Occupational and other exposures associated with male end-stage renal disease: a case/control study

We conducted a case-control study of 325 men ages 30-69 who were diagnosed with end-stage renal disease (ESRD) between 1976 and 1984, and resided in four urban areas of Michigan in 1984. Cases were selected from the Michigan Kidney Registry and excluded men with diabetic, congenital, and obstructive nephropathies. Controls were selected by random-digit dialing and were pair-matched to cases for age, race, and area of residence. Telephone interviews were conducted with 69 percent of eligible cases and 79 percent of eligible controls. Risk of ESRD was significantly related to phenacetin or acetaminophen consumption (odds ratio(OR) = 2.66), moonshine consumption (OR = 2.43), a family history of renal disease (OR = 9.30); and regular occupational exposures to solvents (OR = 1.51) or silica (OR = 1.67). Particular occupational exposures with elevated risk were solvents used as cleaning agents and degreasers (OR = 2.50) silica exposure in foundries or brick factories (OR = 1.92), and silica exposure during sandblasting (OR = 3.83). Little or no trend of increased risk with duration of exposure was found for these occupational exposures, with the exception of silica in sandblasting. Limitations of these data include representativeness of cases, possible overreporting by cases, and misclassification of exposures inherent in self-reports.     

The mortality of lead smelter workers: an update.

OBJECTIVES. Mortality studies of lead workers have shown excesses of nonmalignant renal disease and cerebrovascular disease. Animal studies and one human study have shown excess kidney cancer. We have updated a mortality study of male lead smelter workers (n = 1990). METHODS. An analysis was conducted using standard life table techniques. The updated analysis added 11 years of follow-up and 363 new deaths. RESULTS. The original study had found elevated but nonsignificant risks for kidney cancer, stroke, and nonmalignant renal disease, probably attributable to lead exposure. Deaths from accidents and nonmalignant respiratory disease were significantly elevated, but probably not as a result of lead exposure. In the updated study, no new deaths from nonmalignant renal disease occurred (9 observed, standardized mortality ratio = 1.21). Three more deaths from kidney cancer were observed, yielding a standardized mortality ratio of 1.93 (9 observed, 95% CI = 0.88, 3.67), which increased for those who had worked in areas with the highest lead exposure (8 observed, standardized mortality ratio = 2.39, 95% CI = 1.03, 4.71). Cerebrovascular disease remained elevated for those with more than 20 years of exposure (26 observed, standardized mortality ratio = 1.41, 95% CI = 0.92, 2.07). CONCLUSIONS. This cohort with high lead exposure showed a diminishing excess of death from nonmalignant renal disease, a continued excess from kidney cancer, and an excess of cerebrovascular disease only in those with longest exposure to lead.     

Kidney disease and arthritis in a cohort study of workers exposed to silica.

Silica exposure has been associated with kidney disease and rheumatoid arthritis; an autoimmune mechanism has been proposed. Approximately 2 million people are occupationally exposed to silica in the United States, 100,000 at more than twice the National Institute for Occupational Safety and Health recommended exposure limit of 0.05 mg/m(3). We examined renal disease morbidity and mortality, as well as arthritis mortality, in a cohort of 4,626 silica-exposed workers in the industrial sand industry (an industry previously unstudied). We compared the cohort with the U.S. population and also conducted internal exposure-response analyses using a job-exposure matrix based on more than 4,000 industrial hygiene samples. We found excess mortality from acute renal disease [standardized mortality ratio (SMR) = 2.61, 95% confidence intervals (95% CIs) = 1.49--4.24; 16 deaths], chronic renal disease (SMR = 1.61, 95% CI = 1.13--2.22; 36 deaths), and arthritis (SMR = 4.36, 95% CI = 2.76--6.54; 23 deaths) on the basis of multiple-cause mortality data, which considered any mention of disease on a death certificate. Linking the cohort with the U.S. registry of end-stage renal disease for the years 1977-1996, we found an excess of end-stage renal disease incidence (standardized incidence ratio = 1.97, 95% CI = 1.25--2.96; 23 cases), which was highest for glomerulonephritis (standardized incidence ratio = 3.85, 95% CI = 1.55--7.93; 7 cases). We found increasing end-stage renal disease incidence with increasing cumulative exposure; standardized rate ratios by quartile of cumulative exposure were 1.00, 3.09, 5.22, and 7.79. A positive exposure-response trend was also observed for rheumatoid arthritis on the basis of death certificate data. These data represent the largest number of kidney disease cases analyzed to date in a cohort with well-defined silica exposure and suggest a causal link between silica and kidney disease. Excess risk of end-stage renal disease due to a lifetime of occupational exposure at currently recommended limits is estimated to be 14%, above a background end-stage renal disease risk of 2%.     

