RESUMEN
ß-Chloroprene (2-chloro-1,3-butadiene, CD) is used in the manufacture of polychloroprene rubber. Chronic inhalation studies have demonstrated that CD is carcinogenic in B6C3F1 mice and Fischer 344 rats. However, epidemiological studies do not provide compelling evidence for an increased risk of mortality from total cancers of the lung. Differences between the responses observed in animals and humans may be related to differences in toxicokinetics, the metabolism and detoxification of potentially active metabolites, as well as species differences in sensitivity. The purpose of this study was to develop and apply a novel method that combines the results from available physiologically based kinetic (PBK) models for chloroprene with a statistical maximum likelihood approach to test commonality of low-dose risk across species. This method allows for the combined evaluation of human and animal cancer study results to evaluate the difference between predicted risks using both external and internal dose metrics. The method applied to mouse and human CD data supports the hypothesis that a PBK-based metric reconciles the differences in mouse and human low-dose risk estimates and further suggests that, after PBK metric exposure adjustment, humans are equally or less sensitive than mice to low levels of CD exposure.
Asunto(s)
Carcinógenos/toxicidad , Cloropreno/toxicidad , Neoplasias/inducido químicamente , Medición de Riesgo/métodos , Animales , Carcinógenos/administración & dosificación , Carcinógenos/farmacocinética , Cloropreno/administración & dosificación , Cloropreno/farmacocinética , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Funciones de Verosimilitud , Masculino , Ratones , Neoplasias/epidemiología , Ratas , Ratas Endogámicas F344 , Especificidad de la EspecieRESUMEN
Aspartame is a methyl ester of a dipeptide used as a synthetic nonnutritive sweetener in over 90 countries worldwide in over 6000 products. The purpose of this investigation was to review the scientific literature on the absorption and metabolism, the current consumption levels worldwide, the toxicology, and recent epidemiological studies on aspartame. Current use levels of aspartame, even by high users in special subgroups, remains well below the U.S. Food and Drug Administration and European Food Safety Authority established acceptable daily intake levels of 50 and 40 mg/kg bw/day, respectively. Consumption of large doses of aspartame in a single bolus dose will have an effect on some biochemical parameters, including plasma amino acid levels and brain neurotransmitter levels. The rise in plasma levels of phenylalanine and aspartic acid following administration of aspartame at doses less than or equal to 50 mg/kg bw do not exceed those observed postprandially. Acute, subacute and chronic toxicity studies with aspartame, and its decomposition products, conducted in mice, rats, hamsters and dogs have consistently found no adverse effect of aspartame with doses up to at least 4000 mg/kg bw/day. Critical review of all carcinogenicity studies conducted on aspartame found no credible evidence that aspartame is carcinogenic. The data from the extensive investigations into the possibility of neurotoxic effects of aspartame, in general, do not support the hypothesis that aspartame in the human diet will affect nervous system function, learning or behavior. Epidemiological studies on aspartame include several case-control studies and one well-conducted prospective epidemiological study with a large cohort, in which the consumption of aspartame was measured. The studies provide no evidence to support an association between aspartame and cancer in any tissue. The weight of existing evidence is that aspartame is safe at current levels of consumption as a nonnutritive sweetener.
Asunto(s)
Aspartame/toxicidad , Edulcorantes/toxicidad , Anomalías Inducidas por Medicamentos , Aminoácidos/sangre , Animales , Aspartame/farmacocinética , Estabilidad de Medicamentos , Feto/efectos de los fármacos , Humanos , Pruebas de Mutagenicidad , Neoplasias Experimentales/inducido químicamente , Síndromes de Neurotoxicidad/etiologíaRESUMEN
A cancer dose-response assessment was conducted for acrylonitrile (AN) using updated information on mechanism of action, epidemiology, toxicity, and pharmacokinetics. Although more than 10 chronic bioassays indicate that AN produces multiple tumors in rats and mice, a number of large, well-conducted epidemiology studies provide no evidence of a causal association between AN exposure and cancer mortality of any type. The epidemiological data include early industry exposures that are far higher than occur today and that approach or exceed levels found to be tumorigenic in animals. Despite the absence of positive findings in the epidemiology data, a dose-response assessment was conducted for AN based on brain tumors in rats. Mechanistic studies implicate the involvement of oxidative stress in rat brain due to a metabolite (2-cyanoethylene oxide or CEO, cyanide), but do not conclusively rule out a potential role for the direct genotoxicity of CEO. A PBPK model was used to predict internal doses (peak CEO in brain) for 12 data sets, which were pooled together to provide a consistent characterization of the dose-response relationship for brain tumor incidence in the rat. The internal dose corresponding to a 5% increase in extra risk (ED 05=0.017 mg/L brain) and its lower confidence limit (LED 05=0.014 mg/L brain) was used as the point of departure. The weight-of-evidence supports the use of a nonlinear extrapolation for the cancer dose-response assessment. A quantitative comparison of the epidemiology exposure-response data (lung and brain cancer mortality) to the rat brain tumor data in terms of internal dose adds to the confidence in the nonlinear extrapolation. Uncertainty factors of 200 and 220 (for the oral and inhalation routes, respectively) were applied to the LED 05 to account for interspecies variation, intraspecies variation, and the severity of the response measure. Accordingly, oral doses below 0.009 mg/kg-day and air concentrations below 0.1mg/m(3) are not expected to pose an appreciable risk to human populations exposed to AN.
