Abstract  In a population-based case-referent study, the occupational experience of 86 men with oral or oropharyngeal cancer and 373 referents was analyzed with respect to employment in 41 occupations and 40 industries, as well as to exposure to 16 chemicals, as estimated via a job-exposure matrix. Among the occupations and industries at higher risk were machinery operator (odds ratio [OR] 2.0; 95% confidence interval [95% CI] 1.0-4.0), plumber (OR 5.0, 95% CI 1.2-21.5), building industry (OR 2.5; 95% CI 1.3-4.5), textile industry (OR 2.5; 95% CI 0.6-4.6), and electricity production (OR 2.8; 95% CI 0.7-12.1). All the OR estimates were adjusted for age, education, area of birth, tobacco smoking, and alcohol consumption. An association between formaldehyde exposure and oral cancer was suggested (OR for any exposure 1.6, 95% CI 0.9-2.8; OR for probable or definite exposure 1.8, 95% CI 0.6-5.5). No other chemical included in the matrix showed any risk pattern. The evidence of an association between formaldehyde exposure and oral or oropharyngeal cancer is strengthened by the results of this study.

Abstract  OBJECTIVES: This community based case-referent study was initiated to investigate aetiological factors for squamous cell carcinoma of the upper gastrointestinal tract. METHODS: The study was based on all Swedish men aged 40-79 living in two regions of Sweden during 1988-90. Within that base, efforts were made to identify all incident cases of squamous cell carcinoma of the oral cavity, oropharynx and hypopharynx, larynx, and oesophagus. Referents were selected as a stratified (age, region) random sample of the base. The response was 90% among cases and 85% among referents. There were 545 cases and 641 referents in the final study group. The study subjects were interviewed about several lifestyle factors and a life history of occupations and work tasks. The exposure to 17 specific agents were coded by an occupational hygienist. The relative risk (RR) of cancer was calculated by logistic regression, standardising for age, geographical region, and alcohol and tobacco consumption. RESULTS: Exposure to asbestos was associated with an increased risk of laryngeal cancer, and a dose-response relation was present. The RR was 1.8 (95% confidence interval (95% CI) 1.1 to 3.0) in the highest exposure group. More than eight years of exposure to welding fumes was associated with an increased risk of pharyngeal cancer (RR 2.3 (1.1 to 4.7)), and laryngeal cancer (RR 2.0 (1.0 to 3.7)). There were indications of a dose-response for duration of exposure. Associations were also found for high exposure to polycyclic aromatic hydrocarbons (PAHs) and oesophageal cancer, RR 1.9 (1.1 to 3.2). Exposure to wood dust was associated with a decreased risk of cancer at the studied sites. CONCLUSIONS: Some of the present findings confirm known or suspected associations--such as asbestos and laryngeal cancer. The study indicates that welding may cause an increased risk of pharyngeal as well as laryngeal cancer. The findings corroborate an association between exposure to PAHs and oesophageal cancer.

Abstract  Objective: In order to examine the associations between sinonasal cancer and occupational exposures other than wood dust and leather dust, the data from 12 case–control studies conducted in seven countries were pooled and reanalyzed. Methods: The pooled data set included 195 adenocarcinoma cases (169 men and 26 women), 432 squamous cell carcinomas (330 men and 102 women), and 3136 controls (2349 men and 787 women). Occupational exposures to formaldehyde, silica dust, textile dust, coal dust, flour dust, asbestos, and man-made vitreous fibers were assessed with a job-exposure matrix. Odds ratios (ORs) were adjusted for age, study, wood dust, and leather dust, or other occupational exposures when relevant. 95% confidence intervals (CIs) were estimated by unconditional logistic regression. Results: A significantly increased risk of adenocarcinoma was associated with exposure to formaldehyde. The ORs for the highest level of exposure were 3.0 (CI = 1.5–5.7) among men and 6.2 (CI = 2.0–19.7) among women. An elevated risk of squamous cell carcinoma was observed among men (OR = 2.5, CI = 0.6–10.1) and women (OR = 3.5, CI = 1.2–10.5) with a high probability of exposure to formaldehyde. Exposure to textile dust was associated with non-significantly elevated risk of adenocarcinoma, among women only: the OR for the high level of cumulative exposure was 2.5 (CI = 0.7–9.0). High level of asbestos exposure was associated with a significantly increased risk of squamous cell carcinoma among men (OR = 1.6, CI = 1.1–2.3). Conclusions: The results of this pooled analysis support the hypothesis that occupational exposure to formaldehyde increases the risk of sinonasal cancer, particularly of adenocarcinoma. They also indicate an elevated risk of adenocarcinoma among women exposed to textile dust, and suggest that exposure to asbestos may increase the risk of squamous cell carcinoma.

