Veterans and Agent Orange Update 2014 (2016) / Chapter Skim
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6 Epidemiologic Studies: Background on Multiply Referenced Populations
6 Epidemiologic Studies: Background on Multiply Referenced Populations
Pages 145-262
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From page 145... ...
, and others have not been 1 espite loose usage of "Agent Orange" by many people, in numerous publications, and even in the D title of this series, this committee uses "herbicides" to refer to the full range of herbicide exposures experienced in Vietnam, while "Agent Orange" is reserved for a specific one of the mixtures sprayed in Vietnam.
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From page 146... ...
are provided in Chapter 2. The details of the exposure assessments conducted within individual studies are presented in this chapter, whereas generic issues of exposure assessment are discussed in Chapter 3 along with the special challenges involved in characterizing and reconstructing the herbicide exposures of Vietnam veterans.
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From page 147... ...
The specificity of exposure spans a wide range from the individual exposures of Ranch Hand and Army Chemical Corps (ACC) personnel, as reflected in serum TCDD measurements, to the use of service in Vietnam as a surrogate for TCDD exposure in some studies.
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From page 148... ...
148 FIGURE 6-1 Overview of the individual study populations reviewed by the committee.
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From page 149... ...
Similarly, multiple methods of health outcome ascertainment were used, including veteran self-report and a review of data from the Korean Cancer Incidence Database, the Korea National Health Insurance system, and death records from the National Statistical Office. The committee carefully considered the strengths and limitations of the different methods of exposure and health outcome ascertainment in synthesizing the evidence from the large Korean Veteran study.
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From page 150... ...
(1995) developed several indexes of herbicide exposure of members of the Ranch Hand cohort and tried to relate them to the measurements of serum TCDD from 1987 to 1992.
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From page 151... ...
to control for possible differences in the development of chronic disease that may relate to age, race, or educational and socioeconomic status. To control for the many potential confounders related to the physical and psychophysiologic effects of combat stress and the SEA environment, Ranch Hands were matched to control participants who performed similar combat or combatrelated jobs (AFHS, 1982)
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From page 152... ...
Identical study population counts vary Force Health Study. on occasion within and across cycle what was known to Air Force Health Study (AFHS)
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From page 153... ...
n = 777 ‡ Analyses n = 1,174 this reconstruction should be considered a general overview of AFHS population dynamics. Eligibility in any cycle reflects eligibility in a previous cycle, and not compliance in a previous cycle, corrected for between-cycle newly identified or deceased subjects.
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From page 154... ...
have been deemed not useful for the purposes of the VAO reviews because of the prevalence or cross-sectional nature of the data on only those in the cohort who were still alive and participated in a particular examination. Blood samples for determination of serum TCDD concentrations were drawn at the periodic examinations conducted in 1982 from 36 Ranch Hands (Pirkle et al., 1989)
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From page 155... ...
, which was undertaken by another IOM committee as the AFHS was approaching the end of its data-gathering phase, effectively described the limitations of the AFHS and was quoted in extensive detail in Updates 2006 and 2008. In summary, VAO committees have recognized the following features as the primary strengths and limitations of the AFHS: • The AFHS is one of the most pertinent studies for the VAO reviews, with a study population that was directly exposed to the COIs in the Vietnam War theater.
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From page 156... ...
These data demonstrate the unique TCDD signature experienced from herbicide exposure in Vietnam and indicate that, over time, the elimination rate is higher than the ongoing intake rate from background exposure to TCDD in both groups of Air Force veterans. US Department of Veterans Affairs VA Army Chemical Corps Cohort The study of members of the US ACC was conducted by VA, whose other research efforts on Vietnam veterans are discussed together below.
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From page 157... ...
. The availability of serum TCDD concentrations in a subset of this cohort of Vietnam veterans has made its findings particularly useful in appraising possible associations with various health outcomes.
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From page 158... ...
A comparison group consisted of female veterans who were identified through the same process as the female Vietnam veterans but had not served in Vietnam during their military service. Demographic information and information on overseas tours of duty, unit assignments, jobs, and principal duties
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From page 159... ...
, and military personnel records. When women whose service in the military fell outside the period of interest, whose records were lacking data, or who served in SEA but not in Vietnam were excluded, the analysis included 132 deaths among 4,582 female Vietnam veterans and 232 deaths among 5,324 comparison veterans who served in the military from July 4, 1965, to March 28, 1973.
