Below are the first 10 and last 10 pages of uncorrected machine-read text (when available) of this chapter, followed by the top 30 algorithmically extracted key phrases from the chapter as a whole.
Intended to provide our own search engines and external engines with highly rich, chapter-representative searchable text on the opening pages of each chapter. Because it is UNCORRECTED material, please consider the following text as a useful but insufficient proxy for the authoritative book pages.
Do not use for reproduction, copying, pasting, or reading; exclusively for search engines.
OCR for page 261
Veterans and Agent Orange: Update 2006 6 Cancer Cancer is the second-leading cause of death in the United States. Among men 50–64 years old, the group that includes most Vietnam veterans (see Table 6-1), the risk of dying from cancer nearly equals the risk of dying from heart disease, the main cause of death in the United States (US Census, 1999). About 564,830 Americans of all ages were expected to die from cancer in 2006—more than 1,500 per day. In the United States, one-fourth of all deaths are from cancer (Jemal et al., 2006). This chapter summarizes and presents conclusions about the strength of the evidence from epidemiologic studies regarding associations between exposure to the compounds of interest—2,4-dichlorophenoxyacetic acid (2,4-D), 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) and its contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), picloram, and cacodylic acid—and various types of cancer. If a new study reports on only a single type of cancer and does not revisit a previously studied population, its design information is summarized here with its results; design information on all other new studies can be found in Chapter 4; Appendix C contains cumulative tables that summarize studies that looked at multiple endpoints or involved repeatedly investigated populations that have contributed evidence to this series of reports. In an evaluation of a possible connection between herbicide exposure and risk of cancer, how exposures of study subjects were assessed is of critical importance in determining the overall relevance and usefulness of findings. As noted in Chapter 5, there is a great variety in detail and accuracy of exposure assessment among studies. A few studies used biologic markers of exposure, such as the presence of a compound in serum or tissues; some developed an index of exposure from employment or activity records; and others used surrogate mea-
OCR for page 262
Veterans and Agent Orange: Update 2006 TABLE 6-1 Age Distribution of Vietnam-Era and Vietnam-Theater Male Veterans 2004–2005 (numbers in thousands) Ages Group (Years) Vietnam Era Vietnam Theater N (%) N (%) All ages 7,934 3,853 ≤49 133 (1.6) 32 (0.1) 50–54 1,109 (13.8) 369 (9.4) 55–59 3,031 (37.6) 1,676 (43.1) 60–64 2,301 (28.5) 1,090 (28.0) 65–69 675 (8.4) 280 (7.2) 70–79 511 (6.3) 322 (8.3) ≥80 178 (2.2) 83 (2.1) SOURCE: Table 3-3 (IOM, 1994), updated by 15 years. sures of exposure, such as presence in a geographic locale when herbicides were used. As noted in Chapter 2, inaccurate assessment of exposure can obscure the relationship between exposure and disease. Each section on a type of cancer opens with background information, including data on its incidence in the general US population and known or suspected risk factors. Cancer-incidence data on the general US population are included in the background material to provide a context for consideration of cancer risk in Vietnam veterans; the figures presented are estimates for the entire US population, however, not predictions for the Vietnam-veteran cohort. The incidence figures in this update are adapted to the demographic patterns defined by the 2000 US census data. The data reported are for 1998–2002, the most recent data set available (NCI, 2006). Incidence data are given for all races combined and separately for blacks and whites. The age range of 50–64 years now includes about 80 percent of Vietnam-era veterans, so incidences are presented for three 5-year age groups: 50–54 years, 55–59 years, and 60–64 years. The data were collected for the Surveillance, Epidemiology, and End Results (SEER) program of the National Cancer Institute of the National Institutes of Health and are categorized by sex, age, and race, all of which can have profound effects on risk. For example, the incidence of prostatic cancer is about 4.3 times as high in men who are 60–64 years old than in men 50–54 years old; it is about twice as high in blacks 50–64 years old as in whites in the same age group (NCI, 2006). Many factors can influence incidence, including behavior (such as tobacco and alcohol use and diet), genetic predisposition, and medical history. Those factors can make someone more or less likely than the average to contract a given kind of cancer; they also need to be taken into account in epidemiologic studies of the possible contributions of the compounds of interest. The body of each section on a specific type of cancer includes a summary of the findings described in the previous Agent Orange reports: Veterans and