Asunto(s)
Acrilonitrilo/toxicidad , Neoplasias Encefálicas/inducido químicamente , Carcinógenos/toxicidad , Exposición a Riesgos Ambientales/normas , Neoplasias Pulmonares/inducido químicamente , Acrilonitrilo/administración & dosificación , Administración Oral , Animales , Neoplasias Encefálicas/epidemiología , Neoplasias Encefálicas/mortalidad , Pruebas de Carcinogenicidad , Carcinógenos/administración & dosificación , Relación Dosis-Respuesta a Droga , Humanos , Incidencia , Exposición por Inhalación , Neoplasias Pulmonares/epidemiología , Neoplasias Pulmonares/mortalidad , Metaanálisis como Asunto , Ratones , Modelos Biológicos , Pruebas de Mutagenicidad , Dinámicas no Lineales , RatasRESUMEN
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.
Asunto(s)
Vidrio , Enfermedades Pulmonares/inducido químicamente , Enfermedades Pulmonares/mortalidad , Neoplasias Pulmonares/inducido químicamente , Neoplasias Pulmonares/mortalidad , Exposición Profesional/efectos adversos , Adulto , Estudios de Casos y Controles , Causas de Muerte , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Humanos , Masculino , Enfermedades Profesionales/inducido químicamente , Enfermedades Profesionales/mortalidad , Valor Predictivo de las Pruebas , Riesgo , Fumar/efectos adversos , Análisis de Supervivencia , Sobrevivientes , Factores de Tiempo , Estados Unidos/epidemiologíaRESUMEN
As part of our ongoing mortality surveillance program for the US man-made vitreous fiber (MMVF) industry, we examined mortality from malignant mesothelioma using data from our 1989 follow-up of 3478 rock/slag wool workers and our 1992 follow-up of 32,110 fiberglass workers. A manual search of death certificates for 1011 rock/slag wool workers and 9060 fiberglass workers revealed only 10 death certificates with any mention of the word "mesothelioma." A subsequent review of medical records and pathology specimens for 3 of the 10 workers deemed two deaths as definitely not due to mesothelioma and one as having a 50% chance of being caused by mesothelioma. Two other deaths, for which only medical records were available, were given less than a 50% chance of being due to mesothelioma. Eight of the 10 decedents had potential occupational asbestos exposure inside or outside the MMVF industry. We also estimated the mortality risk from malignant mesothelioma in the cohort using two cause-of-death categorizations that included both malignant and benign coding rubrics. Using the more comprehensive scheme, we observed overall deficits in deaths among the total cohort and fiberglass workers and an overall excess among rock/slag wool workers. The excess in respiratory system cancer is largely a reflection of elevated lung cancer risks that we attributed mainly to confounding by smoking, to exposures outside the MMVF industry to agents such as asbestos, or to one or more of the several co-exposures present in many of the study plants (including asbestos). The second scheme, which focused on pleural mesothelioma in time periods when specific malignant mesothelioma coding rubrics were available, classified only one cohort death as being caused by malignant mesothelioma, compared with 2.19 expected deaths (local county comparison). We conclude that the overall mortality risk from malignant mesothelioma does not seem to be elevated in the US MMVF cohort.
