Mortality from non-malignant respiratory disease in the fibreglass manufacturing industry.

OBJECTIVES: To investigate the question of whether there is an association between workplace exposures and sociodemographic factors and mortality from non-malignant respiratory disease excluding influenza and pneumonia (NMRDxIP) among workers in a fibreglass wool manufacturing facility. METHODS: A case-control study with cases and controls derived from deaths recorded from the Kansas City plant in the Owens Corning mortality surveillance system. The cases are defined as decedents with NMRDxIP as the underlying cause of death. Matched, unadjusted odds ratios (ORs) were used to assess any association between NMRDxIP and cumulative exposure history and sociodemographic factors individually. Matched, adjusted ORs were obtained by conditional logistic regression to estimate the effect of any one variable while controlling for the effect of all the others. RESULTS: Results of the unadjusted analysis, considering variables one at a time, yielded no significant associations between NMRDxIP and any of the exposure or sociodemographic variables. The smoking OR was substantially increased (OR 5.09; 95%CI 0.65 to undeterimed). Also, there were no significant variables in a conditional logistic regression analysis in which all variables were simultaneously adjusted. ORs for respirable glass fibres were below unity at all concentrations of exposure in the adjusted analysis. For respirable silica there was no consistent relation across all exposure levels. The ORs increased through the first three exposure concentrations but decreased for the highest exposure. However, ORs although not significant, are greater than unity for all respirable concentrations of silica exposure. CONCLUSIONS: The findings for Kansas City show no association between respirable glass fibres and NMRDxIP. The adjusted ORs for all exposures to respirable fibres were less than unity. On the other hand, the ORs for silica exposures were all above unity although there was no clear dose-response relation and none of the ORs were significant. Exposures for all substances considered were very low. Further, given the number of cases and controls, the statistical power to detect relatively small increases in risk, if any increase truly exited, was relatively low. The ORs for exposures to silica were all above unity although there was no clear dose-response relation and none of the ORs were significant. These raised ORs for silica suggest that continued surveillance would be prudent.

An historical cohort mortality study of synthetic fiber workers potentially exposed to glycerol polyglycidyl ether.

We report an update of the mortality experience of a cohort of 8878 employees who worked between November 1, 1965, and December 31, 1988, at a synthetic fiber manufacturing facility with potential exposure to glycerol polyglycidyl ether (T55) and were followed through December 31, 1998. The mortality experience of the race/gender groups within the cohort was strikingly similar, with both the all causes of death and all cancer causes of death below unity on both national and local standards. For white men, there were no statistically significant increases for any cause of death, with the exception of benign neoplasms. Thirty-four percent of the cohort had worked at the plant for less than 1 year. Standardized mortality ratios were compiled for those with less than 1 year of employment and for those with 1 year or more of employment. Exclusion of those cohort members who worked less than 1 year had little impact on the standardized mortality ratios.

Orbitally induced oscillations in the East Antarctic ice sheet at the Oligocene/Miocene boundary.

Between 34 and 15 million years (Myr) ago, when planetary temperatures were 3-4 degrees C warmer than at present and atmospheric CO2 concentrations were twice as high as today, the Antarctic ice sheets may have been unstable. Oxygen isotope records from deep-sea sediment cores suggest that during this time fluctuations in global temperatures and high-latitude continental ice volumes were influenced by orbital cycles. But it has hitherto not been possible to calibrate the inferred changes in ice volume with direct evidence for oscillations of the Antarctic ice sheets. Here we present sediment data from shallow marine cores in the western Ross Sea that exhibit well dated cyclic variations, and which link the extent of the East Antarctic ice sheet directly to orbital cycles during the Oligocene/Miocene transition (24.1-23.7 Myr ago). Three rapidly deposited glacimarine sequences are constrained to a period of less than 450 kyr by our age model, suggesting that orbital influences at the frequencies of obliquity (40 kyr) and eccentricity (125 kyr) controlled the oscillations of the ice margin at that time. An erosional hiatus covering 250 kyr provides direct evidence for a major episode of global cooling and ice-sheet expansion about 23.7 Myr ago, which had previously been inferred from oxygen isotope data (Mi1 event).

