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Biomedical subjects

M H Sweeney

Publications and source records attributed to M H Sweeney.

34 records · Page 2Linked to original sources

Evaluation of porphyria cutanea tarda in U.S. workers exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin.

A cross-sectional medical study was performed to evaluate whether occupational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-contaminated substances is associated with porphyria cutanea tarda or porphyrinuria. The exposed participants were employed more than 15 years earlier in the manufacture of sodium trichlorophenol and its derivatives. The referent group consisted of individuals with no occupational exposure to phenoxy herbicides. A total of 281 workers and 260 referents participated. The pattern of urinary porphyrin excretion for each participant was assessed to determine if symptomatic or subclinical porphyria cutanea tarda was present. None of the participants were found to have symptomatic porphyria cutanea tarda. No difference was found between workers and referents in the prevalence of subclinical porphyria cutanea tarda (odds ratio [OR] = 0.93, 95% confidence interval [CI] 0.19, 4.54). There were also no differences in the risk between workers and referents for an out-of-range urinary uroporphyrin or coproporphyrin concentration. In conclusion, this study did not find an elevated risk for porphyria cutanea tarda or porphyrinuria among workers with high serum TCDD levels. Our review of the literature indicates that there is insufficient evidence available to convincingly support or refute an association in humans between TCDD exposure and porphyria cutanea tarda or porphyrinuria.

Adult↗

Peripheral neuropathy after occupational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).

Reports of human exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) describe signs and symptoms consistent with exposure-related peripheral neuropathy. In a cross-sectional study, prevalence of peripheral neuropathy was measured in 265 workers exposed 15 years earlier to chemicals contaminated with TCDD and in 244 unexposed, age-, race-, gender- and community-matched comparisons. Cases of peripheral neuropathy were defined from examination, electrophysiologic and quantitative sensory tests, and symptoms. Exposure was assessed by measuring lipid-adjusted serum TCDD levels. The mean serum TCDD level for workers (220 parts per trillion (ppt)) was significantly higher than for referents (7 ppt) (p < .0001). Thirty-two percent of both worker and referent groups met the case definition for peripheral neuropathy. In the logistic regression analyses, serum TCDD level was not related to peripheral neuropathy. These data suggest that despite continued high serum TCDD levels, peripheral neuropathy is not a long-term sequela of high exposure to TCDD-contaminated chemicals. However, the study cannot preclude the occurrence and subsequent resolution of acute effects caused by high exposure, as experienced in Seveso and possibly by some workers, while exposed to high levels of TCDD-contaminated substances.

Adult↗

Knowledge of medical history information among proxy respondents for deceased study subjects.

Proxy respondents were interviewed for 96 decedents in an occupational cohort. A second respondent was interviewed for 59 decedents. Medical records were reviewed to validate questionnaire information. The percentage of respondents who answered "don't know" (non-response) to questions about medical condition ranged from 5% (cancer and heart disease) to 17% (ulcers). Non-response rates were lowest among spouses, intermediate among children, parents, and siblings, and highest among other relatives and friends. Among 41-55 pairs, depending on the condition, agreement between paired respondents was excellent (kappa > 0.75) for ulcers, cancer, diabetes, and lung disease. A higher percentage of medical records was obtained for decedents with spouse respondents and for decedents with more recent dates of death. Sixty percent or more of the medical records were obtained for patients with cancer (n = 30), heart disease (n = 26), stroke (n = 9), and liver disease (n = 10). The positive predictive value of the proxy respondent information for these conditions was 93, 81, 78, and 60%, respectively.

Cerebrovascular Disorders↗

Cancer mortality in workers exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin.

