Veterans and Agent Orange Update 2010 (2012) / Chapter Skim
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11 Other Health Effects
11 Other Health Effects
Pages 708-758
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From page 708... ...
, picloram, and cacodylic acid -- and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) , a contaminant of 2,4,5-T, and several noncancer health outcomes: respiratory disorders, immune-system disorders, diabetes, lipid and lipoprotein disorders, gastrointestinal and digestive disease (including liver toxicity)
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From page 709... ...
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 noncancerous respiratory disorders is inhalation of cigarette smoke.
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. Many study populations are small, so investigators group deaths from all noncancerous respiratory diseases into one category that combined pneumonia, influenza, and other diseases with COPD and asthma.
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(2006) found that the prevalence of self-reported noncancerous respiratory problems diagnosed by a doctor was significantly increased by about 40–60%, although no differences in the preva lence of respiratory problems was found in the subset of veterans whose serum TCDD was above 2.5 ppt.
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Watanabe Mortality of US Vietnam veterans who and Kang, died during 1965–1988, PMR analysis of 1996 noncancerous respiratory mortality (ICD-8 460–519)
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From page 713... ...
COPD 18 0.8 (0.4–1.2) CDVA, Mortality of male Australian Vietnam veterans 1997a vs Australian population Noncancerous respiratory mortality (ICD-9 460–519)
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From page 714... ...
OCCUPATIONAL IARC Phenoxy Herbicides Cohort (mortality vs national mortality Dioxin, phenoxy rates) herbicides Kogevinas Mortality in international workers producing et al., 1997 or applying phenoxy herbicides, noncancerous respiratory mortality (ICD-9 460–519)
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(illness episodes per 100 person–years, 1953–1989) All noncancerous respiratory diseases (ICD-9 460–519)
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et al., 1986 from noncancerous respiratory diseases (ICD-9 460–519) , 1947–1983 Agricultural Health Study Herbicides Hoppin US AHS -- prevalence at enrollment among et al., 2009 male agricultural workers of: Allergic asthma 2,4,5-T 38 1.4 (1.0–2.2)
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Valcin et al., US AHS -- prevalence at enrollment of chronic 2007 bronchitis in nonsmoking farm women exposed 0.9 (0.7–1.1)
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in Saskatchewan nonasthmatics (1982–1983) Phenoxyacetic herbicide use 71 85.5% vs 88.5% Herbicide and Pesticide Applicators Herbicides Blair et al., Licensed pesticide applicators, Florida, 1983 noncancerous respiratory diseases, (ICD-8 2 0.9 (nr)
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Zone B 22 1.3 (0.9–2.0) Bertazzi 15-yr follow-up of Seveso residents -- mortality et al., 1998; Respiratory disease (ICD-9 460–519)
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From page 720... ...
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; ACC, Army Chemical Corps; AHS, Agri cultural Health Study; CI, confidence interval; COI, chemical of interest; COPD, chronic obstructive pulmonary disease; FEF25-75, forced midexpiratory flow; FEV1, forced expiratory volume in 1 second; FVC, forced vital capacity; HR, hazard ratio; IARC, International Agency for Research on Cancer; ICD-8, International Classification of Diseases, 8th revision; ICD-9, International Classification of Diseases, 9th revision; MCPA, 2-methyl-4-chlorophenoxyacetic acid; MI, Michigan; NIOSH, National Institute for Occupational Safety and Health; nr, not reported; ns, not significant; NZ, New Zealand; PCP, pentachlorophenol; PMR, proportionate mortality ratio; SEA, Southeast Asia; TCDD, 2,3,7,8-tetrachlorodibenzo-p-dioxin; TCP, trichlorophenol; VA, US Department of Veterans Affairs; WV, West Virginia.
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From page 721... ...
