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Objectives: Based on a pooled analysis of data from an international study, evaluate total and cause-specific mortality among hardmetal production workers with emphasis on lung cancer., Methods: Study members were 32,354 workers from three companies and 17 manufacturing sites in five countries. We computed standardized mortality ratios and evaluated exposure-response via relative risk regression analysis., Results: Among long-term workers, we observed overall deficits or slight excesses in deaths for total mortality, all cancers, and lung cancer and found no evidence of any exposure-response relationships for lung cancer., Conclusions: We found no evidence that duration, average intensity, or cumulative exposure to tungsten, cobalt, or nickel, at levels experienced by the workers examined, increases lung cancer mortality risks. We also found no evidence that work in these facilities increased mortality risks from any other causes of death.

Objective: To generate quantitative exposure estimates for use in retrospective occupational cohort mortality studies of the hardmetal industry., Methods: Job-exposure matrices (JEMs) were constructed for cobalt, tungsten, and nickel over the time period 1952 to 2014. The JEMs consisted of job class categories, based on job titles and processes performed, and exposure estimates calculated from available company industrial hygiene measurements., Results: Exposure intervals of one-half order magnitude were established for all three agents. Eight job classes had significantly decreasing time trends for cobalt exposure; no significant time trends were detected for tungsten or nickel exposures., Conclusions: The levels of exposures determined for this study were similar to or lower than those previously reported for the hardmetal industry during the 1952 to 2014 study period.

Objectives: To evaluate total and cause-specific mortality among hardmetal production workers with emphasis on lung cancer., Methods: Subjects were 7304 workers ever employed in one of eight US plants from 1952 to 2008. Vital status through 2012 was determined for 97% of subjects and cause of death for 98.3% of 1087 deaths. We computed standardized mortality ratios (SMRs) and evaluated exposure-response via relative risk regression analysis., Results: We observed overall deficits in deaths for total mortality, all cancers, and lung cancer and found no evidence of any exposure-response relationships for lung cancer., Conclusions: We found no evidence that exposure to tungsten, cobalt, or nickel, at levels experienced by the workers examined, increases lung cancer mortality risks. We also found no evidence that work in the US hardmetal industry increases mortality risks from any other causes of death.

Objective: The aim of this study was to characterize the mortality at two hardmetal production factories in the United Kingdom as part of an international study., Methods: Standardized mortality ratios (SMRs) were calculated on the basis of mortality rates for England and Wales, and local rates. A nested case-control study of lung cancer was undertaken., Results: The cohort comprised 1538 workers, with tracing complete for 94.4%. All-cause mortality was statistically significantly low for all cancers and nonmalignant respiratory disease, and for lung cancer was nonsignificantly low. The SMR for lung cancer for maintenance workers was elevated, based on only six deaths. The odds ratio for lung cancer per year of exposure to hardmetal was 0.93 (0.76 to 1.13)., Conclusions: In this small study, there is no evidence to support that working in the UK hardmetal manufacturing industry increased mortality from any cause including lung cancer.

Objective: The aim of this study was to investigate a cohort in German hardmetal industry, especially relationship between exposures to cobalt, with and without tungsten, and risks of total and cause-specific mortality., Methods: The cohort comprises blue-collar workers at three German plants who were employed in hardmetal processing. Individual cumulative exposures and long-term average concentrations were estimated for cobalt, nickel, tungsten, respirable, and inhalable dust. Standardized mortality ratios (SMRs) were calculated for external comparisons. Time-dependent multivariable Cox models were performed for internal analyses., Results: Elevated SMRs were found for all-cause, heart diseases, and nonmalignant respiratory diseases mortality, but not for lung cancer. Internal analyses did not show increased risks for any endpoints, and no exposure-response relationship was indicated., Conclusions: This study does not provide evidence for elevated lung cancer risks. Methodologic limitations, incomplete ascertainment of death causes in particular, impede conclusions about exposure effects.

Prior investigation on medical laser interaction with tissue has suggested device operational parameter settings influence laser generated air contaminant emission, but this has not been systematically explored. A laboratory-based simulated medical laser procedure was designed and pilot tested to determine the effect of laser operational parameters on the size-specific mass emission rate of laser generated particulate matter. Porcine tissue was lased in an emission chamber using two medical laser systems (CO2, λ = 10,600 nm; Ho:YAG, λ = 2100 nm) in a fractional factorial study design by varying three operational parameters (beam diameter, pulse repetition frequency, and power) between two levels (high and low) and the resultant plume was measured using two real-time size-selective particle counters. Particle count concentrations were converted to mass emission rates before an analysis of variance was used to determine the influence of operational parameter settings on size-specific mass emission rate. Particle shape and diameter were described for a limited number of samples by collecting particles on polycarbonate filters, and photographed using a scanning electron microscope (SEM) to examine method of particle formation. An increase in power and decrease in beam diameter led to an increase in mass emission for the Ho:YAG laser at all size ranges. For the CO2 laser, emission rates were dependent on particle size and were not statistically significant for particle ranges between 5 and 10 µm. When any parameter level was increased, emission rate of the smallest particle size range also increased. Beam diameter was the most influential variable for both lasers, and the operational parameters tested explained the most variability at the smallest particle size range. Particle shape was variable and some particles observed by SEM were likely created from mechanical methods. This study provides a foundation for future investigations to better estimate size-specific mass emission rates and particle characteristics for additional laser operational parameters in order to estimate occupational exposure, and to inform control strategies., (© The Author 2015. Published by Oxford University Press on behalf of the British Occupational Hygiene Society.)

Objective: To reconstruct agent-specific occupational exposures for a cohort of jet engine manufacturing workers for use in an epidemiological mortality study., Methods: Potential chemical and physical exposures at eight jet engine manufacturing and overhaul/repair plants were evaluated for the period 1952 to 2001. Eleven agents were selected for detailed examination, and a job-exposure matrix was constructed., Results: Quantitative exposure estimates were generated for metalworking fluids, nickel, cobalt, chromium, solvents, and incomplete combustion aerosol from metalworking fluids. Qualitative exposure estimates were assigned for ionizing radiation, electromagnetic fields, polychlorinated biphenyls, and lead-cadmium. All exposures showed decreasing trends over the study period., Conclusions: The quantitative exposure levels generated in this study were lower than early contemporaneous professional practice recommendations and were similar to or lower than published data from other industries.

Objective: To determine whether glioblastoma (GB) incidence rates among jet engine manufacturing workers were associated with specific chemical or physical exposures., Methods: Subjects were 210,784 workers employed from 1952 to 2001. We conducted a cohort incidence study and two nested case-control studies with focus on the North Haven facility where we previously observed a not statistically significant overall elevation in GB rates. We estimated individual-level exposure metrics for 11 agents., Results: In the total cohort, none of the agent metrics considered was associated with increased GB risk. The GB incidence rates in North Haven were also not related to workplace exposures, including the "blue haze" exposure unique to North Haven., Conclusions: If not due to chance alone, GB rates in North Haven may reflect external occupational factors, nonoccupational factors, or workplace factors unique to North Haven unmeasured in the current evaluation.

