A case-control study of cancer mortality at a transformer-assembly facility

Summary To address earlier reports of excess cancer mortality associated with employment at a large transformer manufacturing plant, each plant operation was rated for seven exposures: Pyranol (a mixture of poly chlorinated biphenyls and trichlorobenzene), trichloroethylene, benzene, mixed solvents, asbestos, synthetic resins, and machining fluids. Site-specific cancer deaths among active or retired employees were cases; controls were selected from deaths (primarily cardiovascular deaths) presumed to be unassociated with any of the study exposures. Using job records, we then computed person-years of exposure for each subject. All subjects were white males. The only unequivocal association was that of resin systems with lung cancer (odds ratio = 2.2 at 16.6 years of exposure, P = 0.001, in a multiple logistic regression including asbestos, age, year of death, and year of hire). Certain other odds ratios appeared larger, but no other association was so robust and remained as distinct after considering the multiplicity of comparisons. Study power was very limited for most associations, and several biases may have affected our results. Nevertheless, further investigation of synthetic resin systems of the type used in the study plant appears warranted.This research was conducted under contracts with the University of Lowell Research Foundation and General Electric Corporation.     

A real-time in-vivo method for studying the percutaneous absorption of volatile chemicals

Realistic estimates of percutaneous absorption following exposures to solvents in the workplace, or through contaminated soil and water, are critical to understanding human health risks. A method was developed to determine dermal uptake of solvents under non-steady-state conditions using real-time breath analysis in rats, monkeys, and humans. The exhaled breath was analyzed using an ion-trap mass spectrometer, which can quantitate chemicals in the exhaled breath stream in the 1-5 ppb range. The resulting data were evaluated using physiologically-based pharmacokinetic (PBPK) models to estimate dermal permeability constants (Kp) under various exposure conditions. The effects of exposure matrix (soil versus water), occlusion versus non-occlusion, and species differences on the absorption of methyl chloroform, trichloroethylene, and benzene were compared. Exposure concentrations were analyzed before and at 0.5-hour intervals throughout the exposures. The percentage of each chemical absorbed and the corresponding Kp were estimated by optimization of the PBPK model to the medium concentration and the exhaled-breath data. The method was found to be sufficiently sensitive for animal and human dermal studies at low exposure concentrations over small body surface areas, for short periods, using non-steady-state exposure conditions.     

Historical cohort study of spontaneous abortion among fabrication workers in the semiconductor health study: Agent-level analysis

Risk of spontaneous abortion (SAB) was examined in relation to chemical and physical agents in a retrospective study of employees of 14 seminconductor MAnufacturers: After screening over 6,000 employees, 506 current and 385 former workers were eligible. If a woman had multiple eligible pregnancies, one was selected at random. Telephone interviews provided data on demographics and occupational and other exposures during the first trimester. Two groups of chemicals accounted for the 45% excess risk of SAB among fabrication-room (fab) workers: photoresist and developed solvents (PDS), including glycol ethers, and fluoride compounds used in etching. Women exposed to high levels of both these agents were at greater risk (RR = 3.21, 95% confidence interval [CI] = 1.29–5.96). In fab workers without these exposures, SAB rates were not elevated (adjusted relative risk [RR] = 0.98, 95% CI = 0.55-1.69). An association was seen with workplace stress, which was not limited to women exposed to PDS or fluoride, nor did stress explain the associations between these chemicals and SAB.     

Workplace exposure zones for classification of employee exposures to physical and chemical agents.

A method involving classification of employee job tasks into exposure zones is proposed to guide the industrial hygienist in assigning personal samples to employees in a facility. Workers are assigned to an exposure zone on the basis of similar profiles of chemical exposures, ventilation characteristics, and job tasks. Two facilities are used to illustrate the power of the exposure zone method to reduce the number of required samples while increasing the confidence of identifying workers at high risk. Details of the zoning and calculation procedures are described in detail.     

