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Biomedical subjects

A C Pesatori

Publications and source records attributed to A C Pesatori.

At least 19 recordsLinked to original sources

Health status and plasma dioxin levels in chloracne cases 20 years after the Seveso, Italy accident.

BACKGROUND: The Seveso, Italy accident of 1976 exposed a large population to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD or simply dioxin). The accident resulted, mostly among children, in one of the largest ever-reported outbreaks of chloracne, the typical skin disorder due to halogenated-hydrocarbon compounds. OBJECTIVES: Approximately 20 years after the accident, we conducted an epidemiological study in Seveso to investigate (a) the health status of chloracne cases; (b) TCDD-chloracne exposure-response relationship; and (c) factors modifying TCDD toxicity. METHODS: From 1993 to 1998, we recruited 101 chloracne cases and 211 controls. Trained interviewers administered a structured questionnaire assessing, among other epidemiological variables, information on an extensive list of diseases. During the interview, individual pigmentary characteristics were determined. We measured plasma TCDD levels using high-resolution gas chromatography/mass spectrometry. RESULTS: Plasma TCDD was still elevated (> 10 ppt) in 78 (26.6%) of the 293 subjects with adequate plasma samples, particularly in females, in subjects who had eaten home-grown animals, and in individuals with older age, higher body mass index and residence near the accident site. After 20 years, health conditions of chloracne cases were similar to those of controls from the Seveso area. Elevated plasma TCDD was associated with chloracne [odds ratio (OR) = 3.7, 95% confidence interval (CI) 1.6-8.8, adjusted for age, sex and residence]. Chloracne risk was higher in subjects younger than 8 years at the accident (OR = 7.4, 95% CI 1.8-30.3) and, contrary to previous hypotheses, did not increase at puberty onset or in teenage years. Subjects with elevated TCDD levels and light hair colour had higher relative odds of chloracne (OR = 9.2, 95% CI 2.6-32.5). CONCLUSIONS: Dioxin toxicity in chloracne cases was confined to the acute dermatotoxic effects. Chloracne occurrence appeared related to younger age and light hair colour. Age-related dioxin elimination or dilution must be taken into account in interpreting these results.

Accidents, Occupational↗

Health effects of dioxin exposure: a 20-year mortality study.

Follow-up of the population exposed to dioxin after the 1976 accident in Seveso, Italy, was extended to 1996. During the entire observation period, all-cause and all-cancer mortality did not increase. Fifteen years after the accident, mortality among men in high-exposure zones A (804 inhabitants) and B (5,941 inhabitants) increased from all cancers (rate ratio (RR) = 1.3, 95% confidence interval (CI): 1.0, 1.7), rectal cancer (RR = 2.4, 95% CI: 1.2, 4.6), and lung cancer (RR = 1.3, 95% CI: 1.0, 1.7), with no latency-related pattern for rectal or lung cancer. An excess of lymphohemopoietic neoplasms was found in both genders (RR = 1.7, 95% CI: 1.2, 2.5). Hodgkin's disease risk was elevated in the first 10-year observation period (RR = 4.9, 95% CI: 1.5, 16.4), whereas the highest increase for non-Hodgkin's lymphoma (RR = 2.8, 95% CI: 1.1, 7.0) and myeloid leukemia (RR = 3.8, 95% CI: 1.2, 12.5) occurred after 15 years. No soft tissue sarcoma cases were found in these zones (0.8 expected). An overall increase in diabetes was reported, notably among women (RR = 2.4, 95% CI: 1.2, 4.6). Chronic circulatory and respiratory diseases were moderately increased, suggesting a link with accident-related stressors and chemical exposure. Results support evaluation of dioxin as carcinogenic to humans and corroborate the hypotheses of its association with other health outcomes, including cardiovascular- and endocrine-related effects.

Adult↗

Occupational and environmental agents as endocrine disruptors: experimental and human evidence.