Abstract  A practical guide to both general principles and specific methods used to assess exposure to indoor air pollutants. Addressed to public health professionals who lack specialized training in this field, the book aims to facilitate well-designed assessments in order to identify health hazards and support strategies for risk management. Information is specific to the assessment of air pollution exposure in such indoor environments as homes, offices, and various public service buildings. The book has two part. The first, which serves as a general introduction, opens with an explanation of concepts used in exposure assessment and important to the design and interpretation of findings. Against this background, subsequent chapters describe specific direct and indirect methods of exposure assessment, and use the example of volatile organic compounds to show how exposure to mixtures can be measured. Other chapters discuss the influence of temperature and humidity on the indoor environment, provide guidelines for the design of exposure assessment surveys, and discuss the components of quality control. The second and most extensive part describes currently available methods for assessing six gaseous air pollutants, four categories of particulate air pollutants, and three biological contaminants commonly found in indoor environments and representing distinct methodological problems. Each pollutant is covered according to a common format which includes information on health effects, sources, variation of exposure, and the advantages and disadvantages of methods for assessing exposure. Further practical guidance is provided in an annex, which includes short summaries of exposure assessment studies completed or under way in the USA and several European countries.

Abstract  OBJECTIVES: Consolidation of epidemiological data on pancreatic cancer and worksite exposures. METHODS: Publications during 1969-98 were surveyed. Studies without verified exposures were excluded. Meta-analyses were conducted on data from 92 studies covering 161 populations, with results for 23 agents or groups of agents. With a standard format, five epidemiologists extracted risk estimates and variables of the structure and quality of each study. The extracted data were centrally checked. Random meta-models were applied. RESULTS: Based on 20 populations, exposure to chlorinated hydrocarbon (CHC) solvents and related compounds was associated with a meta-risk ratio (MRR) of 1.4 (95% confidence interval (95% CI) 1.0 to 1.8). Nickel and nickel compounds were considered in four populations (1.9; 1.2 to 3.2). Excesses were found also for chromium and chromium compounds (1.4; 0.9 to 2.3), polycyclic aromatic hydrocarbons (PAHs) (1.5; 0.9 to 2.5), organochlorine insecticides (1.5; 0.6 to 3.7), silica dust (1.4; 0.9 to 2.0), and aliphatic and alicyclic hydrocarbon solvents (1.3; 0.8 to 2.8). Evidence on pancreatic carcinogenicity was weak or non-positive for the following agents: acrylonitrile (1.1; 0.0 to 6.2); arsenic (1.0; 0.6 to 1.5); asbestos (1.1; 0.9 to 1.5); diesel engine exhaust (1.0; 0.9 to 1.3); electromagnetic fields (1.1; 0.8 to 1.4); formaldehyde (0. 8; 0.5 to 1.0); flour dust (1.1; 0.3 to 3.2); cadmium and cadmium compounds (0.7; 0.4 to 1.4); gasoline (1.0; 0.8 to 1.2); herbicides (1.0; 0.8 to 1.3); iron and iron compounds (1.3; 0.7 to 2.5); lead and lead compounds (1.1; 0.8 to 1.5); man-made vitreous fibres (1.0; 0.6 to 1.6); oil mist (0.9; 0.8 to 1.0); and wood dust (1.1; 0.9 to 2.5). The occupational aetiological fraction of pancreatic cancer was estimated at 12%. In a subpopulation exposed to CHC solvents and related compounds, it was 29%; to chromium and chromium compounds, 23%; to nickel and nickel compounds, 47%; to insecticides, 33%; and to PAHs, 33%. CONCLUSION: Occupational exposures may increase risk of pancreatic cancer. High quality studies are called for on interactions between occupational, environmental, and lifestyle factors as well as interactions between genes and the environment.