Agreement between two methods for retrospective assessment of occupational exposure intensity to six chlorinated solvents: Data from The National Birth Defects Prevention Study

The wide variety of jobs encountered in population-based studies makes retrospective exposure assessment challenging in occupational epidemiology. In this analysis, two methods for estimating exposure intensity to chlorinated solvents are compared: rated (assigned by an expert rater) and modeled (assigned using statistical models). Estimates of rated and modeled intensities were compared for jobs held by mothers participating in the National Birth Defects Prevention Study with possible exposure to six chlorinated solvents: carbon tetrachloride, chloroform, methylene chloride, perchloroethylene, 1,1,1-trichloroethane, and trichloroethylene. For each possibly exposed job, an industrial hygienist assigned (1) an exposure intensity (rated intensity) and (2) determinants of exposure to be used in a statistical model of exposure intensity (modeled intensity). Of 12,326 reported jobs, between 31 (0.3%) and 746 (6%) jobs were rated as possibly exposed to each of the six solvents. Agreement between rated and modeled intensities was low overall (Spearman correlation coefficient range: ?0.09 to 0.28; kappa range: ?0.23 to 0.43). Although no air measurements were available to determine if rated or modeled estimates were more accurate, review of participants' job titles showed that modeled estimates were often unexpectedly high given the low-exposure tasks found in these jobs. Differences between the high-exposure jobs used to create the statistical models (obtained from air measurements in the published literature) and the low-exposure jobs in the actual study population is a potential explanation for the disagreement between the two methods. Investigators should be aware that statistical models estimating exposure intensity using existing data from one type of worker population might not be generalizable to all populations of workers.     

Occupational exposure to solvents and hairy cell leukaemia

OBJECTIVES: The role of occupational exposures in hairy cell leukaemia was investigated through a multicentre, hospital based, case-control study. This paper analyses the role of exposure to solvents other than benzene in hairy cell leukaemia. METHODS: The study included 226 male cases and 425 matched controls, exposure to solvents was evaluated by expert case by case review of the detailed data on occupational exposures generated by specific interviews. Also, exposure to solvents was evaluated with an independently constructed job exposure matrix (JEM). RESULTS: No association was found between hairy cell leukaemia and previous employment in a job exposed to solvents (odds ratio (OR) 0.9 95% confidence interval (95% CI) 0.6 to 1.3). ORs for the main occupational tasks exposed to solvents were around 1 and did not increase with the frequency or the duration of the tasks. No specific type of paint or glue was found to be significantly associated with hairy cell leukaemia. No association was found with exposure to solvents, taken as a whole, with either expert assessments or the JEM. No association was found with aromatic, chlorinated, or oxygenated subgroups of solvents. The ORs did not increase with the average intensity of exposure assessed by the experts, with the frequency of use, or with the duration of exposure. Finally, no association was found with non-occupational exposure to solvents. CONCLUSIONS: The study did not show any association between exposure to solvents and hairy cell leukaemia.     

Retrospective cohort mortality study of workers at an aircraft maintenance facility. I. Epidemiological results.

A retrospective cohort study of 14,457 workers at an aircraft maintenance facility was undertaken to evaluate mortality associated with exposures in their workplace. The purpose was to determine whether working with solvents, particularly trichloroethylene, posed any excess risk of mortality. The study group consisted of all civilian employees who worked for at least one year at Hill Air Force Base, Utah, between 1 January 1952 and 31 December 1956. Work histories were obtained from records at the National Personnel Records Centre, St. Louis, Missouri, and the cohort was followed up for ascertainment of vital state until 31 December 1982. Observed deaths among white people were compared with the expected number of deaths, based on the Utah white population, and adjusted for age, sex, and calendar period. Significant deficits occurred for mortality from all causes (SMR 92, 95% confidence interval (95% CI) 90-95), all malignant neoplasms (SMR 90, 95% CI 83-97), ischaemic heart disease (SMR 93, 95% CI 88-98), non-malignant respiratory disease (SMR 87, 95% CI 76-98), and accidents (SMR 61, 95% CI 52-70). Mortality was raised for multiple myeloma (MM) in white women (SMR 236, 95% CI 87-514), non-Hodgkin's lymphoma (NHL) in white women (SMR 212, 95% CI 102-390), and cancer of the biliary passages and liver in white men dying after 1980 (SMR 358, 95% CI 116-836). Detailed analysis of the 6929 employees occupationally exposed to trichloroethylene, the most widely used solvent at the base during the 1950s and 1960s, did not show any significant or persuasive association between several measures of exposure to trichloroethylene and any excess of cancer. Women employed in departments in which fabric cleaning and parachute repair operations were performed had more deaths than expected from MM and NHL. The inconsistent mortality patterns by sex, multiple and overlapping exposures, and small numbers made it difficult to ascribe these excesses to any particular substance. Hypothesis generating results are presented by a variety of exposures for causes of death not showing excesses in the overall cohort.     