In the last few years great concern has arisen from the description of adverse endocrine effects of several occupational and environmental chemical agents on human and/or wildlife health. Such agents may exert their effects directly, specifically binding to hormone receptors, and/or indirectly, by altering the structure of endocrine glands and/or synthesis, release, transport, metabolism or action of endogenous hormones. Many studies have been focused on the outcomes of the exposure to those chemicals mimicking estrogenic or androgenic actions. Nonetheless, the disruption of other hormonal pathways is not negligible. This paper reviews the experimental and human evidence of the effects of occupational and environmental chemical agents on hypothalamus-pituitary unit, pineal gland, parathyroid and calcium metabolism and adrenal glands.

Adrenal Glands↗

Gender differences in the healthy worker effect among synthetic vitreous fiber workers.

The aim of this study was to determine whether the healthy worker effect and its component parts operate similarly for women and men. A cohort of workers from 14 synthetic vitreous fiber factories in seven countries, employed for at least 1 year between 1933 and 1977 and followed up to the early 1990s, included 375 deaths and 53,608 person-years among females and 2,568 deaths and 210,073 person-years among males. Standardized mortality ratios for all-cause and circulatory diseases were adjusted for country, age, calendar time, and gender. In addition, internal comparisons were adjusted for time since hire and employment status. The analyses addressed the following: 1) the healthy hire effect, 2) the time since hire effect, and 3) the healthy worker survivor effect. In this cohort, an overall healthy worker effect was not present in either gender. The healthy hire effect, based on standardized mortality ratios for years 1-4 since hire, was observed in males (standardized mortality ratio (SMR) = 0.8; 95% confidence interval (CI): 0.7, 1.0) but was less in females (SMR = 0.9; 95% CI: 0.5, 1.6). The relative risks increased slightly with time since hire in males but not in females. Higher mortality ratios were seen among those leaving employment than among those who remained actively employed; however, this effect was substantially greater for women (relative risk (RR) = 3.4; 95% CI: 1.8, 6.3) than men (RR = 1.8; 95% CI: 1.5, 2.1). The gender difference for active versus inactive status was stronger up to age 60 (men: RR = 1.7; 95% CI: 1.4, 2.0; women: RR = 3.6; 95% CI: 1.8, 7.1) than above that age. In conclusion, it appears that there is a stronger selection of healthy men than women into the workforce, while health-related selection out of the workforce is stronger for women than men.

Adult↗

Mortality study in an Italian oil refinery: extension of the follow-up.

This article present the results of the extension of the follow-up of a cohort of workers employed in an Italian oil refinery. 1,583 workers employed in 1949-1982 in a northern Italy oil refinery plant were followed-up for mortality as of May 31, 1991. Environmental measurements documented potential exposure to benzene. Standardized mortality ratios (SMR) and their 95% confidence intervals (95% CI) were calculated using as references national (1949-1968) and regional mortality rates (1969-1991). Elevated mortality from lymphoma (seven deaths, SMR 190, 95% CI 76-391) and leukemia (eight deaths, SMR 225, 95% CI 97-443) was observed. No consistent trends by length of employment or time since first exposure were apparent. Nonetheless, the excess risk was particularly and significantly increased among workers with 15 or more years of employment, and 30 or more years since first employment. The findings of elevated mortality from leukemia and lymphoma are in agreement with those of other oil refinery studies. Chance, confounding, or other biases might have played a marginal, if any, role in determining the results. Exposure to benzene is a biologically plausible explanation.

Carcinogens↗

Non-neoplastic mortality of European workers who produce man made vitreous fibres.

