Abstract  Zircons from an eclogite and a diamond-bearing metapelite near the Kimi village (north-eastern Rhodope Metamorphic Complex, Greece) have been investigated by Micro Raman Spectroscopy, SEM, SHRIMP and LA-ICPMS to define their inclusion mineralogy, ages and trace element contents. In addition, the host rocks metamorphic evolution was reconstructed and linked to the zircon growth domains. The eclogite contains relicts of a high pressure stage (ca. 700 degrees C and > 17.5 kbar) characterised by matrix omphacite with Jd(40-35). This assemblage was overprinted by a lower pressure, higher temperature metamorphic event (ca. 820 C and 15.5-17.5 kbar), as indicated by the presence of clinopyroxene (Jd(35-20)) and plagioclase. Biotite and pargasitic amphibole represent a later stage, probably related to an influx of fluids. Zircons separated from the eclogite contain magmatic relicts indicating Permian crystallization of a quartz-bearing gabbroic protolith. Inclusions diagnostic of the high temperature, post-eclogitic overprint are found in metamorphic zircon domain Z2 which ages spread over a long period (160-95 Ma). Based on zircon textures, zoning and chemistry, we suggest that the high-temperature peak occurred at or before ca. 160 Ma and the zircons were disturbed by a later event possibly at around 115 Ma. Small metamorphic zircon overgrowths with a different composition yield an age of 7913 Ma, which is related to a distinct amphibolite-facies metamorphic event. The metapelitic host rock consists of a mesosome with garnet, mica and kyanite, and a quartz- and plagioclase-bearing leucosome, which formed at granulate-facies conditions. Based on previously reported micro-diamond inclusions in garnet, the mesosome is assumed to have experienced UHP conditions. Nevertheless, (U)HP mineral inclusions were not found in the zircons separated from the diamond-bearing metapelite. Inclusions of melt, kyanite and high-Ti biotite in a first metamorphic zircon domain suggest that zircon formation occurred during pervasive granulate-facies metamorphism. An age of 171 +/- 1 Ma measured on this zircon domain constrains the high-temperature metamorphic event. A second, inclusion-free metamorphic domain yielded an age of 160 +/- 1 Ma that is related to decompression and melt crystallization. The similar age data obtained from the samples indicate that both rock types recorded a high-T metamorphic overprint at granulate-facies conditions at ca. 170-160 Ma. This age implies that any high pressure or even ultra-high pressure metamorphism in the Kimi Complex occurred before that time. Our findings define new constraints for the geodynamic evolution for the Alpine orogenic cycle within the northernmost Greek part of the Rhodope Metamorphic Complex. It is proposed that the rocks of the Kimi Complex belong to a suture zone squeezed between two continental blocks and result from a Paleo-ocean basin, which should be located further north of the Jurassic Vardar Ocean. (C) 2007 Elsevier B.V. All rights reserved.

Abstract  HEEP COPYRIGHT: BIOL ABS. Bilateral pleural calcifications occur endemically in regions with dispersed asbestos outcroppings which were not economically exploited. Detailed epidemiological and mineralogical studies were done. Asbestos in the form of anthophyllite and tremolite was a constant finding in the soil of the yards and fields of plaque carriers. The possible etiologic significance of sepiolite, an amphibole derivative frequently discovered in soil samples is discussed. The soil of the yard and field of a family with 3 plaque carriers (Rhodope Mountains, S.E. Bulgaria) contained the fibrous mineral sepiolite as most important amphibole variety (up to 5% of the soil samples), whereas anthophyllite and tremolite asbestos were scarce. Such mineralogic findings and published reference to the biological effects of sepiolite in vitro make the participation of the fibrous silicate sepiolite in the formation of endemic pleural plaques very probable.

Abstract  To assess the risk of lung cancer and mesothelioma after environmental exposure to crocidolite for 20-30 years, a retrospective cohort study was carried out in farmers who had been exposed to crocidolite in environment. 1610 subjects were followed up for 9 years (Jan. 1, 1987 Dec. 31, 1995). The control group consisted of 7646 farmers who resided in the noncrocidolite pollution rural area in the same province. The results showed that the annual mortality rate was 43.75 per 100,000 population for lung cancer, and 36.46 per 100,000 for mesothelioma. Significantly high risks of lung cancer (RR 5.67) and mesothelioma (RR 182.3) were noted. These results demonstrate a strong causal association between lung cancer, mesothelioma and exposure to crocidolite.