OCR for page 263
Veterans and Agent Orange: Update 2006 Agent Orange: Health Effects of Herbicides Used in Vietnam, hereafter referred to as VAO (IOM, 1994); Veterans and Agent Orange: Update 1996, referred to as Update 1996 (IOM, 1996); Update 1998 (IOM, 1999); Update 2000 (IOM, 2001); Update 2002 (IOM, 2003); and Update 2004 (IOM, 2005). That is followed by a discussion of the most recent scientific literature, a discussion of biologic plausibility, and a synthesis of the material reviewed. Where appropriate, the literature is discussed by exposure type (occupational, environmental, or service in Vietnam). Each section ends with the committee’s conclusion regarding the strength of the evidence from epidemiologic studies. The categories of association and the committee’s approach to categorizing the health outcomes are discussed in Chapters 1 and 2. As explained in the following paragraphs, this committee has slightly modified the format in which it has satisfied the other two aspects of its charge. Biologic plausibility corresponds to the third element of the committee’s congressionally mandated statement of task. In previous updates, it had been discussed in the conclusion section for each health outcome after a statement of the committee’s judgment about the adequacy of the epidemiologic evidence of an association between exposure to the compounds of interest and the outcome. In fact, the degree of biologic plausibility itself influences whether the committee perceives positive findings to be indicative of a pattern of association or the product of statistical fluctuations. To provide the reader with a more logical sequence, in this update sections on biologic plausibility have been placed between the presentation of epidemiologic evidence and the synthesis of the evidence, which leads to the committee’s conclusion about the adequacy of the evidence to support an association. Information on biologic mechanisms that could contribute to the generic (rather than tissue- or organ-specific) carcinogenic potential of the compounds of interest is summarized in the section on biologic plausibility that precedes the synopsis of conclusions for the entire chapter. It distills toxicologic information concerning the mechanisms by which the compounds of interest affect carcinogenesis, as presented in more detail in Chapter 3; such information, of course, applies to all the cancer sites discussed individually in this chapter. When biologic plausibility is discussed in the chapter’s sections on particular cancer types, the generic information is implicit, and only toxicologic information peculiar to carcinogenesis at the site in question has been presented. Considerable uncertainty remains about the magnitude of potential risk posed by exposure to the compounds of interest. Many of the occupational, environmental, and veterans studies reviewed by the committee did not control fully for important confounders. There is not enough information about individual Vietnam veterans to compare with exposures presented in scientific research studies. The committee therefore cannot accurately estimate the risk to Vietnam veterans that is attributable to exposure to the compounds of interest. Previous reports in the VAO series have had a rather formulaic statement to that effect as the third
OCR for page 264
Veterans and Agent Orange: Update 2006 entry in the conclusion section for each cancer type, corresponding to the second element in the committee’s statement of task as dictated by the congressional mandate. The (at least currently) insurmountable problems of deriving meaningful estimates of the risks of various health outcomes to Vietnam veterans are explained in Chapter 1 and the summary of this report, but the point is no longer reiterated for every health outcome addressed. AN EXHAUSTIVE AND UNAMBIGUOUS SYSTEM FOR ADDRESSING CANCER TYPES The Department of Veterans Affairs (VA) requested that the present committee ensure that evaluations of the possibility of associations between exposures to the compounds of interest and various types of cancer be framed in such a fashion that a corresponding conclusion would be available for any type of cancer that might be diagnosed in a veteran and that it would be clear which conclusion would be applicable when a veteran filed a claim. VA also expressed concern that the episodic nature of the VAO series may have interfered with recognition and evaluation of cumulatively usable amounts of epidemiologic information