Reanalysis of mortality from lung cancer among diatomaceous earth industry workers, with consideration of potential confounding by asbestos exposure.

OBJECTIVE: To evaluate the potential for confounding from asbestos exposure, primarily chrysotile, on the relation between crystalline silica and mortality from lung cancer among diatomaceous earth (diatomite) workers. METHODS: A reanalysis of a cohort mortality study of diatomite workers was performed to take into account quantitative estimates of asbestos exposure. The reanalysis was limited to a subset of the original cohort, comprising 2266 white men for whom asbestos exposure could be reconstructed with greatest confidence. Comparisons between mortality from lung cancer (standardised mortality ratios (SMR)) were made between rates for 1942-87 for United States white men, and workers cross classified according to cumulative exposures to crystalline silica and asbestos. Comparisons of internal rates, involving Poisson regression modeling, were conducted for exposure to crystalline silica, with and without adjustment for asbestos exposure. Exposures were lagged by 15 years to take into account disease latency. RESULTS: There was an overall excess of lung cancer (SMR 1.41; 52 observed). The SMRs for four categories of increasing crystalline silica among the workers not exposed to asbestos were 1.13, 0.87, 2.14, 2.00. An SMR of 8.31 (three observed) was found for workers with the highest cumulative exposure to both dusts. Internal analysis, after adjustment for asbestos exposure, yielded rate ratios for categories of exposure to crystalline silica: 1.00 (reference), 1.37, 1.80, and 1.79. CONCLUSIONS: Asbestos exposure was not an important confounder of the association between crystalline silica and mortality from lung cancer in this cohort. Although based on a small number of deaths from lung cancer, the data suggest possible synergy between these exposures. An extended follow up of this cohort is in progress and should enable better assessments of independent and combined effects on risk of lung cancer.     

Cancer risks in the optical manufacturing industry.

A mortality odds ratio (MOR) study has been conducted to explore the cancer risks of exposures experienced in the production of optical lenses and metal spectacle frames. Male death certificates were obtained from a Massachusetts town where a large optical industry is located. Craftsmen, foremen, and operatives of non-optical industries, such as woollen textile workers and workers in the optical company with short-term or no exposure, were chosen as reference workers their incomes were similar to those of the exposed workers. Cardiovascular disease (total 714) is chosen as the reference disease to explore cancers (total 232). An excess risk of total cancers observed = 70, expected = 48) has formed among lens workers. The excess may be accounted for mainly by the excess risk of gastrointestinal cancers; the standardised MORs (sMOR) for medium and long-term exposure were 2.2 and 2.5. The excess was especially evident for colorectal cancers; the sMORs for medium and long-term exposures were 3.2 and 2.6. Excess risks of gastrointestinal cancers (sMOR = 2.9) and colorectal cancers (sMOR = 3.4) were found among metal frame workers with long-term (employed for more than 29 years) exposure, but the number of exposed cases was small (9 and 6 respectively). These results suggest that exposure to abrasives or cutting oil mists or both, possibly by ingestion, might increase the risk of gastrointestinal (especially colorectal) cancers among lens and metal spectacle frame manufacturers.     

Mortality among workers in the diatomaceous earth industry.

