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Biomedical subjects

M A Fingerhut

Publications and source records attributed to M A Fingerhut.

At least 19 recordsLinked to original sources

Evaluation of cardiovascular outcomes among U.S. workers exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin.

Some animal studies and some human studies suggest that exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) may be associated with adverse effects on the cardiovascular system. As part of a cross-sectional medical study comparing workers employed 15 years earlier in the manufacture of 2,4,5-trichlorophenol or one of its derivatives at two U.S. chemical plants with an unexposed comparison group, we examined the association between TCDD exposure and various cardiovascular outcomes. A total of 281 workers and 260 unexposed referents participated. The workers had substantial exposure to TCDD, as demonstrated by significantly elevated mean serum TCDD concentration of 220 pg/g of lipid, compared with 7 pg/g of lipid among the referents. No significant association was found between TCDD exposure and any of the cardiovascular outcomes including myocardial infarction, angina, cardiac arrhythmias, hypertension, and abnormal peripheral arterial flow. Although our study had sufficient statistical power to detect an elevated risk for cardiac arrhythmias, hypertension, and abnormal peripheral arterial flow, it had low power (approximately 50%) to detect an elevated risk for myocardial infarction and angina. Our review of the literature suggests that our negative findings are consistent with those from other cross-sectional medical studies. Although several mortality studies of TCDD-exposed cohorts found significantly increased risks for cardiovascular disease mortality, similar increased risks were not observed in other mortality studies. The data available do not provide definitive conclusions but indicate that further examination of the association between TCDD exposure and cardiovascular disease should be pursued.

Aged↗

Total serum testosterone and gonadotropins in workers exposed to dioxin.

Human reproductive endocrine data may be an important source of epidemiologic information in regard to the toxic potential of 2,3,7,8-tetrachlorodibenzo-p-dioxin (dioxin). The association of serum dioxin with total serum testosterone, luteinizing hormone, and follicle-stimulating hormone was examined in 248 chemical production workers from New Jersey and Missouri plants and 231 nonexposed neighborhood referents who participated in a medical evaluation in 1987. In linear regression analyses, current serum dioxin was positively and significantly related to luteinizing hormone and follicle-stimulating hormone and inversely related to total testosterone after adjustment for potential confounders (p < 0.05). These trends were also apparent in logistic regression analyses, in which the authors examined the odds ratios of high luteinizing hormone (> 28 IU/liter), high follicle-stimulating hormone (> 31 IU/liter), and low testosterone (< 10.4 nmol/liter) by serum dioxin quartiles. There was a greater prevalence of high luteinizing hormone among workers in the second (odds ratio (OR) = 1.9, 95% confidence interval (CI) 0.7-5.5), third (OR = 2.5, 95% CI 0.9-7.3), and fourth (OR = 1.9, 95% CI 0.7-5.0) quartiles of serum dioxin compared with referents. For follicle-stimulating hormone, the authors observed a greater prevalence of high follicle-stimulating hormone among workers in the fourth quartile (OR = 2.0, 95% CI 0.7-5.6) compared with referents. Similarly, the prevalence of low testosterone was two to four times greater among workers in the second (OR = 3.9, 95% CI 1.3-11.3), third (OR = 2.7, 95% CI 0.9-8.2), and fourth quartiles (OR = 2.1, 95% CI 0.8-5.8) than among referents. The trends observed in these data offer human evidence of alterations in male reproductive hormone levels associated with dioxin exposure. The results support the animal literature in which dioxin-related effects have been observed on the hypothalamic-pituitary-Leydig-cell axis and on testosterone synthesis.

Adult↗

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↗

Identification of soft tissue sarcoma deaths in cohorts exposed to dioxin and to chlorinated naphthalenes.