Objective: To evaluate mortality rates among a cohort of jet engine manufacturing workers., Methods: Subjects were 222,123 workers employed from 1952 to 2001. Vital status was determined through 2004 for 99% of subjects and cause of death for 95% of 68,317 deaths. We computed standardized mortality ratios and modeled internal cohort rates., Results: Mortality excesses reported initially no longer met the criteria for further investigation. We found two chronic obstructive pulmonary disease-related mortality excesses that met the criteria in two of eight study plants., Conclusions: At the total cohort level, chronic obstructive pulmonary disease-related categories were not related to any factors or occupational exposures considered. A full evaluation of these excesses was limited by lack of data on smoking history. Occupational exposures received outside of work or uncontrolled positive confounding by smoking cannot be ruled out as reasons for these excesses.

Objective: To determine whether glioblastoma (GB) incidence rates among jet engine manufacturing workers were associated with workplace experiences with specific parts produced and processes performed., Methods: Subjects were 210,784 workers employed between 1952 and 2001. We conducted nested case-control and cohort incidence studies with focus on 277 GB cases. We estimated time experienced with 16 part families, 4 process categories, and 32 concurrent part-process combinations with 20 or more GB cases., Results: In both the cohort and case-control studies, none of the part families, process categories, or both considered was associated with increased GB risk., Conclusions: If not due to chance alone, the not statistically significantly elevated GB rates in the North Haven plant may reflect external occupational factors or nonoccupational factors unmeasured in the current evaluation.

Objective: We attempted to examine non-malignant central nervous system (CNS) neoplasms incidence rates for workers at 8 jet engine manufacturing facilities in Connecticut. The objective of this manuscript is to describe difficulties encountered regarding these analyses to aid future studies., Methods: We traced the cohort for incident cases of CNS neoplasms in states where 95% of deaths in the total cohort occurred. We used external and internal analyses in an attempt to obtain the true risk of non-malignant CNS in the cohort. Because these analyses were limited by data constraints, we conducted sensitivity analyses, including using state driver's license data to adjust person-year stop dates to help minimize underascertainment and more accurately determine cohort risk estimates., Results: We identified 3 unanticipated challenges: case identification, determination of population-based cancer incidence rates, and handling of case underascertainment. These factors precluded an accurate assessment of non-malignant CNS neoplasm incidence risks in this occupational epidemiology study., Conclusions: The relatively recent (2004) mandate of capturing non-malignant CNS tumor data at the state level means that, in time, it may be possible to conduct external analyses of these data. Meanwhile, similar occupational epidemiology studies may be limited to descriptive analysis of the non-malignant CNS case characteristics.

A novel screening tool method to select chemicals for exposure reconstruction was developed and validated using data generated for a hypothetical work force consisting of 10 job classes (ranging from 10,000 to 55,000 person-years). To achieve the required efficiency in the reconstruction of exposures, this method treats each product (defined as a part or process) as an "exposure." Exposure to 10 products was assigned to each job class at random using a computer program. The expected rate of a given disease was assumed to be constant throughout the job classes (tested at five levels), and the observed numbers of cases in the job classes were generated based on neutral deviations from background with error rates of ± 1% to 16%. One job class was assigned to be the "excess-class" and the number of cases in that class was increased by a factor of Q, which was set at levels that ranged from 1.25 to 5. All of the experimental conditions were replicated 10,000 times in a Monte Carlo scheme for scenarios in which each job class had been designated as the excess-class. Following each run, significant excesses (if any) were determined using a modified version of Daniel's method, and the percentages of false positive and false negative identifications were tabulated. We found that the sensitivity of the method is largely dependent on the relative risk (Q) associated with the exposure. Specifically, the results indicate that as the relative risk increases, the percentage of false negative identifications of the excesses is reduced to nearly 0% and the percentage of false positive identifications is approximately 13%. When applied to real data, should an association be detected between any product and a health outcome, this preliminary analysis will yield a reduced "product" set that can then be investigated in detail and the agents involved considered further for quantitative reconstruction. The proposed method is highly efficient and has the potential to benefit future complex exposure reconstruction studies, particularly when there is no predetermined exposure associated with an observed increase in a cause-specific health end point.

Purpose: To compare ascertainment of central nervous system (CNS) neoplasms with the use of mortality and incidence data as part of an occupational epidemiology study., Methods: Deaths were identified by matching the cohort of 223,894 jet engine manufacturing employees to the U.S. Social Security Administration death files and the National Death Index. Incident cancer cases were identified by matching the cohort to 19 state cancer registries., Results: We identified 718 cases overall: 59% by the use of both mortality and cancer incidence tracing; 24% by the use of only mortality tracing, and 17% by the use of only cancer incidence tracing. Compared with state cancer registries, death certificates missed 38% of the malignant, more than six times the benign and nearly 1.5 times the unspecified CNS cases. The positive predictive value of death certificates, with cancer registry as gold standard, was 6% for unspecified, 35% for benign, and 86% for malignant histologies., Conclusions: Death certificates seriously underascertained benign and unspecified CNS tumors; analyses determined with mortality data would not accurately capture the true extent of disease among the cohort. Most state cancer registries have only collected nonmalignant CNS tumor information since 2004, which currently limits the usefulness of state cancer registries as a source of nonmalignant CNS tumor identification. Underascertainment of CNS deaths could seriously affect interpretation of results, more so if examining nonmalignant CNS., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Objective: To explore a perceived unusual occurrence of glioblastoma at one jet engine manufacturing facility located in North Haven (NH), Connecticut (CT)., Methods: Subjects were 212,513 workers ever employed in 1 of 8 manufacturing facilities from 1952 to 2001 and at risk from 1976 to 2004. We identified 722 cases of CNS neoplasms mainly by tracing through 19 state cancer registries. We computed standardized incidence ratios (SIRs) based on CT state and national rates and modeled internal relative risks (RRs)., Results: We found overall deficits in cases for glioblastoma (275 cases, SIR = 0.77, CI = 0.68-0.87) and most other histology categories examined. NH workers had a not statistically significant overall 8% excess in glioblastoma (43 cases, SIR = 1.08, CI = 0.78-1.46). Salaried NH workers had a statistically significant twofold risk of glioblastoma compared with hourly workers (17 cases, RR = 2.04, CI = 1.15-3.57). Other subgroups of NH workers revealed elevated but not statistically significant glioblastoma risks but little evidence of an association with duration of employment or time since first employment., Conclusions: Incidence rates for glioblastoma and other malignant CNS neoplasm histologies were not elevated in the total cohort. The glioblastoma excesses observed among NH workers may reflect external occupational factors, non-occupational factors or workplace factors unique to NH unmeasured in the current study., (Copyright 2010 S. Karger AG, Basel.)

Objectives: To evaluate further elevated mortality risks from respiratory system cancer (RSC) and lymphatic and hematopoietic tissue cancers (LHTC) in a cohort of 1466 male workers employed full-time in pharmaceutical production., Methods: We computed standardized mortality ratios, and in nested case-control studies of RSC and LHTC, evaluated mortality risks by plant exposures with adjustment for potential confounding factors., Results: Subjects with potential plant exposure had no elevated RSC risk and a statistically significant LHTC excess. The case-control study found many RSC risks reduced with adjustment for smoking, and LHTC risks increased with increasing levels of average exposure to dimethyl-formamide., Conclusions: RSC mortality risks decreased, and we found limited evidence that positive confounding by smoking may explain some remaining excess risks. For LHTC, increased mortality risks and exposure-response patterns in the case-control study may indicate a possible workplace association.

