Veterans and Agent Orange Update 2008 (2009) / Chapter Skim
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9 Other Health Effects
9 Other Health Effects
Pages 546-650
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From page 546... ...
For each type of health outcome, background information is followed by a brief summary of the findings described in earlier reports by the Institute of Medicine (IOM) Committee to Review the Health Effects in Vietnam Veterans of Exposure to Herbicides.
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From page 547... ...
. If chloracne occurs, it appears shortly after the chemical exposure, not after a long latent period; therefore, new cases of chloracne among Vietnam veterans would not be the result of exposure during the Vietnam War.
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From page 548... ...
Recent work with a constitutively activated form of the aryl hydrocarbon receptor (AHR) implicated additional inflammation-related mechanisms by which TCDD exposure may lead to chloracne (Tauchi et al., 2005)
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From page 549... ...
Conclusion On the basis of numerous epidemiologic studies of occupationally and environmentally exposed populations and supportive toxicologic information, previous VAO committees have consistently concluded that there is sufficient evidence of an association between exposure to at least one chemical of interest and chloracne. Because TCDD-associated chloracne becomes evident shortly after exposure, there is no risk of new cases long after service in Vietnam.
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From page 550... ...
showed no difference in uroporphyrin or coproporphyrin concentrations in urine between Ranch Hands and controls. There were no indications of the clinical appearance of PCT in Ranch Hands.
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From page 551... ...
. Synthesis No epidemiologic data have emerged in the last decade that refute the conclusion of previous VAO committees that there is limited or suggestive evidence of an association between the chemicals of interest and PCT.
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From page 552... ...
Because Vietnam veterans received health screenings before entering military service, few severe hereditary chronic lung disorders are expected in that population. The most important risk factor for many nonmalignant respiratory disorders is inhalation of cigarette smoke.
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From page 553... ...
. In contrast, in the US Army Chemical Corps cohort of Vietnam veterans, Kang et al.
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From page 554... ...
Update of the Epidemiologic Literature Vietnam-Veteran Studies Since Update 2006, there have been no publications concerning nonmalignant respiratory outcomes in Vietnam veterans. Occupational Studies The continuing AHS has generated several new publications concerning respiratory health problems.
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From page 555... ...
Sprayed herbicides in Vietnam vs never 140 1.6 (1.3–2.1) ADVA, Third Australian Vietnam Veterans Mortality Study 2005b Deployed veterans vs Australian population All branches Respiratory system diseases 239 0.8 (0.7–0.9)
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From page 556... ...
Watanabe Mortality of US Vietnam veterans who died et al., 1996; during 1965–1988, PMR analysis of nonmalignant respiratory mortality (ICD 8 460–519)
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From page 557... ...
Spouses exposed to phenoxy herbicides 16 1.4 (0.7–2.7) Hoppin US AHS -- prevalence at enrollment of chronic et al., 2007b bronchitis in private applicators exposed to: 2,4-D 78 1.1 (0.9–1.4)
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From page 558... ...
Pneumonia 4 0.6 (0.2–1.4) Studies Reviewed in Update 2000 Steenland NIOSH mortality study of chemical workers at et al., 1999 12 plants in US exposed to TCDD, nonmalignant respiratory mortality (ICD-9 460–519)
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From page 559... ...
Zober et al., German workers exposed to trichlorophenol Illness episodes 1994 contaminated with TCDD from an accident at per 100 BASF plant, 1953–1989; exposed vs unexposed person-years workers -- prevalence (cohort/reference) nonmalignant respiratory diseases (ICD-9 All nr 33.7/31.0 460–51)
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From page 560... ...
nr 8.0/7.5 (p = 0.31) Studies Reviewed in VAO Coggon Production of phenoxy herbicides, chlorophenols et al., 1991 in four British plants, mortality from nonmalignant respiratory diseases, 1963–1985 8 0.7 (0.3–1.3)
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From page 561... ...
Children nr -3.8 (p < 0.05) Studies Reviewed in Update 2000 Bertazzi 20-year follow-up of Seveso residents -- mortality et al., 2001 from respiratory disease (ICD-9 460–519)
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From page 562... ...