Abstract  Asbestos induces DNA and chromosomal damage, but the DNA repair pathways protecting human cells against its genotoxicity are largely unknown. Polymorphisms in XRCC1 have been associated with altered susceptibility to asbestos-related diseases. However, it is unclear whether oxidative DNA damage repaired by XRCC1 contributes to asbestos-induced chromosomal damage.

We sought to examine the importance of XRCC1 in protection against genotoxic effects of crocidolite and Libby amphibole asbestos.

We developed a genetic model of XRCC1 deficiency in human lung epithelial H460 cells and evaluated genotoxic responses to carcinogenic fibers (crocidolite asbestos, Libby amphibole) and nongenotoxic materials (wollastonite, titanium dioxide).

XRCC1 knockdown sensitized cells to the clastogenic and cytotoxic effects of oxidants [hydrogen peroxide (H₂O₂), bleomycin] but not to the nonoxidant paclitaxel. XRCC1 knockdown strongly enhanced genotoxicity of amphibole fibers as evidenced by elevated formation of clastogenic micronuclei. Crocidolite induced primarily clastogenic micronuclei, whereas Libby amphibole induced both clastogenic and aneugenic micronuclei. Crocidolite and bleomycin were potent inducers of nuclear buds, which were enhanced by XRCC1 deficiency. Libby amphibole and H₂O₂ did not induce nuclear buds, irrespective of XRCC1 status. Crocidolite and Libby amphibole similarly activated the p53 pathway.

Oxidative DNA damage repaired by XRCC1 (oxidized bases, single-strand breaks) is a major cause of chromosomal breaks induced by crocidolite and Libby amphibole. Nuclear buds are a novel biomarker of genetic damage induced by exposure to crocidolite asbestos, which we suggest are associated with clustered DNA damage. These results provide mechanistic evidence for the epidemiological association between XRCC1 polymorphisms and susceptibility to asbestos-related disease.

Abstract  Knowledge of mortality patterns following exposure to asbestos has been determined mostly from cohort studies of men who were exposed to asbestos in their workplace. Women are more likely to have obtained their asbestos exposure domestically or from their environment.

2552 women and girls are documented to have lived in the blue asbestos mining and milling township of Wittenoom between 1943 and 1992 and were not involved in asbestos mining or milling. Quantitative asbestos exposure measurements were derived from periodic dust surveys undertaken in the industry and around the township. Death records were obtained for the period 1950-2004. Standardised mortality ratios (SMRs) were calculated to compare the Wittenoom women's mortality with that of the Western Australian female population.

There were 425 deaths, including 30 from malignant mesothelioma. There was excess mortality for all causes of death (SMR = 1.13), all neoplasms (SMR = 1.42), symptoms, signs and ill defined conditions (SMR = 6.35), lung cancer (SMR = 2.15) and pneumoconiosis (SMR = 11.8). Mortality from cancer of the ovary (SMR = 1.52), upper aerodigestive cancers (SMR = 2.70) and tuberculosis (SMR = 5.38) was increased but not significantly. The risk of death from mesothelioma was increased, but not significantly, in residents known to have lived with or washed the clothes of an Australian Blue Asbestos Company asbestos worker (HR = 2.67, 95% CI 0.77 to 9.21; HR = 2.61, 95% CI 0.85 to 7.99, respectively).

Women who were former residents of Wittenoom, exposed to asbestos in their environment or in their home, have excess cancer mortality, including mesothelioma, compared with the Western Australian female population.

Abstract  BACKGROUND:Several papers have reported state-wide projections of mesothelioma deaths, but few have computed these predictions in selected exposed groups. OBJECTIVE: To predict the future deaths attributable to asbestos in a cohort of railway rolling stock workers. METHODS: The future mortality of the 1,146 living workers has been computed in term of individual probability of dying for three different risks: baseline mortality, lung cancer excess, mesothelioma mortality. Lung cancer mortality attributable to asbestos was calculated assuming the excess risk as stable or with a decrease after a period of time since first exposure. Mesothelioma mortality was based on cumulative exposure and time since first exposure, with the inclusion of a term for clearance of asbestos fibres from the lung. RESULTS: The most likely range of the number of deaths attributable to asbestos in the period 2005-2050 was 15-30 for excess of lung cancer, and 23-35 for mesothelioma. CONCLUSION: This study provides predictions of asbestos-related mortality even in a selected cohort of exposed subjects, using previous knowledge about exposure-response relationship. The inclusion of individual information in the projection model helps reduce misclassification and improves the results. The method could be extended in other selected cohorts.