Mortality from nephritis and nephrosis in the fibreglass manufacturing industry.

OBJECTIVES: To investigate the question of whether there is an association between exposure to silica or respirable glass fibre and mortality from nephritis or nephrosis among workers in fibrous glass wool manufacturing facilities. METHODS: A case-control study with cases and controls derived from the Owens Corning mortality surveillance system. Two case-control analyses were carried out, one where the cases are defined with nephritis or nephrosis as the underlying cause of death and one where cases are defined as those where nephritis or nephrosis is either the underlying or a contributing cause of death. RESULTS: There is no consistent relation between respirable fibres or respirable silica and nephritis or nephrosis when the analysis is based either on underlying cause only or on underlying plus contributing cause of death. None of the sociodemographic variables considered suggests an increased risk when considering both underlying and contributing cause of death. CONCLUSIONS: These data would seem to support the contention that the most accurate picture of renal disease will be gained from the use of all information on the death certificate and not only the underlying cause. For these data, all odds ratios (ORs) for respirable fibres and silica based on both underlying and contributing cause of death are < 1 with the exception of the highest exposure to silica which is slightly > 1 (OR = 1.04). Although these results do not prove that there is no association between nephritis and nephrosis and exposure to fibreglass or silica in the fibreglass manufacturing environment, they do not support the assertion that such an association exists.

Historical cohort mortality study of a continuous filament fiberglass manufacturing plant. II. Women and minorities.

An historical cohort mortality study was undertaken at Owens Corning's continuous filament fiberglass manufacturing plant in Anderson, South Carolina. The cohort included 1074 white women, 130 black women, and 494 black men who worked for a minimum of one year from the opening of the plant in 1951 through December 31, 1991. This represents the largest single cohort of white women assembled to date in either a wool or continuous filament fiberglass manufacturing facility and represents the first study of a cohort of black men and women in the man-made vitreous fiber industry. Over 95% of the women and minorities included in this report held production positions in the plant. There were no significant excesses or deficits in mortality by cause, including cancer causes, among white women, with the exception of motor-vehicle accidents, when compared with national mortality. Among black men, standardized mortality ratios (SMRs) for heart disease are significantly below one, and SMRs for all cancers combined are below unity on both national and local standards. Lung cancer SMRs are below unity for both white women and black men.

Historical cohort mortality study of a continuous filament fiberglass manufacturing plant. I. White men.

An historical cohort mortality study of a continuous filament fiberglass manufacturing plant was undertaken to determine whether an elevated lung cancer risk would be observed on a cohort basis. A nested case-control study of white male lung cancer deaths was incorporated into the study design. An interview survey to obtain information on sociodemographic factors, including smoking, and an historical environmental reconstruction to identify elements in the plant environment to which workers might be exposed were included in the study design. Respirable glass (Beta) fibers were produced only from 1963 to 1968. The lung cancer odds ratio (OR) among those workers exposed to respirable glass fibers is below unity, as are ORs for exposure to asbestos, refractory ceramic fibers, respirable silica (except for the lowest exposure level), total chrome and arsenic. There is a suggestion of an increase with exposure among smokers only for exposure to formaldehyde, although the OR for the highest level is based on only one case and is not likely to be meaningful. None of these plant exposures suggests an increase in lung cancer risk for this population. Although the lung cancer standardized mortality ratios are slightly elevated, results of the case-control investigation confirm that neither respirable glass fibers nor any of the substances investigated as part of the plant environment are associated with an increase in lung cancer risk for this population.

Adjustment for the confounding effect of cigarette smoking in an historical cohort mortality study of workers in a fiberglass manufacturing facility.