ABBREVIATIONS: 2,4-D, 2,4-dichlorophenoxyacetic acid; 2,4,5-T, 2,4,5-trichlorophenoxyacetic acid; 2,4,5-TP, 2-(2,4,5-trichlorophenoxy) propionic acid; AFHS, Air Force Health Study; AHS, Agricultural Health Study; CI, confidence interval; COPD, chronic obstructive pulmonary disease; FEF25–75, forced midexpiratory flow; FEV1, forced expiratory volume in 1 second; FVC, forced vital capacity; ICD-8, International Classification of Diseases, 8th revision; ICD-9, International Classification of Diseases, 9th revision; MCPA, 2-methyl-4-chlorophenoxyacetic acid; NIOSH, National Institute for Occupational Safety and Health; nr, not reported; PCDD, polychlorinated dibenzo-pd ioxin; PCP, pentachlorophenol; PMR, proportionate mortality ratio; SMR, standardized mortality ratio; TCDD, 2,3,7,8-tetrachlorodibenzo-p-dioxin; USDA, US Department of Agriculture.
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From page 563... ...
. Biologic Plausibility Acute nonmalignant respiratory disorders, including pneumonia and other respiratory infections, can be increased in frequency and severity when the normal defense mechanisms of the lower respiratory tract are compromised.
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From page 564... ...
Synthesis Results of the studies of mortality from nonmalignant respiratory diseases reported in Update 2006 and earlier VAO reports (ADVA, 2005b,c; Anderson et al., 1986; Becher et al., 1996; Blair et al., 1983, 2005; Bullman and Kang,
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From page 565... ...
. A 4-fold excess prevalence in chronic bronchitis and emphysema was found in a health-status study of Australian army Vietnam veterans (O'Toole et al., 1996)
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From page 566... ...
, and no conclusions can be drawn. Conclusion On the basis of the evidence reviewed here and in previous VAO reports, the committee concludes that there is inadequate or insufficient evidence of an association between exposure to the chemicals of interest and mortality from all nonmalignant respiratory diseases or the prevalence of wheeze or asthma, COPD, and farmer's lung.
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From page 567... ...
Such confounders include age, vaccination status, the virulence of the pathogen, the presence of other diseases (such as diabetes) , stress, smoking, and the use of drugs or alcohol.
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From page 568... ...
(2004) that found no excess in postservice mortality in male US Army Vietnam veterans related to endocrine, nutritional, and metabolic diseases or to immune disorders and concurred with the conclusion of the previous review committees.
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From page 569... ...
(2007a) investigated the concentrations of persistent organic pollutants in adipose tissue of 1,721 adults in the 1999–2002 National Health and Nutrition Examination Survey (NHANES)
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From page 570... ...
(2004) found no increase in deaths of Vietnam veterans that could be attributed to immune-system disorders.
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From page 571... ...
Few effects of phenoxy herbicide or cacodylic acid exposure on the immune system have been reported in animals or humans, and no clear association between such exposure and autoimmune or allergic disease has been found. Conclusion On the basis of the evidence reviewed here and in previous VAO reports, the committee concludes that there is inadequate or insufficient evidence to determine whether there is an association between exposure to the chemicals of interest and immune suppression, allergy, or autoimmune disease.
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From page 572... ...
nr nr Total cholesterol ≥ 240 mg/dL 13.8 17.3 nr nr LDL cholesterol ≥ 130 mg/dL 33.8 31.7 nr nr HDL cholesterol < 40 mg/dL 24.9 6.7 nr nr 390–459 All circulatory disorders 37.6 34.9 409,900 454,600 390–398 Rheumatic fever and rheumatic heart disease nr nr 1,022 2,226 401–404b Hypertensive disease 24,000 33,300 401 Essential hypertension nr nr nr nr 402 Hypertensive heart disease nr nr nr nr 403 Hypertensive renal disease nr nr nr nr 404 Hypertensive heart and renal disease nr nr nr nr 410–414, 429.2 Ischemic, coronary heart disease 8.6 6.8 232,100 213,600 410, 412 Acute, old myocardial infarction 4.7 2.7 80,100 70,900 411 Other acute, subacute forms of ischemic heart disease nr nr nr nr 413 Angina pectoris 4.3 4.5 nr nr 414 Other forms of chronic ischemic heart disease nr nr nr nr 429.2 Cardiovascular disease, unspecified 8.6 6.8 232,100 213,600 415–417b Diseases of pulmonary circulation nr nr nr nr 420–429 Other forms of heart disease (such as pericarditis, endocarditis, myocarditis, cardiomyopathy) nr nr nr nr 426–427 Arrhythmias nr nr nr nr 428 Heart failure 3.2 2.0 126,200 166,100 430–438b Cerebrovascular disease (such as hemorrhage, occlusion, transient cerebral ischemia; includes mention of hypertension in ICD-401)
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From page 573... ...
