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.

Observed versus predicted carboxyhemoglobin levels in cellulose triacetate workers exposed to methylene chloride.

BACKGROUND: Occupational exposure to methylene chloride, together with carboxyhemoglobin concentrations, has not been studied previously. METHODS: Carboxyhemoglobin levels were measured in non-smoking employees exposed to varying concentrations of methylene chloride during the manufacture of cellulose triacetate fibers. The observed carboxyhemoglobin levels were compared to predicted concentrations using a pharmacokinetic model. RESULTS: The presence of carboxyhemoglobin in non-smokers exposed to methylene chloride results primarily from the metabolism of methylene chloride in the liver and exhibits a linear dose-response relationship. The observed levels of carboxyhemoglobin in non-smokers at the end of an 8-hour shift depend upon exposures to methylene chloride that day but are independent of occupational exposures on previous days. The observed daily concentrations of carboxyhemoglobin are consistent with predicted concentrations using a pharmacokinetic model. While varying exposure patterns were shown to change the rate of metabolite formation at the end of shift, these same exposure patterns had almost no effect on the total amount of carbon monoxide in the blood. CONCLUSION: While the present study addresses the relationship between methylene chloride, carbon monoxide, carboxyhemoglobin and ischemic heart disease, it does not address the issue of tumorigenicity, which is also the basis for the current U.S. Occupational Health and Safety workplace exposure limit of 25 ppm. This study provides support for the conclusion that the current American Conference of Governmental Industrial Hygienists 8-hour Threshold Limit Value of 50 ppm adequately protects human health with regard to ischemic heart disease and carboxyhemoglobin formation among non-smokers.

Cohort mortality study of prostate cancer among chemical workers.

A retrospective cohort mortality study was conducted at a chemical plant producing acetic acid and acetic anhydride, two chemicals essential in the synthesis of cellulose triacetate fiber. Previously, we reported excess mortality from biliary tract and prostate cancers among workers in cellulose triacetate fiber manufacturing plants. In the present investigation, an excess of prostate cancer (SMR = 330.4; 95% confidence interval = 121.3-719.1) was observed among former chemical plant workers, some of whom had been exposed to both acetic acid and acetic anhydride. These apparent increases in mortality are difficult to interpret biologically, particularly in light of recent suggestions concerning the role of endocrine factors. Additional work is planned to more fully characterize potential occupational exposures that might explain the etiology of prostate cancer.

A cohort mortality study of cellulose triacetate-fiber workers exposed to methylene chloride.

The purpose of this study of 3211 cellulose-fiber production workers was to evaluate earlier findings of excess biliary tract and liver cancer in a similarly exposed cohort reported in 1990. Mortality from biliary tract and liver cancer was not increased in this study population, and there was no excess mortality from pancreatic cancer. Mortality was not elevated for cancers of the lung or liver, sites at which tumors were induced in experimental animals exposed to methylene chloride. Men with 20 or more years of employment exhibited increased mortality from prostate cancer, whereas women who also had 20 or more years of employment experienced higher-than-expected mortality from cervical cancer. Although these apparent increases in mortality are difficult to interpret biologically and are not consistent with previous studies, they require further investigation.

Carboxyhemoglobin levels in methylene chloride-exposed employees.

The Occupational Safety and Health Administration (OSHA) has proposed a reduction in the permissible exposure limit for methylene chloride from 500 parts per million (ppm) to 25 ppm (8-hour time-weighted average [TWA]). Part of the rationale for lowering the standard is a concern over potentially adverse cardiac effects secondary to elevated carboxyhemoglobin (COHb) levels as a by-product of methylene chloride metabolism. Employees exposed to methylene chloride as part of a triacetate fiber production process had average values of COHb ranging between 1.77% and 4.00% in the nonsmoking group and between 4.95% and 6.35% in a smoking group, with individually measured methylene chloride exposures averaging up to 99 ppm (8-hour TWA). A dose-response effect was seen only in the nonsmoking group. Additional daily cumulative exposure to methylene chloride did not produce increased levels of COHb. Data from this study support the fact that the COHb levels resulting from exposure to methylene chloride at or below the current American College of Government Industrial Hygienists limit of 50 ppm (8-hour TWA) are of a sufficiently low level that they are unlikely to produce adverse cardiac effects in humans.

Cross-sectional follow-up of a flu-like respiratory illness among fiberglass manufacturing employees: endotoxin exposure associated with two distinct sequelae.