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  In this investigation, the combination of 1-beta-D-arabinofuranosylcytosine and hydroxyurea was used to inhibit the polymerase step of DNA excision repair. The DNA single-strand breaks (SSB), which accumulated in the presence of these agents, were measured by alkaline elution. With this approach, DNA SSB were detected in normal human fibroblasts after exposure to trans-platinum(II)diamminedichloride, formaldehyde, or potassium chromate. These agents all share the common feature that they induce DNA-protein cross-links in mammalian cells. In the case of trans-platinum(II)diamminedichloride or formaldehyde, the frequency of these SSB was markedly less in excision-deficient xeroderma pigmentosum cells. With chromate, a high level of SSB was induced in both normal and xeroderma pigmentosum cells; these results indicate that chromate damage to DNA is repaired by a mechanism different than the classical excision pathway since xeroderma pigmentosum cells responded normally. Several other agents were investigated with this approach, and no SSB were detected with nickel sulfate, 12-O-tetradecanoylphorbol-13-acetate or asbestos fibers in the presence of the polymerase inhibitor. This approach was found to be a very sensitive method to detect DNA excision repair.

Abstract  Quantitative estimates of the risk of lung cancer or mesothelioma in humans from asbestos exposure made by the U. S. Environmental Protection Agency (EPA) make use of estimates of potency factors based on phase-contrast microscopy (PCM) and obtained from cohorts exposed to asbestos in different occupational environments. These potency factors exhibit substantial variability. The most likely reasons for this variability appear to be differences among environments in fiber size and mineralogy not accounted for by PCM.

In this article, the U. S. Environmental Protection Agency (EPA) models for asbestos-related lung cancer and mesothelioma are expanded to allow the potency of fibers to depend upon their mineralogical types and sizes. This is accomplished by positing exposure metrics composed of nonoverlapping fiber categories and assigning each category its own unique potency. These category-specific potencies are estimated in a meta-analysis that fits the expanded models to potencies for lung cancer (K(L)'s) or mesothelioma (K(M)'s) based on PCM that were calculated for multiple epidemiological studies in our previous paper (Berman and Crump, 2008). Epidemiological study-specific estimates of exposures to fibers in the different fiber size categories of an exposure metric are estimated using distributions for fiber size based on transmission electron microscopy (TEM) obtained from the literature and matched to the individual epidemiological studies. The fraction of total asbestos exposure in a given environment respectively represented by chrysotile and amphibole asbestos is also estimated from information in the literature for that environment. Adequate information was found to allow K(L)'s from 15 epidemiological studies and K(M)'s from 11 studies to be included in the meta-analysis.

Since the range of exposure metrics that could be considered was severely restricted by limitations in the published TEM fiber size distributions, it was decided to focus attention on four exposure metrics distinguished by fiber width: "all widths," widths > 0.2 mu m, widths < 0.4 mu m, and widths < 0.2 mu m, each of which has historical relevance. Each such metric defined by width was composed of four categories of fibers: chrysotile or amphibole asbestos with lengths between 5 mu m and 10 mu m or longer than 10 mu m. Using these metrics three parameters were estimated for lung cancer and, separately, for mesothelioma: K(LA), the potency of longer (length > 10 mu m) amphibole fibers; rpc, the potency of pure chrysotile (uncontaminated by amphibole) relative to amphibole asbestos; and rps, the potency of shorter fibers (5 mu m < length < 10 mu m) relative to longer fibers.

For mesothelioma, the hypothesis that chrysotile and amphibole asbestos are equally potent (rpc = 1) was strongly rejected by every metric and the hypothesis that (pure) chrysotile is nonpotent for mesothelioma was not rejected by any metric. Best estimates for the relative potency of chrysotile ranged from zero to about 1/200th that of amphibole asbestos (depending on metric). For lung cancer, the hypothesis that chrysotile and amphibole asbestos are equally potent (rpc = 1) was rejected (p <= .05) by the two metrics based on thin fibers (length < 0.4 mu m and < 0.2 mu m) but not by the metrics based on thicker fibers.