In 1999, in response to a request from the Department of Veterans Affairs, IOM called together a committee to conduct an interim review of the scientific evidence regarding type 2 diabetes. That review focused on information published after the deliberations of the Update 1998 committee and resulted in the report Veterans and Agent Orange: Herbicide/Dioxin Exposure and Type 2 Diabetes, hereafter referred to as Type 2 Diabetes (IOM, 2000)
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From page 574... ...
. The study population included military personnel who were part of Operation Ranch Hand, did not have a diagnosis of diabetes before the end of their service in Vietnam, and participated in at least one of five in-person examinations conducted in 1982–1997.
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From page 575... ...
AFHS, 2005 AFHS -- 2002 examination cycle Ranch Hand veterans -- relative risk with 2-fold increase in 1987 TCDD 1.3 (1.1–1.5) ADVA, Australian Vietnam veterans vs Australian 2005b population -- mortality 55 0.5 (0.4–0.7)
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From page 576... ...
Studies Reviewed in VAO AFHS, 1991 AFHS -- 1987 examination cycle -- elevation Significance of in blood glucose with serum TCDD slope Ranch Hand veterans and comparisons 85 p = 0.001, p = 0.028
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From page 577... ...
18 0.6 (0.4–1.0) Studies Reviewed in Update 2002 Steenland Ranch Hand veterans, workers exposed to et al., 2001 TCDD-contaminated products compared with nonexposed comparison cohorts Ranch Hands 147 1.2 (0.9–1.5)
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From page 578... ...
Diabetes among multiple causes 58 1.1 (0.8–1.4) Studies Reviewed in Update 1998 Sweeney Dioxin-exposed workers in two chemical et al., plants 1.1, p < 0.003 1997/1998 Ramlow PCP production workers -- mortality 4 1.2 (0.3–3.0)
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From page 579... ...
OCDD > 90th percentile vs nondetectable 31 2.1 (0.9–5.2) Studies Reviewed in Update 2006 Chen HL Residents around 12 municipal waste et al., 2006 incinerators in Taiwan -- prevalence of physician-diagnosed diabetes with TEQs for serum TCDD/Fs in logistic model adjusted for age, sex, smoking, BMI 29 2.4 (0.2–31.9)
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From page 580... ...
preopionic acid; AFHS, Air Force Health Study; AHS, Agricultural Health Study; BMI, body mass index; CDC, Centers for Disease Control and Prevention; CI, confidence interval; HbA1c, hemoglobin A1c; HDL, high-density lipoprotein; HpCDD, 1,2,3,4,6,7,8-heptachlorodibenzo-p-dioxin; HxCDD, 1,2,3,6,7,9-hexachlorodibenzo-p-dioxin; IU, international unit; NHANES, National Health and Nutrition Examination Survey; NIOSH, National Institute for Occupation Safety and Health; nr, not reported; ns, not significant; OCDD, 1,2,3,4,6,7,8,9-octachlorodibenzo-p-dioxin; OR, odds ratio; PCB, polychlorinated biphenyl; PCDD, polychlorinated dibenzo-p-dioxin; PCP, pentachlorophenol; SEA, Southeast Asia; TCDD, 2,3,7,8tetrachlorodibenzo-p-dioxin; TCDD/Fs, dioxins and furans combined; TCDF, tetrachlorodibenzofuran; TCP, trichlorophenol; TEF, toxicity equivalency factor; TEQ, total equivalent quotient; VES, Vietnam Experience Study. aGiven when available; results other than estimated risk explained individually.
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From page 581... ...