In 1986 a statistically significant lung cancer SMR based on U.S. white male national mortality rates was reported for male fibrous glass workers for follow-up through 1982 of a cohort of U.S. man-made mineral fiber workers. The Newark, Ohio, plant of Owens-Corning, which comprised 38% of the fibrous glass workers in that cohort, also exhibited a statistically significant lung cancer standardized mortality ratio based on U.S. white male mortality rates. A case-control study of the Newark workers demonstrated that a history of cigarette smoking and not exposure to respirable glass is the most important factor in lung cancer risk for workers at the Newark plant. We provide an estimate of the extent of confounding by cigarette smoking for the Newark plant nationally based lung cancer standardized mortality ratio with data not previously available and which suggests that adjusting for the confounding effect of cigarette smoking could reduce the lung cancer standardized mortality ratio to a non-statistically significant level.

Epidemiology studies of synthetic vitreous fibers: methods used and current studies.

Epidemiologic designs (case control, cohort, and surveillance) and measures of association are discussed in the context of studies in the Synthetic Vitreous Fibers industry. Current investigations including a case control study for Owens-Corning's Newark, Ohio plant and a Corporate-wide Mortality Surveillance System are described. The importance of internal validity and the need to account for confounding are demonstrated. Estimates of the prevalence of smoking developed for the Newark plant and the U.S. population have been used to adjust a previously reported statistically significant lung cancer Standardized Mortality Ratio (SMR) for Owens-Corning's Newark plant. After adjusting for the confounding effect of cigarette smoking, the Newark SMR based on national mortality rates is reduced to a statistically insignificant 107.7, a level quite similar to that obtained using local mortality rates. While smoking does not account for all of the excess lung cancer mortality in this population compared to U.S. mortality, these investigations make it clear that plant exposures including respirable glass fibers are not responsible for the remaining excess; rather, this excess reflects the effect of some unknown set of social, demographic, or chance factors.

A case-control study of malignant and non-malignant respiratory disease among employees of a fiberglass manufacturing facility. II. Exposure assessment.

A case-control study of malignant and non-malignant respiratory disease among employees of the Owens-Corning Fiberglas Corporation's Newark, Ohio plant was undertaken. The aim was to determine the extent to which exposures to substances in the Newark plant environment, to non-workplace factors, or to a combination may play a part in the risk of mortality from respiratory disease among workers in this plant. A historical environmental reconstruction of the plant was undertaken to characterise the exposure profile for workers in this plant from its beginnings in 1934 to the end of 1987. The exposure profile provided estimates of cumulative exposure to respirable fibres, fine fibres, asbestos, talc, formaldehyde, silica, and asphalt fumes. Employment histories from Owens-Corning Fiberglas provided information on employment characteristics (duration of employment, year of hire, age at first hire) and an interview survey obtained information on demographic characteristics (birthdate, race, education, marital state, parent's ethnic background, and place of birth), lifetime residence, occupational and smoking histories, hobbies, and personal and family medical history. Matched, unadjusted odds ratios (ORs) were used to assess the association between lung cancer or non-malignant respiratory disease and the cumulative exposure history, demographic characteristics, and employment variables. Only the smoking variables and employment characteristics (year of hire and age at first hire) were statistically significant for lung cancer. For non-malignant respiratory disease, only the smoking variables were statistically significant in the univariate analysis. Of the variables entered into a conditional logistic regression model for lung cancer, only smoking (smoked for six months or more v never smoked: OR = 26.17, 95% confidence interval (95% CI) 3.316-206.5) and age at first hire (35 and over v less than 35: OR = 0.244, 95% CI 0.083-0.717) were statistically significant. There were, however, increased ORs for year of employment (first hired before 1945 v first hire after 1945: OR = 1.944, 95% CI 0.850-4.445), talc (cumulative exposure >1000 fibres/ml days v never exposed: OR = 1.355, 95% CI 0.407-5.515), and asphalt fumes (cumulative exposure >0.01 mg/m(3) days v never exposed: OR 1.131, 95% CI 0.468-2.730). For non-malignant respiratory disease, only the smoking variable was significant in the conditional logistic regression analysis (OR = 2.637, 95% CI 1.146-6.069). There were raised ORs for the higher cumulative exposure categories for respirable fibres, asbestos, silica, and asphalt fumes. For both silica and asphalt fumes, ORs were more than double the reference groups for all exposure categories. A limited number of subjects were exposed to fine fibres. The scarcity of cases and controls limits the extent to which analyses for fine fibre may be carried out. Within those limitations, among those who had worked with fine fibre, the unadjusted, unmatched OR for lung cancer was (1.0 (95% CI 0.229-4.373) and for non-malignant respiratory disease, the OR was 1.5 (95% CI 0.336-6.702). The unadjusted OR for lung cancer for exposure to fine fibre was consistent with that for all respirable fibre and does not suggest an association. For non-malignant respiratory disease, the unadjusted OR for fine fibre was opposite in direction from that for all respirable fibres. Within the limitations of the available data on fibre, there is o suggestion that exposure to fine fibre has resulted in an increase in risk of lung cancer. The increased OR for non-malignant respiratory disease is inconclusive. The results of this population, in this place and time, neither respirable fibres nor any of the substances investigated as part of the plant environment are statistically significant factors for lung cancer risk although there are increased ORs for exposure to talc and asphalt fumes. Smoking is the most important factors in risk for lung cancer in this population. The situation is less clear for non-malignant respiratory disease. Unlike lung cancer, non-malignant respiratory represents a constellation of outcomes and not a single well defined end point. Although smoking was the only statistically significant factor for non-malignant respiratory disease in this analysis, the ORs for respirable fibres, asbestos, silica, and asphalt fumes were greater than unity for the highest exposure categories. Although the raised ORs for these substances may represent the results of a random process, they may be suggestive of an increased risk and require further investigation.