OBJECTIVE: To study mortality from non-neoplastic diseases among European workers who produce man made vitreous fibres (MMVF). METHODS: 11,373 male workers were studied, who were employed for at least 1 year in the production of rock or slag wool (RSW), glass wool (GW), and continuous filament (CF) in 13 factories from seven European countries. Workers were followed up from the beginning of production, between 1933 and 1950 to 1990-2 and contributed 256,352 person-years of observation. Standardised mortality ratios (SMRs) were calculated with national mortalities for reference; an internal exposure-response analyses based on multivariate Poisson regression models was also conducted. RESULTS: Mortality from bronchitis, emphysema, and asthma was not increased (SMR 1.03, 95% confidence interval (95% CI) 0.82 to 1.28). In RSW workers, there was no overall increase in mortality from non-malignant renal diseases (SMR 0.97, 95% CI 0.36 to 2.11), although there was the suggestion of an increase in risk with duration of employment. Mortality from ischaemic heart disease was not increased overall (SMR 1.03, 95% CI 0.96 to 1.11), but RSW and CF workers with > or = 30 years since first employment had a higher risk. RSW and CF workers showed an increased mortality from external causes, mainly motor vehicle accidents and suicide, which was higher among workers with a short duration of employment. CONCLUSIONS: Mortality from most non-neoplastic diseases does not seem to be related to employment in the MMVF industry. The results on mortality from ischaemic heart disease and non-malignant renal diseases, however, warrant further investigations.

Cause of Death↗

Mortality of short-term workers in two international cohorts.

The purpose of this study was to compare the pattern of mortality of blue-collar workers employed less and more than 1 year in the man-made vitreous fiber (MMVF) and the reinforced plastic industries, the latter group being exposed to styrene. We conducted an analysis among 21,784 workers with less than 1 year of employment (short-term workers) and 19,117 workers with 1 or more years of employment (long-term workers) employed in eight European countries. We conducted analyses based on external as well as internal comparisons. In both cohorts, the standardized mortality ratio for all causes among short-term workers was approximately 40% higher, compared with that for longer-term workers. In internal comparisons, the difference was reduced to 9% in the MMVF cohort and 11% in the styrene cohort. Workers with less than 1 month of employment displayed an increased mortality in both cohorts and in most countries. The increased mortality among short-term workers was not concentrated shortly after they quit employment. In both cohorts, short-term workers had a higher mortality from external causes, while little difference was seen in mortality from ischemic heart disease and malignant neoplasms. Although extra-occupational factors may contribute to increase the mortality of short-term workers and, in particular, of those employed for less than 1 month, the difference observed in analyses adjusted for characteristics of employment suggested a relatively small difference in mortality from most causes.

Adult↗

Dioxin exposure and non-malignant health effects: a mortality study.

OBJECTIVE: To investigate, in a population heavily exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), the possible unusual occurrence of diseases other than cancer. METHODS: Five year extension of the follow up of the cohort involved in the Seveso accident. Soil measurements identified three exposure zones: (A) highest contamination, (B) substantial, and (R) low but higher than background contamination. Blood TCDD measurements, although limited in number, confirmed zone exposure ranking. The 15 year mortality in the exposed cohort was compared with that of a large population in the surrounding non-contaminated territory. Relative risks (RRs) and 95% confidence intervals (95% CIs) were estimated with Poisson regression techniques. RESULTS: The already noted increased occurrence of cardiovascular deaths was confirmed, in particular in zone A, among males for chronic ischaemic heart disease (five deaths, RR 3.0, 95% CI 1.2 to 7.3), and among females for hypertensive disease (three deaths, RR 3.6, 95% CI 1.2 to 11.4) and chronic rheumatic heart disease. Novel findings were the increase of chronic obstructive pulmonary disease, most notably among males in zone A (four deaths, RR 3.7, 95% CI 1.4 to 9.9) and females in zone B (seven deaths, RR 2.4, 95% CI 1.1 to 5.1); and from diabetes, which was significantly increased in females in zone B (13 deaths, RR 1.9, 95% CI 1.1 to 3.2). In zone R, chronic ischaemic heart disease (males and females), hypertension (females), and diabetes (females) showed less pronounced, although significant excesses. CONCLUSIONS: As well as high TCDD exposure, the accident caused a severe burden of strain in the population. Both these factors might have contributed to the noted increased risks (in particular, circulatory and respiratory). The cardiovascular and immune toxicity of TCDD, as well as its complex interaction with the endocrine system, might be relevant to the explanations of these findings. These results, although not conclusive, concur with previous data in suggesting cardiopulmonary and endocrine effects in humans highly exposed to TCDD.