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From page 160... ...
Cypel and Kang (2008) conducted a mortality study of female Vietnam veterans and compared their mortality with that in a control group of women who were in military service but did not participate in the Vietnam War.
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From page 161... ...
Whereas all reports from the female US Vietnamveterans cohort provide direct information on the health and mortality status of female military personnel who served in Vietnam, results must be taken in the context of limitations. Specifically, female veterans likely experienced low herbicide exposure because they were not involved in applying herbicides or engaged in direct combat, and had in-country tours of duty that were generally 1 year in length and at fixed locations that were away from known defoliated areas.
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From page 162... ...
, a computer database containing health information on Vietnam veterans who voluntarily undergo examinations in a VA hospital. The AO Registry was set up in 1978 to monitor those health complaints or problems of Vietnam veterans that could be related to herbicide exposure during their military service in Vietnam.
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From page 163... ...
The final analyses in that study included 97 testicular-cancer cases and 311 controls. A surrogate metric for herbicide exposure was developed by using the branch of service, combat MOSCs, geographic area of service in Vietnam, location of military units in relation to herbicide-spraying missions, and the length of time between spray missions and military operations in sprayed areas.
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From page 164... ...
This involved determining the proximity of troops to herbicide spraying by using military records to track troop movement and using the HERBS tapes to locate herbicide-spraying patterns. The CDC birth-defects study developed an exposure-opportunity index to score herbicide exposure (Erickson et al., 1984a,b)
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From page 165... ...
The CDC validation study concluded that study participants could not be distinguished from controls on the basis of serum TCDD. In addition, neither record-derived estimates of exposure nor self-reported exposure to herbicides could predict Vietnam veterans with currently high serum TCDD (CDC, 1988b, 1989b)
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From page 166... ...
Prior exposure to herbicides was crudely classified as "yes" or "no" within the electronic medical record system in a variable called "AO exposure" and yielded an overall prevalence of 7.5 percent. In a multiple logistic regression analysis, herbicide exposure (compared to no exposure)
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From page 167... ...
(2008) examined the association between herbicide exposure and prostate cancer in all Vietnam-era veterans using the VA health system in northern California; the reliability of this study of about 13,000 men is limited by its reliance on self-reported exposure status and by the exclusion of prostate cases diagnosed
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From page 168... ...
VAO summarized those studies, and no additional studies have been published on these study populations. Australian Vietnam-Veteran Studies Over many years the Australian government has commissioned studies to follow health outcomes in two sets of Australian veterans who served in Vietnam.
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From page 169... ...
The purpose of this study was to better understand the long-term impacts of service on the health and welfare of the families of Australian Vietnam veterans. From the roster of Australian Vietnam veterans, more than 10,000 Australians who had served in the Vietnam War were randomly selected and contacted, along with their family members, for potential participation in the study.
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From page 170... ...
Australian Conscripted Army National Service The Australian Conscripted Army National Service study population is a subset of the veterans considered in the overall Australian Vietnam Veterans study group. The 19,240 conscripted male Army veterans deployed to Vietnam ("National Service" veterans)
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From page 171... ...
to other era veterans and to all other fathers for all birth anomalies and for seven diagnostic groups. Korean Vietnam-Veteran Studies Study of TCDD Concentrations in Korean Vietnam Veterans Military personnel of the Republic of Korea served in Vietnam from 1964 through 1973.
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From page 172... ...
The remaining 12 samples were intended to correspond to 12 exposure categories; each was created by pooling blood samples from 60 veterans. The 12 exposure categories ultimately were reduced to four exposure groups, each representing a quartile of 180 Vietnam veterans but characterized by only three serum TCDD measurements.
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From page 173... ...
Responses to six questions on a postal survey were used to derive a four-tiered categorization of self-perceived herbicide exposure (Yi et al., 2013a)
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From page 174... ...
Using these multiple methods for exposure classification and health outcome ascertainment, associations between metrics of herbicide exposure potential and health outcomes were derived. First, in some analyses, the health experiences of Korean Vietnam veterans, given their exposure status, was compared to the health status of age-matched adults in the Korean general population.
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From page 175... ...