Abstract  Research was conducted in order to assess potential exposure to asbestos while harvesting firewood from amphibole-contaminated trees near Libby, MT, USA. Three firewood-harvesting simulations took place in the summer and fall of 2006 in the Kootenai Forest inside the US Environmental Protection Agency (EPA) restricted zone surrounding the former W.R. Grace vermiculite mine. Another simulation was conducted near Missoula, MT, USA, which served as the control. The work practices following each simulation were consistent throughout each trial. Personal breathing zone (PBZ) asbestos concentrations were measured by phase contrast microscopy (PCM) and transmission electron microscopy (TEM). Surface wipe samples of personal protective clothing were measured by TEM. The mean (n = 12) PBZ PCM sample time-weighted average (TWA) concentration was 0.29 fibers per milliliter, standard deviation (SD = 0.54). A substantial portion (more than five fibers per sample) of non-asbestos fibers (cellulose) was reported on all PBZ samples (excluding field blanks) when analyzed by TEM. The mean (n = 12) PBZ TEM sample TWA concentration for amphibole fibers <5-microm long was 0.15 fibers per milliliter (SD = 0.21) and the mean (n = 12) PBZ TEM concentration for amphibole fibers >5-microm long was 0.07 fibers per milliliter (SD = 0.08). Substantial amphibole fiber concentrations were revealed on Tyvek clothing wipe samples. The mean concentration (n = 12) was 29 826 fibers per square centimeter (SD = 37 555), with 91% (27 192 fibers per square centimeter) comprised fibers <5-microm long. There were no significant differences in PBZ and wipe sample concentrations among the tasks performed by four investigators. Each of these three simulations were consistent in demonstrating that amphibole fibers are released from tree reservoirs during firewood-harvesting activities in asbestos-contaminated areas and that the potential for exposure exists during such activities.

Abstract  This report provides an update of the mortality experience of a cohort of South Carolina asbestos textile workers.

A cohort of 3072 workers exposed to chrysotile in a South Carolina asbestos textile plant (1916-77) was followed up for mortality through 2001. Standardised mortality ratios (SMRs) were computed using US and South Carolina mortality rates. A job exposure matrix provided calendar time dependent estimates of chrysotile exposure concentrations. Poisson regression models were fitted for lung cancer and asbestosis. Covariates considered included sex, race, age, calendar time, birth cohort and time since first exposure. Cumulative exposure lags of 5 and 10 years were considered by disregarding exposure in the most recent 5 and 10 years, respectively.

A majority of the cohort was deceased (64%) and 702 of the 1961 deaths occurred since the previous update. Mortality was elevated based on US referent rates for a priori causes of interest including all causes combined (SMR 1.33, 95% CI 1.28 to 1.39); all cancers (SMR 1.27, 95% CI 1.16 to 1.39); oesophageal cancer (SMR 1.87, 95% CI 1.09 to 2.99); lung cancer (SMR 1.95, 95% CI 1.68 to 2.24); ischaemic heart disease (SMR 1.20, 95% CI 1.10 to 1.32); and pneumoconiosis and other respiratory diseases (SMR 4.81, 95% CI 3.84 to 5.94). Mortality remained elevated for these causes when South Carolina referent rates were used. Three cases of mesothelioma were observed among cohort members. Exposure-response modelling for lung cancer, using a linear relative risk model, produced a slope coefficient of 0.0198 (fibre-years/ml) (standard error 0.00496), when cumulative exposure was lagged 10 years. Poisson regression modelling confirmed significant positive relations between estimated chrysotile exposure and lung cancer and asbestosis mortality observed in previous updates of this cohort.

This study confirms the findings from previous investigations of excess mortality from lung cancer and asbestosis and a strong exposure-response relation between estimated exposure to chrysotile and mortality from lung cancer and asbestosis.