The "all widths" and widths < 0.4 mu m metrics provide the best fits to both the lung cancer and mesothelioma data over the other metrics evaluated, although the improvements are only marginal for lung cancer. That these two metrics provide equivalent (for mesothelioma) and nearly equivalent (for lung cancer) fits to the data suggests that the available data sets may not be sufficiently rich (in variation of exposure characteristics) to fully evaluate the effects of fiber width on potency. Compared to the metric with widths > 0.2 mu m with both rps and rpc fixed at 1 (which is nominally equivalent to the traditional PCM metric), the "all widths" and widths < 0.4 mu m metrics provide substantially better fits for both lung cancer and, especially, mesothelioma.

Although the best estimates of the potency of shorter fibers (5 < length < 10 mu m) is zero for the "all widths" and widths < 0.4 mu m metrics (or a small fraction of that of longer fibers for the widths > 0.2 mu m metric for mesothelioma), the hypothesis that these shorter fibers were nonpotent could not be rejected for any of these metrics. Expansion of these metrics to include a category for fibers with lengths < 5 mu m did not find any consistent evidence for any potency of these shortest fibers for either lung cancer or mesothelioma.

Despite the substantial improvements in fit over that provided by the traditional use of PCM, neither the "all widths" nor the widths < 0.4 mu m metrics (or any of the other metrics evaluated) completely resolve the differences in potency factors estimated in different occupational studies. Unresolved in particular is the discrepancy in potency factors for lung cancer from Quebec chrysotile miners and workers at the Charleston, SC, textile mill, which mainly processed chrysotile from Quebec. A leading hypothesis for this discrepancy is limitations in the fiber size distributions available for this analysis. Dement et al. (2007) recently analyzed by TEM archived air samples from the South Carolina plant to determine a detailed distribution of fiber lengths up to lengths of 40 mu m and greater. If similar data become available for Quebec, perhaps these two size distributions can be used to eliminate the discrepancy between these two studies.