A cohort mortality study was conducted among workers from two plants in the diatomaceous earth mining and processing industry in California. Diatomaceous earth consists of the skeletal remains of diatoms. Exposure to amorphous (non-crystalline) and crystalline silica in the form of quartz results from open pit mining and exposure to crystalline silica (principally cristobalite) occurs in the processing of the material. Lung cancer and non-malignant respiratory diseases have been the health outcomes of greatest concern. The main study cohort included 2570 white men (533 Hispanic and 2017 non-Hispanic workers) who were employed for at least 12 months cumulative service in the industry and who had worked for at least one day during the follow up period, 1942-87. Vital status was ascertained for 91% of the cohort and death certificate information was retrieved for 591 of 628 (94%) identified deaths. The all causes combined standardised mortality ratio (SMR) was slightly increased (SMR = 1.12; 628 observed) compared with rates among US white males. The principal contributors to this excess were increased risks from lung cancer (SMR = 1.43; 59 observed) and non-malignant respiratory disease (NMRD) excluding infectious diseases and pneumonia (SMR = 2.59; 56 observed). The excess of lung cancer persisted when local county rates were used for comparison (SMR = 1.59). Internal rate comparisons by Poisson regression analysis were conducted to assess potential dose-response relations for lung cancer and NMRDs. Mortality trends were examined in relation to duration of employment in dust exposed jobs and with respect to an index of cumulative exposure to crystalline silica. The crystalline silica index was a semiquantitative measure that combined information on duration of exposure, differences in exposure intensity between jobs and calendar periods, the crystalline content of the various product mixes, and the use of respiratory protection devices. Increasing gradients of risk were detected for lung cancer and NMRD with both exposure indices. The relative risk trends for lung cancer and NMRD with crystalline silica exposure lagged 15 years were respectively: 1.00, 1.19, 1.37, and 2.74, and 1.00, 1.13, 1.58, and 2.71. Based on a review of available but limited data on cigarette smoking in the cohort and from application of indirect methods for assessing confounding variables, it seems unlikely that smoking habits could account for all of the association between exposure to dust and lung cancer. The intense and poorly controlled dust exposures encountered before the 1950s were probably the most aetiologically significant contributors to risks from lung cancer and NMRDs. The absence of an excess of lung cancer among workers hired since 1960, and the finding of no deaths attributed to pneumoconiosis as an underlying cause of death among workers hired since 1950 indicate that exposure reductions in the industry during the past 40 years have been successful in reducing excess risks to workers. Further mortality follow up of the cohort and the analysis of radiographic data will be needed to determine conclusively the long term patterns of disease risks in this industry.     

Mortality among employees of lead battery plants and lead-producing plants, 1947-1980

Two cohorts of male lead workers, 4 519 battery plant workers and 2 300 lead production workers, all of whom had been employed for at least one year during the period 1 January 1946 through 31 December 1970, were observed for mortality during the 34 years from 1 January 1947 through 31 December 1980. Vital status as of the closing date was determined for 94.7% of the former group and 91.6% of the latter. There were 1 718 deaths in the first cohort and 621 in the second. Mortality from all causes combined was significantly greater than expected in each cohort, the standardized mortality ratio (SMR) being 107 and 113, respectively. Among the battery plant workers the greater than expected mortality rate resulted in large part from a significant number of excess deaths from malignant neoplasms (SMR 113), other hypertensive disease (mainly renal) (SMR 320), chronic nephritis (SMR 222), and a group of ill-defined conditions (SMR 355). Among the lead production workers the pattern was similar, with a significant number of excess deaths from other hypertensive disease (SMR 475), hypertensive heart disease (SMR 203), chronic nephritis (SMR 265), and ill-defined conditions (SMR 214). There was also a significant excess of deaths from external causes (SMR 143). The SMR for total malignancies was 113, but this value was not significantly elevated at the 5% level. In neither cohort were deaths from cerebrovascular disease in significant excess, the SMR being 93 and 132, respectively. A proportionate mortality analysis showed that the excess deaths from cerebrovascular disease and from hypertensive heart disease among smelter workers were in part due to the high proportion of nonwhites in the smelter populations. The stomach, liver, and lungs were the sites responsible for most excess cancer deaths in both cohorts, but the elevated SMR values were statistically significant only for gastric and lung cancers in battery plant workers. There were no excess deaths from malignancies of the kidney, brain, or lymphopoietic system in either cohort. It is impossible to relate the observed mortality to levels of lead exposure; because of meager quantitative information prior to 1960. It is known that past exposures had been very high. Ethnicity, diet, alcohol, and cigarette smoking could not be ruled out as possible confounding etiologic factors for the cancer deaths.     

Mortality from lung cancer and respiratory disease among pottery workers exposed to silica and talc

A cohort mortality study of white men employed for at least one year between 1939 and 1966 at three plants of a single United States company was conducted to evaluate the risk of lung cancer and nonmalignant respiratory disease among workers exposed to silica dust and nonfibrous (nonasbestiform) talc in the manufacture of ceramic plumbing fixtures. Follow-up of 2,055 men through January 1, 1981, indicated a substantial excess of nonmalignant respiratory disease among those with high levels of exposure to silica dust (standardized mortality ratio = 2.26). The risk of nonmalignant respiratory disease rose with the number of years exposed, was not further enhanced by talc exposure, and appeared to be appreciably lower among those exposed in more recent time periods. For lung cancer, men exposed to high levels of silica dust with no talc exposure had a nonsignificant standardized mortality ratio of 1.37. However, those exposed to nonfibrous talc in addition to high levels of silica had a significant 2.5-fold excess risk of lung cancer. Among this group, the lung cancer standardized mortality ratio rose with increasing years of talc exposure to 3.64 among those exposed for 15 or more years. Although the role of silica as a cofactor cannot be ruled out, these data suggest that nonfibrous talc exposure is associated with excess lung cancer risk.     