Identification of soft tissue sarcomas (STSs) in epidemiologic mortality studies is complicated by nosologic coding rules that require that STSs arising in a visceral organ must be coded in the International Classification of Diseases (ICD) category for that organ, rather than in the ICD category for malignant neoplasms of connective tissue. Moreover, prior studies have shown poor agreement between diagnoses recorded on death certificates compared with those in hospital records for these tumors. We reviewed deaths from STS among workers in a registry of 6,716 dioxin-exposed workers at the National Institute for Occupational Safety and Health (NIOSH) and in a NIOSH cohort mortality study of 10,240 workers exposed to chlorinated naphthalenes. We identified 19 subjects with STSs. Of these, 17 (89%) were identifiable by reading the entries on selected death certificates, and two (11%) were found only by reviewing medical records of cases coded to ICD categories likely to have contained STS. Of the 17 STSs identified from death certificates, only nine (53%) had been coded as underlying cause of death to the ICD category "malignant neoplasms of soft and connective tissue." Medical records were obtained for 14 of the 17 cases (82%), and in each case, the STS diagnosis was verified. Tissue blocks from tumors were available for review in nine of the 17 cases identified from death certificates, and the diagnosis of STS was verified in seven (78%). Nosologic rules reduce the sensitivity of cohort mortality studies to detect excesses of STS.(ABSTRACT TRUNCATED AT 250 WORDS)

Cause of Death↗

Mortality of workers employed in shoe manufacturing.

A retrospective cohort mortality study was conducted among 7814 white shoe manufacturing workers followed from 1940 through 1982. The workers were potentially exposed to solvents (including toluene) and solvent-based adhesives. Benzene may have been present as an impurity of toluene. Mortality due to leukemia and aleukemia was not statistically significantly elevated. Statistically significant excess mortality due to cancer of the trachea, bronchus and lung was observed in the total cohort [standardized mortality ratio (SMR) 147, 95% confidence interval (95% CI) 120-180] and showed a statistically significant trend in standardized relative risk with increasing potential latency, but not with increasing duration of employment. Chronic nonmalignant respiratory disease was significantly elevated among the men (SMR 158, 95% CI 114-217) but was less than expected among the women (SMR 79), a finding suggesting a possible contribution of smoking to the mortality from respiratory cancer. However, adjustment for the potential effects of smoking did not completely eliminate the increased risk for lung cancer.

Adult↗

Impact of polychlorinated dibenzo-p-dioxins, dibenzofurans, and biphenyls on human and environmental health, with special emphasis on application of the toxic equivalency factor concept.

A scientific evaluation was made of the mechanisms of action of polychlorinated dibenzo-p-dioxins, dibenzofurans and biphenyls. Distinction is made between the aryl-hydrocarbon (Ah) receptor-mediated and non-Ah receptor-mediated toxic responses. Special attention is paid to the applicability of the toxic equivalency factor (TEF) concept.

Animals↗

Colon and stomach cancer mortality among automotive wood model makers.

Automotive wood model makers have been reported to be at excess risk for colon and other cancers in recent epidemiologic studies. To further explore these risks, we conducted a retrospective cohort mortality study, with follow-up from 1940 through 1984, of 2294 white male wood model makers employed at any time until 1980 by three US auto makers. Using US mortality rates for comparison, we found elevated standardized mortality ratios of 1.2 (95% CI, 0.8-1.9) for colon cancer and 1.6 (95% CI, 0.9-2.6) for stomach cancer. We also conducted nested case-control studies for 20 colon and 17 stomach cancer cases and 543 age-matched controls. We found no trend of increased risk for colon or stomach cancer mortality with increased exposure to wood dust or to duration employed in wood model making.

Automobiles↗

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↗

Enhancing the quality of epidemiologic studies.

Three principles can improve epidemiologic studies (1) Conduct open scientific review of research protocols and final reports, (2) Disseminate study results to all appropriate parties, and (3) Incorporate new scientific methods into the research and utilize expertise from other disciplines. The procedures we describe are used within the Industrywide Studies Branch of the National Institute for Occupational Safety and Health to implement these principles.

Clinical Protocols↗

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↗

An evaluation of reports of dioxin exposure and soft tissue sarcoma pathology among chemical workers in the United States.

A review of employment records and tissue specimens of seven workers, reported previously as having occupational dioxin exposure and soft tissue sarcomas, confirms that four workers had employment of 2 to 19 years in the production of 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) or trichlorophenol, products contaminated with 2,3,7,8-tetrachlorodibenzodioxin, the most toxic dioxin isomer. Of these individuals, two have confirmed soft tissue sarcomas. In addition three individuals who worked for companies which made 2,4,5-T also have confirmed soft tissue sarcomas. Their employment records do not show specific assignment to 2,4,5-T or trichlorophenol departments; however, one individual worked for 10 d in the production of pentachlorophenol, which is contaminated with different isomers of dioxin. Methodological problems are discussed which must be addressed in the epidemiologic evaluation of the outcome of soft tissue sarcoma.

Chemical Industry↗