. Similarly, the examination of cancer incidence will not suffer from a potential healthy soldier effect when an internal control group is used so long as the veteran groups are similar or adjusted for potential confounding variables, such as military rank.
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From page 176... ...
Specifically, Vietnam veterans and military rank subcohorts experienced a higher incidence of several cancers, including prostate cancer, T-cell lymphoma, lung cancer, bladder cancer, kidney cancer, and colon cancer, than the general population. This study did not examine cancer incidence and cancer mortality in terms of herbicide exposure during military service in Vietnam.
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From page 177... ...
From this model, veterans were classified as low versus high exposure or in four categories consisting of none, low, moderate, or high exposure. The serum TCDD concentrations among the Korean Vietnam veterans were lower than those reported in other studies of Korean and US Vietnam veterans, and such concentrations were not associated with herbicide exposure indices or with age, BMI, or smoking.
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From page 178... ...
Overall, and compared to "low" exposure," "high" herbicide exposure was associated with a significantly higher prevalence of hypothyroidism, autoimmune thyroiditis, other endocrine gland disorders including pituitary gland disorders, amyloidosis, and Alzheimer disease. The objective classification of both herbicide exposure and disease prevalence is considered a strength of this study versus other reports from the Korean study that were based on self-report data.
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From page 179... ...
Their status with respect to cancer incidence and mortality were determined from 1988 through 2008. This cohort comprised 84 percent of all 3,322 Vietnam veterans from New Zealand who had survived service in Vietnam.
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From page 180... ...
Other occupationally exposed groups included were pulp-and-paper workers exposed to dioxins through bleaching processes that use chlorinated compounds and sawmill workers exposed to chlorinated dioxins, which can be contaminants of the chlorophenates used as wood preservatives. Studies of Herbicide Production Workers International Agency for Research on Cancer Phenoxy Herbicide Cohort A multisite study by IARC involved 18,390 production workers and phenoxy herbicide sprayers working in 10 countries (Saracci et al., 1991)
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From page 181... ...
International Agency for Research on Cancer Subcohorts In addition to the NIOSH cohort and its component subcohorts (discussed below) , several of the subcohorts that make up the IARC cohort have generated independent reports that have been evaluated separately by VAO committees to garner additional insights, such as the results associated with TCDD concentrations measured in various subjects: Austrian production workers (Jäger et al., 1998; Neuberger et al., 1998, 1999)
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From page 182... ...
. Several of the component cohorts have not been the subject of any separate publications: Australian herbicide sprayers, Canadian herbicide sprayers, Finnish production workers, two cohorts of Italian production workers, and Swedish production workers.
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From page 183... ...
No new studies have been published on these workers since Update 2000. Dutch Production Workers The two Dutch subcohorts of the IARC cohort consist of 2,106 male workers employed in two manufacturing factories producing and formulating chlorophenoxy herbicides: 2,4,5-T in factory A from 1955 through 1985 and 2-methyl-4-chlorophenoxyacetic acid (MCPA)
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From page 184... ...
of the production workers in these two Dutch chemical factories. On the basis of an assumption of first-order TCDD elimination with an estimated half-life of 7.1 years, the measured TCDD concentrations were extrapolated to the time of maximum TCDD exposure of a group of 47 workers.
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From page 185... ...
Rather than being the type of health outcomes that VAO committees assess for association with herbicide exposure, the measures considered in these studies of the Dutch production workers provide information on biologic plausibility for
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From page 186... ...
Additional information is available only on the Boehringer–Ingelheim cohort, and the workers involved in the 1953 accident have been studied separately. New Zealand Production Workers The mortality status of the New Zealand cohort that was incorporated into the original IARC cohort was followed through 2000 by 't Mannetje et al.
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From page 187... ...
(2009a) described the group's serum TCDD concentrations overall, and Burns et al.
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From page 188... ...
(2004) studied three birth outcomes -- birth weight, preterm delivery, and birth defects -- in the offspring of the cohort members by comparing serum TCDD concentrations with those in a reference population.
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. Occupational exposure to TCDD-contaminated processes was confirmed by measuring serum TCDD in 253 cohort members.
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(2011) have reported on cancer incidence in 2,4-D production workers in the Dow Midland plant.
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From page 191... ...
