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11 Other Health Effects
Pages 672-720

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From page 672...
... The sections in this chapter of other health outcomes include chloracne, porphyria cutanea tarda, other metabolic and digestive disorders (diabetes mellitus, alterations in hepatic enzymes, lipid abnormalities, and gastrointestinal ulcers) , immune system disorders (immune modulation, autoimmunity)
From page 673...
... Doseresponse relationships between TCDD exposure and chloracne are addressed briefly. The inadequacies of chloracne as a human biomarker of dioxin
From page 674...
... Epidemiologic Studies of Chloracne Occupational Studies Several reports have detailed the mortality experience and incidence of chloracne among a group of 2,192 employees of Dow Chemical, Michigan Division, who were potentially exposed to TCDD through the manufacture of higher chlorinated phenols beginning in the 1930s (Cook et al., 1980; Bond et al., 1987; Bond et al., 1989a,b)
From page 675...
... 22 of 41 workers still had mild forms of chloracne at follow-up. Workers involved in the manufacture of 2,4,5-T were examined in a mortality study 20 to 30 years after the initial exposure (Suskind, 1985~.
From page 676...
... Numerous epidemiologic studies have analyzed population groups in the surrounding region to define the potential adverse health impact of this disaster. Potential exposure zones at Seveso were identified using TCDD levels in soil samples taken immediately after the accident (Bisanti et al., 1980~.
From page 677...
... Children developed chloracne more frequently than adults, but this was not related to serum TCDD levels. The authors concluded that there had been minimal, if any, adverse health effects of TCDD observed in this population to date, with the exception of chloracne; and that chloracne was an indicator, but neither a sensitive nor a dose related indicator of TCDD exposure.
From page 678...
... Attempts to document medical records or physical examination results more proximal to the Vietnam exposure period were not discussed. In a followup report on serum TCDD analysis of the 1987 examination results for the Air Force Ranch Hand study, no cases of chloracne were identified, and no dermatologic endpoints were consistently related to the current body burden of TCDD (AFHS, 1991 b)
From page 679...
... PORPHYRIA CUTANEA TARDA Porphyria cutanea tarda (PCT) is an uncommon disorder of porphyrin metabolism manifested in patients by thinning and blistering of the skin in sun-exposed areas, in addition to hyperpigmentation (excess pigment in skin)
From page 680...
... In addition, serum TCDD levels were not associated with uroporphyrin or coproporphyrin levels. However, careful urinary porphyrin studies were not conducted during the period of acute exposure.
From page 681...
... Vietnam Veterans Studies The baseline study of the U.S. Air Force Ranch Hands (1984)
From page 682...
... The epidemiologic evidence associating PCT and TCDD is sparse because PCT is rare and because of methodological problems. However, case studies and animal studies show that PCT may be associated with TCDD exposure in genetically predisposed individuals.
From page 683...
... OTHER METABOLIC AND DIGESTIVE DISORDERS Several other metabolic and digestive disorders (diabetes mellitus, hepatic enzymes, lipid abnormalities, and gastrointestinal ulcers) have been reported in the scientific literature as possibly associated with TCDD or herbicide exposure.
From page 684...
... A1though the correlation was statistically significant, the glucose values were not outside the normal range. An increased risk of diabetes was noted among Ranch Hands with the highest serum TCDD levels in reference to the comparison group.
From page 685...
... Summary for Diabetes Mellitus Limited information suggests the possibility of increased glucose intolerance and diabetes in chemical production workers and Ranch Hand veterans exposed to TCDD, but the data are inconclusive. Additional information on the pharmacokinetics of dioxin metabolism, particularly with regard to total body fat, is necessary in order to interpret epidemiologic studies indicating an association between TCDD exposure and serum glucose levels.
From page 686...
... The degree of severity of chloracne was positively correlated with soil concentrations of TCDD at the sampling point of each child's residence. A medical evaluation of 41 individuals exposed to TCDD-contaminated waste oils in Times Beach, Missouri, who had participated in a study of TCDD levels in adipose tissue found no association between adipose tissue TCDD levels and GGT levels or alterations in any other liver enzymes (Webbetal.,1989~.
From page 687...
... . Vietnam Veterans Studies Serum TCDD levels were found to be positively and significantly associated with elevated GOT levels in the 1991 Ranch Hand serum TCDD analysis (AFHS, 1991b)
From page 688...
