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Biomedical subjects

L T Stayner

Publications and source records attributed to L T Stayner.

At least 19 recordsLinked to original sources
PubMed2004

Mortality among a cohort of garment workers exposed to formaldehyde: an update.

AIMS: To evaluate the mortality experience of 11 039 workers exposed to formaldehyde for three months or more in three garment plants. The mean time weighted average formaldehyde exposure at the plants in the early 1980s was 0.15 ppm but past exposures may have been substantially higher. METHODS: Vital status was updated through 1998, and life table analyses were conducted. RESULTS: Mortality from all causes (2206 deaths, standardised mortality ratio (SMR) 0.92, 95% CI 0.88 to 0.96) and all cancers (SMR 0.89, 95% CI 0.82 to 0.97) was less than expected based on US mortality rates. A non-significant increase in mortality from myeloid leukaemia (15 deaths, SMR 1.44, 95% CI 0.80 to 2.37) was observed. Mortality from myeloid leukaemia was greatest among workers first exposed in the earliest years when exposures were presumably higher, among workers with 10 or more years of exposure, and among workers with 20 or more years since first exposure. No nasal or nasopharyngeal cancers were observed. Mortality from trachea, bronchus, and lung cancer (147 deaths, SMR 0.98, 95% CI 0.82 to 1.15) was not increased. Multiple cause mortality from leukaemia was increased almost twofold among workers with both 10 or more years of exposure and 20 years or more since first exposure (15 deaths, SMR 1.92, 95% CI 1.08 to 3.17). Multiple cause mortality from myeloid leukaemia among this group of workers was also significantly increased (8 deaths, SMR 2.55, 95% CI 1.10 to 5.03). CONCLUSIONS: Results support a possible relation between formaldehyde exposure and myeloid leukaemia mortality. Previous epidemiological studies supporting a relation between formaldehyde exposure and leukaemia mortality have been primarily of formaldehyde exposed professional groups, not formaldehyde exposed industrial workers. Limitations include limited power to detect an excess for rare cancers such as nasal and nasopharyngeal cancers and lack of individual exposure estimates.

Adolescent↗
PubMed2001

Methodological issues of using observational human data in lung dosimetry models for particulates.

INTRODUCTION: The use of human data to calibrate and validate a physiologically based pharmacokinetic (PBPK) model has the clear advantage of pertaining to the species of interest, namely humans. A challenge in using these data is their often sparse, heterogeneous nature, which may require special methods. Approaches for evaluating sources of variability and uncertainty in a human lung dosimetry model are described in this study. METHODS: A multivariate optimization procedure was used to fit a dosimetry model to data of 131 U.S. coal miners. These data include workplace exposures and end-of-life particle burdens in the lungs and hilar lymph nodes. Uncertainty in model structure was investigated by fitting various model forms for particle clearance and sequestration of particles in the lung interstitium. A sensitivity analysis was performed to determine which model parameters had the most influence on model output. Distributions of clearance parameters were estimated by fitting the model to each individual's data, and this information was used to predict inter-individual differences in lung particle burdens at given exposures. The influence of smoking history, race and pulmonary fibrosis on the individual's estimated clearance parameters was also evaluated. RESULTS: The model structure that provided the best fit to these coal miner data includes a first-order interstitialization process and no dose-dependent decline in alveolar clearance. The parameter that had the largest influence on model output is fractional deposition. Race and fibrosis severity category were statistically significant predictors of individual's estimated alveolar clearance rate coefficients (P < 0.03 and P < 0.01-0.06, respectively), but smoking history (ever, never) was not (P < 0.4). Adjustments for these group differences provided some improvement in the dosimetry model fit (up to 25% reduction in the mean squared error), although unexplained inter-individual differences made up the largest source of variability. Lung burdens were inversely associated with the miners' estimated clearance parameters, e.g. individuals with slower estimated clearance had higher observed lung burdens. CONCLUSIONS: The methods described in this study were used to examine issues of uncertainty in the model structure and variability of the miners' estimated clearance parameters. Estimated individual clearance had a large influence on predicted lung burden, which would also affect disease risk. These findings are useful for risk assessment, by providing estimates of the distribution of lung burdens expected under given exposure conditions.

Body Burden↗
PubMed2001

A biomathematical model of particle clearance and retention in the lungs of coal miners.