Asunto(s)
Vidrio , Mesotelioma/inducido químicamente , Mesotelioma/mortalidad , Exposición Profesional/efectos adversos , Neoplasias del Sistema Respiratorio/inducido químicamente , Neoplasias del Sistema Respiratorio/mortalidad , Adulto , Causas de Muerte , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Humanos , Masculino , Mesotelioma/patología , Persona de Mediana Edad , Enfermedades Profesionales/inducido químicamente , Enfermedades Profesionales/mortalidad , Factores Sexuales , Encuestas y Cuestionarios , Análisis de Supervivencia , Textiles/efectos adversos , Estados Unidos/epidemiologíaRESUMEN
The most recent findings of our nested case-control study of respiratory system cancer (RSC) among male fiberglass workers showed some evidence of elevated RSC risk associated with non-baseline levels of average intensity of exposure (AIE) to respirable fibers (RFib). When adjusted for smoking, this was not statistically significant, and no trend was apparent with increasing levels of exposure. Similar findings for RSC were noted for both cumulative exposure (Cum) and AIE to formaldehyde (FOR). In this reanalysis of our nested case-control study, we explored a possible exposure-response relationship between RSC and exposure to RFib or FOR using exposure weighting as an alternative characterization of exposure. Because of the uncertainties in selecting an appropriate exposure-weighting scheme, a range of plausible time lags and unlagged/lagged time windows was considered. As in the initial analysis of the nested case-control study, RFib and FOR exposures were categorized at the deciles of the RSC case distribution. For none of the exposure weighting schemes considered did we observe an increasing RSC risk with increasing levels of RFib_Cum or RFib_AIE. The exposure-weighted estimated risk ratios (RR) for both RFib_Cum and RFib_AIE were generally lower than those obtained from an unweighted model. For FOR_Cum, RRs were generally lower for the time-lagged and unlagged time window models than for the unweighted models, although some decile-specific RRs were higher for the lagged time window models. The exposure-weighted RRs for FOR_AIE were generally lower than the unweighted RRs for all of the weighting schemes considered. This reanalysis in terms of categorized exposures reveals no exposure-response relationships that were undetected in the original analysis where unweighted exposure measures were used. In the schemes considered, exposure weighting generally reduced the estimated risk of RSC.
Asunto(s)
Vidrio , Exposición Profesional/efectos adversos , Neoplasias del Sistema Respiratorio/inducido químicamente , Adulto , Estudios de Casos y Controles , Estudios de Cohortes , Estudios de Seguimiento , Formaldehído/efectos adversos , Humanos , Masculino , Enfermedades Profesionales/inducido químicamente , Enfermedades Profesionales/mortalidad , Neoplasias del Sistema Respiratorio/mortalidad , Riesgo , Sensibilidad y Especificidad , Análisis de Supervivencia , Factores de Tiempo , Estados Unidos/epidemiologíaRESUMEN
As part of the 1992 update of an historical cohort study of 32,110 workers employed for at least 1 year in any of 10 US fiberglass manufacturing plants, a nested case-control study was done in which data on tobacco smoking were obtained for 631 male case subjects with respiratory system cancer (RSC) and 570 control subjects matched on age and year of birth. In this more extensive analysis of the nested case-control data, we provide a detailed assessment of the most prominent findings from the initial report. We expand the scope of the analysis to consider quantitative measures of exposure to respirable fibers (RFib), formaldehyde (FOR), and silica (Sil) and consider these and other exposures together in the same model. We investigate the functional form of possible exposure-response relationships between RSC risk, RFib, and FOR. In addition, we address the statistical issues of collinearity, effect modification, and potential confounding by coexposures. All analyses are adjusted for smoking. Neither measure of exposure to RFib (average intensity of exposure or cumulative exposure) was statistically significantly associated with RSC risk in any of the hundreds of fractional polynomial models considered. This more extensive analysis has substantiated our initial finding of no apparent exposure-response relationship between RSC risk and either cumulative or average intensity of exposure to RFib at the levels experienced by these workers. This study provides some evidence of increased RSC risk among workers at the higher observed levels of average intensity of exposure to FOR and/or Sil. No positive associations were identified between RSC risk and any of the other exposures considered in this case-control study.
