Current fiber measurement techniques arose primarily due to health concerns over asbestos exposure. Fiber toxicity appears to be primarily a function of fiber concentration, dimensions and durability in the lungs. There are two basic approaches to fiber measurement. Fibers can be collected on filters and counted or analyzed by light or electron microscopy; alternatively, fibers can be detected directly using a combination of fiber alignment and light scattering techniques. All of these measurement approaches work best when the fibers are simple rod-shaped particles. However, most fibers can exist as curved rods, complex bundles of fibrils, and agglomerates of fibers and compact particles. These non-ideal shapes contribute to measurement bias and variability.

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The Bazhenovskoye chrysotile asbestos deposit has been exploited for 115 years. All the technological operations in the quarry are accompanied by the formation of high-dispersion asbestoscontaining aerosols. The dust concentrations at the miner's working places for the last 30 years (1970-2000) were at or below the Russian MACs_m.s. level (4.0 mg/m³). The seasonal precipitation amount in the deposit area causes a rise in dust content in certain periods. The maximum density of asbestos respirable fibres exceeded 2.7 f/cm³. All the identified fibres belonged to chrysotile asbestos, and no amphibole asbestos, such as tremolite asbestos, has been identified. An excessive dust level remains, despite the dust content level decrease, at the work sites of oversized lump drillers and unloaders, and oncopathology heightened risk remains in these occupational groups, as a result.

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The world production of asbestos has been declining dramatically in recent years, particularly in Europe and the United States. However, increases have occurred in Asian nations and chrysotile is the dominant fiber used. Important uses are in cement products, wallboards, friction products and textiles. From studies in the United States and Great Britain, chrysotile has been shown to increase the risk of lung cancer and to produce mesothelioma in exposed workers.

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In Japan, crocidolite had been used for asbestos cement pipe and spraying, and amosite had been used for building board and spraying. These two types of asbestos had stopped to use in Japan in the late 1970s. An extreme increase in imported asbestos (all 3 commercial types) was observed between 1960 and 1974. In 1960, 77, 000 tons of asbestos were imported, and reached the peak as 352, 316 tons in 1974. This extreme rise of asbestos imports corresponds with the recent rapid increase in mortality of malignant pleural mesothelioma. Between 1995 and 1999, an estimated mean annual death from pleural mesothelioma was about 500. The annual number of compensated occupational respiratory cancers due to asbestos exposure has also been increasing. Up to the end of March 2000, 162 cases with malignant mesothelioma and 197 cases with lung cancer were compensated. As for lung cancer, epidemiological studies are scanty in Japan. Limited environmental data of the working places in asbestos textile factories suggests that heavy asbestos exposure in the past made deaths from respiratory diseases. Less asbestos exposure will enable exposed workers to survive enough to reach cancer age. Even now smoking rate among males in Japan are over 50%. So lung cancer deaths caused by the interaction between smoking and asbestos exposure will be continuing.

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In 1950s and 60s, asbestosis had been a major health hazard for asbestos exposed workers. In the late 1970s, lung cancers with or without asbestosis were found among asbestos workers. All cohort studies on asbestos workers and on chrysotile miners in China showed excess deaths from lung cancer. In a large scale of cohort study on asbestos workers, a synergistic effect was found between cigarette smoking and asbestos exposure in the production of lung cancer. There have been not so many cases of malignant mesotheliomas reported, so far. In the cohort of chrysotile miners, 4 cases of pleural mesothelioma were observed. In the large scale of cohort study on asbestos workers in 9 factories using only chrysotile only one case of pleural mesothelioma was detected for 10 years' observation. In another 2 cohort studies, 2 cases of peritoneal mesotheliomas were found, one in Shanghai asbestos factory where a small amount of crocidolite had been used in 1960s, and one in Anqing asbestos factory that was located near tremolite mine. Further study is needed especially for the relationship between exposure to Chinese chrysotile and malignant mesotheliomas.