Over a period of 10 years, employees in a manufacturing plant experienced sporadic flu-like episodes after work in a basement containing a recirculated washwater mist. We report a cross-sectional study to define the flu-like illness and bioaerosol exposures. High concentrations of gram-negative bacteria (GNB) (> 10(7) cfu/ml) and endotoxin (range 34-46 micrograms/ml) were found in the water. Mist contained > 10(3) cfu/m3 of GNB, and endotoxin up to 13,900 to 27,800 ng/m3. Few fungi and thermotolerant Bacillus species and no Actinomycetes, Legionella species, or amoeba were found in washwater. Airborne levels of fungi were of the same species and magnitudes as outdoor samples. Subjects volunteered (n = 28) because of a history of flu-like symptoms or were randomly selected (n = 102) from workers with and without current exposure to the basement. No acute cases were examined. Cases did not fulfill criteria for hypersensitivity pneumonitis (HP) and high levels of IgG antibodies to water-borne antigens were not observed. However, among 20 subjects indicating a history of severe flu-like episodes (severe basement flu, SBF), diffusion capacity (DLCO) was significantly lower (p = 0.015) than among other workers. The prevalence of SBF was independent of smoking. Cases occurred in clusters, and SBF was more common among workers with intermittent exposure to the basement (19 cases) than with daily exposure (1 case). These findings suggest that SBF and associated chronically depressed DLCO resulted from toxic injury following high-level endotoxin exposure. Asthma was prevalent in the study population, particularly among employees with daily, rather than intermittent, exposure to endotoxin-containing mist (odds ratio 6.7, p = 0.02). Thus, endotoxin exposure in this study was associated with two distinct sequelae depending on the temporal pattern of exposure.

Polypropylene production workers and colorectal cancer in Germany: a brief report.

OBJECTIVE: A retrospective cohort study of 640 male polypropylene production workers in Germany was performed to evaluate the reported association between colorectal cancer and polypropylene. METHOD: The follow up period was 1956 to 1990. Expected numbers of cancers were derived from incidence rates adjusted for age and calendar year from the Saarland cancer registry. RESULTS: Three colorectal cancers were identified compared with 4.0 expected (standardised incidence ration (SIR) = 0.75, 95% confidence interval (95% CI): 0.15-2.19). For total cancers there were 27 cases in the cohort compared with 35.4 expected (SIR = 0.76, 95% CI: 0.50-1.11). DISCUSSION: These results do not support earlier reports of a link between polypropylene production and colorectal cancer, but are consistent with a number of recent investigations of polypropylene production workers that have reported no association with risk of colorectal cancer. Due to the small size of this and other similar studies, however, a small to moderate increase in risk cannot be ruled out.

Mortality among synthetic fiber workers exposed to glycerol polyglycidyl ether.

We studied mortality among 8,878 employees who worked at any time from 1965 to 1988 at a synthetic fibers plant in North Carolina that used a finishing agent containing glycerol polyglycidyl ether. Some glycidyl ethers are mutagenic and tumorigenic in laboratory animals. The main route of exposure to workers was inhalation of the spray mist, although there was also skin contact. We identified 553 deaths in the cohort and the standardized mortality ratio (SMR) from all causes of death combined was 0.80. For most causes of death, mortality rates in the cohort were similar to mortality rates in the U.S. population. Among categories with at least five observed deaths, the largest effect estimate was for cancer of the central nervous system (SMR = 1.77), and the SMR for lung cancer was 0.94. The cancer categories of central nervous system (brain) and "other" lymphopoietic cancers (lymphoma and myeloma) showed weak associations with duration of employment. In case-control analyses in which we utilized work history data to compute effect estimates by duration of exposure, we found no increased risk of lung cancer or brain cancer among employees with more than 5 years of exposure. Effect estimates for lymphoma and myeloma tended to increase with duration of exposure, although there were only seven deaths in this category and the effect estimates were very imprecise. To date, this study has identified no clear carcinogenic effect of glycerol polyglycidyl ether, but plausible induction periods have not yet elapsed. The cohort should continue to be monitored to obtain more precise estimates after moderate or long induction times.

The accuracy of auscultatory detection of fetal cardiac decelerations: a computer simulation.

To evaluate current practices of auscultation for the detection of decelerations, we used a computer to generate contractions and late decelerations and perform the counting. The baseline rate ranged from 110 to 180 beats/min. The duration of the deceleration ranged from 1 to 2 minutes, and the amplitude of the deceleration ranged from 10 to 90 beats/min. The onset of the decelerations ranged from 0.4 to 0.7 of the length of the contraction. Counting was begun at 80%, 100%, and 120% of the contraction length. The duration of counting varied between 15 and 60 seconds. A multicount algorithm obtained three 10-second counts separated by 5 seconds. Results were classified by the ability to detect rates below 120, 100, or 80 beats/min (threshold determination) or 20 and 25 beats/min below the baseline rate (subtraction determination). The baseline rate and deceleration amplitude had the greatest effect on accuracy. The higher the baseline rate and the smaller the deceleration amplitude, the less accurate was detection. Multiple counts were more accurate than the single-count strategy, and subtraction detection was more accurate than threshold detection. The effects of counting error are briefly described. This model, which requires clinical confirmation, nevertheless emphasizes the potential inaccuracies of many popular schemes of auscultatory surveillance, even for the detection of prolonged or sustained decelerations. Certain modifications of auscultatory practice may improve the accuracy of this technique.