Asunto(s)
Vidrio , Minerales/efectos adversos , Exposición Profesional/efectos adversos , Neoplasias del Sistema Respiratorio/inducido químicamente , Adulto , Estudios de Casos y Controles , Estudios de Cohortes , Estudios de Seguimiento , Formaldehído/efectos adversos , Humanos , Masculino , Enfermedades Profesionales/inducido químicamente , Enfermedades Profesionales/mortalidad , Valor Predictivo de las Pruebas , Tiempo de Reacción/fisiología , Neoplasias del Sistema Respiratorio/mortalidad , Factores de Riesgo , Fumar/efectos adversos , Sobrevivientes , Estados Unidos/epidemiologíaRESUMEN
As part of our ongoing mortality surveillance program for the US man-made vitreous fiber industry, we surveyed a random sample of study members to estimate tobacco-smoking habits for the total cohort. Separate sampling frames were constructed for four study groups: male and female workers within the fiberglass and rock/slag wool subcohorts. The frames included all persons who had worked a year or more between 1945 and 1986 (with some exceptions), and who were alive as adults (18+ years) on January 1, 1980, the year the age distribution of the cohort most resembled the US comparison population. Subjects were randomly selected from the frames, and a structured telephone interview was administered to the subject or a proxy respondent between January 1995 and December 1997. Using survey data, we estimated the point prevalence of ever and current cigarette smoking on January 1, 1980, and made comparisons with other occupational groups and general populations. Overall response rates (interviews/targeted sample) were greater than 78% for each of the four study groups. From our estimates, we infer that male workers from both the fiberglass and rock/slag wool cohorts and female rock/slag wool workers had higher rates of ever smoking than the corresponding general populations of the United States and most of the states where the study plants were located. These findings suggest that at least part of the elevated externally standardized mortality ratios (US and regional rate-based) for respiratory system cancer noted among male subjects and the male-dominated total cohort in our previous cohort analyses were due to uncontrolled positive confounding by smoking.
Asunto(s)
Vidrio , Enfermedades Profesionales/inducido químicamente , Enfermedades Profesionales/mortalidad , Exposición Profesional/efectos adversos , Adolescente , Adulto , Factores de Edad , Anciano , Estudios de Casos y Controles , Estudios de Cohortes , Recolección de Datos , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Sensibilidad y Especificidad , Factores Sexuales , Fumar/efectos adversos , Fumar/epidemiología , Análisis de Supervivencia , Estados Unidos/epidemiologíaRESUMEN
To date, the US cohort study of man-made vitreous fiber workers has provided no consistent evidence of a relationship between man-made vitreous fiber exposure and mortality from malignant or non-malignant respiratory disease. Nevertheless, there have been small, overall excesses in respiratory system cancer (RSC) among workers from the fiberglass and rock/slag wool production plants included in the study that were unexplained by estimated worker exposures to respirable fiber or other agents present in the plants. The present investigation was designed to provide a quantitative estimate of the extent to which the overall excess in RSC mortality observed at the total cohort level among male fiberglass and rock/slag wool workers is a result of the positive confounding effects of cigarette smoking. Because cigarette-smoking data were neither available nor obtainable at the individual level for all members of the fiberglass and rock/slag wool cohorts, we used the "indirect" method to adjust RSC standardized mortality ratios (SMRs) at the group (cohort and plant) level. Our adjustment suggested that cigarette smoking accounts for all of the 7% and 24% excesses in RSC observed, respectively, for the male fiberglass and rock/slag wool cohorts in the latest mortality updates. The same conclusion was reached regardless of which of several alternative formulations were used to adjust local rate-based RSC SMRs. We found that our smoking adjustments were robust with respect to several alternative characterizations and (with the exception of one fiberglass plant) produced adjusted RSC SMRs that were lower than their unadjusted counterparts. Further, all statistically significantly elevated unadjusted SMRs were reduced to not statistically significant levels. These results reaffirm that RSC SMRs based on US and local rates must take into account the potential confounding effects of cigarette smoking. They also suggest that the use of local county mortality rate-based SMRs may not help to adjust for cigarette smoking to the degree suggested by some investigators.