Objective: To evaluate the long-term mortality experience of workers exposed to arsenic, cadmium, and other substances at a copper mine and smelter in Copperhill, Tennessee studied earlier as part of an industry-wide study., Methods: Subjects were 2,422 male workers employed three or more years in the smelter or mill between 1/1/46 until the plant strike and scale-down of operations in April 1996. Vital status was determined through 2000 for 99.4% of subjects and cause of death for 91.3% of 878 deaths. Historical exposures were estimated for lead, SO(2), arsenic, cadmium, dust, and cobalt. We computed standardized mortality ratios (SMRs) based on U.S. and local county rates and modeled internal relative risks (RRs)., Results: We observed overall deficits in deaths based on national and local county comparisons from all causes, all cancers and most of the cause of death categories examined. We found limited evidence of increasing mortality risks from cerebrovascular disease with increasing duration and cumulative arsenic exposure, but no evidence of an exposure-response relationship for cadmium exposure and bronchitis., Conclusions: Our limited evidence of an association between inhaled arsenic exposure and CVD is an exploratory finding not observed in other epidemiology studies of more highly exposed occupational populations. Possible alternative explanations include chance alone and uncontrolled confounding or effect modification by co-exposures or other factors correlated with arsenic exposure and unique to the Copperhill facility.

The authors traced incidence of central nervous system cancer in a large occupational cohort of jet engine manufacturing workers from 1976 to 2004 in the 24 US states that comprised 95% of the cohort deaths. The cohort of approximately 224,000 employees was matched with cancer registry data; all central nervous system cancer matches were requested with their diagnostic data. This paper highlights the obstacles encountered while conducting this retrospective cancer incidence study. The authors spent approximately 700 hours completing applications and obtaining the cohort matches. Approximately 70% of the cases were identified in the state in which the facility of interest is located. In addition to the large amount of time involved, identified issues include complicated approval processes, high costs, temporal differences among the registries, and registry agency difficulty in performing the matching. Several states do not allow individual-level data to be used for research purposes. Researchers can gain important cancer incidence information by matching retrospective cohorts to multiple state cancer registries. However, they should carefully weigh the time and costs required and plan accordingly. Despite some serious obstacles, many of which are potentially resolvable, cancer incidence studies of retrospective cohorts using multiple cancer registries are feasible.

Nondestructive testing is any technique used to inspect the integrity of a manufactured item without diminishing its future usefulness. Magnetic particle inspection is one type of nondestructive testing that uses electromagnetism in the inspection procedure, thus potentially exposing the operator to magnetic fields. During magnetic particle inspection, investigators took peak magnetic field measurements of 8 turbine engine shafts at a turbine engine overhaul and repair center. They recorded 95 peak magnetic field measurements, ranging from < 0.1 to 29.27 mT. The exposure values measured were among the highest reported in the occupational setting. Further work is needed to characterize magnetic field exposures in magnetic particle inspection operations--in particular, by differentiating magnetic field magnitude by current frequency--and to understand exposure as it relates to different types of magnetic particle inspection devices.

Objective: To investigate further the possibility that the large nasopharyngeal cancer (NPC) mortality excess among a cohort of formaldehyde-exposed workers may be related to occupational factors external to the study plant., Methods: Subjects were 7345 workers employed at a plastics-producing plant (1941-1984) in Wallingford, Connecticut evaluated independently as part of a National Cancer Institute cohort study. Vital status for 98% of the cohort and cause of death for 95% of 2872 deaths were determined through 2003. Reconstructed worker exposures to formaldehyde were used to compute unlagged and lagged exposure measures. We computed standardized mortality ratios (SMRs) based on US and local county rates. In a nested case-control study we evaluated mortality risks from NPC and from all other pharyngeal cancers combined (AOPC) in relation to formaldehyde exposure while accounting for potential confounding or effect modification by smoking or external (non-Wallingford) employment. Job applications, Connecticut commercial city directories and a previous survey were used to assign subjects to three external job groups., Results: We observed no new deaths from NPC and one additional AOPC death (pharynx unspecified) yielding, respectively, SMRs of 4.43 (7 deaths, 95% CI=1.78-9.13) and 1.71 (16 deaths, 95% CI=1.01-2.72). Five of seven NPC cases worked in silver smithing (including brass plating and other jobs related to silver or brass) or other metal work (including steel working and welding), and this type of work was relatively rare in the remaining study population (OR=14.41, 95% CI=1.08-82.1). For AOPC, we found a moderate increase in risk for other metal work (OR=1.40, 95% CI=.31-5.1). Interaction models suggested that NPC and AOPC risks were not elevated in subjects exposed only to formaldehyde., Conclusions: The results of our nested case-control study suggest that the large nasopharyngeal cancer mortality excess in the Wallingford cohort may not be due to formaldehyde exposure, but rather reflects the influence of external employment in the ferrous and non-ferrous metal industries of the local area that entailed possible exposures to several suspected risk factors for upper respiratory system cancer (e.g., sulfuric acid mists, mineral acid, metal dusts and heat). Our findings may also help to explain why the associations with formaldehyde and nasopharyngeal cancer reported in the 1994 update of the 10-plant NCI formaldehyde cohort study were unique to the Wallingford plant (Plant 1 in NCI study). Further updates of the NCI formaldehyde cohort study should include co-exposure data on silver smithing and other metal work for all study plants to help explain the unique findings for nasopharyngeal cancer in Plant 1 compared with the other nine plants.

In a four-facility occupational epidemiology study of chloroprene monomer and polymer production workers, the chloroprene (CD) and vinyl chloride monomer (VCM) exposures were modeled for plant specific job title classes. In two facilities an acetylene-based process was used and in the other two plants only a butadiene-based process was used in the monomer synthesis. In the Acetylene process VCM was an undesirable by-product to be removed. In the newer butadiene-based process, VCM was not involved and the exposures to CD were considerably lower than they were in the earlier years. One of the limiting factors was the operator rotation within a number of job titles. This rotation and inability to differentiate between job titles subsumed in job classifications recorded in the work histories required an exposure classification scheme based on an order of magnitude separation of exposure classes. In the four facilities with considerable variation in the mix of the production methods, the CD exposures were remarkably similar in both calculated and measured values. The reductions in exposures were much more dependent upon the improvement of the production methods, rather than deliberate exposure control for occupational hygiene considerations. This is reasonable since the exposures were generally lower than the coeval exposure limits and/or guidelines. The estimated exposures were less than 100 ppm in the pre-1960 era and less than 10 ppm in the 1960-1980 era, less than 1 ppm 1980-1990 era and less than 0.5 ppm thereafter. The exposures were categorized in four classes for VCM and six classes for CD. The characteristic class exposure values were used to cumulate individual exposures over time with a quantification of the potential range for exposures that are reasonably certain to ascribe correct ranking to job classes.