BACKGROUND: In both animal and epidemiologic studies, exposure to dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin, or TCDD) has been associated with an increased risk of cancer. METHODS: We conducted a retrospective cohort study of mortality among the 5172 workers at 12 plants in the United States that produced chemicals contaminated with TCDD. Occupational exposure was documented by reviewing job descriptions and by measuring TCDD in serum from a sample of 253 workers. Causes of death were taken from death certificates. RESULTS: Mortality from several cancers previously associated with TCDD (stomach, liver, and nasal cancers, Hodgkin's disease, and non-Hodgkin's lymphoma) was not significantly elevated in this cohort. Mortality from soft-tissue sarcoma was increased, but not significantly (4 deaths; standardized mortality ratio [SMR], 338; 95 percent confidence interval, 92 to 865). In the subcohort of 1520 workers with greater than or equal to 1 year of exposure and greater than or equal to 20 years of latency, however, mortality was significantly increased for soft-tissue sarcoma (3 deaths; SMR, 922; 95 percent confidence interval, 190 to 2695) and for cancers of the respiratory system (SMR, 142; 95 percent confidence interval, 103 to 192). Mortality from all cancers combined was slightly but significantly elevated in the overall cohort (SMR, 115; 95 percent confidence interval, 102 to 130) and was higher in the subcohort with greater than or equal to 1 year of exposure and greater than or equal to 20 years of latency (SMR, 146; 95 percent confidence interval, 121 to 176). CONCLUSIONS: This study of mortality among workers with occupational exposure to TCDD does not confirm the high relative risks reported for many cancers in previous studies. Conclusions about an increase in the risk of soft-tissue sarcoma are limited by small numbers and misclassification on death certificates. Excess mortality from all cancers combined, cancers of the respiratory tract, and soft-tissue sarcoma may result from exposure to TCDD, although we cannot exclude the possible contribution of factors such as smoking and occupational exposure to other chemicals.

Bronchial Neoplasms↗

Evaluation of chronic bronchitis, chronic obstructive pulmonary disease, and ventilatory function among workers exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is produced as an undesirable contaminant in the manufacture of 2,4,5-trichlorophenol (TCP) and its derivatives. There is considerable concern about the health effects that may be associated with exposure to TCDD-contaminated substances. A cross-sectional medical study that included a comprehensive medical history, medical examination, and measurement of pulmonary function was conducted on workers employed more than 15 yr earlier in the manufacture of NaTCP and its derivatives at two chemical plants. The workers had substantial exposure to substances contaminated with TCDD, as evidenced by a mean serum TCDD level, lipid adjusted, of 200 ppt compared with a mean of 7 ppt in the unexposed reference group. The comparison group consisted of individuals with no occupational exposure to phenoxy herbicides who lived in the same communities as the workers. A total of 281 workers and 260 unexposed referents participated in the medical examination. Logistic and linear regression analyses, which contained categorical and continuous measures of TCDD exposure, were performed to control for important confounders, including cigarette and alcohol consumption. No difference was found between workers and referents in the risk for chronic bronchitis or COPD. Analysis of the ventilatory function data revealed no association between history of exposure to substances contaminated with TCDD and the forced expiratory volume at one second (FEV1), forced vital capacity (FVC), or the ratio of FEV1 to FVC (FEV1/FVC%).

Bronchitis↗

Chloracne associated with employment in the production of pentachlorophenol.

To evaluate the association between exposure to pentachlorophenol (PCP) and the occurrence of chloracne, we studied the medical and personnel records for individuals employed in the manufacturing of PCP. Forty-seven cases of chloracne were identified among 648 workers (7.0%) assigned to PCP production at a single plant between 1953 and 1978. The annual incidence rate varied considerably, ranging from 0 (in 1953) to 1.46 (in 1978). No linear trend in the risk of chloracne was observed with the duration of employment in the pentachlorophenol department. Workers with a documented episode of direct skin contact with PCP had a significantly increased risk of chloracne compared with workers who did not have a documented episode of direct skin contact (cumulative incidence ratio = 4.6; 95% confidence interval 2.6-8.1). Our results confirm that chloracne is associated with exposure to PCP contaminated with hexachlorinated, heptachlorinated, and octachlorinated dibenzo-p-dioxins and dibenzofurans.

Acne Vulgaris↗

Levels of polychlorinated dibenzo-p-dioxins and dibenzofurans in workers exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin.