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Biological effects of asbestos fibers were reviewed in relation to the polyclonal activation of human lymphocytes and to the release of free radicals from human neutrophils in Vitro. Chrysotile, crocidolite, and amosite asbestos activate CD4⁺ T lymphocytes polyclonally, followed by activationinduced cell death (a type of apoptosis). The activation is HLA class II dependent, and certain Vβ repertoire, e.g. Vβ 5.3, are detected among the fractionated T cells with a high Ca⁺⁺ level that had been stimulated by asbestos fibers. These observations support the possibility that asbestos acts as a superantigen, and that asbestos stimulate lymphocytes repeatedly in vivo. It has been reported that asbestos-induced cytotoxicity can be suppressed by the scavengers of superoxide or hydroxyl radical. Some of these scavengers such as dimethylsulfoxide (DMSO) or retinoic acid are known as inducers of cell differentiation. The biological functions of DMSO for cell differentiation of HL-60 cells to neutrophils are suppressed by co-culturing of crocidolite asbestos, because DMSO reacts with the hydroxyl radical released after the stimulation with crocidolite and spent itself. Superoxide dismutase (SOD) inhibited the effects of crocidolite, reacting rapidly with •O^-₂ before the secondary release of OH. It seems to be probable that asbestos fibers, especially crocidolite, suppress the tissue cell differentiation by releasing free radicals and by wasting inducers of cell differentiation as radical scavengers.

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Asbestos substitutes have been used recently in industrial various applications. Since certain asbestos substitutes have similar characteristics of asbestos, they require urgent in vitro and in vivo evaluation of these asbestos substitutes prior to occupational applications. Though in vitro studies do not offer precise assessment of toxicity of the fibers, it is possible to provide useful information as to the biological effects of asbestos and its substitutes. This review articles described the findings of in vitro experiments in investigation of biological effects of asbestos and man made mineral fibers (MMMF) and their correlation with in vivo assays; 1. Cytotoxicity, geometry and dimension of fibers. 2. In vitro biological effects of fibers on a mass basis and a numerical basis. 3. Mechanism of cytotoxicity, carcinogenecity and cell proliferation including in vitro cytokines production. The relationships between the in vitro and the in vivo biological effects of fibers do not always coincide. Therefore, safety of the fibers must be assessed in both in vivo and in vitro using an inert fiber as negative control. Additionally, evaluation of safety of these fibers in vitro must be conducted in comparable concentrations, sizes and numbers of fibers for used in in vivo experiments.

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Pneumoconiosis that pursues a chronic course may result from repeated injury and repair caused by dust particles that remain in the lungs, leading to fibrosis. We will introduce in vivo studies concerning these processes using animals exposed to man-made mineral fibers and asbestos. We will report on whether there are developmental changes with the mineral fiber and animal model in proinflammatory cytokine, chemokine, free radicals, proteinase and other genes that lead to injury, as well as in genes that effect repair such as growth factor, and we will also report on the effects of surfactant protein and clara cell secretory protein on fibrosis.

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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.

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Man-made organic fibers (MMOFs) have been manufactured for over 50 years. Until recently, there have been few concerns raised regarding the safety of organic fiber dusts. This is due, in large part, to the perception that the dimensions of most, if not all, of these products were too large to be inhaled into the distal lungs of workers, i.e., were considered to be nonrespirable. A brief review of some of the issues related to organic fiber toxicology is presented herein. Some of the organic fiber-types used in commerce are identified and some fundamental tenets of fiber toxicology are discussed. In addition, the European Union, in their recent consideration for banning chrysotile asbestos fibers, evaluated some organic fiber substitutes and compared them to the hazards of asbestos. A brief review of their conclusions is described below. Finally, the results of some recent studies assessing the mechanisms of biodegradability of para-aramid respirable-sized, fiber-shaped particulates (RFP) are presented. Para-aramid (p-aramid) RFP are the most extensively-studied respirable organic fiber-type and RFP is the new term which describes respirable-sized organic fibers (ECETOC, 1996) (1). The results of these studies provide clues regarding the mechanism(s) of p-aramid RFP shortening in the lungs of exposed animals, and may be relevant for humans.