As part of an historical cohort study to investigate the mortality experience of industrial workers exposed to chloroprene (CD) and other substances, including vinyl chloride monomer (VC), we analyzed mortality from all cancers combined, respiratory system (RSC) and liver cancer in relation to CD and VC exposures. Subjects were 12,430 workers ever employed at one of two U.S. sites (Louisville, KY (n=5507) and Pontchartrain, LA (n=1357)) or two European sites (Maydown, Northern Ireland (n=4849) and Grenoble, France (n=717)). Historical exposures for individual workers were estimated quantitatively for CD and VC. For sites L, M, P and G, respectively, average intensity of CD exposures (median value of exposed workers in ppm) were 5.23, 0.16, 0.028 and 0.149 and median cumulative exposures (ppm years) were 18.35, 0.084, 0.133 and 1.01. For sites L and M, respectively, average intensity of VC exposures (median value of exposed workers in ppm) was 1.54 and 0.03 and median cumulative exposures (ppm years) were 1.54 and 0.094. We performed relative risk (RR) regression modeling to investigate the dependence of the internal cohort rates for all cancers combined, RSC and liver cancer on combinations of the categorical CD or VC exposure measures with adjustment for potential confounding factors. We categorized exposure measures into approximate quartiles based on the distribution of deaths from all cancers combined. We also considered 5- and 15-year lagged exposure measures and adjusted some RR models for worker pay type (white/blue collar) as a rough surrogate for lifetime smoking history. All modeling was site-specific to account for exposure heterogeneity. We also computed exposure category-specific standardized mortality ratios (SMRs) to assess absolute mortality rates. With the exception of a one statistically significant association with duration of exposure to CD and all cancers combined in plant M, we observed no evidence of a positive association with all cancers, RSC or liver cancer and exposure to CD and/or VC using both the unlagged and lagged exposure measures: duration, average intensity or cumulative exposure to CD or VC; time since first CD or VC exposure; and duration of CD exposure or time since first CD exposure in presence or absence of VC exposure. We observed elevated and statistically significantly elevated RRs for some analysis subgroups, but these were due to inordinately low death rates in the baseline categories. With the possible exception of all cancer mortality in plant G, our additional adjustment of RRs for pay type revealed no evidence of positive confounding by smoking. We conclude that exposures to CD or VC at the levels encountered in the four study sites do not elevate mortality risks from all cancers, RSC or liver cancer. This conclusion is corroborated by our analysis of general mortality patterns among the CD cohort reported in our companion paper [G. Marsh, A. Youk, J. Buchanich, M. Cunningham, N. Esmen, T. Hall, M. Phillips, Mortality patterns among industrial workers exposed to chloroprene and other substances. I. General mortality patterns, Chem.-Biol. Interact., submitted for publication].

We conducted an historical cohort study to investigate the mortality experience of industrial workers potentially exposed to chloroprene (CD) and other substances, including vinyl chloride (VC), with emphasis on cancer mortality, including respiratory system (RSC) and liver. In 1999, the International Agency for Research on Cancer (IARC) classified CD as a possible carcinogen (Group 2B); VC was classified in 1987 as a known human carcinogen (Group 1). Subjects were 12,430 workers ever employed at one of two U.S. industrial sites (Louisville, KY (n=5507) and Pontchartrain, LA (n=1357)) or two European sites (Maydown, Northern Ireland (n=4849) and Grenoble, France (n=717)), with earliest CD production dates ranging from 1942 (L) to 1969 (P). Two sites (L and M) synthesized CD with the acetylene process that produced VC exposures. We determined vital status through 2000 for 95% of subjects and cause of death for 95% of the deaths. Historical exposures for individual workers were estimated quantitatively for CD and VC. Workers ever exposed to CD ranged from 92.3% (M) to 100% (G); to VC from 5.5% (M) to 22.7% (L). We computed standardized mortality ratios (SMRs) (using national and regional standard populations) in relation to selected demographic, work history and exposure factors. We used worker pay type (white or blue collar) as a rough surrogate for lifetime smoking history. For the combined cohort, SMRs (95% CIs) for all causes combined, all cancers combined, RSC and liver cancer were, respectively, 0.72 (0.69-0.74), 0.73 (0.68-0.78), 0.75 (0.67-0.84) and 0.72 (0.43-1.13). Site-specific (L, M, P and G, respectively) SMRs were: for all cancers combined: 0.75 (0.69-0.80), 0.68 (0.56-0.80), 0.68 (0.47-0.95) and 0.59 (0.36-0.91); for RSC: 0.75 (0.66-0.85), 0.79 (0.58-1.05), 0.62 (0.32-1.09) and 0.85 (0.41-1.56); for liver cancer: 0.90 (0.53-1.44) (17 deaths), 0.24 (0.01-1.34) (1 death), 0.0 (0-2.39) (no deaths) and 0.56 (0.01-3.12) (1 death). Among all workers ever exposed to CD, SMRs were: for all cancers combined: 0.71 (0.66-0.76); for RSC: 0.75 (0.67-0.84); for liver cancer: 0.71 (0.42-1.14). We also observed no increased mortality risks among cohort subgroups defined by race, gender, worker pay type, worker service type (short/long term), time period, year of hire, age at hire, duration of employment, the time since first employment, and CD or VC exposure status (never/ever exposed). In summary, our study has many strengths and is the most definitive study of the human carcinogenic potential of exposure to CD conducted to date. We conclude that persons exposed to chloroprene or vinyl chloride at the levels encountered in the four study sites did not have elevated risks of mortality from any of the causes of death examined, including all cancers combined and lung and liver cancer, the cancer sites of a priori interest. This conclusion is corroborated by our detailed analyses of mortality in relation to qualitative and quantitative exposures to CD and VC at each of the four study sites, reported in our companion paper (Marsh et al., submitted for publication).

The classification of jobs or workers by exposure is an important undertaking in any occupational epidemiological study. Hitherto, the exposure classification designs have been strongly motivated by a desire to generate a sufficient number of exposure classes for the determination of a potential exposure-response relationship. Thus, the partitioning of exposures has been more or less arbitrary. The misclassification problems created by the selection of an arbitrary number of exposure assignment classes have not been addressed. In any quantitative exposure classification scheme, specific job titles may be indistinguishable in existing employment records; therefore, between worker variability must be addressed when characterizing worker exposures. Also, industrial hygiene exposure measurements frequently used to characterize worker exposures are often treated as valid representations of exposures; but they are neither random nor systematic evaluations of worker exposures. As a result they do not represent sampling from the proper exposure stratification of workers. These observations suggest that the selection of exposure groups should be based on a more rigorous examination of the data and its limitations. Considering the probability of any given worker being placed into the proper class as the probability of finding the mean exposure for that worker within the class boundary, the general equations to quantify the misclassification rates for any classification design as well as the exposure class limits and their width for any acceptable misclassification rate are developed. If between worker variability could not be calculated from the available exposure measurements, then it might be estimated from the proper data compiled from the literature. By considering an acceptable level of exposure misclassification, it is possible to calculate the allowable number of exposure classes and the proper partitioning ratio for these classes. Thus, the trade-off between misclassification and number of exposure classes might be a satisfactory solution to this difficulty encountered in occupational epidemiology.