Abstract  The most recent update of the U.S. Environmental Protection Agency (EPA) health assessment document for asbestos (Nicholson, 1986, referred to as “the EPA 1986 update”) is now 20 years old. That document contains estimates of “potency factors” for asbestos in causing lung cancer (KL’s) and mesothelioma (KM’s) derived by fitting mathematical models to data from studies of occupational cohorts. The present paper provides a parallel analysis that incorporates data from studies published since the EPA 1986 update. The EPA lung cancer model assumes that the relative risk varies linearly with cumulative exposure lagged 10 years. This implies that the relative risk remains constant after 10 years from last exposure. The EPA mesothelioma model predicts that the mortality rate from mesothelioma increases linearly with the intensity of exposure and, for a given intensity, increases indefinitely after exposure ceases, approximately as the square of time since first exposure lagged 10 years. These assumptions were evaluated using raw data from cohorts where exposures were principally to chrysotile (South Carolina textile workers, Hein et al., 2007; mesothelioma only data from Quebec miners and millers, Liddell et al., 1997) and crocidolite (Wittenoom Gorge, Australia miners and millers, Berry et al., 2004) and using published data from a cohort exposed to amosite (Paterson, NJ, insulation manufacturers, Seidman et al., 1986). Although the linear EPA model generally provided a good description of exposure response for lung cancer, in some cases it did so only by estimating a large background risk relative to the comparison population. Some of these relative risks seem too large to be due to differences in smoking rates and are probably due at least in part to errors in exposure estimates. There was some equivocal evidence that the relative risk decreased with increasing time since last exposure in theWittenoom cohort, but none either in the South Carolina cohort up to 50 years from last exposure or in the New Jersey cohort up to 35 years from last exposure. The mesothelioma model provided good descriptions of the observed patterns of mortality after exposure ends, with no evidence that risk increases with long times since last exposure at rates that vary from that predicted by the model (i.e., with the square of time). In particular, the model adequately described the mortality rate in Quebec chrysotile miners and millers up through >50 years from last exposure. There was statistically significant evidence in both the Wittenoom and Quebec cohorts that the exposure intensity-response is supralinear1 rather than linear. The best-fitting models predicted that the mortality rate varies as [intensity]0.47 for Wittenoom and as [intensity]0.19 for Quebec and, in both cases, the exponent was significantly less than 1 (p < .0001). Using the EPA models, KL’s and KM’s were estimated from the three sets of raw data and also frompublished data covering a broader range of environments than those originally addressed in the EPA 1986 update. Uncertainty in these estimates was quantified using “uncertainty bounds” that reflect both statistical and nonstatistical uncertainties. Lung cancer potency factors (KL’s) were developed from 20 studies from 18 locations, compared to 13 locations covered in the EPA 1986 update. Mesothelioma potency factors (KM’s) were developed for 12 locations compared to four locations in the EPA 1986 update. Although the 4 locations used to calculate KM in the EPA 1986 update include one location with exposures to amosite and three with exposures to mixed fiber types, the 14 KM’s derived in the present analysis also include 6 locations in which exposures were predominantly to chrysotile and 1 where exposures were only to crocidolite. The KM’s showed evidence of a trend, with lowest KM’s obtained fromcohorts exposed predominantly to chrysotile and highest KM’s from cohorts exposed only to amphibole asbestos, with KM’s from cohorts exposed to mixed fiber types being intermediate between the KM’s obtained from chrysotile and amphibole environments. Despite the considerable uncertainty in the KM estimates, the KM from the Quebec mines and mills was clearly smaller than those from several cohorts exposed to amphibole asbestos or a mixture of amphibole asbestos and chrysotile. For lung cancer, although there is some evidence of larger KL’s fromamphibole asbestos exposure, there is a good deal of dispersion in the data, and one of the largest KL‘s is from the South Carolina textile mill where exposures were almost exclusively to chrysotile. This KL is clearly inconsistent with the KL obtained from the cohort of Quebec chrysotile miners and millers. The KL’s and KM’s derived herein are defined in terms of concentrations of airborne fibers measured by phase-contrast microscopy (PCM), which only counts all structures longer than 5 μm, thicker than about 0.25 μm, and with an aspect ratio ≥3:1. Moreover, PCM does not distinguish between asbestos and nonasbestos particles. One possible reason for the discrepancies between the KL’s and KM’s from different studies is that the category of structures included in PCM counts does not correspond closely to biological activity. In the accompanying article (Berman and Crump, 2008) the KL’s and KM’s and related uncertainty bounds obtained in this article are paired with fiber size distributions from the literature obtained using transmission electron microscopy (TEM). The resulting database is used to define KL’s and KM’s that depend on both the size (e.g., length and width) and mineralogical type (e.g., chrysotile or crocidolite) of an asbestos structure. An analysis is conducted to determine how well different KL and KM definitions are able to reconcile the discrepancies observed herein among values obtained from different environments.

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  The results of field, petrographic and geochemical work of the granitoids of Hutti-Gurgunta area in the northern part of Eastern Dharwar Craton (EDC) is presented in this paper. This crustal section comprises polyphase banded to foliated TTG gneisses, middle amphibolite facies Gurgunta schist belt and upper greenschist facies Hutti schist belt and abundant granite plutons. The focus of the present study is mainly on basement TTG gneisses and a granite pluton (similar to 240 sq km areal extent), to discuss crustal accretion processes including changing petrogenetic mechanism and geodynamic setting. The TTGs contain quartz, plagioclase, lesser K-feldspar and hornblende with minor biotite while the granite contain quartz, plagioclase, K-feldspar and hornblende. Late stage alteration (chloritisation, sericitisation and epidotisation) is wide spread in the entire area. A huge synplutonic mafic body which is dioritic to meladioritic in composition injects the granite and displays all stages of progressive mixing and hybridization. The studied TTGs and granite show distinct major and trace element patterns. The TTGs are characterized by higher SiO2, high Al2O3, and Na2O, low TiO2, Mg#, CaO, K2O and LILE, and HFS elements compared to granite. TTGs define strong trondhjemite trend whilst granite shows calc-alkaline trend. However, both TTGs and granite show characteristics of Phanerozoic high-silica adakites. The granite also shows characteristics of transitional TTGs in its high LILE, and progressive increase in K2O with differentiation. Both TTGs and granite define linear to sub-linear trends on variation diagrams. The TTGs show moderate total REE contents with fractionated REE patterns (La/Yb-N = 17.73-61.73) and slight positive or without any significant Eu anomaly implying little amount of amphibole or plagioclase in residual liquid. On the other hand, the granite displays poor to moderate fractionation of REE patterns (La/Yb-N = 9.06-67.21) without any significant Eu anomaly. The TTGs have been interpreted to be produced by low-K basaltic slab melting at shallow depth, whereas the granite pluton has been formed by slab melting at depth and these melts interacted with peridotite mantle wedge. Such changing petrogenetic mechanisms and geodynamic conditions explain increase in the contents of MgO, CaO, Ni and Cr from 2700 Ma to 2500 Ma granitoids in the EDC.