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.

Cancer in relatives of retinoblastoma patients.

Medical histories with emphasis on malignant disease were obtained on 1,269 first and second degree relatives of 93 probands with retinoblastoma and on 671 first and second degree relatives of 50 age-matched control children. The number of nonocular malignancies expected to occur in first and second degree relatives of the probands were calculated using the observed number of neoplasms in control families as the standard. Using a Poisson distribution to evaluate the findings, a statistically significant excess of cancer was found in relatives of the probands with retinoblastoma. Gastrointestinal malignancies were particularly common in this population.

Lymphocyte subpopulations in Graves' ophthalmopathy.

We assessed the percentages of T-lymphocyte subsets, B lymphocytes, monocytes, and granulocytes in the mononuclear cell preparations of euthyroid patients with minimal and severe Graves' ophthalmopathy. Patients with active Werner class 4-5 and class 6 ophthalmopathy had statistically significant elevations of suppressor/cytotoxic T8+ lymphocytes. During successful corticosteroid therapy, the number of T8+ lymphocytes returned to the normal range. Mirroring these results, the T4/T8 ratio was initially depressed in patients with class 4-5 ophthalmopathy and increased during therapy. Our previous observations noted a decreased number of rosette-forming T lymphocytes in patients with severe ophthalmopathy. In this study, however, there were normal percentages of T3+ and T11+ lymphocytes, suggesting that the T lymphocytes are present in peripheral blood but they cannot form rosettes. There was a slight reduction of the percentage of the T11+ (erythrocyte receptor) lymphocytes in the patients with class 4-5 ophthalmopathy; however, it was not statistically significant. No significant differences were evident in any of the other T-lymphocyte subsets, B lymphocytes, monocytes, or granulocytes studied. We conclude that Graves' ophthalmopathy is characterized by a surface membrane defect associated with increased percentages of suppressor/cytotoxic T8+ lymphocytes. Successful corticosteroid therapy reverses these findings.

Growth rates and doubling times of posterior uveal melanomas.

Seventeen patients having a posterior uveal melanoma underwent enucleation following documentation of tumor growth. Duration of follow-up from diagnosis to enucleation ranged from 3 weeks to 30 months. The mean rate of enlargement in cubic tumor volume was 56.3 mm3/mo for eight spindle cell melanomas and 270.3 mm3/mo for nine mixed cell melanomas. The mean tumor doubling time calculated according to the exponential growth equation was 291.6 days for the eight spindle cell melanomas and 128.2 days for the nine mixed cell melanomas. The mean mitotic activity was 3.5 mf/40 hpf for the eight spindle cell melanomas and 5.4 mf/40 hpf for the nine mixed cell melanomas. These results suggest that mixed cell posterior uveal melanomas generally grow faster and have shorter doubling times than do spindle cell melanomas.

Laryngeal cancer and occupational exposure to sulfuric acid.

Workers on an ethanol unit which used sulfuric acid in strong concentrations at a large refinery and chemical plant in Baton Rouge, Louisiana were reported, in 1979, at excess risk for upper respiratory cancer. The carcinogen implicated by indirect evidence was diethyl sulfate. However, with the continued use of sulfuric acid in the same plant, and with additional cases not attributable to the ethanol process, the hypothesis of an association between sulfuric acid exposure and upper respiratory cancer was tested. Each of 50 confirmed cases of upper respiratory cancer diagnosed between 1944 and 1980, was matched to at least three controls on sex, race, age, date of initial employment, and duration of employment. Thirty-four of the 50 cases were laryngeal cancers. Data were obtained from existing plant records. Retrospective estimates of exposure were made without regard to case or control status. Findings from conditional logistic regression techniques were supported by other statistical methods. Among workers classified as potentially highly exposed, four-fold relative risks for all upper respiratory cancer sites combined were exceeded by the relative risk for laryngeal cancer specifically. Exposure-response and consistency across various comparisons after controlling statistically for tobacco-use, alcoholism and other previously implicated risk factors, suggest increased cancer risk with higher exposure.

Visual results following cobalt plaque radiotherapy for posterior uveal melanomas.