When the subgroup of ACC Vietnam veterans who reported spaying herbicides was compared to the ACC Vietnam veterans who did not report spraying herbicides, a nonsignificantly elevated risk for death due to the less specific category of noncancerous respiratory system disease was reported (adjusted RR = 2.24, 95% CI 0.42–11.83)
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of several chronic lower respiratory diseases were significantly elevated in the Australian Vietnam Veterans (n = 450) for bronchitis (RP = 2.90, 95% CI 2.18–3.63)
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Biologic Plausibility Evaluation of the biological plausibility of chemicals of interest inducing or contributing to the development of lung diseases is hampered by the lack of animal models to study endpoints such as COPD or asthma, because these diseases usually develop in humans in response to additional co-factors (i.e., smoking/ air pollution)
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. Acute noncancerous respiratory disorders, including pneumonia and other respiratory infections, also can be increased in frequency and severity when the normal defense mechanisms of the lower respiratory tract are compromised.
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added 14 years of observation and found an increased risk of death from noncancerous respiratory diseases on the cusp of statistical significance (adjusted RR = 2.20, 95% CI 0.99–4.91)
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Almost all the studies of mortality in industrial cohorts considered in the VAO updates assessed only the nonspecific category of mortality due to noncancerous respiratory disease, and no significant excesses were reported (Becher et al., 1996; Burns et al., 2001; Kogevinas et al., 1997; Ott and Zober, 1996; Steenland et al., 1999; 't Mannetjie et al., 2005)
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From page 727... ...
The NIOSH cross-sectional study of production workers exposed to TCDD (Calvert et al., 1991) did not show an increase in COPD or chronic bronchitis, or altered pulmonary function measures associated with el evated serum TCDD concentration in workers compared to a community-based referent population.
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The committee's consultation with Dr. Enright increased its concern (as delineated at the beginning of this section on respiratory diseases)
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The findings presented on asthma in male and female farmers did not constitute evidence of an association with the herbicides of interest. 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 noncancerous respiratory diseases or from COPD specifically.
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Other risk factors include genetic predisposition (such as some blood and human leukocyte antigen [HLA] types)
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. A study of Army Chemical Corps Vietnam veterans reported in Update 2006 found an increased rate of hepatitis associated with Vietnam service but
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and found no excess in deaths related to digestive diseases or in the subset of deaths specifically related to cirrhosis. The reports to date have been inconsistent, and interpretation of individual studies is difficult because of a lack of information on alcohol consumption and other risk factors.
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deaths in the third follow-up results of a retrospective cohort study of two Dutch chlorophenoxy herbicide manufacturing factories, producing mainly 2,4,5-T (Factory A) and 4-chloro-2-methylphenoxyacetic acid, 4-chloro-2-methylphenoxy propanoic acid, and 2,4-D (Factory B)
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Environmental Studies No environmental studies of gastrointestinal diseases have been published since the 2008 review. Biologic Plausibility The liver is a primary target for the toxicity of many chemicals.
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THYROID HOMEOSTASIS Clinical disruptions of thyroid function include various disorders grouped in ICD-9 242.8 and 246.8. The thyroid gland secretes the hormones thyroxine (T4)
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. Both conditions are diagnosed on the basis of blood concentrations of thyroid hormones, TSH, and other proteins (antithyroid antibodies)
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. In contrast, the fetus is highly sensitive to alterations in thyroid hormones, and alterations in thyroid homeostasis can hamper the development of many organ systems, including the nervous and reproductive systems; such findings are discussed in Chapter 8, which addresses potential consequences of Vietnam veterans' exposure to herbicides on their offspring.
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(2010) published a study of pesticide use and self-reported history of physician-diagnosed thyroid disease among women in the Agricultural Health Study.