Asunto(s)
Vidrio , Exposición Profesional/efectos adversos , Neoplasias del Sistema Respiratorio/inducido químicamente , Adolescente , Adulto , Estudios de Casos y Controles , Estudios de Cohortes , Humanos , Masculino , Enfermedades Profesionales/inducido químicamente , Prevalencia , Riesgo , Fumar/efectos adversos , Fumar/epidemiología , Breas/efectos adversos , Estados Unidos/epidemiologíaRESUMEN
Data and procedures used to reconstruct the history of exposures at each of the 15 plants (19 distinct sites) are presented. The assessment consisted of five steps: (1) develop a Technical History of operations, stable periods, and time points of changes relevant for exposures, and identify the presence of potentially confounding co-exposures; (2) develop a set of unique department-job names with descriptions and a Job Dictionary for all verbatim names in work histories; (3) collect all company and other exposure data (> 1600 observed), and develop quantitative fiber, formaldehyde, and silica exposure estimates; (4) integrate estimates with the Technical History to make Exposure Extrapolation Tables; and (5) use the the Tables with job data to develop an Exposure Matrix for each plant. Nineteen Exposure Matrices were made, with 82 to 621 lines, covering up to 54 years of operations.
Asunto(s)
Vidrio/análisis , Exposición Profesional/análisis , Contaminantes Ocupacionales del Aire/análisis , Estudios de Cohortes , Empleo , Estudios de Seguimiento , Formaldehído/análisis , Humanos , Perfil Laboral , Textiles/análisis , Factores de Tiempo , Estados Unidos/epidemiología , Lugar de TrabajoRESUMEN
UNLABELLED: All jobs held by a cohort of US man-made vitreous fiber production workers were analyzed for airborne fiber exposure. This exposure-specific job analysis was part of an exposure assessment for an epidemiologic study of mortality patterns, with particular focus on respiratory cancer, among 35,145 workers employed in 10 fiberglass and five rock or slag wool plants. The exposure assessment was conducted from the start-up date of each plant (1917 to 1946) to 1990. For the job analysis, 15,465 crude department names and 47,693 crude job titles were grouped into 1668 unique department and job pairs (UDJobs), which represented a job title linked to a specific department within each plant. Every UDJob was evaluated according to a set of job elements related to airborne fiber exposure. The distribution of the cohort person-years by UDJob and the job-exposure elements was then evaluated. The results show the main departments and jobs that employed the workers for each plant. The distribution of person-years varies across the job-exposure elements. The same job title was used in different departments within and across plants. When job titles not linked to departments were evaluated, the values of the job-exposure elements varied considerably across all plants and within plant. IN CONCLUSION: (1) exposure misclassification could occur if job title alone were used for the exposure assessment; (2) the job-exposure elements analysis provides an efficient way to identify major job determinants of exposure without relying on the more detailed, resource-intensive task-based approach; and (3) the evaluation of the cohort person-years by UDJobs and job-exposure elements is an effective way to identify which plants, departments, and jobs have sufficient information for making precise risk estimates in the broader epidemiologic study.
Asunto(s)
Contaminantes Ocupacionales del Aire/análisis , Vidrio/análisis , Exposición Profesional/análisis , Estudios de Cohortes , Humanos , Sensibilidad y Especificidad , Textiles/análisis , Factores de Tiempo , Estados Unidos/epidemiología , Lugar de TrabajoRESUMEN
PURPOSE: To compare the three national-scale death identification services used in our two-stage vital status tracing protocol, Pension Benefit Information Company (PBI), Social Security Administration (SSA), and the Health Care Financing Administration (HCFA), with respect to death identification and confirmation rate, and relevant demographic variables. METHODS: Information on 31,223 subjects with unconfirmed vital status in an ongoing occupational cohort mortality study was simultaneously submitted to PBI, SSA, and HCFA to identify subjects deceased as of December 31, 1992. Subjects whose dates of death were between 1979 and 1992 were then sent to the National Death Index (NDI) to obtain death certificate numbers and supplemental states of death. RESULTS: PBI identified and confirmed the highest number deaths in this cohort. PBI and SSA identified a higher proportion of deaths for persons who died in earlier years and/or who died at a younger age, for both confirmed and unconfirmed deaths. HCFA identified fewer deaths overall and had a smaller proportion of unconfirmed deaths. These deaths occurred in later years among older subjects and had the highest proportion of females. NDI provided exact matches for 92-96% of deaths identified by each of the three services. CONCLUSIONS: PBI was the most comprehensive service, especially for identifying younger subjects and those with an earlier date of death, while HCFA may help to identify deceased female subjects. SSA data can be purchased and used for periodic updates or interactively to identify deaths among subjects with poor identifiers (such as incorrect or missing social security numbers or misspelled names). Because each service makes a valuable contribution to the identification of deceased cohort subjects, all three should be considered for optimal mortality follow-up.