A case-control study of malignant and non-malignant respiratory disease among employees of a fiberglass manufacturing facility.

A case-control study was conducted to determine the influence of non-workplace factors on risk of respiratory disease among workers at the Owens-Corning Fiberglas plant in Newark, Ohio. Cases and controls were drawn from a historical cohort mortality study conducted on behalf of the Thermal Insulation Manufacturers Association (TIMA) of workers employed at Newark for at least one year between 1 January 1940 and 31 December 1963 and followed up to the end of 1982. The TIMA study reported a statistically significant increase in respiratory cancer (compared with national death rates). Interviews were completed for 144 lung cancer cases and 299 matching controls and 102 non-malignant respiratory disease cases and 201 matching controls. Unadjusted odds ratios (ORs) were used to assess the association between lung cancer or non-malignant respiratory disease and birthplace, education, income, marital state, smoking with a duration of six months or more, age at which smoking first started, and duration of smoking. Only the smoking variables were statistically significant. For lung cancer, of the variables entered into a conditional logistic regression model, only the smoking OR of 23.4 (95% CI 3.2-172.9) was statistically significant. For non-malignant respiratory disease no variables entered into the final model were statistically significant. Results of the interview portion of our case-control study clearly indicate that smoking is the most important non-workplace factor for risk of lung cancer in this group of workers. Smoking does not seem to play as important a part, however, for non-malignant respiratory disease. Prevalence of cigarette smoking at the Newark plant was estimated for birth cohorts by calendar year. Corresponding data for the United States were compiled from national smoking surveys. Prevalence of cigarette smoking for Newark in 1955 appears to be sufficiently greater than the corresponding United States data in 1955 to suggest that some of the previously reported excess of lung cancer for Newark based on United States mortality may be accounted for by differences in the prevalence of cigarette smoking between white men in Newark and those in the United States as a whole.

Asphalt and risk of cancer in man.

Epidemiological publications regarding the carcinogenic potential of asphalt (bitumen) are reviewed. In 1984 the International Agency for Research on Cancer (IARC) stated that there is "inadequate evidence that bitumens alone are carcinogenic to humans." They did, however, conclude that animal data provided sufficient evidence for the carcinogenicity of certain extracts of steam refined and air refined bitumens. In the absence of data on man, IARC considered it reasonable to regard chemicals with sufficient evidence of carcinogenicity in animals as if they presented a carcinogenic risk to man. Epidemiological data for man accumulated since the IARC report do not fulfil the criteria for showing a causal association between exposure to asphalt and development of cancer. The studies cited all suffer from a lack of data on exposure or potential confounders, which are necessary to establish whether or not such an association may or may not exist. In view of the evidence (or lack thereof) regarding asphalt today, an appropriate public health attitude suggests at least that action be taken to protect those working with asphalt by monitoring the workplace, taking whatever steps are possible to minimise exposures and to inform workers of potential hazards. At the same time, a need exists for well designed analytical epidemiological studies to determine whether a risk of cancer in man exists from exposure to asphalt.