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In Japan, chrysotile is still permitted to use under the Ordinance on Prevention of Hazards due to Specified Chemical Substances. In recent years many countries have introduced a policy of prohibiting the use of asbestos, based on clinical and epidemiological studies. In light of this, it is important to evaluate the airborne asbestos concentrations in workplaces and also estimate the number of related disease cases in order to discuss the ban of asbestos use. The survey covered 528 workplaces in 145 plants and included 2795 asbestos handling workers from 1985 to 1998. These plants were belonging to the Japan Asbestos Association (JAA) as member companies. In Japan, nearly all of the asbestos using manufacturing companies are members of JAA. In our study, all of the workplaces were divided under each separate manufacturing process and classified into 3 categories of Control Classes. Of the 454/528 (86.0%) workplaces classified as Control Class 1 are improved to 376/378 (99.5%). Though in the cases of small enterprises, other factors such as a shift in product lines, and the economic recession, as well as efforts, contributed to improvements in working conditions. JAA recommended self-administered concentrations of 1.0 f/ml (compatible to <0.3 f/ml in personal exposure level) in 1991 to promote further improvements of the work environment. From this point of view, exposure limits can almost be technically achieved in Japan, and it is expected that asbestos related disease could be expected to decrease in 20 to 30 years later. This survey will become basic material for verifications whether we could control asbestos related diseases enough in such well-controlled work environment.

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Airborne fiber concentrations and size distributions of both asbestos and nonasbestos fibers were determined at property boundaries of 4 serpentinite quarries producing crushed stone (quarry property boundary), 10 sites within 10 km of the area with serpentinite outcrops (serpentinite area), and 2 sites in a reference area. The asbestos was identified in 7 rock and 3 soil samples collected in the serpentinite area. The geometric means of airborne concentrations of asbestos and nonasbestos fibers longer than 0.2 μm in length were: 384 and 447 fibers/liter (f/L) in the quarry property boundary (in operation), 12 and 124 f/L in the quarry property boundary (in closed), 5 and 103 fibers/liter in the serpentinite area, and less than 2 and 59 fibers/liter in the reference area, respectively. There was a significant difference in airborne concentrations of both asbestos and nonasbestos fibers among the areas. Ttremolite/actinolite were found with chrysotile in the stones. Airborne concentrations of tremolite/actinolite were higher than those of chrysotile at the quarry property boundary and in the serpentinite area. Tremolite/actinolite were also found in the soils. There was no significant difference among the areas in the arithmetic means of fiber size distribution of both asbestos and nonasbestos fibers.

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Lung deposition of fibrous aerosol was studied by using a model of the lung bifurcation with dimensions based on the symmetric model A of Weibel. The fibrous aerosols were introduced to the model under steady inspiratory flow conditions. Glass fibers depositing in the daughter tubes and these escaping from them were observed under a scanning electron microscope (SEM). The deposited fractions were calculated for each length and diameter using a bivariate lognormal distribution. In this study the authors propose empirical equations to estimate total deposited fractions of fibrous aerosol at upper bronchi. The dimensionless relationship among deposited fractions Fd, Stokes number St for randomly-oriented fibers and interception parameter I were used to estimate the deposited fraction at arbitrary position in the upper bronchi. The calculation procedure for Fd(St, I) consists of two steps: the determination of the four deposited fractions, Fd_n for each I_n (n=1 4) followed by interpolation or extrapolation from Fd_n to find the deposited fraction Fd at a given I. With this procedure, it is possible to determine the deposited fraction Fd in the range of 2 × 10^-3<St<5 × 10^-2 and 5 × 10^b-4<I<5 × 10^-2. Penetration from the trachea to the 10th generation of lung bifurcation was calculated for several cases of fiber diameter, length and flow rate. In the case corresponding to an inspiration of 500 cm³ air at a constant rate for 2 s, more than half of the fibers with a length of 100 μm and diameter of 3 μm are deposited at upper bronchi but more than 90% of fibers of the same length and 1 μm in diameter pass through the region.