Abstract  This epidemiological study was conducted to determine whether high-resolution computed tomography (HRCT) is useful to screen for pulmonary abnormalities in people exposed to vermiculite containing asbestos. During June-September 2001, we evaluated HRCT of 353 people in Libby, MT, who had been exposed to asbestiform minerals associated with vermiculite. Of these, 334 participants of the summer 2000 medical testing program underwent HRCT of the chest at St. John's Lutheran Hospital and 19 eligible people who recently had undergone an HRCT scan at the same facility and under the same testing protocol allowed the study reviewers to use that scan. All 353 study participants were former vermiculite mine/mill workers (n = 55), their household contacts (n = 99), and people exposed to vermiculite through recreational or other activities (n = 199). Participants' 2000 medical testing results indicated only one of the three B-reader chest radiograph reviewers had reported a pleural abnormality (indeterminate chest radiograph). Three expert computer tomography (CT) scan evaluators reviewed the HRCT scans and identified pleural abnormalities in 98 (27.8%) of the 353 participants whose previous chest radiographs were classified indeterminate. Of these 98 people, 69 (70.4%) were either former vermiculite mine/mill workers or household contacts, and 40 (40.8%) showed pleural calcification on HRCT. Thirty out of the 40 people with pleural calcification reported having no occupational exposure to either Libby vermiculite or asbestos. Our findings indicate that low-dose HRCT can be considered for screening certain former vermiculite mine/mill workers and their household contacts who have indeterminate chest radiographs and may be useful for diagnosing a suspicious finding on a chest radiograph, particularly in a high-risk person.

Abstract  Fibrous tremolite is a widespread amphibole asbestiform mineral, airborne fibres of which constitute an environmental hazard in Libby, Montana, northern California, and elsewhere.

To determine excess risk from lung cancer, mesothelioma, and all-cause mortality in a cohort of men exposed to tremolite, but no other form of asbestos.

Mortality by certified cause and various measures of exposure to tremolite and related amphibole fibres was assessed in a cohort of 406 vermiculite mineworkers in Libby, Montana, employed before 1963 and followed until 1999.

Total deaths were: lung cancer 44 (SMR 2.40), non-malignant respiratory disease (NMRD) 51 (SMR 3.09), all causes 285 (SMR 1.27); included among the total were 12 deaths ascribed to mesothelioma (4.21% of all deaths). Adjusted linear increments in relative risks (per 100 f/ml.y), estimated by Poisson regression, were: lung cancer (0.36, 95% CI 0.03 to 1.20), NMRD (0.38, 95% CI 0.12 to 0.96), and all deaths (0.14, 95% CI 0.05 to 0.26).

The all-cause linear model would imply a 14% increase in mortality for mine workers exposed occupationally to 100 f/ml.y or about 3.2% for a general population exposed for 50 years to an ambient concentration of 0.1 f/ml. Amphibole fibres, tremolite in particular, are likely to be disproportionately responsible for cancer mortality in persons exposed to commercial chrysotile, but to what extent cannot be readily assessed.

Abstract  Mining, handling, processing, and personal or commercial use of asbestos-contaminated vermiculite have led to widespread contamination of the Libby, Montana, area. We initiated a medical testing program in response to reports of respiratory illness in the community. The purpose of this analysis was to identify and quantify asbestos-related radiographic abnormalities among persons exposed to vermiculite in Libby and to examine associations between these outcomes and participants' self-reported exposures. A cross-sectional interview and medical testing were conducted in Libby from July through November 2000 and from July through September 2001. A total of 7,307 persons who had lived, worked, or played in Libby for at least 6 months before 31 December 1990 completed the interview. Of those, 6,668 participants > or = 18 years of age received chest radiographs to assess the prevalence of pleural and interstitial abnormalities. We observed pleural abnormalities in 17.8% of participants and interstitial abnormalities in < 1% of participants undergoing chest radiography. We examined 29 occupational, recreational, household, and other exposure pathways in the analysis. The prevalence of pleural abnormalities increased with increasing number of exposure pathways, ranging from 6.7% for those who reported no apparent exposures to 34.6% for those who reported > or = 12 pathways. The factors most strongly associated with pleural abnormalities were being a former W.R. Grace worker, being older, having been a household contact of a W.R. Grace worker, and being a male. In addition to being a former W.R. Grace worker, environmental exposures and other nonoccupational risk factors were also important predictors of asbestos-related radiographic abnormalities.