Review of employment and chemical production records at a Missouri chemical plant and of questionnaires with self-reported occupational exposure to 2,3,7,8-tetrachloro-dibenzo-p-dioxin (2,3,7,8-TCDD) for 16 Missouri workers has explained the wide diversity of 2,3,7,8-TCDD levels previously reported in the workers' adipose tissue (3.5-750 ppt on whole-weight basis). We show that the highest exposures reported to date in the United States occurred in a group of nine production workers who made products contaminated with 2,3,7,8-TCDD. The nine workers had adipose tissue levels with a mean of 246 ppt and a range of 42 to 750 ppt. Seven persons who worked at the same chemical company, but not in the 2,3,7,8-TCDD-contaminated process, had a mean of 8.7 ppt and a range of 3.5 to 25.8 ppt. We also report serum levels of 2,3,7,8-TCDD in these individuals. The adipose tissue from a subset of four production workers with elevated levels of 2,3,7,8-TCDD and seven Missouri residents with normal 2,3,7,8-TCDD levels was also analyzed for other isomers of the PCDDs and PCDFs. The mean adipose tissue level of 2,3,7,8-TCDD in the subset of production workers was 45 times higher than the mean level in the unexposed Missouri residents, but similar levels of the other PCDDs and PCDFs were found in both groups.

Adipose Tissue↗

Mortality among retired fur workers. Dyers, dressers (tanners) and service workers.

A retrospective cohort mortality study was conducted on 807 fur dyers, fur dressers (tanners), and fur service workers who were pensioned between 1952 and 1977 by the Fur, Leather and Machine Workers Union of New York City. Workplace exposures of fur workers varied with job category. Dyers were exposed to oxidative dyes used in commercial hair dyes; dressers and service workers were exposed to tanning chemicals. In a comparison with the New York City population, no significant increases in mortality were observed among the fur dyers. Among fur dressers, mortality from all malignant neoplasms [standardized mortality ratio (SMR) 151] and lung cancer (SMR 232) was significantly elevated, as was mortality from cardiovascular disease (SMR 126) among fur service workers. When examined by ethnic origin, the elevated SMR values and directly age-adjusted rate ratios suggested that foreign-born fur dressers and eastern European-born fur workers experienced the highest risks for lung and colorectal cancers, respectively. These data support previous findings of increased mortality from colorectal cancer in the foreign-born population of the United States and suggest a possible occupational etiology for the observed lung cancer excess.

Adult↗

An investigation of mortality from cancer and other causes of death among workers employed at an east Texas chemical plant.

The cause-specific mortality of 2,510 males employed at an east Texas chemical plant was examined in a historical prospective study to evaluate a suspected increase in deaths from multiple myeloma and brain cancer. Potential exposures from chemicals, either used in manufacturing processes or produced during the study period 1952-1977, included the fuel additive tetraethyl lead, ethylene dibromide and dichloride, inorganic lead, and vinyl chloride monomer. Overall mortality for all workers (156 observed vs. 211.14 expected) and for workers first employed between 1952 and 1959 (131 observed vs. 167.33 expected) when tetraethyl lead was the single major product was lower than expected when compared to the United States general population. There were no significant increases in mortality from malignancies or other causes of death. The deficits may be due to the small number of total deaths, and the low power for detecting excess risk of mortality from multiple myeloma (Z1-beta = 27, alpha = .05), brain cancer (Z1-beta = 31, alpha = .05), or other rare causes of death; lack of complete workplace exposure data for production workers; and the absence of historical measurements on the extent of environmental exposure to tetraethyl lead and other chemicals.

Actuarial Analysis↗

Evaluation of serum lipid concentrations among U.S. workers exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin.

2,3,7,8-Tetrachlorodibenzo-p-dioxin alters lipid metabolism in animals; however, evidence for such an effect in humans is conflicting. This conflict was addressed using data from a cross-sectional medical study conducted between 1987 and 1988. The exposed participants had been employed at least 15 y earlier in the manufacture of 2,4,5-trichlorophenol or one of its derivatives at two chemical plants in the United States. A total of 281 workers and 260 unexposed referents participated. Workers had substantial exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin, evidenced by a median serum 2,3,7,8-tetrachlorodibenzo-p-dioxin concentration of 406.6 femtograms/gram of serum (fg/g serum), compared with 36.9 fg/g serum among the referents. A slight association between triglyceride concentration and serum 2,3,7,8-tetrachlorodibenzo-p-dioxin concentration was found (p = .05). Over the range of observed 2,3,7,8-tetrachlorodibenzo-p-dioxin values (i.e., 37-19000 fg/g serum), triglyceride concentration increased only about 0.4 mmol/I. No association was found between an abnormally elevated triglyceride (i.e., > 2.82 mmol/I) concentration and serum 2,3,7,8-tetrachlorodibenzo-p-dioxin concentration. An association was also found between serum 2,3,7,8-tetrachlorodibenzo-p-dioxin concentration and an abnormal high-density lipoprotein concentration (p = .09). in summary, there was evidence of an effect on lipid metabolism in a group of workers with high serum 2,3,7,8-tetrachlorodibenzo-p-dioxin concentrations. The influence of serum 2,3,7,8-tetrachlorodibenzo-p-dioxin on lipid concentrations, however, was small, compared with the influence of other factors.