Retrospective cohort mortality study of workers at an aircraft maintenance facility. I. Epidemiological results

A retrospective cohort study of 14,457 workers at an aircraft maintenance facility was undertaken to evaluate mortality associated with exposures in their workplace. The purpose was to determine whether working with solvents, particularly trichloroethylene, posed any excess risk of mortality. The study group consisted of all civilian employees who worked for at least one year at Hill Air Force Base, Utah, between 1 January 1952 and 31 December 1956. Work histories were obtained from records at the National Personnel Records Centre, St. Louis, Missouri, and the cohort was followed up for ascertainment of vital state until 31 December 1982. Observed deaths among white people were compared with the expected number of deaths, based on the Utah white population, and adjusted for age, sex, and calendar period. Significant deficits occurred for mortality from all causes (SMR 92, 95% confidence interval (95% CI) 90-95), all malignant neoplasms (SMR 90, 95% CI 83-97), ischaemic heart disease (SMR 93, 95% CI 88-98), non-malignant respiratory disease (SMR 87, 95% CI 76-98), and accidents (SMR 61, 95% CI 52-70). Mortality was raised for multiple myeloma (MM) in white women (SMR 236, 95% CI 87-514), non-Hodgkin's lymphoma (NHL) in white women (SMR 212, 95% CI 102-390), and cancer of the biliary passages and liver in white men dying after 1980 (SMR 358, 95% CI 116-836). Detailed analysis of the 6929 employees occupationally exposed to trichloroethylene, the most widely used solvent at the base during the 1950s and 1960s, did not show any significant or persuasive association between several measures of exposure to trichloroethylene and any excess of cancer. Women employed in departments in which fabric cleaning and parachute repair operations were performed had more deaths than expected from MM and NHL. The inconsistent mortality patterns by sex, multiple and overlapping exposures, and small numbers made it difficult to ascribe these excesses to any particular substance. Hypothesis generating results are presented by a variety of exposures for causes of death not showing excesses in the overall cohort.     

Retrospective exposure assessment for benzene in the Australian petroleum industry

An excess of lympho-haematopoietic (LH) cancers has been identified in the Australian petroleum industry through the Health Watch surveillance programme. A nested case-control study is being conducted to investigate this excess. This paper describes the methods used to provide quantitative estimates of benzene exposure for each of the subjects in the case-control study. Job histories were compiled for each subject from interviews and company employment records. Site visits and telephone interviews were used to identify the tasks included in each job title. Details about the tasks such as their frequency, the technology in use and about changes that had taken place over the years were also gathered. Exposure dated back to the late 1940s for a few subjects. Collaborating petroleum companies provided recent benzene exposure monitoring data. These were used to generate Base Estimates of exposure for each task, augmented with data from the literature where necessary. Past exposures were estimated from the Base Estimates by means of an exposure algorithm. The modifying effects of technological changes and changes to the product were used in the algorithm.The algorithm was then computed to give, for each job, for each subject, an estimate of average benzene exposure in ppm in the workplace atmosphere (Workplace Estimate). This value was multiplied by the years for which the job was held and these values summed to give an estimate of Cumulative Estimate of benzene in ppm-years. The occupational hygienists performing the exposure assessment did so without knowledge of the case or control status of subjects.Overall exposures to benzene in the Australian petroleum industry were low, and virtually all activities and jobs were below a time-weighted average of 5 ppm. Exposures in terminals were generally higher than at refineries. Exposures in upstream areas were extremely low. Estimates of Cumulative Estimate to benzene ranged from 0.005 to 50.9 ppm-years.     