Abstract  Background: Asbestos inhalation is recognized as an exposure that increases the risk for the development of lung disease. It is unique among dusts in that it is both a carcinogen and capable of inducing extrapulmonary responses such as pleural thickening and fibrosis as well as malignancy. One feature of asbestos suggested as crucial in its pathological activity is its fibrous morphology. Long fibers that have been inhaled are cleared less readily and are thus more persistent in the body. Furthermore certain experimental models link fiber length to levels of risks for development of certain diseases. The present review will survey the data on this subject. Methods: The review considers experimental models that have been used to assess the response to various lengths of fibers in animal models in addition to data obtained from studies of human materials. The review also emphasizes the importance in defining the method by which a sample is categorized. Results: Data are offered which support the potential for longer fibers as well as shorter fibers to contribute to pathological responses. Conclusions: The data presented argue that asbestos fibers of all lengths induce pathological responses and that caution should be exerted when attempting to exclude any population of inhaled fibers, based on their length, from being contributors to the potential for development of asbestos-related diseases.

Abstract  To elucidate the features of the asbestos fibers contributing to the induction of human malignant mesothelioma, we used high-resolution analytical electron microscopy to determine the type, number, and dimensions of asbestos fibers in lung and mesothelial tissues in 168 cases of mesothelioma. Results: 1. Asbestos fibers were present in almost all of the lung and mesothelial tissues from the mesothelioma cases. 2. The most common types of asbestos fibers in lung were either an admixture of chrysotile with amphiboles, amphibole alone, and occasionally chrysotile alone. In mesothelial tissues, most asbestos fibers were chrysotile. 3. In lung, amosite fibers were greatest in number followed by chrysotile, crocidolite, tremolite/actinolite, and anthophyllite. In mesothelial tissues, chrysotile fibers were 30.3 times more common than amphiboles. 4. In some mesothelioma cases, the only asbestos fibers detected in either lung or mesothelial tissue were chrysotile fibers. 5. The average number of asbestos fibers in both lung and mesothelial tissues was two orders of magnitude greater than the number found in the general population. 6. The majority of asbestos fibers in lung and mesothelial tissues were shorter than 5 micro m in length. Conclusions: 1) Fiber analysis of both lung and mesothelial tissues must be done to determine the types of asbestos fibers associated with the induction of human malignant mesothelioma; 2) short, thin asbestos fibers should be included in the list of fiber types contributing to the induction of human malignant mesothelioma; 3) Results support the induction of human malignant mesothelioma by chrysotile.

Abstract  Asbestos fibers in occupationally exposed individuals relocate from the lung to extrapulmonary sites. A mechanism for relocation is via the lymphatic circulation. Indeed, asbestos fibers have been found in lymph nodes as well as pleural plaques. Our laboratory has recently shown that asbestos fibers also reach the mesentery and omentum in the peritoneal area where a small percentage of mesotheliomas occurs in exposed individuals. The present study uses light and analytical transmission electron microscopy for defining the asbestos burden in digested lung, omentum, and mesentery tissues from individuals considered as representing the general population in East Texas. The findings, when compared with previous data from occupationally exposed individuals, indicate extreme contrasts as to the level and types of fiber burden between individuals representing the groups.

Abstract  BACKGROUND: The thoracic lymph nodes are a part of the clearance system from lung tissue. Accumulation of dust in these nodes are known to occur following some types of exposure. However, no information exists as to asbestos content in lymph nodes from the general population. METHODS: The study cohort consisted of 21 individuals previously defined as nonoccupationally exposed to asbestos. Tissue burden of asbestos obtained from lung analysis by analytical electron microscopy was compared with burden in the lymph nodes. RESULTS: No asbestos fibers were detected in nodes from 8 cases. The majority of the fibers found in lymph nodes were short (<5 microm) and most often noncommercial amphiboles. Ferruginous bodies (FBs) were detected in lymph node from only two samples. CONCLUSIONS: The total asbestos burden in the lung tissue from these individuals was quite low. However, in 12 of the 13 cases that had positive nodes, the tissue burden in the node was appreciably heavier per gram than in the lung. This raises the question as to whether the lymph nodes, though less efficient clearance, may be better indicators of lifetime exposure to dust than lung tissue.