Quantitative exposure-response for silica dust and lung cancer in Vermont granite workers

BACKGROUND: Excess lung cancer mortality among the exposed Vermont granite workers has been reported. These studies were based on job and tenure surrogates, with the potential for misclassification and inability to evaluate quantitative exposure-response. METHODS: Industrial hygiene data collected from 1924 to 1977 was analyzed in conjunction with mortality data to examine quantitative exposure-response for silica, lung cancer, and other lung diseases. A person-years analysis was undertaken by cumulative exposure group, including lagged and unlagged tabulations. Poisson models were fitted to untransformed and log transformed exposure. RESULTS: The results indicated a clear relationship of lung cancer, tuberculosis, pneumoconiosis, non-malignant lung disease, and kidney cancer with cumulative exposure. An exposure to 0.05 mg/m(3) from age 20 to 64 was associated with a lifetime excess risk of lung cancer for white males of 27/1,000. CONCLUSIONS: The results of this study of workers exposed almost exclusively to silica and no other major occupational confounding exposures indicate a clear exposure-response for lung cancer.     

One agent, many diseases: exposure-response data and comparative risks of different outcomes following silica exposure

BACKGROUND: Evidence in recent years indicates that silica causes lung cancer, and probably renal disease, in addition to its well-known relationship to silicosis. There is also suggestive evidence that silica can cause arthritis and other auto-immune diseases. Silica has, therefore, joined a handful of other toxic exposures such as tobacco smoke, dioxin, and asbestos which cause multiple serious diseases. METHODS: The available exposure-response data for silica and silicosis, lung cancer, and renal disease are reviewed. We compare the corresponding excess risks (or absolute risks in the case of silicosis) of death or disease incidence by age 75 for these three diseases, subsequent to a lifetime (45 years) of exposure to silica at current US standard (0.1 mg/m(3) respirable crystalline silica). RESULTS: The absolute risk of silicosis, as defined by small opacities greater than or equal to ILO classification 1/1 on an X-ray, ranges from 47% to 77% in three cohort studies with adequate follow-up after employment. The absolute risk of death from silicosis is estimated at 1.9% (0.8%-2.9%), based on a pooled analysis of six cohort studies. The excess risk of lung cancer death, assuming US male background rates, is 1.7% (0.2%-3.6%), based on a pooled analysis of ten cohort studies. The excess risk of end-stage renal disease (assuming male background rates) is 5.1% (2.2%-7.3%), based on a single cohort. The excess risk of death from renal disease is estimated to be 1.8% (0.8%-9.7%), based on a pooled analysis of three cohorts. CONCLUSIONS: Keeping in mind that the usual OSHA acceptable excess risk of serious disease or death for workers is 0.1%, it is clear that the current standard is far from sufficiently protective of workers' health. Perhaps surprisingly, kidney disease emerges as perhaps a higher risk than either mortality from silicosis or lung cancer, although the data are based on fewer studies.     

Mortality at an automotive engine foundry and machining complex

Mortality was analyzed for an automotive engine foundry and machining complex, with process exposures derived from department assignments. Logistic regression models of mortality odds ratios (ORs) were calculated for 2546 deaths, and numbers of work-related deaths were estimated. Lung cancer mortality in the foundry was increased where cleaning and finishing of castings was performed (OR, 1.7; 95% CI, 1.15 to 2.4 [at mean exposure duration of exposed cases]) and in care-making after 1967 (OR, 1.5; 95% CI, 1.11 to 2.0). Black workers had excess lung cancer mortality in machining heat-treat operations (OR, 2.5, 95% CI, 1.4 to 4.3) and excess nonmalignant respiratory disease mortality in molding (OR, 2.5; 95% CI, 1.16 to 5.5) and core-making (OR, 2.7; 95% CI, 1.25 to 5.8). Stomach cancer mortality was elevated among workers with metalworking fluid exposures in precision grinding (OR, 2.4; 95% CI, 1.14 to 5.1). Heart disease mortality was increased among all workers in molding (OR, 1.6; 95% CI, 1.09 to 2.3), as was stroke mortality among workers exposed to metalworking fluids (OR, 1.8; 95% CI, 1.22 to 2.7). Malignant and nonmalignant liver disease mortality was elevated in assembly/testing and precision grinding. In this modern foundry, 11% of deaths were estimated to be work-related despite it's being largely in regulatory compliance over its 40-year existence. Machining plant exposures accounted for 3% or more of deaths there.     