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Asbestos fibers in the lung and mesothelial tissues (mesotheliomatous tissue and hyaline plaque) taken from 151 human malignant mesothelioma cases were identified and characterized by high resolution analytical electron microscopy. Asbestos fibers were present in almost all of the lung tissue as well as in the mesothelial tissue. The most common asbestos types seen in the lung were an admixture of chrysotile with amphiboles followed by amphiboles alone and chrysotile alone. The majority of asbestos types seen in the mesothelial tissues were chrysotile alone, followed by chrysotile plus amphibole and amphibole alone. A disproportion of asbestos types between the lung and mesothelial tissues was frequently observed. The most common pattern of the disproportion was chrysotile plus amphibole(s) in the lung and chrysotile only in the mesothelial tissues, followed by amphibole(s) in the lung and chrysotile only in the mesothelial tissues. Such a disproportion was considered to have been caused by chrysotile fiber's strong capacity to translocate from the lung to mesothelial tissues. The number of asbestos fibers in the lung was 456.4 × 10⁶ fibers/dry gram in maximum, 0.08 × 10⁶ fibers/dry gram in minimum and 105 × 10⁶ fibers/dry gram on average; in the mesothelial tissues it was 240.0 × 10⁶ fibers/dry gram in maximum, 0.03 × 10⁶ fibers/dry gram in minimum and 49.84 × 10⁶ fibers/dry gram on average. These numbers were greater than those seen in the general population. The majority of asbestos fibers detected in the lung and mesothelial tissues were shorter than 5 μm in length. Asbestos fibers fit to Stanton's hypothetical dimensions (≥8.0 μm in length and ≤0.25 μm in diameter) were only 4.0%, since the majority of these fibers were shorter (<8 μm) and thinner (<0.25 μm) fibers. We concluded that such short, thin asbestos fibers should not be excluded from those contributing to the induction of human malignant mesothelioma. The present study supports that chrysotile asbestos can induce human malignant mesothelioma, since, in some of the mesothelioma cases, asbestos fibers detected in both the lung and mesothelial tissues, or lung tissue alone or mesothelial tissues alone were exclusively chrysotile fibers.

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A series of 557 malignant mesotheliomas of the pleura diagnosed in the Trieste-Monfalcone area, Italy, in the period 1968-2000 were reviewed. The series included 492 men and 65 women, aged between 32 and 93 years (median age 69 years). Necropsy findings were available in 456 cases (82%). Occupational histories were obtained from the patients themselves or from their relatives by personal or telephone interviews. Routine lung sections were examined for asbestos bodies in 442 cases. In 109 cases isolation and counting of asbestos bodies were performed. A majority of people had histories of working in the shipyards. Asbestos bodies were observed in lung sections in 67% of the cases. Lung asbestos body burdens after isolation ranged between 20 bodies and about 10 millions of bodies/g dried tissue. Latency periods (time intervals between first exposure to asbestos and death) ranged between 14 and 75 years (mean 48.8 years, median 51.0). Latency periods among insulators and dock workers were shorter than among the other categories. High asbestos consumption occurred in many countries in the 1960s and in the 1970s. The data on latency periods obtained in the present study suggest that a world mesothelioma epidemic has to be expected in the coming decades.

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We tried to evaluate the carcinogenic risk of man-made mineral fiber based on the mesothelioma incidence in female F344 rats after intraperitoneal administration. Rats (female F344/ Nslc, 5-week-old, n=330) were observed for 2 years after the intraperitoneal administration of 5 to 20 mg of 9 types of the JFM (Japan Fibrous Material Research Association) standard fiber samples (glass wool, rock wool, micro fiber glass, three types of refractory fiber, potassium titanate whisker, silicon carbide whisker, titanium oxide whisker), wollastonite (natural fiber) and UICC chrysotile B. All rats administered 10 mg of silicon carbide whisker had developed peritoneal mesothelioma within a year. The cumulative incidence of peritoneal mesothelioma at the end of the experiment was 85% for 10mg UICC chrysotile B, 77% for 10 mg of potassium titanate whisker, 70% for 5 mg of silicon carbide whisker, 20% for 5 mg of potassium titanate whisker, 20% for 20 mg of refractory fiber 2 and 10% for 20 mg of refractory fiber 1. Carcinogenicity was estimated 2.4 times for silicon carbide whisker and 0.23 for potassium titanate whisker in comparison with UICC chrysotile B. It has been well documented from several experimental studies that man-made fibers are safer than asbestos because of the different durability in the lung. Present results consistently suggest that man-made fibers with high durability have similar or higher risk as carcinogen than asbestos.