The cohort of TCP workers who were potentially exposed specifically to TCDD is one of the eight cohorts in the NIOSH cohort of dioxin-exposed US workers that were entered into the IARC phenoxy herbicides cohort. Collins et al.
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(2009c) conducted a mortality study of the Dow PCP production workers with the accrual of years at risk starting at the beginning of 1940.
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From page 193... ...
The authors used their data to estimate worker exposure at the time of exposure termination by using several pharmacokinetic models. They concluded that their findings were consistent with those of other studies that reported high serum dioxin concentrations in chlorophenol workers after occupational exposure.
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From page 194... ...
Paired t tests and F tests were used to test for changes in the assessments obtained repeatedly during follow-up visits; Spearman's rank correlation coefficient was used to test the association between health outcomes (such as color-vision impairment) and risk factors (such as concentrations of TCDD and carbohydrate-deficient transferring)
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From page 195... ...
When compared to the general population, all-cause mortality was similar, yet cancer mortality overall and mortality for several specific types of cancer was higher in the automobile factory workers. Other Chemical Plants Several studies have reviewed the health outcomes in UK chemical workers exposed to TCDD as a result of an industrial accident in 1968 (Jennings et al., 1988; May, 1982, 1983)
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From page 196... ...
; studies of vested members of the United Paperworkers International Union (Solet et al., 1989) ; and studies of cancer incidence in male paperworkers in Finland (Jappinen and Pukkala, 1991)
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From page 197... ...
(2009) studied serum dioxin concentrations in 94 former sawmill workers in New Zealand who were classified as exposed (71)
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From page 198... ...
According to the policy established by the Agent Orange Act of 1991, studies of Vietnam veterans are presumed to involve relevant exposure, as are studies of workers at a particular plant during a period when it is known to have been producing phenoxy herbicides or other chemicals recognized as having been contaminated with TCDD. American Herbicide-User Studies Agricultural Health Study The US Agricultural Health Study (AHS)
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From page 199... ...
Weighting factors for the key exposure variables were developed from the literature on pesticide exposure. This quantitative approach has the potential to improve the accuracy of exposure classification for the cohort but has not yet been used in published epidemiologic studies.
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From page 200... ...
All have developed pesticide-exposure estimates or exposure categories from self-administered questionnaires. Using various subsets of the study population, they have addressed a variety of health outcomes: doctor visits resulting from pesticide exposure (Alavanja et al., 1998)
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From page 201... ...
Risk estimates were calculated by using unconditional logistic regression for various exposures and controlling for age, smoking, and diabetes. Hoppin et al.
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From page 202... ...
based on intensity-weighted lifetime days of exposure were used for other chemicals, including 2,4-D, 2,4,5-T, and 2,4,5-TP. Unconditional logistic regression was used to estimate the association between melanoma and exposure with adjustments for age, sex, and other variables "as indicated" (apparently selection through an unspecified variable selection procedure)
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From page 203... ...
and on cancer incidence through 2002 (Alavanja et al., 2005) have been retained in the results tables for health outcomes were added.
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From page 204... ...
in 1,291 candidate genes was performed at the NCI's Core Genotype Facility. Unconditional logistic regression was used to estimate ORs and 95 percent CIs for the associations between prostate cancer and the main effect for pesticide exposure, the main effect for genetic markers, and the interaction between pesticide exposure and genetic markers, adjusted for age and state.
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From page 205... ...
Since Update 2012, a large series of papers has been published from the AHS cohort. These are described briefly below, prioritizing first the health outcomes of most interest in light of evidence considered thus far by VAO committees.
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From page 206... ...
More details on these individual health outcomes are provided in the individual chapters concerning health outcomes of interest to the committee. Rinsky et al.
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From page 207... ...
A significant limitation of this analysis is that the assessment of thyroid disease was based on a lifetime history of disease because thyroid disease was not reported at baseline and information on age of diagnosis was incomplete at follow-up. Thus, this analysis is based on the untested and unconfirmed assumptions that essentially all reports of thyroid disease at follow-up assessments were incident cases, and that the prevalence of thyroid disease at study entry did not differ between the pesticide exposure groups.
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From page 208... ...
: Occupational Exposures in Insecticide Applications and Some Pesticides. Given the time span, and the fact that this paper was a review article and not a new data-based analysis, it was deemed of very little value by the committee other than the authors' conclusions on the potential relationships between occupational pesticide exposure and different types of cancer.