To understand better the factors influencing the relationships among airborne particle exposure, lung burden, and fibrotic lung disease, we developed a biologically based kinetic model to predict the long-term retention of particles in the lungs of coal miners. This model includes alveolar, interstitial, and hilar lymph node compartments. The 131 miners in this study had worked in the Beckley, West Virginia, area and died during the 1960s. The data used to develop this model include exposure to respirable coal mine dust by intensity and duration within each job, lung and lymph node dust burdens at autopsy, pathological classification of fibrotic lung disease, and smoking history. Initial parameter estimates for this model were based on both human and animal data of particle deposition and clearance and on the biological and physical factors influencing these processes. Parameter estimation and model fit to the data were determined using least squares. Results show that the end-of-life lung dust burdens in these coal miners were substantially higher than expected from first-order clearance kinetics, yet lower than expected from the overloading of alveolar clearance predicted from rodent studies. The best-fitting and most parsimonious model includes processes for first-order alveolar-macrophage-mediated clearance and transfer of particles to the lung interstitium. These results are consistent with the particle retention patterns observed previously in the lungs of primates. The findings indicate that rodent models extrapolated to humans, without adjustment for the kinetic differences in particle clearance and retention, would be inadequate for predicting lung dust burdens in humans. Also, this human lung kinetic model predicts greater retained lung dust burdens from occupational exposure than predicted from current human models based on lower exposure data. This model is useful for risk assessment of particle-induced lung diseases, by estimating equivalent internal doses in rodents and humans and predicting lung burdens in humans with occupational dust exposures.

Air Pollutants, Occupational↗
PubMed2000

Human cancer risk and exposure to 1,3-butadiene--a tale of mice and men.

OBJECTIVES: The purpose of this study was to evaluate empirically the relevance of animal-bioassay-based models for predicting human risks from exposure to 1,3-butadiene (BD) using epidemiologic data. METHODS: Relative-risk results obtained with a regression model in a recent epidemiologic study were used to estimate leukemia risk for occupational and environmental exposures to BD and to compare these estimates with those previously derived from an analysis of animal bioassay data. RESULTS: The estimates of risk were found to be highly dependent on the model used when low levels of exposure were evaluated that are of environmental concern, but not at the levels of occupational concern. For example, at the level (1 part per million) of the recently revised standard of the Occupational Safety and Health Administration in the United States the estimates of lifetime excess risk ranged from 1 to 8 per 1000 workers. The range of the risk estimates derived from the epidemiologic models was remarkably similar to the range of risk estimates for occupational exposures (1 to 9 per thousand) previously developed by Dankovic et al in 1993 from an analysis of a mouse bioassay study for lymphocytic lymphoma. CONCLUSIONS: Results for BD seem to provide another example of a high degree of concordance between the risk predictions from models of toxicologic and epidemiologic data, particularly at occupational levels of exposure.

Adult↗
PubMed1998

Trends in rates of occupational fatal injuries in the United States (1983-92).

OBJECTIVES: An updated version of a national surveillance system of traumatic occupational fatalities was used to explore adjusted and unadjusted trends in rates of fatal injury. METHODS: Data from the national traumatic occupational fatalities surveillance system were combined with data on employment from the United States Bureau of Labor Statistics. Poisson regression was then used to examine trends in rates of occupational fatality injuries while controlling for demographic and workplace characteristics. RESULTS: Adjusted annual changes in rates of fatal injuries ranged from a decline of 6.2% for workers in technical and administrative support occupations--for example, health, science, and engineering technicians, pilots, computer programmers--to an increase of 1.6% in machine operators, assemblers, and inspectors. For industries, annual changes ranged from a decline of 5.3% for workers in public administration--for example, justice, public order, and safety workers--to an increase of 2.6% for workers in the wholesale trade. By comparison, the annual decline over all industries and occupations was 3.1%. In many industries and occupations, an effect modification of annual trends by the age of the worker was also found with the oldest workers experiencing either no decline or a significant increase in rates of fatal injuries. CONCLUSIONS: This general pattern of decline, adjusted for the effects of demographic characteristics of the worker population, is encouraging; however, increases in rates of fatal injuries found in particular industries and occupations, suggest appropriate targets for increased injury prevention efforts.

Accidents, Occupational↗
PubMed1997

Estimating benchmark concentrations and other noncancer endpoints in epidemiology studies.

Methods for evaluating the hazards associated with noncancer responses with epidemiologic data are considered. The methods for noncancer risk assessment have largely been developed for experimental data, and are not always suitable for the more complex structure of epidemiologic data. In epidemiology, the measurement of the response and the exposure is often either continuous or dichotomous. For a continuous noncancer response modeled with multiple regression, a variety of endpoints may be examined: (1) the concentration associated with absolute or relative decrements in response; (2) a threshold concentration associated with no change in response; and (3) the concentration associated with a particular added risk of impairment. For a dichotomous noncancer response modeled with logistic regression, concentrations associated with specified added/extra risk or with a threshold responses may be estimated. No-observed-effect concentrations may also be estimated for categorizations of exposures for both continuous and dichotomous responses but these may depend on the arbitrary categories chosen. Respiratory function in miners exposed to coal dust is used to illustrate these methods.