(2006) studied the association between blood concentrations of six persistent organic pollutants including two dioxin congeners (1,2,3,4,6,7,8heptacholorodibenzo-p-dioxin [HpCDD]
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From page 582... ...
Serum concentrations were related to diagnosed and undiagnosed diabetes (based on a reading of hemoglobin A1c [HbA1c] over 6.1%)
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From page 583... ...
(2007) gathered health and exposure histories and measured serum concentrations of 17 PCDD and PCDF congeners in 47 potentially exposed people.
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From page 584... ...
who had chloracne than in cohort members who had not had chloracne; the risks in those with chloracne compared with the referent population would be more extreme. The results of the study were not reported in terms of dioxin-like activity, so they do not directly contribute to the evidence considered for Vietnam veterans; however, in light of the well-known association between chloracne and AHR activation and dioxin-like activity, they are consistent with an association between exposure to the chemicals of interest and diabetes.
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From page 585... ...
Many of them are also risk factors for hypertension and ischemic heart disease. Synthesis A large number of relevant studies have been published since Update 2006.
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From page 586... ...
However, exposure estimates are based on questionnaire results, so exposure misclassification could lead to estimates biased toward no effect. There were a number of surveys of blood concentrations of various persistent organic pollutants that have dioxin-like activity and the prevalence of diabetes or related metabolic derangements (such as insulin resistance and the metabolic syndrome)
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From page 587... ...
Diabetes mellitus and the metabolic syndrome are associated with increased triglycerides and decreased HDL. Other diseases (thyroid and renal disorders)
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From page 588... ...
(2008b) examined metabolic and dietary correlates of serum concentrations of persistent organic pollutants in a survey of 1,274 Japanese adults 15–73 years old.
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From page 589... ...
ns O'Toole Australian Vietnam veterans compared with et al., 1996 Australian population 20 Cholesterol 3.0 (1.3–4.7) Studies Reviewed in VAO AFHS, Air Force Ranch Hand veterans (1987 exam data)
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From page 590... ...
1984; Wolfe Model 1: Ranch Hand vs comparisons 1,027 et al., 1990 Cholesterol ns Triglycerides ns HDL cholesterol ns OCCUPATIONAL Studies Reviewed in Update 2004 Hu et al., Workers exposed to PCDD/Fs in Taipei City -- 2003 above median vs below median 133 Total cholesterol 2.8 (1.0–7.9) Triglycerides 1.5 (0.5–4.3)
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From page 591... ...
Lee DH NHANES cross-sectional survey of persistent et al., 2007c organic pollutants (≥ 75th percentile vs < 25th percentile) HDL (< 1.1 mmol/L in men or < 1.4 mmol/L in women)
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From page 592... ...
. The mechanism underlying altered lipid metabolism has not been elucidated, but the high-dose studies in animal models provide some evidence of biologic plausibility that TCDD exposure can directly alter serum lipid and lipoprotein concentrations.
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From page 593... ...
GASTROINTESTINAL AND DIGESTIVE DISEASE, INCLUDING LIVER TOXICITY This section discusses a variety of conditions encompassed by ICD-9 520– 579: diseases of the esophagus, stomach, intestines, rectum, liver, and pancreas. Details on peptic ulcer and liver disease, the two conditions most often discussed in the literature reviewed, are provided below.
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From page 594... ...
Increases in serum bilirubin and in the serum concentrations of some hepatic enzymes -- aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and γ-glutamyltransferase (GGT) -- are commonly noted in liver disorders.
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From page 595... ...
A study of Vietnam veterans reported in Update 2006 found an increased rate of hepatitis associated with Vietnam service but not with a history of spraying herbicide (Kang et al., 2006)
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From page 596... ...
The liver can be damaged if metabolism of a chemical results in the production of a reactive intermediate that is more toxic than the parent chemical. Changes in serum concentrations of liver enzymes are biomarkers for liver toxicity, and their magnitude correlates with the degree of liver damage.
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From page 597... ...
Synthesis There is no evidence that Vietnam veterans are at greatly increased risk for serious liver disease, and reports of increased risk of abnormal liver-function tests have been mixed. Although increased rates of gastrointestinal disease have not been reported, the possibility of a relationship between dioxin exposure and subtle alterations in the liver and in lipid metabolism cannot be ruled out.