A mortality study of workers at seven beryllium processing plants.

The International Agency for Research on Cancer (IARC) has found that the evidence for the carcinogenicity of beryllium is sufficient based on animal data but "limited" based on human data. This analysis reports on a retrospective cohort mortality study among 9,225 male workers employed at seven beryllium processing facilities for at least 2 days between January 1, 1940, and December 31, 1969. Vital status was ascertained through December 31, 1988. The standardized mortality ratio (SMR) for lung cancer in the total cohort was 1.26 (95% confidence interval [CI] = 1.12-1.42); significant SMRs for lung cancer were observed for two of the oldest plants located in Lorain, Ohio (SMR = 1.69; 95% CI = 1.28-2.19) and Reading, Pennsylvania (SMR = 1.24; 95% CI = 1.03-1.48). For the overall cohort, significantly elevated SMRs were found for "all deaths" (SMR = 1.05; 95% CI = 1.01-1.08), "ischemic heart disease" (SMR = 1.08; 95% CI = 1.01-1.14), "pneumoconiosis and other respiratory diseases" (SMR = 1.48; 95% CI = 1.21-1.80), and "chronic and unspecified nephritis, renal failure, and other renal sclerosis" (SMR = 1.49; 95% CI = 1.00-2.12). Lung cancer SMRs did not increase with longer duration of employment, but did increase with longer latency (time since first exposure). Lung cancer was particularly elevated (SMR = 3.33; 95% CI = 1.66-5.95) among workers at the Lorain plant with a history of (primarily) acute beryllium disease, which is associated with very high beryllium exposure. The lung cancer excess was not restricted to plants operating in the 1940s, when beryllium exposures were known to be extraordinarily high. Elevated lung cancer SMRs were also observed for four of the five plants operating in the 1950s for workers hired during that decade. Neither smoking nor geographic location fully explains the increased lung cancer risk. Occupational exposure to beryllium compounds is the most plausible explanation for the increased risk of lung cancer observed in this study. Continued mortality follow-up of this cohort will provide a more definitive assessment of lung cancer risk at the newer plants and among cohort members hired in the 1950s or later at the older plants. Further clarification of the potential for specific beryllium compounds to induce lung cancer in humans, and the possible contribution of other exposures in specific processes at these plants, would require a nested case-control study. We are currently assessing whether available industrial hygiene data would support such an analysis.     

Mortality of a cohort of tin miners 1941-86.

The mortality patterns of United Kingdom tin miners were examined in relation to calendar period and duration of underground work with particular attention to lung cancer and exposure to radon. Subjects were all men who had worked for at least one year between 1941 and 1984 at one of two United Kingdom tin mines and for whom a complete work history could be constructed from mine records. Standardised mortality ratios (SMRs) were calculated using national (England and Wales) rates. The pattern of SMRs in relation to potential explanatory variables was analysed using Poisson regression methods. Mortalities from lung cancer and silicosis (including silicotuberculosis) were significantly raised and showed a significant relation with duration of underground work (mortality from stomach cancer was raised in both underground and surface workers, but not significantly). Excess mortality from silica related disease declined steeply from 35% among workers first exposed before 1920 to 1% among those first exposed after 1950. Thirteen surface workers with known exposure to arsenic had high rates of lung and stomach cancer. The SMR for lung cancer showed a consistent pattern in relation to duration of underground exposure, rising from 83 (observed/expected = 8/9.6) for surface workers (without exposure to arsenic) to 447 (15/3.4) for workers with more than 30 years underground exposure. Examination of the SMR for lung cancer by total underground exposure, age, and time since last exposure gave rise to a model for the expression of risk which depends only on total exposure and time since exposure. The fitted model implies that the effect of exposure to radon in a given year has no effect on risk for 10 years, then rapidly rises to a maximum from which the excess risk then declines, halving every 4.3 years. There were no direct measurements of historic radon levels. A conservative estimate based on measurements taken since 1969 by the National Radiological Protection Board and the Mines and Quarries Inspectorate is that the annual dose to an underground worker was about 10 working level months (WLM). Given this assumption, the risk/exposure slope implied by the present data, and the model fitted to it, was somewhat lower than that given in the fourth Committee on the Biological Effects of Ionisation Radiation (BEIR IV) report (about 40% lower for lifetime exposures). The present data also imply different risks depending on the age at exposure, with relatively higher lifetime risks for exposure at older ages, and relatively lower risks for exposures at younger ages. In conclusion, there was a clear relation between exposure to radon and death from lung cancer. The relative risk of lung cancer due to exposure to radon was not constant in cessation of exposure. The lifetime excess risk of lung cancer implied by these data for 40 years exposure at the current statutory limit of four WLM a year starting at age 20, was about 8% (79 excess deaths per 1000 exposed), assuming average smoking habits among the exposed workers. Control of dust concentrations in the mines has substantially reduced--and may have eliminated--direct mortality from silica related disease.     