Asunto(s)
Centers for Medicare and Medicaid Services, U.S./estadística & datos numéricos , Certificado de Defunción , Mortalidad , Pensiones/estadística & datos numéricos , United States Social Security Administration/estadística & datos numéricos , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Bases de Datos Factuales , Etnicidad/estadística & datos numéricos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedades Profesionales/mortalidad , Estados Unidos/epidemiologíaRESUMEN
OBJECTIVES: The present study provides additional analyses of data obtained earlier on lung cancer risk among workers with acrylonitrile exposure. METHODS: The original authors provided the data. For total mortality and the cancer sites of a priori interest (lung, stomach, brain, breast, prostate, and the lymphatic and hematopoietic systems), standardized mortality ratios (SMR) and 95% confidence intervals (95% CI) were computed, the total United States and surrounding counties being used as standard populations. Regional rate-based SMR values were also computed between lung cancer and cumulative acrylonitrile exposure. RESULTS: Except for lung cancer, the external comparisons corroborated the earlier internal comparisons (no increased cancer mortality risk). For lung cancer, the external comparisons revealed death deficits for the unexposed workers (SMR 0.68, 95% CI 0.5-0.9) and all categories of acrylonitrile-exposed workers. The SMR obtained using external rates and the most exposed group (SMR 0.92. 95% CI 0.6-1.4) differed from the corresponding relative risk (RR) of the internal rates (RR 1.5, 95% CI 0.9-2.4). CONCLUSIONS: The analysis of the present study provides little evidence that acrylonitrile exposure increases the mortality risk of cancers of a priori interest, including lung cancer. The lung cancer findings of the external comparison differed from the earlier findings of the internal comparisons. Selection bias (as the healthy worker effect) was probably not responsible. Additional follow-up and analyses, especially of the unexposed workers with low lung cancer rates, may help elucidate the internal and external comparison differences. Results from both comparisons should be presented when the relative risks differ markedly, as both have advantages and disadvantages.
Asunto(s)
Acrilonitrilo/efectos adversos , Carcinógenos/efectos adversos , Causas de Muerte , Industria Química , Neoplasias Pulmonares/inducido químicamente , Neoplasias Pulmonares/mortalidad , Exposición Profesional/efectos adversos , Acrilonitrilo/química , Adulto , Neoplasias de la Mama/inducido químicamente , Neoplasias de la Mama/mortalidad , Carcinógenos/química , Neoplasias del Sistema Nervioso Central/inducido químicamente , Neoplasias del Sistema Nervioso Central/mortalidad , Estudios de Cohortes , Intervalos de Confianza , Bases de Datos Factuales/normas , Femenino , Neoplasias Hematológicas/inducido químicamente , Humanos , Incidencia , Masculino , Persona de Mediana Edad , National Institute for Occupational Safety and Health, U.S. , Neoplasias de la Próstata/inducido químicamente , Neoplasias de la Próstata/mortalidad , Sistema de Registros , Factores de Riesgo , Neoplasias Gástricas/inducido químicamente , Neoplasias Gástricas/mortalidad , Análisis de Supervivencia , Estados Unidos/epidemiologíaRESUMEN
OBJECTIVES: To examine the association between exposure to acrylonitrile (AN) and cancer mortality by performing an independent and extended historical cohort study of workers from a chemical plant in Lima, Ohio included in a recent NCI-NIOSH study. METHODS: Subjects were 992 white males who were employed for three or more months between 1960 and 1996. We identified 110 deaths and cause of death for 108. Worker exposures were estimated quantitatively for AN and qualitatively for nitrogen products. Statistical analyses included U.S. and local county-based SMRs and internal relative risk regression of internal cohort rates. RESULTS: No statistically significant excess mortality risks were observed among the total cohort for the cancer sites implicated in previous studies: stomach, lung, breast, prostate, brain, and hematopoietic system. We observed a statistically significant bladder cancer excess based on four deaths (SMR=7.01, 95% CI=1.91-17.96) among workers not exposed to AN. Among 518 AN-exposed workers, we observed a not statistically significant excess of lung cancer based on external (SMR=1.32, 95% CI=.60-2.51) and internal (RR=1.98, 95% CI=.60-6.90) comparisons. Although the trends were not statistically significant, exposure-response analyses of internal cohort rates showed monotonically increasing lung cancer rate ratios with increasing AN exposure, with RRs exceeding 2.0 in the highest exposure categories. CONCLUSIONS: With the possible exception of lung cancer, this study provides little evidence that exposure to AN at levels experienced by Lima plant workers is associated with an increased risk of death from any cause including the implicated cancer sites.