Age Factors↗
PubMed1997

A re-examination of risk estimates from the NIOSH Occupational Noise and Hearing Survey (ONHS)

This paper describes a new analysis of data from the 1968-72 National Institute for Occupational Safety & Health (NIOSH) Occupational Noise and Hearing Survey (ONHS). The population consisted of 1172 (792 noise-exposed and 380 "controls") predominately white male workers from a cross section of industries within the United States. The analysis focused on how risk estimates vary according to various model assumptions, including shape of the dose-response curve and the amount of noise exposure among low-noise exposed workers (or controls). Logistic regression models were used to describe the risk of hearing handicap in relation to age, occupational noise exposure, and duration exposed. Excess risk estimates were generated for several definitions of hearing handicap. Hearing handicap is usually denoted as an average hearing threshold level (HTL) of greater than 25 dB for both ears at selected frequencies. The frequencies included in the biaural averages were (1) the articulation-weighted average over 1-4 kHz, (2) the unweighted average over 0.5, 1, and 2 kHz, and (3) the unweighted average over 1, 2, and 3 kHz. The results show that excess risk estimates for time-weighted average sound levels below 85 dB were sensitive to statistical model form and assumptions regarding the sound level to which the "control" group was exposed. The choice of frequencies used in the hearing handicap definition affected the magnitude of excess risk estimates, which depended on age and duration of exposure. Although data were limited below 85 dB, an age-stratified analysis provided evidence of excess risks at levels ranging from 80 to 84 dB, 85-89 dB, and 90-102 dB. Due to uncertainty in quantifying risks below 85 dB, new data collection efforts should focus on better characterization of dose-response and longitudinal hearing surveys that include workers exposed to 8-hour time-weighted noise levels below 85 dB. Results are compared to excess risk estimates generated using methods given by ANSI S3.44-1996.

Adolescent↗
PubMed1996

Occupational exposure to chrysotile asbestos and cancer risk: a review of the amphibole hypothesis.

OBJECTIVES: This article examines the credibility and policy implications of the "amphibole hypothesis," which postulates that (1) the mesotheliomas observed among workers exposed to chrysotile asbestos may be explained by confounding exposures to amphiboles, and (2) chrysotile may have lower carcinogenic potency than amphiboles. METHODS: A critical review was conducted of the lung burden, epidemiologic, toxicologic, and mechanistic studies that provide the basis for the amphibole hypothesis. RESULTS: Mechanistic and lung burden studies do not provide convincing evidence for the amphibole hypothesis. Toxicologic and epidemiologic studies provide strong evidence that chrysotile is associated with an increased risk of lung cancer and mesothelioma. Chrysotile may be less potent than some amphiboles for inducing mesotheliomas, but there is little evidence to indicate lower lung cancer risk. CONCLUSIONS: Given the evidence of a significant lung cancer risk, the lack of conclusive evidence for the amphibole hypothesis, and the fact that workers are generally exposed to a mixture of fibers, we conclude that it is prudent to treat chrysotile with virtually the same level of concern as the amphibole forms of asbestos.

Animals↗
PubMed1995

Exposure-response analysis of mortality among coal miners in the United States.

The quantitative relationship between exposure to respirable coal mine dust and mortality from nonmalignant respiratory diseases was investigated in a study of 8,878 working male coal miners who were medically examined from 1969 to 1971 and followed to 1979. Exposure-related mortality was evaluated using Cox proportional hazards modeling for underlying or contributing causes of death and modified lifetable methods for underlying causes. For pneumoconiosis mortality, the lifetable analyses showed increasing standardized mortality ratios (SMRs) with increasing cumulative exposure category. Significant exposure-response relationships for mortality from pneumoconiosis (p < 0.001) and from chronic bronchitis or emphysema (p < 0.05) were observed in the proportional hazards models after controlling for age and smoking. No exposure-related increases in lung cancer or stomach cancer were observed. Pneumoconiosis mortality was found to vary significantly by the rank of coal dust to which miners were exposed. Miners exposed at or below the current U.S. coal dust standard of 2 mg/m3 over a working lifetime, based on these analyses, have an elevated risk of dying from pneumoconiosis or from chronic bronchitis or emphysema.