Mortality from lung cancer among workers employed in formaldehyde industries

A historical cohort of 26,561 workers employed in ten facilities was assembled to evaluate cancer risks associated with exposure to formaldehyde. Historical exposures to formaldehyde by job, work area, plant, and calendar time were estimated using monitoring data available from participating plants, comments from long-term workers and company officials, exposure evaluations from walk-through surveys conducted by project industrial hygienists, and results from monitoring specifically performed for this project. A previous report of findings from this study noted a 30% excess mortality from lung cancer among wage workers. The relative risk for lung cancer (whether estimated by SMRs or SRRs) 20 or more years after first exposure did not generally rise with increasing exposure to formaldehyde. Various estimates of exposure were investigated including duration, intensity, peak, cumulative, and average, and by exposures lagged by 5, 10, 20, and 30 years. The excess did not appear to arise gradually, but emerged suddenly among workers whose total cumulative exposure was less than 0.1 ppm-years. Slightly positive, but nonsignificant, exposure-response associations between lung cancer and level of formaldehyde occurred in only a few out of a large number of comparisons (e.g., for persons hired before the start dates for the study and for workers also exposed to particulates). There was a lack of consistency among the various plants for risk of lung cancer, with six plants having elevated SMRs and four plants having deficits. Mortality from lung cancer was more strongly associated with exposure to other substances including phenol, melamine, urea, and wood dust than with exposure to formaldehyde. Workers exposed to formaldehyde without exposure to these substances did not experience an elevated mortality from lung cancer. The risk did not increase with cumulative levels of formaldehyde among those exposed to other substances and there was a slightly negative trend for those exposed to formaldehyde alone. Although some role for formaldehyde, particularly in association with other substances, in the excess of lung cancer seen among these workers cannot be ruled out, these findings suggest that exposure to phenol, melamine, urea, wood dust or other exposures also occurring in the area where these substances were used (i.e., production of resin and molding compounds) may play a more primary role. This association should be further evaluated in other studies that include workers from resin and molding compound operations.     

Mortality of a cohort of tin miners 1941-86

The mortality patterns of United Kingdom tin miners were examined in relation to calendar period and duration of underground work with particular attention to lung cancer and exposure to radon. Subjects were all men who had worked for at least one year between 1941 and 1984 at one of two United Kingdom tin mines and for whom a complete work history could be constructed from mine records. Standardised mortality ratios (SMRs) were calculated using national (England and Wales) rates. The pattern of SMRs in relation to potential explanatory variables was analysed using Poisson regression methods. Mortalities from lung cancer and silicosis (including silicotuberculosis) were significantly raised and showed a significant relation with duration of underground work (mortality from stomach cancer was raised in both underground and surface workers, but not significantly). Excess mortality from silica related disease declined steeply from 35% among workers first exposed before 1920 to 1% among those first exposed after 1950. Thirteen surface workers with known exposure to arsenic had high rates of lung and stomach cancer. The SMR for lung cancer showed a consistent pattern in relation to duration of underground exposure, rising from 83 (observed/expected = 8/9.6) for surface workers (without exposure to arsenic) to 447 (15/3.4) for workers with more than 30 years underground exposure. Examination of the SMR for lung cancer by total underground exposure, age, and time since last exposure gave rise to a model for the expression of risk which depends only on total exposure and time since exposure. The fitted model implies that the effect of exposure to radon in a given year has no effect on risk for 10 years, then rapidly rises to a maximum from which the excess risk then declines, halving every 4.3 years. There were no direct measurements of historic radon levels. A conservative estimate based on measurements taken since 1969 by the National Radiological Protection Board and the Mines and Quarries Inspectorate is that the annual dose to an underground worker was about 10 working level months (WLM). Given this assumption, the risk/exposure slope implied by the present data, and the model fitted to it, was somewhat lower than that given in the fourth Committee on the Biological Effects of Ionisation Radiation (BEIR IV) report (about 40% lower for lifetime exposures). The present data also imply different risks depending on the age at exposure, with relatively higher lifetime risks for exposure at older ages, and relatively lower risks for exposures at younger ages. In conclusion, there was a clear relation between exposure to radon and death from lung cancer. The relative risk of lung cancer due to exposure to radon was not constant in cessation of exposure. The lifetime excess risk of lung cancer implied by these data for 40 years exposure at the current statutory limit of four WLM a year starting at age 20, was about 8% (79 excess deaths per 1000 exposed), assuming average smoking habits among the exposed workers. Control of dust concentrations in the mines has substantially reduced--and may have eliminated--direct mortality from silica related disease.     