... Epidemiologic Studies of Lipid Abnormalities Occupational and Environmental Studies Among Czechoslovakian TOP workers studied by Jirasek and colleagues (1974) , lipid metabolism was altered in more than 50 percent of the 55 individuals tested; the majority of individuals with altered lipid levels showed elevated serum triglyceride and cholesterol levels.
From page 689...
... Vietnam Veterans Studies In the follow-up of the Ranch Hand cohort reported in 1984 and 1987, no alterations in lipid values were recognized in the total group (AFHS, 1984; Wolfe et al., 1990~. However, the serum dioxin analyses of the 1987 follow-up examination data found that the ratios of cholesterol to HDL cholesterol and to triglycerides were both positively correlated with serum TCDD levels in the Ranch Hands (AFHS, l991b)
From page 690...
... A positive association was noted between serum TCDD levels and triglycerides among Ranch Hands. Further research on the pharmacokinetics of TCDD and its relation to percentage body fat will be important in understanding the significance of these associations.
From page 691...
... Vietnam Veterans Studies The serum TCDD analysis of the Ranch Hand Study did not find an increase in the risk of upper gastrointestinal ulcer in Vietnam veterans with elevated TCDD levels (AFHS, 199 lb)
From page 692...
... Increased Risk of Disease Among Vietnam Veterans Given the large uncertainties that remain about the magnitude of potential risk from exposure to herbicides in the occupational, environmental. and veterans studies that have been reviewed, inadequate control for important confounders in these studies, and the lack of information needed to extrapolate from the level of exposure in the studies reviewed to that of individual Vietnam veterans, it is not possible for the committee to quantify the degree of risk likely to have been experienced by Vietnam veterans because of their exposure to herbicides in Vietnam.
From page 693...
... Immune suppression can also occur in patients with autoimmune disease (discussed further below) ; for example, in systemic lupus erythematosus, the suppression of complement levels and leukocyte function has been noted.
From page 694...
... recovery from immune suppression related to TCDD exposure, or (3) the gathering of incorrect information in the initial test (Allison and Lewis, 1986~.
From page 695...
... The groupings of individuals were confirmed by measurements of serum TCDD levels, although the authors indicate that some outliers in the nonexposed group may have been exposed to base perimeter spraying. The skin response to recall antigens was uninterpretable due to energy in 4 of 17 controls and 0 of 10 exposed veterans.
From page 696...
... The study did not control for confounders such as smoking. Studies to date of individuals involved in Operation Ranch Hand, which include a records-based and serum TCDD measure of exposure, and specific tests for immune function, have not revealed any indication of overt immune suppression (Wolfe et al., 1985, 1990~.
From page 697...
... Epidemiologic Studies of Autoimmunity Occupational and Environmental Studies An assessment of immunological abnormalities among 18 workers involved in the manufacture of 2,4,5-T and exposed to TCDD during an industrial accident 17 years earlier, found no change in many of the immune parameters examined (Jennings et al., 1988~. However, an increase was
From page 698...
... Diabetes was increased in a population of the Ranch Hands (as discussed in the earlier section on diabetes) ; however it is unclear at this time if this is an autoimmune disease or adult-onset diabetes related to increased body fat.
From page 699...
... The studies that are reviewed here are divided into two categories-morbidity studies and mortality studies. In the morbidity studies, a variety of methods were used to assess the circulatory system, including assessing symptoms or history, performing physical examination of the heart and peripheral arteries, and assessing Doppler measurement of peripheral pulses, electrocardiogram results, and chest radiographs.
From page 700...
... These included the following: overall circulatory deaths among pesticide applicators (Blair, 1983~; ischemic heart disease among soil/forest conservation workers (Alavanja et al., 1989J; hypertensive and ischemic heart disease deaths among 2-methyl-4-chlorophenoxyacetic acid (MCPA) manufacturers/sprayers (Coggon et al., 1986~; and circulatory diseases among production workers of phenoxy herbicides and chlorophenols (Coggon et al., 1991~.
From page 701...
... from 1976 to 1981 and in the full tenyear follow-up period, 1976- 1986, (RR = 1.6, CI 1.2-2.1 ~ and an increase in hypertensive vascular disease deaths among females in the first five-year period (RR = 2.4, CI 1.4-4.31. These studies are limited for the purpose of assessing relationships between circulatory deaths and TCDD exposure.
From page 702...
... , there were no significant differences in proportionate mortality ratios for circulatory diseases. A proportionate mortality study comparing Wisconsin Vietnam veterans with Wisconsin Vietnam era veterans (Anderson et al., 1986)
From page 703...