Abstract  New geochemical and isotopic data are presented from the oldest part of the Cumbre Vieja volcano, La Palma (Canary Islands), located near the assumed emergence of the Canary mantle plume. The volcanics comprise a suite dominated by basanite flows with subordinate amounts of phono-tephrite, tephri-phonolite and phonolite flows and intrusives. Two compositionally different basanite groups have been identified, both with HIMU (high-mu)-type incompatible trace element characteristics: Primitive high-MgO basanites (10.7-12.1% MgO), found only at the base of a stratigraphic profile near Fuencaliente on the south coast, and intermediate-MgO basanites (6.0-7.3% MgO), exposed in the upper part of the profile and widespread on the east coast of La Palma. The high-MgO basanites are interpreted as near-primary mantle melts (primary composition 14-15% MgO) derived by progressive melting (2.9% to 4.5%) of a common lithospheric mantle source. Model calculations indicate that it is not possible to generate the intermediate-MgO basanites from the high-MgO group by crystal fractionation of observed phenocrysts. Relative to intermediate-MgO basanites, the high-MgO flows have lower concentrations of LIL and HFS elements, except for Ti, which is markedly enriched in the primitive rocks (3.7-4.7% TiO2 vs 3.4-3.9% TiO2)Fuencaliente volcanics display limited temporal isotopic variations suggested to be a result of mixing of melts originating from the rising plume and the metazomatized lithospheric mantle. Sr-87/Sr-86 and Nd-143/Nd-144 ratios range 0.70305-0.70311 and 0.51285-0.51291, respectively, while the corresponding ranges in Pb-isotope ratios are Pb-206/Pb-204= 19.46-19.64, Pb-207/Pb-204=15.55-15.61, and Pb-208/Pb-204=39.16-39.53. The overall variation of the Cumbre Vieja isotopic data can be accounted for by mixtures of three mantle components in the proportions 72-79% plume source (LVC=low velocity component), 9-16% depleted mantle (DM) and up to 12% enriched mantle (EMI). Negative Delta 7/4 Pb (-0.6 to -5.4) in the Cumbre Vieja volcanics suggest derivation from a young HIMU mantle source. The relative abundance of plume source material increase in younger rocks in the Fuencaliente section, suggesting waning plume-lithosphere interaction during the emplacement of this part of the Cumbre Vieja volcano. The high-MgO volcanics define regular and systematic geochemical trends, interpreted as partial melting trends, when plotted against abundances of highly incompatible elements (P, Ce). Evaluation of minor and trace element variation in consecutive melts suggests control by residual amphibole, phlogopite, garnet and a Ti-bearing phase, possibly ilmenite. The melting mode changed gradually, allowing increasing input from residual phlogopite during partial melting. The residual mineralogy constrains the source region of the high-MgO basanites to the lowermost oceanic lithospheric mantle, presumably around 100 km depths. (c) 2005 Elsevier B.V. All rights reserved.