Effects of heat and other agents on amino acid uptake in Escherichia coli.

In Escherichia coli K1060 grown at 37 degrees C we observed that the uptake of both L-[3H]leucine and L-[35S]methionine was inhibited by exposure of the cells to 48 degrees C. The calcium channel blockers diltiazem and verapamil, and the anti-arrhythmic agent quinidine, inhibited the uptake of L-[3H]leucine at both 37 degrees C and 48 degrees C. Verapamil also inhibited the uptake of L-[35S]methionine at 37 degrees C, but at 48 degrees C protected against some of the heat-induced decrease in the uptake of this amino acid. The local anaesthetic procaine markedly inhibited the uptake of both labelled amino acids at temperatures between 37 degrees C and 48 degrees C. Amino acid uptake and cell killing were not correlated.

A study of the effects of nabumetone (BRL 14777), a novel anti-inflammatory drug, on cell infiltration into sterile cotton pellets implanted in rats.

Nabumetone a new non-steroidal anti-inflammatory drug is active in reducing the DNA content of implanted cotton pellets in rats on various dosing regimens. The effect of nabumetone can be seen during the early and late phases of the cellular reaction to the implant implicating effects upon polymorphonuclear leucocytes and monocytes. The levels of two lysosomal enzymes are reduced in the exudate by the drug treatment.

Stimulation of DNA synthesis in bacterial DNA--membrane complexes after low doses of ionizing radiation.

DNA--membrane complexes from three strains of E. coli were irradiated and changes in the rates of DNA synthesis were observed. Doses from 1--10 krad to complexes from W3110 and pol A1 strains gave up to a 100 per cent increase in DNA synthesis; under the same conditions, no change was observed in Bs-1. The degree of stimulation did not depend on the presence of oxygen during irradiation, and a post-irradiation incubation was necessary to achieve activation. The properties of all three complexes were similar when unirradiated. Irradiation of intact organisms under conditions which produced marked, oxygen-dependent inhibition of the Bs-1 complex had no significant effect on those from W3110 and Pol A1. Enhanced DNA synthesis is concluded to be due wholly to repair of preexisting DNA. It is further postulated that DNA synthesis in untreated complexes (E. coli B's, W3110 and Pol A1) is mainly of the repair-type and does not necessarily take place at the site of DNA--membrane attachment.

The synthesis of DNA by DNA-membrane complexes from irradiated E. coli B/r and Bs-1: the role of the membrane.

DNA-membrane complexes were isolated from lysed E. coli B/r and Bs-1, either by low g forces from a low salt solution, or by high g forces through a discontinuous sucrose gradient. The latter method was more gentle. Irradiation of the intact bacteria had no effect on the membrane macromolecules or on RNA components of these complexes. DNA loss was not significant after irradiation under anoxic conditions but complexes isolated from from Bs-1 irradiated in air showed an appreciable decrease in DNA content. In the presence of the appropriate nucleotide mixture, both 'free' DNA, found in the supernatant fractions, and rapidly sedimented membrane-associated DNA were able to synthesize DNA in the absence of added polymerase. DNA synthesis associated with 'free' DNA was more sensitive to radiation than that associated with DNA bound to the membrane, which appeared to moderate the effects of radiation on new DNA synthesis. It is concluded that the depression of DNA synthesis is primarily a result of irradiation-induced changes on genome-DNA. The interpretation of earlier work from our laboratories that DNA-membrane complexes contained the macromolecular structure which responded to radiation with a high o.e.r. is not supported by the evidence in this work.