As part of an historical cohort study to investigate the mortality experience of industrial workers exposed to chloroprene (beta-CD) and other substances, all available industrial hygiene exposure monitoring data were collected and summarized. From discussions with on-site industrial hygiene personnel, it was apparent that these data were not collected for epidemiological purposes and, therefore, their use in characterization of exposures was problematic as the data mostly pertained to samples collected to investigate the performance of specific tasks. These data were, however, informative for validating the exposure modeling process used to estimate historical exposures. The data summarized below clearly indicate that exposures to beta-CD were lowered across the time period of this study. Typically, the exposures recorded were less than the occupational exposure limits of the periods in which the exposures were recorded. Additionally, exposure measurements recorded in the recent past do not represent the exposure actually experienced by the worker as a strict personal protective equipment use program has been in place for the facilities studied since the mid-1980s.

In the occupational hygiene component of occupational epidemiological studies the goal is to assign group average exposure levels that can be used to compute individual cumulative exposures. This task requires the availability of sufficient amounts of proper individual exposure level data. Typically, the required data are either sparse, completely lacking or happenstance data collected for purposes not suitable for the aims of the study. In the epidemiological study of mortality patterns among industrial workers exposed to chloroprene and other substances, we developed and used a process analysis and modeling based exposure reconstruction to augment, extrapolate, or interpolate the available exposure data. The models developed utilize equations based on the engineering principles and chemistry associated with the processes as determined from the process documentation and task performance habits as determined from interviews of knowledgeable personnel. The resulting equations are tractable and provide a general basis for calculating exposure levels for vapors. The validation of the results with available exposure measurements suggests that comprehensive process analysis and modeling may be used to reconstruct exposures or to evaluate exposure potential with scientifically defensible methods. Furthermore, even in the absence of validating data, the methodology developed has potentially very useful applications in predicting exposure levels to newly synthesized substances. Properly interpreted, the limitations of modeling can be minimized to obtain scientifically reasonable results.

Beryllium metal and its oxide and alloys are materials of industrial significance with recognized adverse effects on worker health. Currently, the degree of risk associated with exposure to these materials in the workplace is assessed through measurement of beryllium aerosol mass concentration. Compliance with the current mass-based occupational exposure limit has proven ineffective at eliminating the occurrence of chronic beryllium disease (CBD). The rationale for this research was to examine the mechanism of beryllium bioavailability, which may be pertinent to risk. The authors tested the hypothesis in vitro that dissolution of particles engulfed by macrophages is greater than dissolution in cellular medium alone. Physicochemical changes were evaluated in vitro for well-characterized high-purity beryllium oxide (BeO) particles in cell-free media alone and engulfed by and retained within murine J774A.1 monocyte-macrophage cells. The BeO particles were from a commercially available powder and consisted of diffuse clusters (aerodynamic diameter range 1.5 to 2.5 microm) of 200-nm diameter primary particles. Following incubation for 124 to 144 hours, particles were recovered and recharacterized. Recovered particles were similar in morphology, chemical composition, and size relative to the original material, confirming the relatively insoluble nature of the BeO particles. Measurable levels of dissolved beryllium, representing 0.3% to 4.8% of the estimated total beryllium mass added, were measured in the recovered intracellular fluid. Dissolved beryllium was not detected in the extracellular media. The BeO chemical dissolution rate constant in the J774A. 1 cells was 2.1 +/- 1.7 x 10(-8)g/(cm2 . day). In contrast, the BeO chemical dissolution rate constant in cell-free media was < 8.1 x 10(-9)g/(cm2 . day). In vivo, beryllium dissolved by macrophages may be released in the pulmonary alveolar environment, in the lymphatic system after transport of beryllium by macrophages, or in the alveolar interstitium after migration and dissolution of beryllium particles in tissue. These findings demonstrate a mechanism of bioavailability for beryllium, are consistent with previously observed results in canine alveolar macrophages, and provide insights into additional research needs to understand and prevent beryllium sensitization and CBD.

Estimation and Assessment of Substance Exposure (EASE) is an artificial intelligence program developed by UK's Health and Safety Executive to assess exposure. EASE computes estimated airborne concentrations based on a substance's vapor pressure and the types of controls in the work area. Though EASE is intended only to make broad predictions of exposure from occupational environments, some occupational hygienists might attempt to use EASE for individual exposure characterizations. This study investigated whether EASE would accurately predict actual sampling results from a chemical manufacturing process. Personal breathing zone time-weighted average (TWA) monitoring data for two volatile organic chemicals--a common solvent (toluene) and a specialty monomer (chloroprene)--present in this manufacturing process were compared to EASE-generated estimates. EASE-estimated concentrations for specific tasks were weighted by task durations reported in the monitoring record to yield TWA estimates from EASE that could be directly compared to the measured TWA data. Two hundred and six chloroprene and toluene full-shift personal samples were selected from eight areas of this manufacturing process. The Spearman correlation between EASE TWA estimates and measured TWA values was 0.55 for chloroprene and 0.44 for toluene, indicating moderate predictive values for both compounds. For toluene, the interquartile range of EASE estimates at least partially overlapped the interquartile range of the measured data distributions in all process areas. The interquartile range of EASE estimates for chloroprene fell above the interquartile range of the measured data distributions in one process area, partially overlapped the third quartile of the measured data in five process areas and fell within the interquartile range in two process areas. EASE is not a substitute for actual exposure monitoring. However, EASE can be used in conditions that cannot otherwise be sampled and in preliminary exposure assessment if it is recognized that the actual interquartile range could be much wider and/or offset by a factor of 10 or more.

Purpose: To examine mortality among workers in a pharmaceutical production plant and to address community concerns about 1980 to 1990 increases in local county cancer mortality rates., Methods: Subjects were 1999 workers with some full-time employment during the period between 1970 and 1996. We identified deaths through the year 2000 and reconstructed exposures to nine chemical agents with available exposure measurements. Data analyses included standardized mortality ratios (SMRs) and time trends in local cancer mortality rates., Results: We observed deficits in deaths from all causes combined, all cancers combined, and most cause of death categories examined. Male workers with potential plant exposure had excesses in deaths from all lymphatic-hematopoietic tissue cancers (LHTC), in particular non-Hodgkin's lymphoma (NHL), and respiratory system cancers (RSC) that were larger among long-term workers, but the pattern of findings suggested the excesses were probably not related to occupational factors at the plant. The increase in local county cancer mortality rates was simply the upward cycle of a periodic trend that peaked in 1990 and returned to 1980 levels in 2000., Conclusions: With the possible exceptions of LHTC, in particular NHL, and RSC, this study provided no evidence of elevated total or cause-specific cohort mortality risks. It does not appear that plant factors played a role in the 1980 to 1990 increases in local county cancer mortality rates.