Mortality study of gold miners exposed to silica and nonasbestiform amphibole minerals: An update with 14 more years of follow-up

We have updated a study of 3,328 gold miners who worked underground for at least 1 year between 1940-1965 in South Dakota, extending the follow-up from 1977 to 1990. The exposures of concern were silica and nonasbestiform amphibole minerals. The lung cancer standardized mortality ratio (SMR) was 1.13 (95% confidence interval [CI] 0.94-1.36, 115 observed) when the U.S. population was used as the referent group, increasing to 1.25 (95% CI 1.03-1.51) when the county was used as the referent, and to 1.27 (1.02-1.55) for person-time with more than 30 years potential latency. However, lung cancer mortality did not show a positive exposure-response trend with estimated cumulative dust exposure. Data on smoking habits suggested that the miners smoked slightly more than the U.S. population in a 1960 cross-sectional survey. In contrast to lung cancer, other diseases known to be associated with silica exposure (tuberculosis and silicosis) were significantly increased (SMR = 3.44 and 2.61) and exhibited clear exposure-response trends. Nonmalignant renal disease, also associated with silica exposure, was elevated for those hired in early years and showed a significant positive exposure-response trend. Multiple-cause analysis revealed significant excesses of arthritis, musculoskeletal diseases (including systemic lupus and sclerosis), and skin conditions (including scleroderma and lupus), diseases of autoimmune origin which have been associated with silica exposure in other studies. Multiple cause analysis also showed a significant excess of diseases of the blood and blood-forming organs.     

Differences in mortality by radiation monitoring status in an expanded cohort of Portsmouth Naval Shipyard workers

Studies of leukemia and lung cancer mortality at the Portsmouth Naval Shipyard (PNS) have yielded conflicting results. In an expanded cohort of PNS workers employed between 1952 and 1992 and followed through 1996, the all-cause standardized mortality ratio (SMR) was 0.95 (95% confidence interval, 0.93-0.96). Employment duration SMRs were elevated with confidence intervals excluding 1.00 for lung cancer, esophageal cancer, and all cancers combined. Leukemia mortality was as expected overall, but standardized rate ratio analyses showed a significant positive linear trend with increasing external radiation dose. The role of solvent exposures could not be evaluated. Findings differed by radiation monitoring subcohort, with excess asbestosis deaths limited to radiation workers and several smoking-related causes of death higher among nonmonitored workers. At PNS, asbestos exposure and possibly smoking could be nonrandomly distributed with respect to radiation exposure, suggesting potential for confounding in internal analyses of an occupational cohort.     

Historical cohort study of US man-made vitreous fiber production workers: I. 1992 fiberglass cohort follow-up: initial findings

This 1986 to 1992 update and expansion of an earlier historical cohort study examined the 1946 to 1992 mortality experience of 32,110 workers employed for 1 year or more during 1945 to 1978 at any of 10 US fiberglass (FG) manufacturing plants. Included are (1) a new historical exposure reconstruction for respirable glass fibers and several co-exposures (arsenic, asbestos, asphalt, epoxy, formaldehyde, polycyclic aromatic hydrocarbons, phenolics, silica, styrene, and urea); and (2) a nested, matched case-control study of 631 respiratory system cancer (RSC) deaths in male workers during 1970 to 1992 with interview data on tobacco smoking history. Our findings to date from external comparisons based on standardized mortality ratios (SMRs) in the cohort study provide no evidence of excess mortality risk from all causes combined, all cancers combined, and non-malignant respiratory disease. Also, excluding RSC, we observed no evidence of excess mortality risk from any of the other cause-of-death categories considered. For RSC among the total cohort, we observed a 6% excess (P = 0.05) based on 874 deaths. Among long-term workers (5 or more years of employment) we observed a not statistically significant 3% excess based on 496 deaths. Among the total cohort, we observed increases in RSC SMRs with calendar time and time since first employment, but these were less pronounced among long-term workers. RSC SMRs were not related to duration of employment among the total cohort or long-term workers. In an externally controlled analysis of male workers at risk between 1970 and 1992, we observed no association between RSC SMRs and increasing exposure to respirable FG. Our findings to date from internal comparisons based on rate ratios in the case-control study of RSC were limited to analyses of categorized study variables with and without adjustment for smoking. On the basis of these analyses, the duration of exposure and cumulative exposure to respirable FG at the levels encountered at the study plants did not appear to be associated with an increased risk of RSC. RSC risk also did not seem to increase with time since first employment. There is some evidence of elevated RSC risk associated with non-baseline levels of average intensity of exposure to respirable glass, but when adjusted for smoking this was not statistically significant, and there was no apparent trend with increasing exposure. This same pattern of findings was observed for duration of exposure, cumulative exposure, and average intensity of exposure to formaldehyde. None of the other individual co-exposures encountered in the study plants appeared to be associated with an increased risk of RSC. The primary focus of ongoing analyses is to determine the extent to which our present findings are robust to alternative characterizations of exposure.     