Accidents, Occupational↗

2,3,7,8-Tetrachlorodibenzo-p-dioxin plasma levels in Seveso 20 years after the accident.

In 1976, near Seveso, Italy, an industrial accident caused the release of large quantities of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) into the atmosphere, resulting in the highest levels of the toxicant ever recorded in humans. The contaminated area was divided into three zones (A, B, R) corresponding to decreasing TCDD levels in soil, and cohort including all residents was enumerated. The population of the surrounding noncontaminated area (non-ABR) was chosen as referent population. Two decades after the accident. plasma TCDD levels were measured in 62 subjects randomly sampled from the highest exposed zones (A and B) and 59 subjects from non-ABR, frequency matched for age, gender, and cigarette smoking status. Subjects living in the exposed areas have persistently elevated plasma TCDD levels (range = 1.2-89.9 ppt; geometric mean = 53.2 and 11.0 ppt for Zone A and Zone B, respectively). Levels significantly decrease by distance from the accident site (p = 0.0001), down to general population values (4.9 ppt) in non-ABR, thus validating the original zone classification based on environmental measurements. Women have higher TCDD levels than men in the entire study area (p = 0.0003 in Zone B; p = 0.007 in non-ABR). This gender difference persists after adjustment for location within the zone, consumption of meat derived from locally raised animals, age, body mass index, and smoking. There is no evidence for a gender difference in exposure, so variation in metabolism or elimination due to body fat or hormone-related factors may explain this finding. Elevated TCDD levels in women may contribute to adverse reproductive, developmental, and cancer outcomes.

Accidents, Occupational↗

The Seveso studies on early and long-term effects of dioxin exposure: a review.

The industrial accident that occurred in the town of Seveso, Italy, in 1976 exposed a large population to substantial amounts of relatively pure 2,3,7,8-tetrachlorodibenzo-p-dioxin. Extensive monitoring of soil levels and measurements of a limited number of human blood samples allowed classification of the exposed population into three categories, A (highest exposure), B (median exposure), and R (lowest exposure). Early health investigations including liver function, immune function, neurologic impairment, and reproductive effects yielded inconclusive results. Chloracne (nearly 200 cases with a definite exposure dependence) was the only effect established with certainty. Long-term studies were conducted using the large population living in the surrounding noncontaminated territory as reference. An excess mortality from cardiovascular and respiratory diseases was uncovered, possibly related to the psychosocial consequences of the accident in addition to the chemical contamination. An excess of diabetes cases was also found. Results of cancer incidence and mortality follow-up showed an increased occurrence of cancer of the gastrointestinal sites and of the lymphatic and hematopoietic tissue. Experimental and epidemiologic data as well as mechanistic knowledge support the hypothesis that the observed cancer excesses are associated with dioxin exposure. Results cannot be viewed as conclusive. The study is continuing in an attempt to overcome the existing limitations (few individual exposure data, short latency period, and small population size for certain cancer types) and to explore new research paths (e.g., differences in individual susceptibility).

Adolescent↗

Exposure to dioxin and nonneoplastic mortality in the expanded IARC international cohort study of phenoxy herbicide and chlorophenol production workers and sprayers.