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From page 598... ...
Additional information available to the committees responsible for Update 1996, Update 1998, Update 2000, Update 2002, and Update 2004 did not change that conclusion. The committee responsible for Update 2006 reviewed both new studies and intensively revisited all the studies related to ischemic heart disease and hypertension that had been discussed in previous updates and concluded that there is limited or suggestive evidence to support an association between exposure to the herbicides used in Vietnam and hypertension.
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From page 599... ...
data Vietnam veterans vs nonVietnam veterans Hypertension requiring medication 496 1.06 (0.89–1.27) Adjusted for age, race, rank, Heart disease diagnosed by physician 243 1.09 (0.87–1.38)
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From page 600... ...
6 0.55 Not adjusted for known risk factors. AFHS, 2005 Air Force Health Study, 2002 exam cycle (1,951 [Largely supersedes participants)
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From page 601... ...
10 2.16 (0.98–4.77) Model 4: RH subjects with 1987 serum TCDD Relative risk for 2-fold increase readings in serum TCDD 748 Essential hypertension 1.11 (0.98–1.25)
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From page 602... ...
Served in Vietnam vs never-deployed to SEA Circulatory diseases (ICD-8 390–458)
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From page 603... ...
Ischemic heart diseases 8 0–15 years since discharge 117 0.77 (0.31–1.55) > 15 years since discharge 1.14 (0.87–1.50)
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From page 604... ...
for later time. Studies of Australian Vietnam veterans ADVA, 2005b Australian Vietnam veterans vs general male population -- mortality Circulatory disease 1,767 0.88 (0.84–0.92)
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From page 605... ...
Crane et al., 1997a Australian Vietnam veterans -- mortality [largely superseded (1980–1994)
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From page 606... ...
risk factors. Other circulatory diseases (excluding above and hemorrhoids)
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From page 607... ...
. Ischemic heart disease 38 1.0 (0.7–1.4)
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From page 608... ...
exposure. Ischemic heart diseases (ICD 410–414)
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From page 609... ...
Ischemic heart disease (ICD 410–414)
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From page 610... ...
344.7–3890.2 1.96 (1.15–3.34) p-trend = 0.01 Ischemic heart disease (ICD 410–414)
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From page 611... ...
-- mortality Hypertensive, ischemic heart disease (ICD 401–414, 428–429) 337 vs national rates 0.81 (0.73–0.90)
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From page 612... ...
69 0.96 (0.74–1.21) Not adjusted for known risk Ischemic heart disease (ICD 410–414)
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From page 613... ...
Serum TCDD ≥ 238 pg/g of lipid nr 0.97 (0.51–1.87) Suskind and Monsanto workers at Nitro, West Hertzberg, 1984 Virginia -- morbidity Workers exposed to 2,4,5-T production (204)
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From page 614... ...
] Ischemic heart disease 16 0.7 (0.4–1.1)
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From page 615... ...
Myocardial infarction 67 0.72 (0.56–0.92) Other ischemic heart diseases 72 0.41 (0.32–0.52)
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From page 616... ...
447 1.0 (0.9–1.1) Chronic ischemic heart diseases (ICD 412, 414)
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From page 617... ...
(TEF = 0.1) family history of myocardial ≤ 26.1 1.0 infarction.
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From page 618... ...
Karouna-Renier Superfund site caused by wood-treatment et al., 2007 -- new facility in Pensacola, Florida -- 47 workers, study residents -- prevalence Hypertension defined by self-report, medication use, 1.1 (1.1–1.2) [error likely; Adjusted for age, race, sex, or two readings of systolic blood pressure greater published OR and lower BMI, tobacco and alcohol use, than 140 mmHg or diastolic blood pressure greater confidence limit identical to worker status.
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From page 619... ...