Mortality among retired fur workers. Dyers, dressers (tanners) and service workers

A retrospective cohort mortality study was conducted on 807 fur dyers, fur dressers (tanners), and fur service workers who were pensioned between 1952 and 1977 by the Fur, Leather and Machine Workers Union of New York City. Workplace exposures of fur workers varied with job category. Dyers were exposed to oxidative dyes used in commercial hair dyes; dressers and service workers were exposed to tanning chemicals. In a comparison with the New York City population, no significant increases in mortality were observed among the fur dyers. Among fur dressers, mortality from all malignant neoplasms [standardized mortality ratio (SMR) 151] and lung cancer (SMR 232) was significantly elevated, as was mortality from cardiovascular disease (SMR 126) among fur service workers. When examined by ethnic origin, the elevated SMR values and directly age-adjusted rate ratios suggested that foreign-born fur dressers and eastern European-born fur workers experienced the highest risks for lung and colorectal cancers, respectively. These data support previous findings of increased mortality from colorectal cancer in the foreign-born population of the United States and suggest a possible occupational etiology for the observed lung cancer excess.     

Beryllium sensitization and disease among long-term and short-term workers in a beryllium ceramics plant

OBJECTIVE: Workers at a beryllium ceramics plant were tested for beryllium sensitization and disease in 1998 to determine whether the plant-wide prevalence of sensitization and disease had declined since the last screening in 1992; an elevated prevalence was associated with specific processes or with high exposures; exposure-response relationships differed for long-term workers hired before the last plant-wide screening and short-term workers hired since then. METHODS: Current workers were asked to complete a questionnaire and to provide blood for the beryllium lymphocyte proliferation test (BeLPT). Those with an abnormal BeLPT were classified as sensitized, and were offered clinical evaluation for beryllium disease. Task- and time-specific measurements of airborne beryllium were combined with individual work histories to compute mean, cumulative, and peak beryllium exposures for each worker. RESULTS: The 151 participants represented 90% of 167 eligible workers. Fifteen (9.9% of 151) had an abnormal BeLPT and were split between long-term workers (8/77 = 10.4%) and short-term workers (7/74 = 9.5%). Beryllium disease was detected in 9.1% (7/77) of long-term workers but in only 1.4% (1/74) of short-term workers (P = 0.06), for an overall prevalence of 5.3% (8/151). These prevalences were similar to those observed in the earlier survey. The prevalence of sensitization was elevated in 1992 among machinists, and was still elevated in 1998 among long-term workers (7/40 = 18%) but not among short-term workers (2/36 = 6%) with machining experience. The prevalence of sensitization was also elevated in both groups of workers for the processes of lapping, forming, firing, and packaging. The data suggested a positive relationship between peak beryllium exposure and sensitization for long-term workers and between mean, cumulative, and peak exposure and sensitization for short-term workers, although these findings were not statistically significant. Long-term workers with either a high peak exposure or work experience in forming were more likely to have an abnormal BeLPT (8/51 = 16%) than the other long-term workers (0/26, P = 0.05). All seven sensitized short-term workers either had high mean beryllium exposure or had worked longest in forming or machining (7/55 = 13% versus 0/19, P = 0.18). CONCLUSIONS: A plant-wide decline in beryllium exposures between the 1992 and 1998 surveys was not matched by a decline in the prevalence of sensitization and disease. Similar to findings from other studies, beryllium sensitization/disease was associated with specific processes and elevated exposures. The contrast in disease prevalence between long-term and short-term workers suggests that beryllium sensitization can occur after a short period of exposure, but beryllium disease usually requires a longer latency and/or period of exposure. The findings from this study motivated interventions to more aggressively protect and test workers, and new research into skin exposure as a route of sensitization and the contribution of individual susceptibility.