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  As evidenced by the recent report of the Commission of the European Communities (CEEC) project (Detection of Aneugenic Chemicals-CEEC project, 1993), there currently is a great deal of effort towards developing and validating assays to detect aneuploidy-inducing chemicals. In this report, we describe the utility of the Syrian hamster embryo (SHE) cell transformation assay for detecting carcinogens with known or suspected aneuploidy-inducing activity. The following carcinogens were tested: asbestos, benomyl, cadmium chloride, chloral hydrate, diethylstilbestrol dipropionate, and griseofulvin. Thiabendazole, a noncarcinogen, was also tested. Chemicals of unknown or inconclusive carcinogenicity data, colcemid, diazepam, econazole nitrate, and pyrimethamine were also evaluated. All of the above chemicals except thiabendazole induced a significant increase in morphological transformation (MT) in SHE cells. Based on these results as well as those published in the literature previously, the SHE cell transformation assay appears to have utility for detecting carcinogens with known or suspected aneuploidy-inducing ability.

Abstract  Results on 105 cases with histopathologically confirmed non-Hodgkin's lymphoma (NHL) and 335 controls from a previously published case-control study on malignant lymphoma are presented together with some extended analyses. No occupation was a risk factor for NHL. Exposure to phenoxyacetic acids yielded, in the univariate analysis, an odds ratio of 5.5 with a 95% confidence interval of 2.7-11. Most cases and controls were exposed to a commercial mixture of 2,4-dichlorophenoxyacetic acid and 2,4,5-trichlorophenoxyacetic acid. Exposure to chlorophenols gave an odds ratio of 4.8 (2.7-8.8) with pentachlorophenol being the most common type. Exposure to organic solvents yielded an odds ratio of 2.4 (1.4-3.9). These results were not significantly changed in the multivariate analysis. Dichlorodiphenyltrichloroethane, asbestos, smoking, and oral snuff were not associated with an increased risk for NHL. The results regarding increased risk for NHL following exposure to phenoxyacetic acids, chlorophenols, or organic solvents were not affected by histopathological type, disease stage, or anatomical site of disease presentation. Median survival was somewhat longer in cases exposed to organic solvents than the rest. This was explained by more prevalent exposure to organic solvents in the group of cases with good prognosis NHL histopathology.

Abstract  Exposures to an amphibole fiber in Libby, Montana cause increases in malignant mesothelioma (MM), a tumor of the pleural and peritoneal cavities with a poor prognosis. Affymetrix microarray/GeneSifter analysis was used to determine alterations in gene expression of a human mesothelial cell line (LP9/TERT-1) by a non-toxic concentration (15×10(6) μm2/cm2) of unprocessed Libby six-mix and negative (glass beads) and positive (crocidolite asbestos) controls. Because manganese superoxide dismutase (MnSOD; SOD2) was the only gene upregulated significantly (p < 0.05) at both 8 and 24 h, we measured SOD protein and activity, oxidative stress and glutathione (GSH) levels to better understand oxidative events after exposure to non-toxic (15×10(6) μm2/cm2) and toxic concentrations (75×10(6) μm2/cm2) of Libby six-mix.

Exposure to 15×10(6) μm2/cm2 Libby six-mix elicited significant (p < 0.05) upregulation of one gene (SOD2; 4-fold) at 8 h and 111 gene changes at 24 h, including a 5-fold increase in SOD2. Increased levels of SOD2 mRNA at 24 h were also confirmed in HKNM-2 normal human pleural mesothelial cells by qRT-PCR. SOD2 protein levels were increased at toxic concentrations (75×10(6) μm2/cm2) of Libby six-mix at 24 h. In addition, levels of copper-zinc superoxide dismutase (Cu/ZnSOD; SOD1) protein were increased at 24 h in all mineral groups. A dose-related increase in SOD2 activity was observed, although total SOD activity remained unchanged. Dichlorodihydrofluorescein diacetate (DCFDA) fluorescence staining and flow cytometry revealed a dose- and time-dependent increase in reactive oxygen species (ROS) production by LP9/TERT-1 cells exposed to Libby six-mix. Both Libby six-mix and crocidolite asbestos at 75×10(6) μm2/cm2 caused transient decreases (p < 0.05) in GSH for up to 24 h and increases in gene expression of heme oxygenase 1 (HO-1) in LP9/TERT-1 and HKNM-2 cells.