The authors studied noncancer mortality among phenoxyacid herbicide and chlorophenol production workers and sprayers included in an international study comprising 36 cohorts from 12 countries followed from 1939 to 1992. Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin or higher chlorinated dioxins (TCDD/HCD) was discerned from job records and company questionnaires with validation by biologic and environmental measures. Standard mortality ratio analyses suggested a moderate healthy worker effect for all circulatory diseases, especially ischemic heart disease, among both those exposed and those not exposed to TCDD/HCD. In Poisson regression analyses, exposure to TCDD/HCD was not associated with increased mortality from cerebrovascular disease. However, an increased risk for circulatory disease, especially ischemic heart disease (rate ratio [RR] 1.67, 95% confidence interval [Cl] 1.23-2.26) and possibly diabetes (RR 2.25, 95% Cl 0.53-9.50), was present among TCDD/HCD-exposed workers. Risks tended to be higher 10 to 19 years after first exposure and for those exposed for a duration of 10 to 19 years. Mortality from suicide was comparable to that for the general population for all workers exposed to herbicides or chlorophenols and was associated with short latency and duration of exposure. More refined investigations of the ischemic heart disease and TCDD/HCD exposure association are warranted.

Adult↗

Dioxin exposure and cancer risk: a 15-year mortality study after the "Seveso accident".

Dioxin (2,3,7,8-tetrachlorodibenzo-para-dioxin, or TCDD) is a powerful carcinogen in experimental animals, whereas the evidence in humans is limited. We examined cancer mortality from 1976 to 1991 among residents of Seveso, Italy, which was highly contaminated after an industrial accident. The area was divided into zones with decreasing exposure to dioxin (A = highest, B = lower, R = lowest). The population of a surrounding noncontaminated area was used as a reference group. Zone A was small (11,516 person-years); in that zone, we saw a moderate increase in mortality from digestive cancer among women [relative risk (RR) = 1.5; 95% confidence interval (CI) = 0.5-3.5]. In zone B, we also saw excesses at digestive sites (83,610 person-years), 10 years after the accident. Women had an increased mortality from stomach cancer (RR = 2.4; 95% CI = 0.8-5.7), and men had increased mortality from rectal cancer (RR = 6.2; 95% CI = 1.7-15.9). Hematologic neoplasms were increased. The highest risks were seen in zone B for leukemia in men (RR = 3.1; 95% CI = 1.3-6.4), multiple myeloma in women (RR = 6.6; 95% CI = 1.8-16.8), and Hodgkin's disease in both genders (RR = 3.3; 95% CI = 0.4-11.9 in men; and RR = 6.5; 95% CI = 0.7-23.5 in women). Soft tissue sarcoma was elevated only among zone R males (256,408 person-years; RR = 2.1; 95% CI = 0.6-5.4). We found no increase for all-cancer mortality or major specific sites (for example, respiratory among males, breast among females). The specific excesses that we observed were not explained by bias or confounding, and their association with dioxin exposure is plausible. The follow-up is continuing.

Accidents↗

Cohort mortality and nested case-control study of lung cancer among structural pest control workers in Florida (United States).

A previous report on the mortality of this cohort of Florida (United States) pest control workers found the risk of lung cancer was positively associated with the number of years licensed. An additional follow-up (1977-82) of this male cohort confirmed the excess (SMR = 1.4) and the rising risk with increasing number of years licensed (SMR = 2.2 among workers employed more than 20 years). A nested case-control study was undertaken to determine the effects of smoking and the type of pesticide exposure on lung cancer risk. Occupational histories and other data were obtained on 65 deceased lung cancer cases, 122 deceased controls, and 172 living controls. Interviews were conducted with next-of-kin regardless of the vital status of the subject. Odds ratios (OR) were adjusted by age and smoking. Adjustments for diet and other occupations had no effect on risk estimates and were not included in the final model. Using information from licensing records, ORs for lung cancer were greater for workers first licensed before age 40 (OR = 2.4, 95 percent confidence interval [CI] = 1.0-5.9 with deceased controls) and increased from 1.4 (CI = 0.7-3.0) for subjects licensed 10-19 years to 2.1 (CI = 0.8-5.5) for subjects licensed 20 or more years. Using living controls, an association with duration of employment was observed when years of licensure were lagged five years, but was not observed in unlagged analyses. Using information from the questionnaire, the risk of lung cancer was greater among those who worked as pest control operators than non-pest control workers.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Cancer in a young population in a dioxin-contaminated area.