To begin to develop generalized models for estimating personal exposure to ambient air pollutants within diverse populations, the design of the Oklahoma Urban Air Toxics Study incorporated eight dichotomous macroenvironmental and household factors that were hypothesized to be potential determinants of exposure. Personal, indoor, and outdoor samples of volatile organic compounds (VOCs) were collected over 24-h monitoring periods in 42 households, together with activity diaries and data on the participants' residences. The distributions of the VOC concentrations were moderately to highly left-censored, and were mostly bimodal. The ATSDR minimal risk level (MRL) was exceeded in a small number of the samples. Personal and indoor concentrations tended to be higher than outdoor concentrations, indicating that indoor exposures were dominated by indoor sources. However, indoor concentrations were not correlated with the permeability of the residence, suggesting that the observed indoor concentrations reflected mostly localized, short-term emissions. The influence of the eight dichotomous factors and of the presence of an attached garage was evaluated using the Wilcoxon rank-sum test and by comparison of "excursion fractions", that is, the fractions of each distributions exceeding 10% of the MRL. Dry weather and absence of children in the household were found to be associated with higher exposures in personal or indoor exposures. Given the small sample size, it is possible that these factors were confounded with unidentified household characteristics or activities that were the true determinants of exposure.

Aims: To investigate mortality from lung cancer in nickel-cadmium battery workers in relation to cumulative exposure to cadmium hydroxide., Methods: The mortality of a cohort of 926 male workers from a factory engaged in the manufacture of nickel-cadmium batteries in the West Midlands of England was investigated for the period 1947-2000. All subjects were first employed at the plant in the period 1947-75 and employed for a minimum period of 12 months. Work histories were available for the period 1947-86; the factory closed down in 1992. Two analytical approaches were used, indirect standardisation and Poisson regression., Results: Based on serial mortality rates for the general population of England and Wales, significantly increased mortality was shown for cancers of the pharynx (observed (Obs) 4, expected (Exp) 0.7, standardised mortality ratio (SMR) 559, p<0.05), non-malignant diseases of the respiratory system (Obs 61, Exp 43.0, SMR 142, p<0.05), and non-malignant diseases of the genitourinary system (Obs 10, Exp 4.1, SMR 243, p<0.05). Non-significantly increased SMRs were shown for lung cancer (Obs 45, Exp 40.7, SMR 111) and cancer of the prostate (Obs 9, Exp 7.5, SMR 116). Estimated cumulative cadmium exposures were not related to risks of lung cancer or risks of chronic obstructive pulmonary diseases, even when exposure histories were lagged first by 10, then by 20 years., Conclusions: The study findings do not support the hypotheses that cadmium compounds are human lung carcinogens.

The single cut measurement of exposure to respirable dust is the accepted method of exposure classification in occupational hygiene. We previously showed that actual pulmonary tissue dose may be substantially different from the dose expected, or the indicated dose, based on measurements using current single cut methodologies. We now examine exposure misclassification of workers based on any single cut respirable dust measurement using the internationally accepted ISO/ACGIH/CEN single cut respirable dust measurement criteria. Hypothetical aerosols with 12 generalized size distributions typical of the method of aerosol generation (condensation, aged condensation, mechanical low energy, mechanical high energy and mixtures thereof) were assumed. Using previously reported models for sampler penetration and pulmonary deposition, Monte Carlo simulations of actual mass dose to pulmonary tissues in comparison to the dose estimate from an ideal respirable aerosol sampler were carried out. Measurement-based indicated doses were used to classify exposures into five exposure categories and these classifications were compared with the 'true' classifications from the dose-based exposure estimates. Misclassification rates were generally severe and were greatest for aerosols with mass median aerodynamic diameter (MMAD) <1 microm (approximately 100%) and MMAD 5-15 microm (65-95%). Misclassification rates were moderate (<20%) only for extremely coarse aerosols of MMAD>15 microm. Misclassification rates for oral and nasal breathing at 750 and 1500 ml tidal volume and 15 breaths/min were similar for each aerosol examined.

This research focused on comparing a modified 37-mm (Mod37) sampling cassette with an IOM inhalable dust sampler. Paired IOM and Mod37 breathing-zone air samples were collected for workers engaged in corrosion control maintenance operations on several types of aircraft at several U.S. Air Force bases in the United States. Sampled operations included hand and power sanding, blow-down and wipe-down to remove dust, and spray finishing. The cassettes' interior surfaces were swabbed and the swabs combined with the filters for chromium analysis by NIOSH Method 7300. This approach utilized total chromium as a sensitive surrogate indicator of total aspirated mass. The influences of work location, work type, sample duration, and sampler type on measured concentration were evaluated using analysis of variance techniques. Only work type (process) was found to be a statistically significant predictor of measured concentration. The relationship between IOM- and Mod37-measured values for paired samples was evaluated by work type using linear regression techniques. Linear regressions showed that the modified 37-mm cassette over-samples aerosol by 35 percent compared to the IOM when a wide range of aerosol concentrations and compositions for divergent work tasks in multiple field locations are sampled. Interpretation of these results in light of previous results involving filter-only Mod37 analyses suggests that while the Mod37 has a higher aspiration efficiency than the IOM, substantial Mod37 wall losses result in underestimation of exposure when only the 37-mm filter is analyzed rather than filters plus wall swabs.

Objectives: To assess the possible relationship between formaldehyde exposure and mortality risk from pharyngeal cancer (PC), in particular nasopharyngeal cancer (NPC)., Methods: Subjects were 7328 workers employed at a plastics-producing plant (1941-1984). Vital status for 98% of the cohort and cause of death for 95% of 2872 deaths were determined. Reconstructed exposures to formaldehyde, particulates and pigment were used to compute several exposure measures. Standardized mortality ratios (SMRs) were computed for several demographic, work history and formaldehyde exposure variables. In a nested case-control study, seven cases of NPC and 15 cases of other PC were matched on race, sex, age and year of birth to four controls from the cohort. Among interviewed subjects, lifetime smoking history was determined using respondents or proxies for all but one control subject., Results: Statistically significant 2.23-fold and fivefold excesses for PC and NPC, respectively, were observed. Fivefold range NPC excesses were observed for both short ( < 1 year) and long-term workers and were concentrated among workers hired during 1947-1956. Only three NPC cases were exposed to formaldehyde for longer than one year, and each had low average intensity of formaldehyde exposure (0.03-0.60 ppm). Only a few exposure measures revealed some evidence of an association with all PC or NPC. For all PC combined, adjustment for smoking and year-of-hire in the case-control study generally corroborated findings from the cohort study., Conclusions: Overall, the pattern of findings suggests that the large, persistent nasopharyngeal and other PC excesses observed among the Wallingford workforce are not associated with formaldehyde exposure, and may reflect the influence of nonoccupational risk factors or occupational risk factors associated with employment outside the Wallingford plant.

The influences of aerosol size distribution and breath tidal volume on respirable dose estimates were examined for mouth breathing using the ACGIH/ISO/CEN criterion for respirable-equivalent aerosols. Actual tissue doses predicted from a set of pulmonary empirical deposition equations, the Heyder-Rudolf equations, were compared with deposition assumed to occur under the penetration-based respirable dust sampling criterion. Deposition estimate errors ranged from approximately 1/10- to 10-fold, with aerosol mass median aerodynamic equivalent diameter and geometric standard deviation as well as tidal volume each showing a substantial influence under appropriate conditions. These findings demonstrate that reliance on respirable aerosol sampling data obtained with devices performing on a penetration-based sampling criterion may lead to erroneous dose-response relationships in exposure standard development as well as exposure misclassification errors during epidemiological studies. A more reliable dose estimate would be obtained using devices with collection efficiency performance closely matching the alveolar deposition prediction curves of Heyder and Rudolf. We believe that if it is not currently required, the development of a deposition-based aerosol sampling methodology will soon be required for the determination and quantification of inhaled aerosol-induced adverse health effects.