Coal Mining↗
PubMed1995

Assessment of silicosis risk for occupational exposure to crystalline silica.

Epidemiologic studies of workers exposed to silica were reviewed to identify data on airborne concentrations of quartz that are not associated with an increased risk of silicosis, the lowest concentrations associated with silicosis, and studies that used statistical models to quantitate the risk of silicosis as a function of silica exposure. The no observed adverse effect levels varied from 7 to 100 mu g center dot m-3, and the lowest observed adverse effect levels ranged from 8 to 252 mu g center dot m-3 in five different cohorts. Studies using quantitative exposure-response models revealed a wide difference in the cumulative risk estimates for silicosis. The differences in the risk estimates and the no observed and lowest observed effect levels may have been the result of errors in exposure estimates, physicochemical characteristics of silica and quartz content of the dust, cohort differences, and reader variability. Further research is needed to define the dose-response relationship between silica exposure and silicosis.

Crystallization↗
PubMed1994

Statistical model for prediction of retrospective exposure to ethylene oxide in an occupational mortality study.

Since direct measures of individual exposure seldom exist for the entire period of an occupational mortality study, retrospective exposure estimates are necessary. This is often done in a subjective manner involving a consensus of opinion from a panel of epidemiologists and industrial hygienists. An alternative method utilizing a statistical model provides a more objective procedure for retrospective exposure assessment. The development of a weighted multiple regression model is presented for estimation of exposure levels to ethylene oxide (ETO) for inclusion in a cohort mortality study of workers in the sterilization industry. Three steps in development of the model are described: (1) data acquisition and assessment, (2) model building, and (3) evaluation of the model. The final model explained a remarkable 85% of the variability in 205 average measurements of ETO levels. Exposure factors included in the model were exposure category, product type, size of the sterilization unit, selected engineering controls, days after sterilization, and calendar year. The model was evaluated in two ways: against a set of measurement data not used to develop the model and a panel of 11 industrial hygienists representing the sterilization industry. The model predicted ETO exposures within 1.1 ppm of the validation data set with a standard deviation of 3.7 ppm. The arithmetic and geometric means of the 46 measurements in the validation data set were 4.6 and 2.2 ppm, respectively. The model also outperformed the panel of industrial hygienists relative to the validation data in terms of both bias and precision.

Ethylene Oxide↗
PubMed1993

Comparing toxicologic and epidemiologic studies: methylene chloride--a case study.

Exposure to methylene chloride induces lung and liver cancers in mice. The mouse bioassay data have been used as the basis for several cancer risk assessments. The results from epidemiologic studies of workers exposed to methylene chloride have been mixed with respect to demonstrating an increased cancer risk. The results from a negative epidemiologic study of Kodak workers have been used by two groups of investigators to test the predictions from the EPA risk assessment models. These two groups used very different approaches to this problem, which resulted in opposite conclusions regarding the consistency between the animal model predictions and the Kodak study results. The results from the Kodak study are used to test the predictions from OSHA's multistage models of liver and lung cancer risk. Confidence intervals for the standardized mortality ratios (SMRs) from the Kodak study are compared with the predicted confidence intervals derived from OSHA's risk assessment models. Adjustments for the "healthy worker effect," differences in length of follow-up, and dosimetry between animals and humans were incorporated into these comparisons. Based on these comparisons, we conclude that the negative results from the Kodak study are not inconsistent with the predictions from OSHA's risk assessment model.

Animals↗
PubMed1993

Time-to-tumour risk assessment for 1,3-butadiene based on exposure of mice to low doses by inhalation.

The excess risk for cancer due to lifetime occupational exposure to 1,3-butadiene at the proposed US Occupational Safety and Health Administration standard of 2 ppm was estimated on the basis of a quantitative risk assessment. The risk assessment was based on a recent study by the US National Toxicology Program of the carcinogenicity of butadiene in B6C3F1 mice, using exposure concentrations ranging from 6.25 to 625 ppm butadiene and controls. Cancer risks were estimated using a multistage Weibull time-to-tumour model; the dose was based on the external butadiene concentration, owing to the low-dose linearity of butadiene metabolism. The parameters of the time-to-tumour model were estimated for seven tumour sites in male mice and nine in female mice. The risk estimates were extrapolated from mice to humans on the basis of body weight raised to the three-fourths power, and the median lifespan of mice was equated to a human lifespan of 74 years. Estimates of excess risk for lifetime occupational exposure (8 h/day, 5 days/week, 50 weeks/year, for 45 years) to 2 ppm butadiene ranged from 0.2 per 10,000 workers, based on female mouse heart haemangiosarcomas, to 600 per 10,000 workers, based on female mouse lung tumours. An analysis was performed to assess the effects of varying the modelling assumptions (incidental versus fatal tumours, inclusion or exclusion of the 625-ppm dose group, and basis for interspecies scaling) on the risk estimates from the female mouse lung tumour model. Depending on the assumptions, estimates of lifetime excess risk derived from the female mouse lung model ranged from 60 per 10,000 to 1600 per 10,000. These results suggest that exposures to butadiene in the work place should be reduced to the lowest feasible level.