Libby six-mix causes multiple gene expression changes in LP9/TERT-1 human mesothelial cells, as well as increases in SOD2, increased production of oxidants, and transient decreases in intracellular GSH. These events are not observed at equal surface area concentrations of nontoxic glass beads. Results support a mechanistic basis for the importance of SOD2 in proliferation and apoptosis of mesothelial cells and its potential use as a biomarker of early responses to mesotheliomagenic minerals.

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  A cohort of 1,154 employees, mainly women, who had worked 1940-1945 on the manufacture of military gas masks using filter pads containing 20% crocidolite, was traced through 2003, by which time 65 were known to have died from mesothelioma. The last known death with mesothelioma was in 1994, whereas a further 5 cases would have been expected in those with known duration of exposure. Lung tissue samples, from 50 deaths from mesothelioma and 20 other causes, had been analyzed for mineral fiber content. For ten of the mesothelioma cases data on fiber size were collected. Crocidolite fiber concentrations were analyzed in relation to exposure by time and duration. Fiber concentrations overall fell fairly steadily by decade of death, and increased with length of exposure up to 36 months and then fell sharply. The annual rate of elimination estimated by regression was 7.5% corresponding to a half life of 9.2 years. The proportion of fibers longer than 6 mum increased over time implying that the shorter fibers were eliminated more rapidly than the longer ones. The decline in concentrations with time confirms the hypothesis that crocidolite and, by inference, other amphibole fibers are slowly removed from the lung, but since the longer more carcinogenic fibers were cleared more slowly it is unclear to what extent this clearance explains the slowing down of the increase in mesothelioma mortality from about 40 years from the most recent exposure. The exact biostatistical models which most closely conform with the data remain open to question.

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  Libby, Montana is the site of a large vermiculite deposit that was mined between 1920 and 1990 to extract vermiculite for commercial applications such as insulation, gardening products, and construction materials. The Libby vermiculite deposit also contains amphibole minerals including tremolite, actinolite, richterite, and winchite. Historically, Libby mine workers experienced high exposures to amphibole structures, and, as a group, have experienced the health consequences of those occupational exposures. It has been suggested that Libby residents also have been and continue to be exposed to amphibole structures released during the vermiculite mining operations and therefore are at increased risk for disease. The Agency for Toxic Substance and Disease Registry (ATSDR) conducted two epidemiological-type studies of residents living in Libby and the surrounding areas to assess these risks. The Environmental Protection Agency (EPA) collected and analyzed exposure data in Libby and used those data to project risks of asbestos-associated disease for Libby residents. The EPA has placed the Libby Asbestos Site, which includes the mine and the town of Libby, on its National Priority List of hazardous waste sites in need of clean up. This article presents a review of the exposure studies conducted in Libby and an analysis of health risks based on the data collected in those studies. Libby mine workers have experienced elevated levels of asbestos-associated disease as a consequence of their occupational exposures to amphibole structures. Libby residents' exposures typically are substantially lower than mine workers' historical exposures, and the health risk projections for residents are, accordingly, substantially lower.

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  The case history is presented of a lung transplant recipient who developed malignant mesothelioma. This is thought to be the first such report. Mesothelioma should be suspected in lung transplant recipients with a haemorrhagic pleural effusion in the native lung when there is no convincing evidence for bronchogenic carcinoma or post transplant lymphoproliferative disease, even in the absence of exposure to asbestos.

Abstract  SV40 is a DNA tumor virus thrust upon human populations primarily as a contaminant in various vaccine preparations. Some estimates suggest that millions of people are currently infected with the virus. The virus causes primary brain tumors, bone tumors, lymphomas, and mesotheliomas when injected into some rodent models. It has also been detected in a similar spectrum of human tumors. However, epidemiological studies have failed to conclusively demonstrate a higher incidence of disease in affected populations. To date, over 60 reports from 49 different laboratories have shown SV40 sequences in tissues from human cancer patients. Six studies, however, have failed to detect evidence of virus in similar tissues. Some have suggested that SV40 may act as a cocarcinogen with asbestos to cause mesothelioma formation, or that it may be responsible for the 10-20% of mesotheliomas with no reported history of asbestos exposure. This report briefly covers the historical evidence for SV40 carcinogenesis and then covers experiments now underway to better understand the role of SV40 in human mesotheliomas.