An industrial accident in Seveso, Italy, in 1976, caused contamination of the residential community with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). We investigated cancer occurrence in the first post-accident decade (1977-1986) among nearly 20,000 subjects aged 0-19 years. People who left the area were actively followed with a 99% follow-up rate. For reported cancer cases confirmation was obtained through consultation with original medical records. Two ovarian cancers were observed versus none expected. A suggestive increase was seen for Hodgkin's lymphoma (relative risk [RR] = 2.0; 95% confidence interval [CI] = 0.5-7.6). Myeloid leukaemia showed a clear, but not statistically significant increase (RR = 2.7; 95% CI = 0.7-11.4). The most prominent result concerned thyroid cancer, not just for the magnitude of the increase (two cases, RR = 4.6; 95% CI = 0.6-32.7), but also for its consistency with experimental findings and previous observations in humans. Any conclusive interpretation would be premature because of the short time since initial exposure, ecological definition of exposure status, and limited number of events.

Adolescent↗

Cancer incidence in a population accidentally exposed to 2,3,7,8-tetrachlorodibenzo-para-dioxin.

In 1976, an accident in a plant near Seveso, Italy, exposed the local population to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Persons residing in three zones of decreasing TCDD contamination (A, B, and R) and a reference population were followed up for cancer occurrence in 1977-1986. The most exposed subgroup (A) was small, and only 14 cancer cases were observed. In zone B, hepatobiliary cancer was elevated, especially for those living in the area for > 5 years [relative risk (RR) = 2.8; 95% confidence interval (CI) = 1.2-6.3]. Men exhibited an increase in hematologic neoplasms, most notably lymphoreticulosarcoma (RR = 5.7; 95% CI = 1.7-19.0). Women experienced an increased incidence of multiple myeloma (RR = 5.3; 95% CI = 1.2-22.6) and myeloid leukemia (RR = 3.7; 95% CI = 0.9-15.7). In zone R, the incidence of soft tissue tumors and non-Hodgkin's lymphomas was elevated, particularly among persons living in the area for > 5 years (RR = 3.5; 95% CI = 1.2-10.4 for sarcomas, and RR = 2.0; 95% CI = 1.2-3.6 for non-Hodgkin's lymphomas). Breast cancer among females was below expectations in the most contaminated zones, and a clear deficit for endometrial cancer was observed in zones B and R.

Adult↗

Mortality of a young population after accidental exposure to 2,3,7,8-tetrachlorodibenzodioxin.

The mortality experience of 19,637 people aged 1-19 years living in an area around Seveso, Italy, contaminated by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) after an accidental explosion in a chemical plant was examined for the period 1976-1986. For comparison, the mortality of the population of nearly 100,000 people living in the surrounding districts was examined. People who left the study area were followed up. Vital status ascertainment was successful in over 99% of the cases. A group of 186 children who contracted chloracne, a reversible marker of TCDD intoxication, shortly after the accident were in the study: none of them died during the observation period. Among the exposed, mortality owing to all causes, to all accidents and to all cancers failed to show major departure from expectations. Five leukaemia deaths were observed, four among males and one among females; the corresponding relative risks were 2.1 (95% confidence interval (CI): 0.7-6.9), and 2.5 (95% CI: 0.2-27.0), respectively. Two lymphatic leukaemias among males yielded a RR = 9.6 (95% CI: 0.9-106.0). Mortality owing to congenital anomalies showed a nearly twofold increase in the contaminated area; however, five out of seven observed cases were born before the accident. Interpretation is limited by the small number of deaths, short latency period and low validity of death certificate information for certain causes, and by the definition of exposure which was based merely on residence. The follow-up is continuing. A cancer morbidity study is in progress.

Adolescent↗