on some uncommon cancers; in particular, VA asked for a focused examination of available information on cancer of the tonsil and acute myelogenous leukemia (AML). The committee therefore screened the studies that contributed results on the cancer types discussed in prior updates for results on tonsil cancer, AML, and other uncommon sites while gaining an overview of how cancer sites are typically grouped to report findings. VA had indicated that a grouping system for reporting the committee’s conclusions based on the International Classification of Diseases (ICD) codes would be appropriate to match the diagnostic information presented in veterans’ claims. ICD is used to code and classify mortality data from death certificates. ICD CM (clinical modification) is used to code and classify morbidity data from medical records, hospital records, and surveillance surveys. The 10th edition (ICD-10) came into use in 1999 and constitutes a marked change from the previous four versions that evolved into the ninth edition (ICD-9). ICD-9 was in effect from 1979 to 1998; because ICD-9 is the version most prominent in the research reviewed in this series, it has been used when codes are given for a specific health outcome. The first modification made in this update toward addressing VA’s request was to change the order in which cancer types are discussed, which had evolved from the original VAO report. The more systematic order of major and minor categories of cause of death for cancer sites established by the National Institute for Occupational Safety and Health (NIOSH) is now followed with minor exceptions. The NIOSH groups map the full range of ICD-9 codes for malignant neoplasms (140–208), and this somewhat coarser gradient has been adopted as an exhaustive organizing principle for the present chapter. Appendix B discusses
OCR for page 265
Veterans and Agent Orange: Update 2006 the issue in more detail and delineates the correspondence between the NIOSH cause-of-death groupings and ICD-9 codes (Table B-1); the groupings for mortality are largely congruent with those of the SEER program for cancer incidence (see Table B-2, which presents equivalences between the ICD-9 and ICD-10 systems). The groups provide a comprehensive framework for software routinely used by epidemiologists to generate expected values based on the demographics of the cohort being studied and have well-documented correspondence with the more detailed ICD coding system in its successive iterations (Robinson et al., 2006). When conditions reported on in epidemiologic research are specified in ICD ranges, the specificity may not be as refined as might be desired for some purposes, and errors of misclassification in the research process cannot be excluded, but the grouping intended is unambiguous. This rearrangement following a largely anatomic sequence should make locating a particular cancer easier for readers and facilitated the committee’s identification of ICD codes for malignancies that had not been explicitly addressed in previous updates (as noted in italics in Table B-1). VAO reports’ default category for any health outcome for which no epidemiologic research findings have been recovered has always been “inadequate evidence” of association, which in principle is applicable to specific cancers. In this update, it still is the case that failure to review a specific cancer or other condition separately reflects the paucity of information, so there is indeed inadequate or insufficient information to categorize such a disease outcome. However, in response to VA’s request and in light of our review of how “rare cancers” are grouped or presented when they do have reported results, we state here how each of these previously overlooked ICD codes will be treated in this and future updates: ICD-9 149, other buccal cavity and pharynx—routinely included in full buccal cavity and pharynx range, 140–149. ICD-9 152, small intestine—rarely reported individually; to be encompassed in conclusions for colorectal cancers. ICD-9 156, gallbladder and extrahepatic bile ducts—to be tracked under hepatobiliary cancers. ICD-9 158–159, retroperitoneum and other and unspecified digestive cancers—rarely reported individually; to be encompassed in conclusions for colorectal cancers. ICD-9 162.0, trachea—intended grouping with lung and bronchus has not always been explicitly stated. ICD-9 163, pleura—rarely reported individually and not as yet seen for the chemicals of interest; would be considered with mediastinum and other and unspecified respiratory cancers. ICD-9 164.0, thymus—to be considered with thyroid and other endocrine cancers. ICD-9 164.2–164.9, mediastinum—rarely reported individually and not
OCR for page 266