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From page 209... ...
Vital status and cancer incidence were ascertained through a probabilistic record linkage to the California Cancer Registry for the period 1988–2001. Mills and Yang (2007)
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From page 210... ...
. Potential indirect sources of farm families' herbicide exposure were evaluated through wipe sampling of surfaces and samples of drinking water (Arbuckle et al., 2006)
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From page 211... ...
No reports on relevant health outcomes have been published on participants in this study population since Update 1996. Other Canadian Studies of Agricultural and Forestry Workers Faustini et al.
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From page 212... ...
(1992) determined the cancer incidence in this cohort of Danish gardeners from 1975 to 1984 and compared it with the general Danish population and adjusted for age, sex, and calendar period.
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From page 213... ...
studied cancer incidence overall mortality from 1970 through 1978 in 1,658 male agricultural plant-protection workers in the former German Democratic Republic who spent a portion of at least 5 years in 1948–1972 applying pesticides. Unlike most of the many pesticides thought to have contributed to the exposure of these workers, the phenoxy herbicides were available for use throughout this period.
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From page 214... ...
(2005) evaluated a study population that included herbicide production workers and was a subcohort of the IARC cohort.
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From page 215... ...
. A series of papers from a workshop focused on methods of assessing pesticide exposure in farmworker populations (Arcury et al., 2006; Barr et al., 2006a,b; Hoppin et al., 2006b; Quandt et al., 2006)
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From page 216... ...
The strengths of this study include an objective measurement of COIs to Vietnam veterans and anthropometric measures of infant development. Limitations include only its potential relevance to female Vietnam veterans with
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From page 217... ...
Multiple linear and logistic regression models were fit with adjustment for sex, age, height, weight, current/ex-smoking, and pack-years at enrollment. Analyses were also stratified by gender and smoking status.
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From page 218... ...
participated in a substudy of fish consumption and life habit and provided blood samples that were analyzed for nutrients and environmental contaminants, including dioxins and PCBs. The substudy found higher fish consumption and higher serum dioxins and PCBs in fishermen and their wives than in the general population studied in the 2000 health survey.
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From page 219... ...
(2004, 2010) studied the risk of birth defects attributable to environmental dioxins released from MSWIs in the Rhône-Alpes region (Lyon
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From page 220... ...
Participants were classified as exposed or non-exposed; those exposed were further classified into above or below the median. Multiple logistic regression was used to estimate the association between dioxin exposure and urinary tract birth defects with adjustments for stratification variables (child's sex and year and district of birth)
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From page 221... ...
. Cohort of Entire Exposed Population Data on serum TCDD concentrations in Zone A residents have been presented by Mocarelli et al.
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From page 222... ...
In addition to a 2-year prospective controlled study of workers potentially exposed to TCDD during the cleanup of the most highly contaminated areas after the accident (Assennato et al., 1989a) , studies have examined specific health effects associated with TCDD exposure in Seveso residents -- chloracne, birth defects, and spontaneous abortion -- as well as crude birth and death rates (Bisanti et al., 1980)
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From page 223... ...
(2009) reported on cancer incidence in a 20-year follow-up of the Seveso cohort covering the period 1977–1996.
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From page 224... ...
Seveso Women's Health Study The Seveso Women's Health Study (SWHS) was undertaken to evaluate the association between individual serum TCDD concentrations and reproductive effects in women who resided in Seveso at the time of the 1976 accident.
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From page 225... ...
Adding the questionnaire data improved the regression model to the point that it explained 42 percent of the variability. Those findings demonstrate a significant association between zone of residence and serum TCDD, but much of the variability in TCDD concentration is still unexplained by the models.
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From page 226... ...
. It was a small cohort, so the analyses that could be conducted were curtailed, but the availability of serum TCDD concentrations measured from blood samples gathered fairly soon after the single-substance accident (which minimizes uncertainty about what exposure had been experienced and reduces the need for back-extrapolation)
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From page 227... ...
The association between serum TCDD and TTP was assessed by using a Cox proportional-hazards model to estimate the fecundability ORs and 95 percent CIs. The association between serum TCDD and infertility was assessed by using multiple logistic regression.