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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.

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The author reviewed 1, 517 human malignant mesothelioma cases from 1975 through August 2000. These mesothelioma cases were definite or probable in diagnostic certainty. Sources of these cases varied including asbestos insulation workers, UNARCO workers, Cancer and Leukemia B mesothelioma panel cases and random cases. Pathology materials consisted of autopsy, biopsy and rare cytology specimens. 92.3% of these patients were male, and 85.8% were between 50 and 79 years in age. The major primary site of the tumor was the pleura (73.1%). However, in a group of the asbestos insulation workers, the peritoneum was the more common primary site of malignant mesothelioma, compared to the pleura. Histologically, epithelial cell type was the majority (61.1%), followed by biphasic (22.1%) and fibrosarcomatous (16.4%). A double primary tumor (malignant mesothelioma associated with other cancer) was present in 32 of the 1, 517 cases. These 32 cancers included lung cancers, renal cell carcinomas, colorectal cancers, pancreatic cancers and a cancer of the larynx, which are known to be at higher risk among asbestos insulation workers. The latency period of the vast majority (98.1%) of these mesothelioma cases were longer than 20 years. It is well accepted that cigarette smoking does not contribute to the induction of malignant mesothelioma. Indeed, the present study confirmed that 19.9% of these mesothelioma patients had never smoked cigarettes.

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It has been suggested that oxidative stress is associated with the cancers caused by asbestos. Since construction workers are sometimes exposed to low levels of asbestos, we investigated whether oxidative stress was elevated in construction workers who had been exposed to low levels of asbestos. The subjects were 48 Japanese construction workers. The defined asbestos-exposed group consisted of subjects who had the history of suspected exposure to asbestos and were diagnosed to have irregular opacities or pleural plaques. We measured the amount of 8-oxo-7, 8-dihydro-2'-deoxyguanosine (8-oxodG) and biopyyrins in the urine of the subjects. The results showed that 8-oxodG and biopyyrins levels in the defined asbestos-exposed group were higher, although they were not statistically significant, than those in the control group. In addition, the urinary 8-oxodG levels tended to correlate positively with the duration of suspected exposure to asbestos. These results suggest that even lowlevel asbestos exposure may induce oxidative stress and that the resulting's the oxidative stress might be related to lung cancer in construction workers.

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A 76-year-old male died of lung cancer. At first, he was diagnosed as a silicosis, because he had worked for 30 years as a caster in shipyard and large opacities detected by chest x-ray and CT scanning. After the operation of lung cancer, numerous asbestos bodies were observed in the operated lung tissues. The detailed occupational inquiry revealed his asbestos use as a caster in shipyard. Early stage of asbestosis was suspected by chest CT scanning, but not definitely diagnosed in premortal examinations. Asbestosis, pleural plaques, silicosis and large cell carcinoma of the lung were histopathologically confirmed at the autopsy. A patient with asbestos-induced lung cancer complicated by silicosis was rarely published in the literature.

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This case was a 79-year-old man with pleural plaques, which had been pointed out in the left lung field on chest X-ray six years ago. A new shadow in the right chest appeared in 1999 and was closely examined. Cytological class IV carcinoma was detected in his lung tissue obtained by broncho-fiberscope. Lobectomy of the right upper lobe was performed, and calcified pleural plaques were found on the chest wall. The clinical diagnosis was poorly differentiated squamous cell carcinoma, T1N0M0. In World War II when he was 26 years old, he had worked as a boiler man on a battle cruiser for one year. The amount of asbestos bodies (AB) was 3, 348 per gram dry lung tissue. The cores of AB and asbestos fibers were examined and showed that amosite was the most prevalent and crocidolite, tremolite and chrysotile were present in that order. After leaving the navy, he had worked as a farmer throughout his life, suggesting that he had never contacted asbestos occupationally after being a boiler man. It is strongly suggested that he had been exposed to asbestos during his work as a boiler man and that produced pleural plaques and lung cancer 50 years' later.