A survey of airborne and skin exposures to chemicals in footwear and equipment factories in Thailand

This research reports on a pilot industrial hygiene study that was performed at four footwear factories and two equipment factories in Thailand. Workers in these factories were exposed through inhalation and dermal contact to a large number of organic vapors from solvents and cements that were hand applied. In addition, these workers were exposed to highly toxic isocyanates primarily through the dermal route. A total of 286 personal air samples were obtained at the four footwear factories using organic vapor monitors; individual job tasks were monitored using a real-time MIRAN Spectrometer. A total of 64 surface, tool, or hand samples were monitored for isocyanates using surface contamination detectors. Real-time measurements were also obtained for organic vapors in two equipment factories. From 8% to 21% of the workers sampled in each footwear factory were overexposed to mixtures of chemicals from solvents and cements. Up to 100% of the workers performing specific job tasks were overexposed to mixtures of chemicals. From 39% to 69% of the surface samples were positive for unreacted isocyanates. Many of the real-time measurements obtained in the equipment factories exceeded occupational exposure limits. Personal protective equipment and engineering controls were inadequate in all of the factories.     

Nested case-control study of occupational chemical exposures and prostate cancer in aerospace and radiation workers

BACKGROUND: To date, little is known about the potential contributions of occupational exposure to chemicals to the etiology of prostate cancer. Previous studies examining associations suffered from limitations including the reliance on mortality data and inadequate exposure assessment. METHODS: We conducted a nested case-control study of 362 cases and 1,805 matched controls to examine the association between occupational chemical exposures and prostate cancer incidence. Workers were employed between 1950 and 1992 at a nuclear energy and rocket engine-testing facility in Southern California. We obtained cancer-incidence data from the California Cancer Registry and seven other state cancer registries. Data from company records were used to construct a job exposure matrix (JEM) for occupational exposures to hydrazine, trichloroethylene (TCE), polycyclic aromatic hydrocarbons (PAHs), benzene and mineral oil. Associations between chemical exposures and prostate cancer incidence were assessed in conditional logistic regression models. RESULTS: With adjustment for occupational confounders, including socioeconomic status, occupational physical activity, and exposure to the other chemicals evaluated, the odds ratio for low/moderate TCE exposure was 1.3; 95%CI = 0.8 to 2.1, and for high TCE exposure was 2.1; 95%CI = 1.2 to 3.9. Furthermore, we noted a positive trend between increasing levels of TCE exposure and prostate cancer (P-value for trend = 0.02). CONCLUSION: Our results suggest that high levels of TCE exposure are associated with prostate cancer among workers in our study population.     

Mortality and cancer incidence of aircraft maintenance workers exposed to trichloroethylene and other organic solvents and chemicals: extended follow up