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From page 228... ...
or a self-reported history of physician-diagnosed diabetes. Logistic regression was used to assess the associations between exposures (TEQs for PCDDs, PCDFs, and dioxin-like PCBs and total TEQs)
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From page 229... ...
Multiple logistic regression models were fit to estimate the odds of reporting individual diseases by quartiles (pg/g lipid) for PCDDs/PCDFs, for PCBs, and for all dioxin-like chemicals measured.
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From page 230... ...
Random effects logistic regression models were fit to estimate the odds of elevated maternal blood TEQ concentrations in relation to "black-baby" delivery versus non "black-baby" delivery. Analyses were adjusted for age at delivery, gestational age at birth, birth weight, descendant sex, and consumption of fish (times per week)
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From page 231... ...
(2001) presented rudimentary comparisons of cancer incidence and mortality and reproductive outcomes with regional and national rates; residence in the city of Chapaevsk was used as a surrogate for exposure, and no attempt was made to create exposure categories based on factors that might have influenced the degree of TCDD exposure.
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From page 232... ...
Ordinal logistic regression was used to model the ordinal outcome of number of involved arteries. A Bonferroni adjustment for multiple testing was applied.
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From page 233... ...
This analysis included 1,016 elderly adults from PIVUS with statistical adjustments for sex, blood pressure, antihypertensive treatment, diabetes, and BMI.
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From page 234... ...
. Whereas P450 proteins catalyze reactions involved in drug metabolism and the synthesis of cholesterol, steroids, and other lipids, the direct clinical relevance of this analysis with respect to herbicide exposure and adverse health effects among Vietnam veterans is limited.
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From page 235... ...
Multiple regression models were fitted for each component. In addition, an analysis of the association between each congener and the prevalence of metabolic syndrome was conducted.
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From page 236... ...
. The first two of the control groups made up the 1,167 in the study population.
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From page 237... ...
Diabetes was present in 27 percent of 774 participants; 75 percent of the 27 were taking glycemic control medications. People who had pre-diabetes were identified and were excluded from some regression analyses because they were intermediate between the diabetic and normoglycemic groups.
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From page 238... ...
From 1988 to 2006, 116 received a diagnosis of diabetes; 90 were randomly selected as cases. Controls were randomly selected from those who had not received a diagnosis of diabetes.
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From page 239... ...
Researchers also conduct analyses of the NHANES data for epidemiologic studies and health-science research on serum concentrations of various compounds in association with various health outcomes. Starting with the preparation of Update 2008, VAO committees began seeing a stream of publications addressing possible association of some pesticides and various individual and grouped dioxin-like chemicals with the occurrence of a variety of health outcomes as assessed by the surveys for particular temporal spans.
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From page 240... ...
Although 49 POPs were measured, analysis was restricted to 25, of which at least 60 percent of the study participants had detectable concentrations: three PCDDs, four PCDFs, five dioxin-like PCBs, seven non–dioxin-like PCBs, and six OC pesticides. Logistic regression was used to determine the OR between each outcome (peripheral neuropathy or poor glycemic control)
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From page 241... ...
The summary values were again categorized into quartiles. Logistic regression was used to derive adjusted ORs, which were stratified by sex and adjusted for age, race or ethnicity, povertyincome ratio, BMI, cigarette smoking (never, former, or current)
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From page 242... ...
The study population for the Priority Toxicant Reference Range Study was a subgroup of participants aged 20–59 years in NHANES III (1988–1994) established
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From page 243... ...
Further analysis was conducted with linear regression, and the outcome variables were transformed to a logarithmic scale. The linear-regression models included the following explanatory variables: 2,4-D (binary)
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From page 244... ...
Logistic regression was used to predict the prevalence of health outcomes from TEQs with adjustments for age, race, sex, BMI, tobacco and alcohol use, and worker status. Times Beach and Quail Run Cohorts Several reports have provided information on environmental exposure to TCDD in the Times Beach area of Missouri (Andrews et al., 1989; Patterson et al., 1986)
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From page 245... ...
Marked increases in TCDD concentrations and TEQs were found in ducks, chickens, and fish, but not in pork or beef. The study concluded that food appeared to be responsible for the increase in TCDD in residents of Bien Hoa City even though the original Agent Orange contamination occurred 30 to 40 years before sampling.