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In order to investigate the difference in diurnal variation of autonomic control between young male mild to moderate hypertensive and normotensive white-collar workers, we accessed heart rate variability with ambulatory blood pressure for over 24 hours including work and sleep periods. Both mean systolic and diastolic blood pressures (SBP and DBP) were significantly (p<0.01) higher in hypertensives (HT, n=11) than normotensives (NT, n=11) in all phases, whereas heart rate was not different between them in any phase. Blood pressures during work period (on-duty) were significantly higher than those during non-work period (off-duty) in both NT and HT. High frequency (HF; 0.15-0.40 Hz) power showed a circadian pattern in phase with the sleep-wake cycle. Both HF and low frequency (LF; 0.05-0.15 Hz) powers in HT were significantly lower than that in NT during the sleep period (p<0.05). LF/HF ratio showed a circadian pattern that was almost opposite of the pattern in HF power. Twenty-four-hour average LF/HF in HT was higher than that in NT (p<0.05). Especially during on-duty, LF/HF in HT was significantly higher than in NT (p<0.05). The increase of SBP and LF/HF from off-duty period to on-duty period (ΔSBP and ΔLF/HF) showed significant positive correlation (r=0.67, P<0.05) in HT group, suggesting that the SBP elevation during on-duty in HT may be coupled with sympathetic activation. These results suggest that HT showed significantly reduced parasympathetic control during sleep and an increased sympathetic activity especially during on-duty as compared with NT. Our findings imply that persistence of sympathodominant states together with reduced vagal activity in young mild to moderate hypertensive workers may be related to future cardiovascular disorders.

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The effects on semen and the function of accessory gonad of workers after short and long term exposure to benzene, toluene, and xylene were examined. The semen and blood of 24 married workers exposed to benzene, toluene, and xylene were collected. Routine sperm characteristic, acrosin activity, and Lactate dehydrogenase C4 (LDH-C4) relative activity were detected. The results showed that benzene, toluene, and xylene were found in the blood and semen of some ex-workers at workplaces where the air concentration of benzene, toluene, and xylene exceeded the maximum allowable concentration (MAC). No such solvents were detected in the blood and semen of workers of the control group. The sperm vitality and sperm motility decreased in the exposed workers. The mean acrosin activity, γ-GT activity and LDH-C4 relative activity in the exposed workers were lower, and fructose concentration was higher than those in the control. There were negative correlations between sperm vitality, sperm activity, acrosin activity, or LDH-C4 relative activity and working history. These results suggest that the mixture of these solvents could affect the sperm and the function of accessory gonad. This might be one reason of the abnormal pregnancy outcome among the wives of workers exposed to benzene, toluene, and xylene.

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A baseline survey of 3457 male workers exposed to various forms of dust from 11 medical facilities throughout Japan was carried out in 1978 or 1979. We completed the present follow-up study 15 years later on 693 of the men. Vital capacity (VC) and forced expiratory volume in one second (FEV₁) were analyzed as indices of lung function. We examined factors that affected both baseline and interval changes in VC and FEV₁ by stepwise multiple regression analysis. In the cross-sectional data analysis of baseline, height, profusion rate (PR) and age were selected as predictor variables for VC and FEV₁, additionally duration of working for FEV₁. It indicated that baseline VC decreased by 84.0 ml with each increase in PR classification. Similarly, baseline FEV₁ decreased by 146.6 ml with increasing PR. Baseline VC and FEV₁ were both positively influenced by subject height. In the longitudinal analysis, baseline PR, age and smoking habits were selected for predictor variables for decline of VC and FEV₁. It indicated a negative influence of baseline PR classification on VC and FEV₁ changes (−5.0 and −7.5 ml/y, respectively). Smoking decreased VC and FEV₁ by 6.1 and 5.8 ml/y, respectively.

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In a study of 142 Japanese men from a cross-section of the workforce of a technology development company, we found that the percentage of CD56+ cells was inversely correlated with the number of hours worked per week. A low CD56+ cell percentage was associated with longer weekly working hours and shorter daily sleeping hours.

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