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275 30.5 (p = 0.24) Australian Deployed Army Vietnam Veterans vs General Population All COIs O'Toole Australian Vietnam veterans vs ageet al., 2009 and sex-matched data from general population -- prevalence Disorders of the thyroid gland 450 1.4 (95% CI 0.5–2.2)
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257 26.8 (0.3) Agricultural Health Study Herbicides 2,4-D, 2,4,5-T, dicamba Goldner Thyroid disease among female spouses in et al., 2010 Iowa and North Carolina (1993–2003)
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TSH 385 0.06 (–0.15 to 0.35) Other Environmental Studies dl PCBs/ correlation of Dallaire Cross-sectional study of Inuit residents of 607 et al., 2009 Nunavik (Québec, Canada)
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–0.05 (–0.52 to 0.42) dl compounds Foster et al., Cross-sectional examination of serum from 150 2005 pregnant women attending Canadian prenatal diagnosis clinic TSH correlation coefficient ns (value nr)
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T4 –0.5 (p ≤ .001) T3 ABBREVIATIONS: 2,4-D, 2,4-dichlorophenoxyacetic acid; 2,4,5-T, 2,4,5-trichlorophenol; AFHS, Air Force Health Study; CA, California; CI, confidence interval; COI, chemical of interest; dl, dioxinlike; LD, level of detection; NA, not available; NHANES, National Health and Nutrition Examination Survey; nr, no relationship; ns, nonsignificant; PCB, polychlorinated biphenyls; PCDD, polychlori nated dibenzo-p-dioxins; PCDF, polychlorinated dibenzofurans; ppt, parts per trillion; SE, standard error; SEA, Southeast Asia; RH, Ranch Hand; T3, triiodothyronine; T4, tetraiodothyronine; TCDD, tetrachlorodibenzo-p-dioxin; TEQ, (total)
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. No correlations were observed between the PBDE, PCDD/F, and PCB exposures and the thyroid hormones T3 and TSH.
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Although the overall assessment of the studies to date suggests some variation in thyroid hormone concentrations in relation to TCDD exposure, the functional importance of those changes remains unclear because adaptive capacity should be adequate to accommodate them. It should be noted, however, that although biomarkers of perturbation may be subclinical in most individuals, they may be associated with clear adversity in others.
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From page 746... ...
was studied between 1990–1993 and reexamined in 2005–2006. In the original assessment, 641 Australian Vietnam veterans responded from a random sample of 1,000 selected from the list of Army Veterans deemed eligible for previous studies of Agent Orange; 450 from the original sample responded in this most recent as sessment.
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From page 747... ...
(2009) observed increased risks for several eye conditions among the Australian Vietnam veterans, but the study is limited by the lack of in formation on exposure to the chemicals of interest to the committee, lack of clinical confirmation of the eye conditions, and considerable likelihood of recall bias.
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From page 748... ...
. Other risk factors for loss of bone density include long-acting benzodiazepine or anticonvulsant drug use, previous hyperthyroidism, excessive caffeine intake, and standing 4 or fewer hours per day (Lash, 2009)
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From page 749... ...
Conclusion There is inadequate or insufficient evidence of an association between expo sure to the chemicals of interest and clinical or overt adverse effects of osteoporosis or loss of bone mineral density. SUMMARY On the basis of the occupational, environmental, and veterans studies reviewed and in light of information concerning biologic plausibility, the commit tee reached one of four conclusions about the strength of the evidence regarding
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From page 750... ...
Some studies failed to control for confounding or used inadequate exposure assessment. This category includes noncancerous respiratory disorders, such as COPD, asthma in isolation, pleurisy, pneumonia, and tuberculosis; gastrointestinal diseases; digestive diseases; liver toxicity; disorders of thyroid homeostasis; and disorders of the eyes and bones.
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2005b. The Third Australian Vietnam Veterans Mortality Study 2005.
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From page 752... ...
1991. Evaluation of chronic bronchitis, chronic obstructive pulmonary disease, and ventilatory function among workers exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin.
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1997b. Mortality of National Service Vietnam Veterans: A Report of the 1996 Retrospective Cohort Study of Australian Vietnam Veterans.
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2006a. Pesticides as sociated with wheeze among commercial pesticide applicators in the Agricultural Health Study.
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2008. Pesticides and atopic and nonatopic asthma among farm women in the Agricultural Health Study.
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From page 756... ...
1996. The Australian Vietnam Veterans Health Study: II.
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2009. Rhinitis associated with pesticide exposure among commercial pesticide applicators in the Agricultural Health Study.
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2007. Chronic bronchitis among nonsmoking farm women in the Agricultural Health Study.
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