Visual results of cobalt plaque radiotherapy on the eyes of 77 patients with posterior uveal melanoma in one eye and pretreatment visual acuity of 20/25 or better in both eyes were analyzed using actuarial methods. The study demonstrated that eyes receiving a radiation dose in excess of 5,000 rad to the fovea and/or optic disc commonly lose a substantial amount of vision within 2 to 3 years. It also showed that eyes treated by cobalt plaque radiotherapy for a large posterior uveal melanoma are more likely to suffer profound visual loss than those treated for a medium or small melanoma. The predominant cause of severe visual loss in these patients appeared to be foveal radiation retinopathy.

Prealbumin as a biochemical marker of nutritional adequacy in premature infants.

To determine whether serum prealbumin would be useful in identifying adequacy of protein and calorie intake in premature infants, 17 infants between 26 and 33 weeks gestational age were studied throughout hospitalization. Serial anthropometric measurements, nutritional intake, and serum prealbumin concentrations were correlated. When mean intake of calories and protein was lower than 100 kcal/kg/day and less than 2 gm/kg/day, respectively, there was a significant difference in mean prealbumin values, compared with those in infants with a higher intake (P much less than 0.001). For infants with birth weights of 1000 gm or less, prealbumin correlated with protein intake (r = 0.66) and calorie intake (r = 0.64). In these infants, when protein intake exceeded 2 gm/kg/day, prealbumin concentrations increased to values reported for full-term infants in the first months of life. There was no significant correlation between intake of calories or protein and prealbumin values for infants born weighing greater than 1000 gm. Anthropometric measurements did not correlate with protein or calorie intake. We conclude that prealbumin is a sensitive measure of protein and calorie intake in premature infants, and that the definition of adequate nutrition may be different for premature infants of different birth weights and at various postconceptional ages.

Gamma-glutamyl transpeptidase in the prognosis of patients with uveal malignant melanoma.

A study of 116 patients with histologically proven uveal malignant melanoma suggested that hepatic metastases were present at the same time that the ocular tumor was diagnosed in 15 patients (13%) by serum gamma-glutamyl transpeptidase assay. The average pretherapy gamma-glutamyl transpeptidase levels were statistically higher (P less than .01) in the 28 patients who developed metastases compared with those in 88 patients who have remained clinically free of metastases for a follow-up period of at least two years. The predictive value test indicated that pretherapy gamma-glutamyl transpeptidase levels greater than or equal to 22 IU/ml were increased in patients developing metastasis. With this upper-normal limit, 15 (54%) of the 28 patients who later developed clinical evidence of metastasis had increased pretherapy levels. In comparison, only 12 (14%) of the 88 patients who remained tumor-free for at least two years had increased pretherapy levels. Although not all patients who developed metastases had increased pretherapy levels, most developed increases at some time during the course of their disease. Because the gamma-glutamyl transpeptidase assay can detect hepatic metastases before other liver function assays, it should be included as a routine liver function study for patients with uveal malignant melanoma.

Relationship of site-specific cancer mortality rates to altitude.

Mortality rates for all malignant neoplasms (combined) and for 34 site-specific cancer categories for selected high and low altitude populations are compared using two related techniques: confidence interval overlap for strictly descriptive purposes and analysis of standardized mortality ratios using lower and upper 95% statistical significance factors for the ratio of an observed value of a poisson variable to its expectation. Techniques are employed to minimize confounding due to industrialization, urbanization or selected cultural characteristics. Cancer mortality data for U.S. counties averaged over the 20-year period, 1950--1969, were used. For most comparisons a deficit in cancer mortality in high altitude counties was observed. The largest differences between the low and high altitude groups were found for cancers of the tongue and mouth, esophagus, larynx, lung and melanoma. Some limitations of ecologic studies are discussed.

Obtaining hospital and physician participation in a case-control study of colon cancer.

This paper describes efforts to solicit hospital and physician participation for a case-control study of the etiology of colon cancer in the five Pennsylvania counties of the Philadelphia metropolitan area. Forty-seven of the 70 hospitals in this region were eligible for inclusion in the study. Thirty-seven (79%) agreed to participate, 27 of them within six months of initial contact. The median time to approval of participation was three months and the median number of separate contacts was nine. At least five participating hospitals submitted the protocol to their lawyers and nine required that special procedures be developed for release of patient information. Two hundred fourteen of 256 listed attending physicians were eligible for participation; 161 (75%) permitted all patients to be contacted 23 (11%) permitted some patients to be contacted; 30 (14%) refused all patient contact. A significant association between type of specialty and type of permission was found (p approximately .005). Concerns about confidentiality and lack of personal advantage were frequently cited by non-participants. The validity of case-control studies relying on hospital or physician ascertainment of cases is seriously challenged by such lengthy delays and lack of participation which can result in a biased pool of potential cases.