Abstract  Background: The health effects of asbestos are intimately related to the fate of inhaled fibers in the lungs. The kinetics of asbestos fibers have been studied primarily in rodents. The objective of this study was to explore the application of these kinetic models to human autopsy data. Methods: We analyzed the asbestos fiber content of the lungs of 72 Quebec chrysotile miners and millers and 49 control subjects using analytical transmission electron microscopy. Statistical methods included standard multivariate linear regression and locally weighted regression methods. Results: The lung burdens of asbestos bodies and chrysotile and tremolite fibers were correlated, as were the concentrations of short, medium, and long fibers of each asbestos variety. There were significant associations between the duration of occupational exposure and the burdens of chrysotile and tremolite. The concentration of chrysotile decreased with the time since last exposure but the concentration of tremolite did not. The clearance rate varied inversely with the length of chrysotile fibers. For fibers greater than 10μ in length the clearance half-time was estimated to be 8 years. Conclusions: The patterns in our data are compatible with both of the hypotheses suggested from rodent experiments; the existence of a long-term sequestration compartment and overload of clearance mechanisms in this compartment.

Abstract  The primary aim of this prospective study was to examine the tissues and placentas of autopsied stillborn infants for presence of asbestos fibers. Asbestos burden of lung, liver, skeletal muscle, and placenta digests of 82 stillborn infants was determined using standard bleach digestion technique. The digests were examined by electron microscopy, and the types of fibers determined using energy dispersive x-ray analysis and selected area diffraction analysis. Digests of 45 placentas collected from deliveries of liveborn healthy infants were processed and examined similarly as controls. Asbestos fibers were detected in 50% of the fetal digests and 23% of the placental digests of stillborn infants. Of the fibers present, 88% were chrysotile, 10% were tremolite, and 2% were actinolite and anthophyllite. Fibers measured 0.5-16.73 microgram in length (mean 1.55 microgram), and 0.03-0.8 microgram in width (mean 0.098 microgram). Lungs were most frequently positive for fibers (50%), followed by muscle (37%), placenta (23%), and liver (23%). Mean fiber counts were highest in the liver (58,736 f/g), followed by placenta (52,894 f/g), lungs (39,341 f/g), and skeletal muscle (31,733 f/g). Digests of 15% of the control placentas also showed asbestos fibers, although in very small numbers. The mean fiber count of the stillborn placentas (52,894 f/g) was significantly higher than the mean fiber count of the control placentas (mean 19 f/g) (p = 0.001). A highly significant association was found between fiber presence in stillborns and a maternal history of previous abortions (p = 0.007). A significant association was also found between fiber presence and placental diseases (p = 0.041). An association was suggested between working mothers and fiber presence (p = 0.19), although it did not reach statistical significance. The study documents the presence of small and thin asbestos fibers in stillborn fetal tissues and placenta. Significantly higher number of fibers were found in stillborn tissues compared to controls (liveborn placenta). The absence of a maternal history of asbestos-related occupations suggests that the fibers may have been acquired through environmental exposure.

Abstract  Occupational exposure to asbestos has been on decline in the US over the last 2-3 decades. There is, however, concern that environmental asbestos exposure is increasing through the use of asbestos-containing products (Churg 1988; Edelman 1988; Jarvholm et al. 1988; Sebastein et al. 1989). Most of the previous studies on asbestos exposure have included adult subjects only. However, recent studies have demonstrated asbestos fibers in the tissues and/or placenta digests of a series of autopsied stillborn infants (Haque et al. 1992; 1995; 1996). One of these studies found a highly significant difference (p = 0.001) between the mean asbestos counts of tissues from 92 autopsied stillborn infants (52,894 fibers/g) and 45 control placentas of healthy liveborn infants (19 fibers/g) (Haque et al. 1996). A possible relationship between stillbirths and asbestos fiber presence was also suggested by this study. Additionally, significant association was found between a maternal history of previous abortions and asbestos fiber presence in the stillborn tissues (p = 0.007) (Haque et al. 1996).