ABBREVIATIONS: BMI, body mass index; CDC, Centers for Disease Control and Prevention; CHD, coronary heart disease; HDL, high-density lipoprotein; HpCDD, 1,2,3,4,6,7,8-heptachlorodibenzo-p-dioxin; HpCDF, 1,2,3,4,6,7,8-heptachlorodibenzofuran; HxCDD, 1,2,3,6,7,8-hexachlorodibenzo-p-dixion; HxCDF, 1,2,3,4,7,8-hexachlorodibenzofuran; IARC, International Agency for Research on Cancer; ICD, International Classification of Diseases; MCPA, 2-methyl4,chlorophenoxyacetic acid; NHANES, National Health and Nutrition Examination Survey; NIOSH, National Institute for Occupational Safety and Health; nr, not reported; OCDD, 1,2,3,4,6,7,8,9-octachlorodibenzo-p-dioxin; OR, odds ratio; PCB, polychlorinated biphenyl; PCDD, polychlorinated dibenzo-p-dioxin; PCDD/F, dioxins and furans combined; PCDF, polychlorinated dibenzofuran; PCP, pentachlorophenol; PMR, proportional mortality ratio; POP, persistent organic pollutant; PtCDF, 2,3,4,7,8-pentachlorodibenzofuran; RH, Ranch Hand; SEA, Southeast Asia; SMR, standardized mortality ratio; TCDD, 2,3,7,8-tetrachlorodibenzo-p-dixoin; TCP, trichlorophenol; TEF, toxicity equivalency factor for individual congener; TEQ, toxicity equivalent quotient. aNew citations labeled as such and bolded; section shaded for citations with dose-response information on TCDD..
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From page 620... ...
The five defining components of the metabolic syndrome included high blood pressure (blood pressure above 135/85 mmHg or use of antihypertensive medication)
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From page 621... ...
. There were no associations between any of the five non–dioxin-like PCBs or four other organochlorine pesticides assessed and high blood pressure.
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From page 622... ...
The results of the study were not reported in terms of dioxin-like activity, so they do not contribute directly to the evidence on Vietnam veterans; however, in light of the well-known
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From page 623... ...
Furthermore, the fact of service in Vietnam says little about exposures to the chemicals of interest. Therefore, the findings cannot be considered to be either contradictory or confirmatory of the hypothesis that Agent Orange exposure increases the occurrence of a specific circulatory disease.
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From page 624... ...
In addition to hypertension deaths, they examined deaths from chronic rheumatic heart disease, ischemic heart disease, and cerebrovascular disease, all of which are in the ICD-9 rubric of circulatory disease. Compared with residents of surrounding localities, residents of the most highly exposed zone (Zone A)
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From page 625... ...
had an higher rate of cerebrovascular disease (RR = 1.1, 95% CI 1.0–1.2) and a borderline increase in the rate of ischemic heart disease (RR = 1.06, 95% CI 0.98–1.14)
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From page 626... ...
An additional study in the literature reviewed supports the view that AHR activation may play a role in vascular disease and presumably in ischemic heart disease. The fact that the AHR appears to modulate blood pressure, depending on the partial pressure of oxygen (Lund et al., 2008)
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From page 627... ...
Hypertension Hypertension, typically defined as blood pressure above 140/90 mmHg, affects more than 70 million adult Americans and is a major risk factor for coronary heart disease, myocardial infarction, stroke, and heart and renal failure. The major quantifiable risk factors for hypertension are well established and include age, race, BMI or percentage body fat, and diabetes; the strongest conclusions regarding a potential increase in the incidence of hypertension come from studies that have controlled for these risk factors.
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From page 628... ...
Ischemic Heart Disease Circulatory diseases comprise a group of diverse conditions -- of which hypertension, coronary heart disease, and stroke are the most prevalent -- that account for 75% of deaths from circulatory diseases in the United States. The major quantifiable risk factors for circulatory diseases are similar to those for hypertension and include age, race, smoking, serum cholesterol, BMI or percentage of body fat, and diabetes.
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From page 629... ...
Furthermore, the association persisted after statistical adjustment for a large number of potential confounding risk factors for which the information necessary for adjustment is generally not available in other dioxin-exposed populations. The data on the Seveso incident do not show a dose–response pattern between residence and mortality from ischemic heart disease in that the residential zone with the lowest exposure was the only zone that had a statistically significant increase in mortality.
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From page 630... ...
