measured by scanning electron microscopy (SEM) were 0.51 and 5.5 microns, respectively. The daily average exposure fiber concentration was 2.2 +/- 0.6 mg/m3. Some rats were sacrificed 24 hr after removal from the exposure chamber following the 12 months' exposure. Others were sacrificed 12 months after the end of exposure. The wet organ weights were recorded at the time of death and the silicon content of the lungs was determined by absorption spectrophotometry. After 12 months' exposure, the amount of glass fiber retained in the rat lungs was 1.49 mg, and after 12 months' clearance it was 0.61 mg. The biological half-life in a single exponential model was to be 8.7 months, much longer than the predicted value of 1.5 months obtained in a previous experiment in which rats were exposed for 4 weeks to the same glass fiber.

Biological effects of inhaled magnesium sulphate whiskers in rats.

Male Wistar rats were exposed to two types of magnesium sulphate whiskers by inhalation for six hours a day, five days a week, for four weeks (sub-chronic study), or for one year (chronic study) to clarify the biological effects of the whiskers. There were few whiskers detected in the rat lungs even at one day after the exposure, suggesting that they are dissolved and eliminated rapidly from the lungs. To measure the clearance rate of the whiskers from the lungs, an intratracheal instillation was performed in golden hamsters. The half life of the whiskers in the lung was determined as 17.6 minutes by temporally measuring the magnesium concentration up to 80 minutes after the instillation. A histopathological examination indicated a frequent occurrence of adenoma and carcinoma in the year after chronic exposure, but it was not significantly different between exposed and control rats.

The effect of a palatal resin plate on consonant articulation.

This is the introductory paper of the forthcoming series of papers on the articulation of the Japanese consonants with a full denture and denture plate. The purpose of this research is to examine how the insertion of a full denture and denture plate affects the articulation of the Japanese consonants by comparing the articulation with and without it. The material for the experiment are thirty groups of Japanese words and phrases that are uttered by normal native speakers of Japanese with and without the insertion of a full denture and denture plate. Each of the thirty groups of Japanese words and phrases contains a Japanese consonant to be examined. The phonetic apparatus used are the sound spectrograph, oscillograph, phono-laryngograph, flow-nasalitygraph, etc. The aim of this research is to examine how the insertion of a full denture and denture plate affects the articulation of the Japanese consonants by means of comparing the articulation with and without it. Introduced below are three tables of Japanese consonants/syllables presented by other scholars in Japan. Table 1 is quoted from Bunkacho (The Agency of Cultural Affairs, Japan) (1983). Table 2 is quoted from Kindaichi (1988). Table 3 is quoted from M. Onishi (1984).

Japanese consonants compared with English with regard to prosthodontic dentistry.

This is the introductory paper of the forthcoming series of papers on Japanese consonants compared with English, presented as a basic study for prosthodontic dentistry. Materials for our experiment are fifteen groups of Japanese and English words and phrases to be uttered by normal native speakers of Japanese and English respectively. They are speakers of a modified standard Japanese and the Hichiku (: part of northern Kyushu) accent of Japanese and those of standard British English, General American English and Eastern American English. Each of the fifteen groups of words and phrases contains a set of Japanese and English consonants to be examined and compared with each other. The phonetic apparatus to be used are the sound spectrograph, oscillograph, phono-laryngograph, flow-nasalitygraph, electro-palatograph, etc.