Abstract  The ability of amosite cored asbestos bodies isolated from human lungs to catalyse damage to phi X174 RFI DNA in vitro was measured and compared with that of uncoated amosite fibres with a similar distribution of length. Asbestos bodies (5000 bodies) suspended for 30 minutes in 50 mM NaCl containing 0.5 micrograms phi X174 RFI DNA, pH 7.5, did not catalyse detectable amounts of DNA single strand breaks. Addition of the reducing agent ascorbate (1 mM), however, resulted in single strand breaks in 10% of the DNA. Asbestos bodies in the presence of a low molecular weight chelator (1 mM) and ascorbate catalysed the formation of single strand breaks in 21% of the DNA with citrate or 77% with ethylenediamine tetra-acetic acid (EDTA), suggesting that mobilisation of iron may increase damage to DNA. Preincubation for 24 hours with desferrioxamine B, which binds iron (Fe (III)) and renders it redox inactive, completely inhibited the reactivity of asbestos bodies with DNA, strongly suggesting that iron was responsible. Amosite fibres (5000 fibres/reaction), with a similar length distribution to that of the asbestos bodies, did not catalyse detectable amounts of single strand breaks in DNA under identical reaction conditions. The results of the present study strongly suggest that iron deposits on the amosite core asbestos bodies were responsible for the formation of DNA single strand breaks in vitro. Mobilisation of iron by chelators seemed to enhance the reactivity of asbestos bodies with DNA. It has been postulated that the in vivo deposition of the coat material on to fibres may be an attempt by the lung defenses to isolate the fibre from the lung surface and thus offer a protective mechanism from physical irritation. These results suggest, however, that the iron that is deposited on asbestos fibres in vivo may be reactive, potentially increasing the damage to biomolecules, such as DNA, above that of the uncoated fibres.

Abstract  It is generally accepted that to cause pulmonary disease, mineral fibers must be relatively long and thin but also able to remain in the lung for long periods. This "biopersistence" of fibers is limited by two main mechanisms of fiber clearance: removal by macrophages after phagocytosis and, for some fibers, by actual dissolution. The relative importance of these mechanisms has not been properly evaluated for any type of fiber and will certainly vary with mineral type. The efficiency of macrophage clearance is greatest with short fibers (< 5 microns long) and is reduced as fibers get longer. Fibers > 50 microns long cannot be cleared by macrophages and for some mineral types they may remain in the lung permanently. Others may fracture into shorter lengths, perhaps aided by chemical dissolution, and thus become susceptible to macrophage clearance. However, for a number of areas relating to fiber removal from the lung parenchyma detailed information is still needed: Do dusts differ in their ability to attract macrophages and stimulate these cells to phagocytosis? Following dust uptake what controls the movement of macrophages? Some may penetrate to the interstitium, some phagocytosing fibers in interstitial sites may migrate back to the alveolar space. Some move to the mucociliary escalator and some to the lymphatics. Some, most importantly, move to the pleura. Fibers are found and phagocytosed in the interstitium during the early stages of disease development, but with time many fibers appear isolated in areas of fibrous tissue. Are such fibers subsequently ignored or can they reenter the disease process after years of isolation? Finally, can phagocytosis by macrophages effect dissolution of fibers?(ABSTRACT TRUNCATED AT 250 WORDS)

Abstract  Oncogenesis and in vitro data (reported elsewhere in detail) are compared on the basis of relative activity by mass and by dimensional fiber parameters. When tumor induction is compared to the number of fibers of various lengths and aspect ratios in the dose in rats to the degree of tumor induction, a degree of difference with the long thin fiber concept of tumorigenesis by mineral fibers is noted. Consistency is re-established, however, when cognizance is taken of the change in the length and aspect ratio that took place during residence in the lung. This change resulted in a severalfold excess for ferroactinolite of all fiber lengths with high aspect ratios, produced as a result of longitudinal splitting of the introduced fibers. The response by mass in the in vitro procedures did not mimic oncogenesis. When mass was so adjusted that there were an equal number of mineral fibers, aspect ratio greater than 3, for dose for the two minerals, agreement was closer in both the rabbit alveolar macrophage toxicity test and the clonal cytotoxicity assay in Chinese hamster ovary cells. When activity was related to the number of mineral fibers, the same aspect ratio computed to have been contained in the mass dose, agreement with the relative induction of lung tumors was closer. In all cases, erythrocyte lysis was more active in reflecting the number of mineral fibers.

Abstract  Radiologic signs of pulmonary asbestos disease were found in 11.3 per cent of 274 wives of shipyard workers who were 20 or more years from initial hiring-on in shipyards in Los Angeles County. Asbestosis was also found in 7.6 per cent of 79 sons and 2.1 per cent of 140 daughters of these workers. The wives, sons, and daughters were without occupational exposure. Comparable radiographic signs were not found in comparison groups. It is probable that asbestos exposure in the household places these family members at risk for mesothelioma and lung cancer.

Abstract  BIOSIS COPYRIGHT: BIOL ABS. RRM HUMAN ENVIRONMENTAL TOXICITY CARCINOGEN AIR POLLUTION EFFECTS