OBJECTIVES: To extend the follow up of a cohort of 14,457 aircraft maintenance workers to the end of 1990 to evaluate cancer risks from potential exposure to trichloroethylene and other chemicals. METHODS: The cohort comprised civilians employed for at least one year between 1952 and 1956, of whom 5727 had died by 31 December 1990. Analyses compared the mortality of the cohort with the general population of Utah and the mortality and cancer incidence of exposed workers with those unexposed to chemicals, while adjusting for age, sex and calendar time. RESULTS: In the combined follow up period (1952-90), mortality from all causes and all cancer was close to expected (standardised mortality ratios (SMRs) 97 and 96, respectively). Significant excesses occurred for ischaemic heart disease (SMR 108), asthma (SMR 160), and cancer of the bone (SMR 227), whereas significant deficits occurred for cerebrovascular disease (SMR 88), accidents (SMR 70), and cancer of the central nervous system (SMR 64). Workers exposed to trichloroethylene showed non-significant excesses for non-Hodgkin's lymphoma (relative risk (RR) 2.0), and cancers of the oesophagus (RR 5.6), colon (RR 1.4), primary liver (RR 1.7), breast (RR 1.8), cervix (RR 1.8), kidney (RR 1.6), and bone (RR 2.1). None of these cancers showed an exposure- response gradient and RRs among workers exposed to other chemicals but not trichloroethylene often had RRs as large as workers exposed to trichloroethylene. Workers exposed to solvents other than trichloroethylene had slightly increased mortality from asthma, non- Hodgkin's lymphoma, multiple myeloma, and breast cancer. CONCLUSION: These findings do not strongly support a causal link with trichloroethylene because the associations were not significant, not clearly dose-related, and inconsistent between men and women. Because findings from experimental investigations and other epidemiological studies on solvents other than trichloroethylene provide some biological plausibility, the suggested links between these chemicals and non-Hodgkin's lymphoma, multiple myeloma, and breast cancer found here deserve further attention. Although this extended follow up cannot rule out a connection between exposures to solvents and some diseases, it seems clear that these workers have not experienced a major increase in cancer mortality or cancer incidence.     

Maternal occupational and hobby chemical exposures as risk factors for neural tube defects

In a case-control study, we investigated whether occupational and nonoccupational (hobbies) chemical exposures to women in the periconceptional period increased their risk for having neural tube defect-affected pregnancies. Women were asked about occupational tasks and hobbies performed during the 3 months before through 3 months after conception. Based on her reported occupational tasks and hobbies, an industrial hygienist assigned a priori defined exposure categories to each task and hobby. The exposure categories included 74 chemical groups, 9 "end-use" chemical groups, and organic solvents. Face-to-face interviews were conducted with mothers of 538 (88% of eligible) infants or fetuses with neural tube defect and mothers of 539 (88%) randomly selected, nonmalformed, live-born infants from a population-based 1989-1991 cohort of California births (N = 703,518). Our results suggested that maternal exposures in the periconceptional period to a variety of chemicals associated with occupational and nonoccupational activities did not contribute substantially to risk of neural tube defects in offspring. We observed no effect estimate greater than 2.0 for maternal exposures to the chemical agent groups studied. We did not observe substantially elevated risks associated with maternal exposures to any of the end-use chemical groups or to organic solvents. Considering occupational exposures only among women who worked did not substantially alter results. Adjustment for maternal vitamin use, race/ethnicity, or education level also did not substantially alter the observed associations.     

Personal exposure to volatile organic compounds. I. Direct measurements in breathing-zone air, drinking water, food, and exhaled breath

A pilot study to test methods of estimating personal exposures to toxic substances and corresponding body burdens was carried out between July and December 1980. Individual exposures to about a dozen volatile organic compounds in air and drinking water were measured for nine volunteers in Bayonne and Elizabeth, New Jersey, and for three volunteers in Research Triangle Park, North Carolina during three 3-day visits over the 6-month period. Breath samples were also collected from all subjects on each visit. Composite food samples were collected in each locality. Sampling and analytical methods for air, water, food, and breath were evaluated and found generally capable of detecting concentrations as low as 1 microgram/m3 in air and breath, and 1 ng/g in water and food. About 230 personal air samples, 170 drinking water samples, 66 breath samples, and 4 food samples (16 composites) were analyzed for the target chemicals. Ten compounds were present in air and eight were transmitted mainly through that medium. The two target trihalomethanes (chloroform and bromodichloromethane) were predominantly transmitted through water and beverages. Food appeared to be a minor route of exposure, except possibly for trichloroethylene in margarine. Seven compounds were present in more than half of the breath samples. Diurnal and seasonal variations were noted in air and water concentrations of some compounds, with summer levels generally higher. For some chemicals, weekday air exposures were significantly higher than weekend exposures. Some, but not all, of the potentially occupationally exposed individuals had significantly higher workplace exposures to several chemicals. Distributions of air exposures were closer to log normal than normal for most chemicals. Several chemicals were highly correlated with each other in personal air samples, indicating possible common sources of exposure.     