Administration, Inhalation↗
PubMed1993

Excess hepatobiliary cancer mortality among munitions workers exposed to dinitrotoluene.

An analysis of the mortality experience of workers exposed to dinitrotoluene (DNT) was conducted to test the hypothesis that DNT exposure is associated with an increased risk of cancers of the liver and biliary tract. A total of 4,989 workers exposed to DNT and 7,436 unexposed workers who had worked for at least 5 months at the study facility between January 1, 1949 and January 21, 1980, were included in this investigation. Workers were considered exposed if they had worked at least 1 day on a job with probable exposure to DNT. The vital status as of December 31, 1982, was successfully ascertained for approximately 97% of these workers. Standardized mortality ratios (SMRs) were estimated based upon comparisons with the US population using a modified life-table program. In addition, standardized rate ratios (SRRs) were computed based upon direct comparisons between the DNT and the internal unexposed cohort. An excess of hepatobiliary cancer was observed among workers exposed to DNT in this study. The rate ratio for hepatobiliary cancer was 2.67 (six cases observed) based upon comparison with the US population (SMR = 2.67, 95% CI = 0.98, 5.83), and 3.88 based upon comparison using the internal unexposed referent group (SRR = 3.88, 95% CI = 1.04, 14.41). This study failed to demonstrate an exposure-response relationship between duration of DNT exposure and hepatobiliary cancer mortality. Our study was limited by the small number of workers with long duration of exposure to DNT, and by the lack of quantitative information on exposure to DNT and other chemicals.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Cardiovascular mortality among munitions workers exposed to nitroglycerin and dinitrotoluene.

A retrospective cohort mortality study with 5529 nitroglycerin, 4989 dinitrotoluene, and 5136 unexposed workers compared the mortality of the exposed groups with that of the United States population and that of the unexposed group with life-table analysis and Poisson regression. Mortality from ischemic heart disease was close to that expected, and mortality from cerebrovascular disease was slightly less than that expected, for the workers with both nitroglycerin and dinitrotoluene exposure and for those with dinitrotoluene exposure only. A significant interaction between age and nitroglycerin exposure was detected in the Poisson regression analyses for ischemic heart disease, particularly for workers actively exposed to nitroglycerin. The rate ratio for the workers under 45 years of age and actively exposed to nitroglycerin was 3.30 (95% confidence interval 129-8.48). This study did not show a chronic effect of nitroglycerin or dinitrotoluene exposure on cardiovascular disease risk. Potential biases related to the company's medical screening program may have limited the ability to detect chronic cardiovascular effects.

Adult↗
PubMed1992

Methodologic issues in using epidemiologic studies of occupational cohorts for cancer risk assessment.

This paper focuses on presenting a review and discussion of the major methodologic issues involved in using epidemiologic studies of occupational groups for assessing human cancer risks. Although animal studies have been most often used for quantitative risk assessment, it is generally recognized that well conducted epidemiologic studies would provide the best basis for estimating human risk. However, there are several features related to the design and analysis of epidemiologic studies which frequently limit their usefulness for quantitating risks. The lack of accurate information on exposure in epidemiologic studies is perhaps the most frequently cited limitation of these studies for risk assessment. However, other features of epidemiologic study design such as statistical power, length of follow-up, selection bias, confounding and effect modification may also limit the inferences that can be drawn from these studies. Furthermore even when the aforementioned limitations are overcome, substantial uncertainty exists concerning the choice of an appropriate statistical (or biologic) model for extrapolation beyond the range of exposures observed in a particular study. An empirical example is provided in which estimates of risk varied by nearly 3 orders of magnitude depending on which functional form of the model was chosen. Modeling of epidemiologic data for QRA should be based upon internal comparisons rather than on modeling Standardized Mortality Ratios (SMRs) when possible. Because of the limitations discussed in this paper, epidemiologic data should not be viewed as a panacea for the problems inherent in using animal bioassay data for QRA.(ABSTRACT TRUNCATED AT 250 WORDS)

Bias↗