Adolescent↗

Hepatic and gastrointestinal effects in an occupational cohort exposed to 2,3,7,8-tetrachlorodibenzo-para-dioxin.

OBJECTIVE: To examine the effect of occupational exposure to substances contaminated with 2,3,7,8-tetrachlorodibenzo-para-dioxin (TCDD) on the liver and gastrointestinal system. DESIGN: A medical survey. PARTICIPANTS: The exposed participants were employed at two chemical plants more than 15 years earlier in the manufacture of sodium trichlorophenol and its derivatives. The reference group consisted of individuals with no occupational exposure to phenoxy herbicides and who lived within the communities of the workers. A total of 281 workers and 260 unexposed referents participated in the medical study. MEASUREMENTS AND MAIN RESULTS: The workers had substantial exposure to substances contaminated with TCDD, as evidenced by a mean serum TCDD level, lipid adjusted, of 220 pg per gram of lipid compared with a mean of 7 pg per gram of lipid in the referents. Compared with the unexposed reference group, workers had a statistically significantly elevated risk for an out-of-range gamma-glutamyltransferase (GGT) level (odds ratio, 2.27; 95% confidence interval, 1.17 to 4.39 [unadjusted for confounders]). In multivariate analyses run with logistic regression, a statistically significant interaction was found between TCDD exposure and lifetime alcohol consumption, indicating that the elevated risk for an out-of-range GGT was confined to those workers with a history of alcohol consumption and that the risk among the alcohol-consuming workers for an out-of-range GGT increased with increasing TCDD level. No difference was found between workers and referents for any of the other liver and gastrointestinal outcomes of interest. CONCLUSIONS: This study found no evidence of an elevated risk for clinical hepatic or gastrointestinal disease in a group of workers with high exposure to TCDD. However, TCDD-exposed workers with a history of sufficient alcohol consumption were found to have a statistically significantly elevated risk for an out-of-range GGT compared with referents.

Cross-Sectional Studies↗

Review and update of the results of the NIOSH medical study of workers exposed to chemicals contaminated with 2,3,7,8-tetrachlorodibenzodioxin.

In 1987, the National Institute for Occupational Safety and Health conducted a cross-sectional medical study to examine the long-term health effects of occupational exposure to chemicals and materials contaminated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). This study compared living workers employed more than 15 years earlier in the production of sodium trichlorophenol (NaTCP), and 2,4,5-trichlorophenoxyacetic ester (2,4,5-T ester) with an unexposed comparison group. Health status of the worker and comparison populations was collected through a comprehensive set of standardized interviews and medical examinations. Lipid adjusted serum TCDD levels were also measured. Workers had a statistically significantly elevated mean serum lipid-adjusted TCDD level (workers = 220 pg per g of lipid [range = not detected-3,400 pg per g of lipid], and referents 7 pg per g of lipid [range not detected-20 pg per g of lipid], P < 0.001). Compared to a community-based referent population, the prevalence of chronic bronchitis, chronic obstructive pulmonary disease, peripheral neuropathy, depression, cardiovascular outcomes (myocardial infarction, angina, cardiac arrhythmias, hypertension, and abnormal peripheral arterial flow), abnormal porphyrin levels, and abnormal ventilatory function parameters FEV1.0, FVC, or FEV1.0/FVC% in workers, was not statistically significantly different. In contrast, relationships were observed between serum 2,3,7,8-TCDD levels and the enzyme gamma-glutamyltransferase (GGT), the reproductive hormones serum testosterone, luteinizing, and follicle-stimulating hormones, and abnormal high-density lipoprotein concentration, counts of CD3/Ta1 cells (helper lymphocytes), and fasting serum glucose levels. Current diagnosis of chloracne was associated with the highest levels of serum 2,3,7,8-TCDD. Analysis of other endpoints continues.

Blood Glucose↗