Occupational exposure to airborne nanomaterials: An assessment of worker exposure to aerosolized metal oxide nanoparticles in a semiconductor fab and subfab

This occupational exposure assessment study characterized potential inhalation exposures of workers to engineered nanomaterials associated with chemical mechanical planarization wafer polishing processes in a semiconductor research and development facility. Air sampling methodology was designed to capture airborne metal oxide nanoparticles for characterization. The research team obtained air samples in the fab and subfab areas using a combination of filter-based capture methods to determine particle morphology and elemental composition and real-time direct-reading instruments to determine airborne particle counts. Filter-based samples were analyzed by electron microscopy and energy-dispersive x-ray spectroscopy while real-time particle counting data underwent statistical analysis. Sampling was conducted during worker tasks associated with preventive maintenance and quality control that were identified as having medium to high potential for inhalation exposure based on qualitative assessments. For each sampling event, data was collected for comparison between the background, task area, and personal breathing zone. Sampling conducted over nine months included five discrete sampling series events in coordination with on-site employees under real working conditions. The number of filter-based samples captured was: eight from worker personal breathing zones; seven from task areas; and five from backgrounds. A complementary suite of direct-reading instruments collected data for seven sample collection periods in the task area and six in the background. Engineered nanomaterials of interest (Si, Al, Ce) were identified in filter-based samples from all areas of collection, existing as agglomerates (>500 nm) and nanoparticles (100–500 nm). Particle counts showed an increase in number concentration above background during a subset of the job tasks, but particle counts in the task areas were otherwise not significantly higher than background. Additional data is needed to support further statistical analysis and determine trends; however, this initial investigation suggests that nanoparticles used or generated by the wafer polishing process become aerosolized and may be accessible for inhalation exposures by workers performing tasks in the subfab and fab. Additional research is needed to further quantify the degree of exposure and link these findings to related hazard research.     

A case-control study of chemical exposures and brain tumors in petrochemical workers

The relationship between chemical exposures and deaths attributable to primary brain tumors among employees of a Texas petrochemical plant was investigated. Cases consisted of 21 deaths in which the underlying cause was confirmed as a primary brain tumor. Two control groups of 80 employees each were randomly selected from 450 decedents known to the company in June, 1979. Potential exposures while employed were compared between cases and controls for five known or suspect carcinogens. Exposure potentials were also compared for an additional 37 chemicals to which at least four cases were potentially exposed. Overall and 15-year latency analyses were performed. The proportion of cases exposed to the five potentially carcinogenic chemicals (including vinyl chloride) were lower than or consistent with the proportion of exposed controls. No statistically significant differences between the proportions of cases and controls exposed to the 37 other chemicals were found.     

Spontaneous abortions and congenital malformations among the wives of men occupationally exposed to organic solvents

A case-referent study nested in a cohort monitored biologically for exposure to six organic solvents (styrene, toluene, xylene, tetrachloroethylene, trichloroethylene, and 1,1,1-trichloroethane) was conducted to investigate the effects of paternal exposure on pregnancy outcome. The pregnancies were identified from medical registers. The exposures of the men during the spermatogenesis preceding the pregnancies and of the women during the first trimester of the pregnancies were obtained with questionnaires, and the available biological monitoring measurements were used in the exposure assessment. Factors which significantly increased the odds ratio of spontaneous abortion were paternal exposure to organic solvents in general, high/frequent exposure to toluene or miscellaneous organic solvents (including thinners), and maternal heavy lifting. No significant association between paternal or maternal exposure and congenital malformations was found, but because of the few cases no firm conclusions can be drawn.