Asunto(s)
Acrilonitrilo/efectos adversos , Industria Química , Neoplasias/mortalidad , Compuestos de Nitrógeno/efectos adversos , Exposición Profesional , Adulto , Neoplasias Encefálicas/mortalidad , Neoplasias de la Mama/mortalidad , Estudios de Cohortes , Intervalos de Confianza , Femenino , Neoplasias Hematológicas/mortalidad , Humanos , Neoplasias Pulmonares/mortalidad , Masculino , Persona de Mediana Edad , National Institute for Occupational Safety and Health, U.S. , National Institutes of Health (U.S.) , Ohio/epidemiología , Neoplasias de la Próstata/mortalidad , Análisis de Regresión , Factores de Riesgo , Neoplasias Gástricas/mortalidad , Estados Unidos , Neoplasias de la Vejiga Urinaria/mortalidadRESUMEN
OBJECTIVE: To update the mortality experience of a cohort of 8508 workers with potential exposure to acrylamide at three plants in the United States from 1984-94. METHODS: Analyses of standardised mortality ratios (SMR) with national and local rates and relative risk (RR) regression modelling were performed to assess site specific cancer risks by demographic and work history factors, and exposure indicators for acrylamide and muriatic acid. RESULTS: For the 1925-94 study period, excess and deficit overall mortality risks were found for cancer sites of interest: brain and other central nervous system (CNS) (SMR 0.65, 95% confidence interval (95% CI) 0.36 to 1.09), thyroid gland (SMR 2.11, 95% CI 0.44 to 6.17), testis and other male genital organs (SMR 0.28, 95% CI 0.01 to 1.59), and cancer of the respiratory system (SMR 1.10, 95% CI 0.99 to 1.22); however, none was significant or associated with exposure to acrylamide. A previously reported excess mortality risk of cancer of the respiratory system at one plant remained increased among workers with potential exposure to muriatic acid (RR 1.50, 95% CI 0.86 to 2.59), but was only slightly increased among workers exposed or unexposed to acrylamide. In an exploratory exposure-response analysis of rectal, oesophageal, pancreatic, and kidney cancer, we found increased SMRs for some categories of exposure to acrylamide, but little evidence of an exposure-response relation. A significant 2.26-fold risk (95% CI 1.03 to 4.29) was found for pancreatic cancer among workers with cumulative exposure to acrylamide > 0.30 mg/m3.years; however, no consistent exposure-response relations were detected with the exposure measures considered when RR regression models were adjusted for time since first exposure to acrylamide. CONCLUSION: The contribution of 1115 additional deaths and nearly 60,000 person-years over the 11 year follow up period corroborate the original cohort study findings of little evidence for a causal relation between exposure to acrylamide and mortality from any cancer sites, including those of initial interest. This is the most definitive study of the human carcinogenic potential of exposure to acrylamide conducted to date.
Asunto(s)
Acrilamida/efectos adversos , Neoplasias/mortalidad , Enfermedades Profesionales/mortalidad , Anciano , Anciano de 80 o más Años , Análisis de Varianza , Estudios de Cohortes , Estudios de Seguimiento , Humanos , Ácido Clorhídrico/efectos adversos , Masculino , Persona de Mediana Edad , Neoplasias/inducido químicamente , Enfermedades Profesionales/inducido químicamente , Exposición Profesional/efectos adversos , Neoplasias del Sistema Respiratorio/inducido químicamente , Neoplasias del Sistema Respiratorio/mortalidad , Estados Unidos/epidemiologíaRESUMEN
The effects of exposure misclassification on the interpretation of results of occupational epidemiological studies has been widely investigated and reported. Usually, only the direct effects of misclassification have been considered or simple estimates of misclassification rates have been assigned to various types of exposure estimation processes. Lifelong job profile data obtained from a previously published case-control study provided complete or nearly complete job histories of 511 decedents. An analysis of these work histories and the comparison of exposures related to longest-held job to estimated total lifetime exposures suggest that single job-based exposure estimates may lead to significant exposure misclassification rates. In addition, the appearance of shorter duration jobs in a study population occurring predominantly early in the work history may exacerbate problems associated with exposure misclassification. While few specific suggestions emerge from this analysis, the inclusion of extensive recording of the work history of study subjects emerges as a reasonable basis for the investigation and potential reduction of secondary misclassification of exposures in occupational epidemiological studies.