We examine the potential for reproductive and developmental effects from formaldehyde exposure. Formaldehyde is unlikely to reach the reproductive system in humans in concentrations sufficient to cause damage since it is rapidly metabolized and detoxified upon contact with the respiratory tract. While there are effects seen in in vitro studies or after injection, there is little evidence of reproductive or developmental toxicity in animal studies under exposure levels and routes relevant to humans. Most of the epidemiology studies examined spontaneous abortion and showed some evidence of increased risk (meta-relative risk=1.4, 95% CI 0.9-2.1). We found evidence of reporting biases and publication biases among the epidemiology studies and when these biases were taken into account, we found no evidence of increased risk of spontaneous abortion among workers exposed to formaldehyde (meta-relative risk=0.7, 95% CI 0.5-1.0). The small number of studies on birth defects, low birth weight, and infertility among formaldehyde workers; the limitations in the design of these studies; and the inconsistent findings across these studies make it difficult to draw conclusions from the epidemiology data alone. However, information from experimental studies and studies of metabolism indicate reproductive impacts are unlikely at formaldehyde exposures levels observed in the epidemiology studies., (Copyright 2001 Academic Press.)

Global positioning system (GPS) data recorders were worn by subjects in the Oklahoma Urban Air Toxics Study (OUATS) for automatic logging of their location as they went about their normal daily activities. The location information obtained by the GPS units had an uncertainty of about 10-20 m, which was sufficiently precise to track subjects' movements on trips outside the immediate vicinity of their homes. Due to instrument problems, primarily related to reduced battery life, the units operated for only about 30% of the total monitoring time attempted in 25 trials. The GPS data were compared to time-activity diaries kept by the subjects. In almost all cases, the GPS data confirmed all travel events reported in the subjects' diaries. Additionally, in five out of five trials in which the logging period covered most or all of the subjects' daytime activities, at least one travel event that was not recorded in the diary was detected by GPS. Notwithstanding the limitations of present technology, GPS was found to be a promising means for tracking of research subjects in community-based exposure assessment studies.

Background: Most reviews on the carcinogenicity of formaldehyde have focused on cancers of the respiratory tract. Two recent studies have suggested that exposure to formaldehyde may increase the risk for pancreatic cancer., Methods: We examine 14 epidemiology studies of workers exposed to formaldehyde where pancreatic cancer rates were reported and use meta-analytic techniques to summarize the findings. We also rank formaldehyde exposures for the industries in these studies., Results: We found a small increase of pancreatic cancer risk in the studies overall (meta Relative Risk [mRR] 1.1, 95%CI 1.0-1.3); however, this increased risk was limited to embalmers (mRR 1.3, 95%CI 1.0-1.6) and pathologists and anatomists (mRR 1.3, 95%CI 1.0-1.7). There was no increased risk among industrial workers (mRR 0.9, 95%CI 0.8-1.1) who on average had the highest formaldehyde exposures., Conclusions: A small increased risk of pancreatic cancer from formaldehyde exposure cannot be ruled out from the studies examined. However, the null findings among industrial workers and the lack of biological plausibility would argue against formaldehyde as a cause. The increased risk of pancreatic cancer among embalmers, pathologists, and anatomists may be due to a diagnostic bias or to occupational exposures other than formaldehyde in these professions.

The reliability of multiple regression analysis as a method for determining task-specific exposures from multi-task time-weighted average data was evaluated in comparison with the alternative P-screen method. The performances of the two methods were tested using simulated sample data that were calculated as averages over six tasks, where task-specific concentrations drawn randomly from lognormal distributions were weighted by randomly generated task time-weights. Data sets consisted of 20 or 100 simulated samples. The simulated data sets conformed to requirements inherent in the P-screen method that at least one task be absent from each sample and each task be absent from at least one sample. In thousands of Monte Carlo trials under various conditions, the two methods were found to perform equally well when dichotomous task measures (occurrence/ nonoccurrence) were used. Combining the two methods did not improve reliability appreciably, suggesting that the methods are effectively equivalent when dichotomous task measures are used. When task durations were used as the regressors or time-weights, multiple regression was found to be more reliable than P-screen. It is well recognized that incidental or fundamental collinearities between regressors may undermine multiple regression analyses. The P-screen-related restrictions on the task structure of data sets reduces the potential for problems arising from such collinearities. However, the use of multivariate analysis of multiple-task samples will always be an imperfect substitute for single-task sampling.

A mass based size fractionating aerosol sampling device such as an impactor has a number of experimental measurement errors that can affect the size distribution determination. These errors are not necessarily additive, such as weighing errors, multiplicative such as airflow errors, or a power function such as bounce. In general, the cumulative errors are a combination of different relational scales and they are likely to have different functional forms across the full range of measurements. A complete theory of errors must consider a diverse set of functional relationships between mass, flow, size distribution, and other non-linear parameters such as entry losses and bounce to estimate the error bounds for a measured size distribution and aerosol concentration. In addition, aerosol exposure measurements are single sample events. The theoretical multi-compartment error model is an extension of the Rocke and Lorenzato model of measurement errors in analytical chemistry and it includes generalized parameters for all empirically meaningful transformations. Although the general theory is complicated, heuristic reductions can be made to reduce the estimation process to a manageable size. The numerical examples of error analysis of a hypothetical impactor show that the measured distribution related error bound estimation process is not difficult to perform.

In exposure estimation, personal sampling is the method of choice as it is a nearby representative of the contaminant concentration in the breathing zone. Due to the versatility of the stationary sampling in obtaining much higher sensitivity, in its adaptability to telemetering observations, it may also be an attractive sampling method for many circumstances. However, the two sampling methods differ in many theoretically important ways that go beyond the obvious differences. The theoretical investigation of the stationary and personal sampling methods vis-à-vis sampling for exposure estimation shows that the area sampling can be used to represent personal sampling under restricted conditions. Under the restricted conditions, an area of concentration within specified bounds may be determined in relation to a reasonably well-defined source. The extension of the theory to multiple or ill-defined sources pose potential complications that may be intractable through a theoretical analysis. These limitations and restrictions are inherent to the underlying premises of the two methods; therefore they are not amenable to easy correction. Even though these restrictions may suggest only a limited role for area sampling in exposure assessment, the theory shown also suggests areas of further applied and theoretical research to extend the proper use of area sampling in exposure assessment.