... Among nonherbicide handlers, the level of Agent Orange exposure, based on a score derived from self-reported service locations and military records of spraying locations, and the level of combat experience, were not significantly associated with heart disease. For the self-reported variable of physician-diagnosed hypertension, Vietnam veterans did not differ from Vietnam era veterans.
From page 704...
... They further state that this increase is of concern because Ranch Hand nonflying enlisted personnel have higher current TCDD levels than Ranch Hands in other categories. In addition, they state that current and extrapolated initial TCDD levels were shown to be significantly associated with diabetes and increased cholesterol, HDL cholesterol, and triglyceride abnormalities.
From page 705...
... There were significant increases in risk of essential hypertension and adjusted mean systolic and diastolic blood pressures in Ranch Hands with high current TCDD levels (>33 ppt) compared to comparison subjects in the background category (<10 ppt)
From page 706...
... Possible independent risk factors for coronary artery disease, including cigarette smoking, diabetes, lipid abnormalities, and hypertension were generally not assessed in the mortality studies. The AFHS mortality study (1991a)
From page 707...
... . With regard to other abnormalities on physical examination, the AFHS reported no significant differences between Ranch Hands and the comparison group in heart sounds, marginally higher frequencies of carotid bruits, and significant or marginally more significant differences in peripheral pulses (AFHS, 19901.
From page 708...
... and the following circulatory outcomes: circulatory disease mortality and various subgroups of cardiovascular disease; symptoms or history of circulatory illnesses such as heart disease, hypertension, coronary artery disease, angina, or myocardial infarction; abnormalities on physical examination, electrocardiogram results, and chest radiographs. Biologic Plausibility Limited information from animal studies is available on the potential association between circulatory diseases and exposure to TCDD or the herbicides.
From page 709...
... Studies that are available have focused on enzyme induction, primarily cytochrome P450 in lung tissue (see Chapter 4~. Epidemiologic Studies of Respiratory Disorders Occupational Studies The occupational studies assessing respiratory outcomes can also be divided into mortality and morbidity studies.
From page 710...
... Marine Vietnam era veterans and all Vietnam era veterans. In another proportionate mortality study comparing Wisconsin Vietnam veterans with Wisconsin Vietnam era veterans, the authors reported an increase in PMR among Vietnam veterans due to pneumonia (Anderson et al., 1986~.
From page 711...
... That study is of limited use in evaluating respiratory mortality primarily because of the small number of observed deaths. The latest Ranch Hand pulmonary assessment, examined the following parameters: questionnaire data on the presence of five reported respiratory illnesses asthma, bronchitis, pleurisy, pneumonia, and tuberculosis; physical examination data on asymmetric expansion, hyperresonance, dullness, wheezes, rates, and a composite including all the others; chest x-rays read as normal or abnormal; and pulmonary function test results including FVC, FEVER, FEV~/FVC ratio, and FEFmaX (AFHS, 1990, l991b)
From page 712...
... Models assessing current serum TCDD levels and adjusted for covariates also showed these significant associations. The authors suggested that differences in mean spirometric indices were not clinically significant and might be due in part to associations between body fat and serum TCDD levels.
From page 713...
... (2,4-D; 2,4,5-T and its contaminant TCDD; cacodylic acid; and picloram) and the following respiratory outcomes: mortality from respiratory diseases; symptoms or history of respiratory illnesses such as chronic bronchitis, bronchitis, asthma, pleurisy, pneumonia, tuberculosis, and respiratory conditions; abnormalities on lung or thorax physical examination; pulmonary function test results; and chest radiographs.
From page 714...
... A Review of the Scientific Literature. Agent Orange Scientific Task Force Working with the American Legion, Vietnam Veterans of America, and the National Veterans Legal Services Project.
From page 715...
... 1989a. Follow-up of subjects who developed chloracne following TCDD exposure at Seveso.
From page 716...
... 1992b. Evaluation of porphyria cutanea tarda and porphyrinuria in dioxin-exposed workers.
From page 717...
... 1986. Porphyria cutanea tarda: diagnosis, management, and differentiation from other hepatic porphyrias.
From page 718...
... 1984. Immunologic effects of TCDD exposure in humans.
From page 719...
... Report of the Agent Orange Advisory Committee to the Texas Department of Health. University of Texas System Cancer Center.
From page 720...
... 1985. Iowa Agent Orange Survey of Vietnam Veterans.


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