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From page 246... ...
Multiple linear-regression analyses were conducted with statistical adjustment for age, BMI, employment status, and tobacco use. The limitations of this analysis include the cross-sectional design with exposure assessment occurring many years after presumed herbicide exposure.
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From page 247... ...
; mortality and cancer incidence in two cohorts of Swedish fishermen whose primary exposure route was assumed to be diet (Svensson et al., 1995a) ; the immunologic effects of prenatal and postnatal exposure to PCB or TCDD in Dutch infants from birth to the age of 18 months (Weisglas-Kuperus et al., 1995)
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From page 248... ...
. There was no difference in the body burden between women who had endometriosis and a control group, but the serum dioxin concentrations were substantially higher in the Belgian controls than in a similar group in Italy (45 versus 18 TEQ pg/g of lipid, respectively)
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From page 249... ...
Blood samples were analyzed for PCDD/Fs and PCBs in relation to sexually dimorphic behavior, as reported by parents through completion of the Pre-School Activities Inventory. This analysis provides insight into potential endocrine-disrupting effects of prenatal environmental exposure to dioxins and PCBs in the children of female Vietnam veterans, but the relevance of behavioral sexual dimorphism as a "health" outcome of interest is unclear.
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From page 250... ...
The mothers' fat-in-diet scores were regressed against anogenital distance separately by infant sex and whether the mother consumed seafood, with adjustment for the infant's birth weight and for maternal ethnicity, age, and smoking. Here again, however, direct use of the results from maternal blood samples as done by Vafeiadi et al.
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From page 251... ...
The limitations of this study include its reliance on self-report food-frequency intake to estimate dioxin exposure and its direct relevance only to childbearing female Vietnam veterans. Taiwanese Mother-and-Child Studies A prospective study of healthy Taiwanese mothers and their children recruited during the mothers' pregnancy was conducted as a way to study the
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From page 252... ...
(2006) examined the association between PCDDs, PCDFs, and PCBs measured in the placenta samples and estrogens and metabolites measured in mothers' blood samples by using Pearson correlations, linear and quadratic regressions, and multivariate regression analyses.
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From page 253... ...
Any subject who reported at least 10 hours of pesticide exposure per year was asked to complete a telephone questionnaire on the details of pesticide exposure; in addition, 15 percent of the remaining subjects were randomly selected to answer the telephone survey. A conditional logistic regression stratified on age and province and adjusted for all covariates found to be associated with the outcome at the 0.05 level of significance was used to estimate ORs for specific active ingredients, including dicamba and the phenoxy herbicides 2,4-D, Mecoprop, MCPA, and diclofopmethyl.
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From page 254... ...
The analysis included 316 HL cases and 1,506 control subjects. Multiple logistic regression models were fit with statistical adjustments for age and
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From page 255... ...
This significantly limits direct inference to the effects of herbicide exposure during military service in Vietnam. Children's Oncology Group Study (United States)
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From page 256... ...
Multiple comparisons are a concern. There was generally a low level of occupational pesticide exposure in the study population.
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From page 257... ...
(2012) has reported findings from new analyses of the UMHS sample that incorporated more detailed exposure information that was not used in previous analyses, including years of use and estimated cumulative exposures to categories of pesticides, including phenoxy herbicides, and the use of specific agents, including 2,4-D and dicamba.
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From page 258... ...
conducted a set of case-control studies to evaluate the association between phenoxy herbicide and chlorophenol exposure and STS incidence and mortality in New Zealand. An expanded case series was collected, and additional case-control studies of exposure to phenoxy herbicides or chlorophenols and the risks of malignant lymphoma, NHL, and MM were conducted (Pearce et al., 1985, 1986a,b, 1987)
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From page 259... ...
; birth defects in the offspring of agriculture workers (Nurminen et al., 1994) ; mortality from neurodegenerative diseases associated with occupational risk factors (Schulte et al., 1996)
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From page 260... ...
. Unconditional logistic regression was used to estimate the ORs and CIs for each outcome (all LN, NHL, HL, LPS, and MM)
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From page 261... ...
No specific COIs were reported beyond the broad category "herbicide." Unconditional logistic regression was used to estimate the association between PD and exposure with adjustments for age, sex, and smoking. Firestone et al.
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