Occupational and environmental hygiene sampling strategies are usually dictated by factors that limit sample sizes to relatively small numbers. Often, parameters estimated from small sample sizes are then used to make further estimates of the occurrence of extreme events, which are governed by the underlying exposure distribution. We investigated the limitations superimposed by the number of samples in distinguishing an asymmetric (Lognormal) distribution through the rejection of a hypothesized symmetric (Normal) distribution. Sets of 5 to 250 synthetic samples from underlying Lognormal distributions with unit median were generated for 24 separate geometric standard deviations (GSDs), ranging from 1.25 to 7.00. Each simulated combination was repeated in blocks of 200 and each block was repeated tenfold. The synthetic samples were then tested for goodness of fit for Normality by using the Shapiro and Wilk's W Test. Results indicated that the number of samples required to distinguish between Normal and Lognormal distributions was inversely related to GSD. When GSD = 1.25, 169 samples were required for 90 percent distinction at alpha = 0.05. The criteria for success for GSD of 2.00 and 4.00 were 25 and 15 samples, respectively. These results led to the conclusion that the general inability to distinguish an underlying distribution may impose serious difficulties in the estimation of extreme events associated with occupational and environmental hygiene-related sampling.

The effects of exposure misclassification on the interpretation of results of occupational epidemiological studies has been widely investigated and reported. Usually, only the direct effects of misclassification have been considered or simple estimates of misclassification rates have been assigned to various types of exposure estimation processes. Lifelong job profile data obtained from a previously published case-control study provided complete or nearly complete job histories of 511 decedents. An analysis of these work histories and the comparison of exposures related to longest-held job to estimated total lifetime exposures suggest that single job-based exposure estimates may lead to significant exposure misclassification rates. In addition, the appearance of shorter duration jobs in a study population occurring predominantly early in the work history may exacerbate problems associated with exposure misclassification. While few specific suggestions emerge from this analysis, the inclusion of extensive recording of the work history of study subjects emerges as a reasonable basis for the investigation and potential reduction of secondary misclassification of exposures in occupational epidemiological studies.

Measured airborne concentrations of asbestos are often unavailable to assess different epidemiologic estimates of past personal exposure levels or concentrations near specific operations involving handling asbestos. The purpose of this study was to assess the potential use of a laboratory study in estimating exposure to asbestos in operations that ceased for many years. The asbestos transfer operations were simulated by splitting and boxing 4.5-kg paper bags of chrysotile asbestos in an enclosed chamber ventilated at 28.2 air changes per hour (ACH). Two recirculation fans achieved chamber air mixing. The airborne concentration of asbestos fibers was determined by sampling air through membrane filters at a rate of 10 l/min and by analysing fibers by phase contrast optical microscopy to determine 15-min average airborne concentrations. Samplers were located at four equidistant locations from the operation. Opening a maximum of seven bags in 15 min was associated with an asbestos-in-air concentration of less than 2 x 10(-6) fibers/m3 (f/m3) in splitting open and boxing and less than 0.85 x 10(-6) f/m3 in boxing of pre-split bags. The measured airborne asbestos concentration exhibited a linear trend with the number of bags opened per 15 min. The empirical results were utilised to model fiber concentrations for various ventilation rates. It was concluded that the distribution of the operation within the workday and the ventilation rate are the two most important variables in the determination of the estimated time-weighted average concentration. Splitting open and boxing 32 bags of asbestos over an 8-h period at a rate of 4 bags/h over an 8-h period results in a calculated time-weighted average exposure of about 1 x 10(-6) f/m3 in a work space with 20 ACH and approximately 7 x 10(-6) f/m3 in a work space with 2 ACH. Splitting open and boxing at a rate of 12 bags/h for 2 h and 45 min yielded calculated concentrations less than one-half of the above mentioned values. These results should serve as a useful benchmark for epidemiologists concerned with the magnitude of exposure in historically dusty industrial tasks.

The reconstruction of worker exposures has been the mainstay of modem industrial epidemiologic studies. In most cases, the researchers are faced with the difficult dilemma created by the scarcity of the exposure measurement data vis-à-vis the demands for refined quantification. The 4 industrial epidemiologic studies of workers exposed to acrylonitrile share many similarities to illustrate strengths and weaknesses of the current exposure reconstruction methodologies. The analysis of the reported exposure reconstruction methods and comparative analysis of some of the results suggest that there is a certain degree of conformity in the results of the exposure reconstruction processes in these 4 studies. At the same time, the same analysis invokes some questions with respect to the interpretation of the exposure reconstruction results.

To investigate factors related to lung cancer mortality in four Arizona copper-smelter towns, the authors identified 142 lung cancer cases and 2 matched controls per case from decedent residents during 1979-1990. The authors obtained detailed information on lifetime residential, occupational, and smoking histories via structured telephone interviews with knowledgeable informants. The authors linked estimated historical environmental exposures to smelter emissions (based on atmospheric diffusion modeling of measured sulfur dioxide concentrations) with residential histories to derive individual profiles of residential exposure. The results of this study provided little evidence of a positive association between lung cancer and residential exposure to smelter emissions. Conditional logistic regression analysis revealed a statistically significant positive association between lung cancer and reported employment in copper mines and/or smelters, although specific factors associated with the apparently increased risk among these workers could not be identified in this community-based study.

To investigate factors related to lung cancer mortality in six Arizona copper smelter towns, we identified 185 lung cancer cases and two matched controls per case from decedent residents during 1979-1990. Detailed information on lifetime residential, occupational, and smoking history was obtained by structured telephone interviews with knowledgeable informants. Interviews were completed for 82% of 183 eligible cases and 88% of the targeted number (366) of controls. Estimated historical environmental exposures to smelter emissions, based on atmospheric diffusion modeling of measured SO2 concentrations, were linked with residential histories to derive individual profiles of residential exposure. Occupational histories were characterized by potential exposure to smelter emissions, asbestos, and ionizing radiation. Conditional logistic regression was used to compare study factors in cases and controls with adjustment for potential confounding factors: gender, Hispanic ethnicity, and smoking. In overall and gender-specific analyses, no statistically significant associations were observed between lung cancer risk and any of the measures of residential exposure to smelter emissions considered (town of residence at time of death, highest level of exposure, and duration or cumulative exposure above background levels), or any of the estimated occupational exposures (definite or potential asbestos, potential ionizing radiation, definite or potential smelter). Among male residents of some, but not all, towns, there was some evidence of a positive association between lung cancer risk and reported copper smelter-related employment (reported as definite), with the highest risk observed for Miami, Arizona. This study provided little evidence of a positive association between lung cancer mortality and residential exposure to smelter emissions. Specific factors associated with the apparent heterogeneity in lung cancer risk across study towns cannot be identified in this community-based study.

In this study, we summarize 47 epidemiologic studies related to formaldehyde exposure and use meta-analytic techniques to assess findings for cancers of the lung, nose/nasal sinuses, and nasopharynx. Our analyses indicate that workers with formaldehyde exposure have essentially null findings for lung cancer and a slight deficit of sinonasal cancer. Nasopharyngeal cancer rates were elevated moderately in a minority of studies. Most studies, however, did not find any nasopharyngeal cancers, and many failed to report their findings. After correcting for underreporting, we found a meta relative risk of 1.0 for cohort studies. Case-control studies had a meta relative risk of 1.3. Our review of the exposure literature indicated that the nasopharyngeal cancer case-control studies represented much lower and less certain exposures than the cohort studies. We conclude that the available studies do not support a causal relation between formaldehyde exposure and nasopharyngeal cancer. This conclusion conflicts with conclusions from two previous meta-analyses, primarily because of our consideration of unreported data.