The present committee considers that both conditions are strong risk factors for ischemic heart disease, and many epidemiologic studies show a dose–response relationship between dioxin and ischemic heart disease. Finally, toxicologic data support the biologic plausibility of an association between TCDD exposure and vascular disease.
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From page 631... ...
After consideration of the relative strengths and weaknesses of the evidence regarding the chemicals of interest and ischemic heart disease (ICD-9 410–414) , which includes a number of studies that showed a strong dose–response relationship and that had good toxicologic data demonstrating biologic plausibility, the committee judged that the evidence was adequately informative to advance this health outcome from the "inadequate or insufficient" category into the "limited or suggestive" category, again acknowledging that bias and confounding could not be ruled out.
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From page 632... ...
. In contrast, the fetus is highly sensitive to alterations in thyroid hormones, and alterations in thyroid homeostasis can hamper the development of
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From page 633... ...
The committee responsible for Update 2002 concluded that there was inadequate or insufficient information to determine whether there is an association between exposure to the chemicals of interest and adverse effects on thyroid homeostasis in Vietnam veterans. The committee responsible for Update 2004 concurred.
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From page 634... ...
Although those results are based on the sum of dioxin-like compounds, and not TCDD specifically, they augment information that dioxin-like chemicals are associated with changes in some measures of thyroid function, although not to an extent that result in clinically abnormal concentrations of the hormones. A second study of adults without thyroid disease in the 1999–2002 NHANES examined the association of dioxin-like TEQs with T4 and TSH (Turyk et al., 2007)
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From page 635... ...
Not all mechanisms by which chemicals might affect thyroid homeostasis are understood, and dioxin may act on thyroid function via different mechanisms. Synthesis Numerous animal experiments and several epidemiologic studies have shown that TCDD and dioxin-like compounds appear to exert some influence on thyroid homeostasis.
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From page 636... ...
The committees responsible for Update 1996, Update 1998, Update 2000, Update 2002, Update 2004, and Update 2006 concluded that there was limited or suggestive evidence of an association between exposure to at least one chemical of interest and porphyria cutanea tarda. The scientific literature continues to
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From page 637... ...
The present committee reached consensus that another cardiovascular outcome, ischemic heart disease, belonged in this category. Health Outcomes with Inadequate or Insufficient Evidence to Determine Whether There Is an Association The scientific data on many of the health outcomes reviewed by the present committee were inadequate or insufficient to determine whether there is an association between exposure to the chemicals of interest and the outcomes.
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From page 638... ...
American Journal of Industrial Medicine 16:119–125. Throughout the report the same alphabetic indicator following year of publication is used consistently for the same article when there were multiple citations by the same first author in a given year.
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From page 639... ...
1996. Cancer mortality in German male workers exposed to phenoxy herbicides and dioxins.
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From page 640... ...
1999. Evaluation of diabetes mellitus, serum glu cose, and thyroid function among United States workers exposed to 2,3,7,8-tetrachlorodibenzo p-dioxin.
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From page 641... ...
2001. Dioxin exposure is an environmental risk factor for ischemic heart disease.
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From page 642... ...
2007. Association between serum concentrations of persistent or ganic pollutants and self-reported cardiovascular disease prevalence: Results from the National Health and Nutrition Examination Survey, 1999–2002.
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From page 643... ...
American Journal of Industrial Medicine 50(12)
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From page 644... ...
2003. Impact of Agent Orange exposure among Korean Vietnam veterans.
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From page 645... ...
2003. Cardiac hypertrophy in aryl hydrocarbon receptor null mice is correlated with elevated angiotensin II, endothelin-1, and mean arterial blood pressure.
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From page 646... ...
2006. Cancer mortality in workers exposed to organochlorine compounds in the pulp and paper industry: An international collaborative study.
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From page 647... ...
1996. The Australian Vietnam Veterans Health Study: II.
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From page 648... ...
American Journal of Industrial Medicine 13(1)
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From page 649... ...
American Journal of Industrial Medicine 18:665–673. Thomas TL, Kang H, Dalager N
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From page 650... ...
American Journal of Industrial Medicine 11:685–691. Wolfe WH, Michalek JE, Miner JC, Rahe A, Silva J, Thomas WF, Grubbs WD, Lustik MB, Karrison TG, Roegner RH, Williams DE.
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