Asunto(s)
Contaminantes Ocupacionales del Aire/análisis , Monitoreo del Ambiente/métodos , Anamnesis/métodos , Exposición Profesional/análisis , Exposición Profesional/clasificación , Ocupaciones/estadística & datos numéricos , Anciano , Arizona/epidemiología , Sesgo , Estudios de Casos y Controles , Interpretación Estadística de Datos , Monitoreo del Ambiente/normas , Monitoreo Epidemiológico , Femenino , Humanos , Masculino , Anamnesis/normas , Persona de Mediana Edad , Mortalidad , Reproducibilidad de los Resultados , Factores de TiempoRESUMEN
The Occupational Cohort Mortality Analysis Program (OCMAP) has been redesigned for optimal microcomputer use and extended to include new computing algorithms. The new program, OCMAP-PLUS, offers a comprehensive, flexible, and efficient analysis of incidence or mortality rates and standardized measures in relation to multiple and diverse work history and exposure measures. New features include executable code, minimization of memory requirements, disk file storage of person-day arrays, stratified analyses by geographic area, employment status and up to eight exposure variables, a data imputation algorithm for study members with unknown race, and enhanced algorithms for constructing several time-dependent exposure measures. New modules create grouped data files for Poisson and logistic regression and risk set files for use in relative risk regression analysis. The Mortality and Population Data System (MPDS) provides external comparison rates and proportional mortalities. Analysis from two recent cohort mortality studies illustrate several new features.
Asunto(s)
Métodos Epidemiológicos , Medicina del Trabajo/métodos , Programas Informáticos , Estudios de Cohortes , Humanos , Estadísticas VitalesRESUMEN
To investigate factors related to lung cancer mortality in four Arizona copper-smelter towns, the authors identified 142 lung cancer cases and 2 matched controls per case from decedent residents during 1979-1990. The authors obtained detailed information on lifetime residential, occupational, and smoking histories via structured telephone interviews with knowledgeable informants. The authors linked estimated historical environmental exposures to smelter emissions (based on atmospheric diffusion modeling of measured sulfur dioxide concentrations) with residential histories to derive individual profiles of residential exposure. The results of this study provided little evidence of a positive association between lung cancer and residential exposure to smelter emissions. Conditional logistic regression analysis revealed a statistically significant positive association between lung cancer and reported employment in copper mines and/or smelters, although specific factors associated with the apparently increased risk among these workers could not be identified in this community-based study.
Asunto(s)
Contaminantes Ocupacionales del Aire/efectos adversos , Neoplasias Pulmonares/mortalidad , Enfermedades Profesionales/mortalidad , Población Rural/estadística & datos numéricos , Adulto , Anciano , Arizona/epidemiología , Estudios de Casos y Controles , Causas de Muerte , Cocarcinogénesis , Cobre/efectos adversos , Exposición a Riesgos Ambientales/efectos adversos , Femenino , Encuestas Epidemiológicas , Humanos , Neoplasias Pulmonares/inducido químicamente , Masculino , Persona de Mediana Edad , Minería , Enfermedades Profesionales/inducido químicamente , Factores de Riesgo , Fumar/efectos adversos , Fumar/mortalidad , SoldaduraRESUMEN
We carried out a study of pregnant patients in a health maintenance organization to identify and provide case management of women at risk of preterm labor and to determine important risk factors for preterm labor in a managed care population. Data were collected on 794 women who completed an initial prenatal care visit at HealthAmerica of Pittsburgh between July 15, 1994, and March 31, 1995, and delivered at a local Pittsburgh hospital. The patients were assessed during an initial call to schedule their first prenatal visit and also at the 8- to 15-week and 24- to 28-week prenatal visits. Patients scoring 10 or higher on the risk assessment form were referred to a nurse case manager who provided education and support. Results of a logistic regression analysis suggest that the risk assessment tool was effective in identifying women at risk for preterm labor. "Physical/stressful work", as assessed by the patient, history of a prior preterm birth, and multiple gestation were all statistically significant predictors of preterm birth. Further research is needed to confirm the finding that physical or stressful work is a significant predictor of preterm births and to determine which aspects of the work may increase the patient's risk. This study was based on 8 months of data; however, additional program implementation is needed to evaluate fully the potential long-term benefits of the program.