Veterans and Agent Orange: Update 2006 as yet seen for the chemicals of interest; would be considered with pleura and other and unspecified respiratory cancers. ICD-9 165, other and unspecified respiratory cancers—rarely reported individually and not as yet seen for the chemicals of interest; would be considered with pleura and mediastinum as other respiratory cancers. ICD-9 179, unspecified parts of uterus—to be considered with female reproductive system. ICD-9 181, placenta—to be considered with female reproductive system. ICD-9 183.2–183.9, fallopian tube and other uterine adnexa—to be considered with female reproductive system. ICD-9 184, other female genital organs—to be considered with female reproductive system. ICD-9 187, penis and other male genital organs—to be considered with testis as other male reproductive organs (excluding prostate). ICD-9 189.3–189.9, urethra, paraurethral glands, and other and unspecified urinary—rarely reported individually and not as yet seen for the chemicals of interest; would be considered with bladder cancer. ICD-9 190, eye—to be considered with brain and other parts of nervous system. ICD-9 193, thyroid—to be considered with thymus and other endocrine cancers. ICD-9 194, other endocrine cancers—to be considered with thyroid and thymus as endocrine cancers. ICD-9 195, other and ill-defined sites—rarely reported individually and not as yet seen for the chemicals of interest; would be considered with other and unspecified cancers. ICD-9, 196–198, stated or presumed to be secondary of specified sites— rarely reported individually and not as yet seen for the chemicals of interest; would be considered with other and unspecified cancers. ICD-9, 199, site unspecified—rarely reported individually and not as yet seen for the chemicals of interest; would be considered with other and unspecified cancers. This committee’s search of previously reviewed studies for results on tonsil cancer and AML also identified sets of previously considered papers with reported findings specifically on lip cancer (ICD-9 140) and on tongue cancer (ICD-9 141), which both fall within the range for cancers of the oral (buccal) cavity. The current update includes separate sections discussing the site-specific results. In future updates, however, findings for these sites will be tracked on the results tables for the broader grouping that contains them: buccal cavity, nose, and pharynx (ICD-9 140–149, 160) for tonsil, tongue, and lip, and leukemias (ICD-9 204–208) for AML. For the digestive cancers, in future updates esophageal,
OCR for page 267
Veterans and Agent Orange: Update 2006 stomach, colorectal, hepatobiliary, and pancreatic cancers will be broken out into sections with individual conclusions. Care will be taken to specify as precisely as possible in results tables when findings are being reported for a subsite of a particular grouping. ORAL, NASAL, AND PHARYNGEAL CANCER Oral, nasal, and pharyngeal cancers (ICD-9 140–149, 160) are found in many anatomic subsites, including the structures of the mouth (inside lining of the lips, cheeks, gums, tongue, and hard and soft palate) (ICD-9 140–145), oropharynx (ICD-9 146), nasopharynx (ICD-9 147), hypopharynx (ICD-9 148), other buccal cavity and pharynx (ICD-9 149), and nasal cavity and paranasal sinuses (ICD-9 160). Although those sites are anatomically diverse, cancers that occur in the nasal cavity, oral cavity, and pharynx are for the most part similar in descriptive epidemiology and risk factors. The exception is cancer of the nasopharynx, which has a different epidemiologic profile. The American Cancer Society (ACS) estimated that about 30,990 men and women would receive a diagnosis of oral or pharyngeal cancer in the United States in 2006 and 7,430 men and women would die from these diseases (Jemal et al., 2006). Less than 10 percent as many cancers originate in the nasal cavity. Most oral, nasal, and pharyngeal cancers are squamous-cell carcinomas. Nasopharyngeal carcinoma (NPC) is the most common malignant tumor of the nasopharynx; it is relatively rare in the United States, where it accounts for about 0.25 percent of all cancers. There are three types of NPC: keratinizing squamous-cell carcinoma, nonkeratinizing carcinoma, and undifferentiated carcinoma. The average annual incidences reported in Table 6-2 show that men are at greater risk than women for those cancers and that the incidences increase with age, although there are few cases, and care should be exercised in interpreting the numbers. Tobacco and alcohol use are established risk factors for oral and pharyngeal cancers. Reported risk factors for nasal cancer include occupational exposure to nickel and chromium compounds (Hayes, 1997), wood dust (Demers et al., 1995), and formaldehyde (Blair and Kazerouni, 1997). Conclusions from VAO and Updates The committee responsible for VAO concluded that there was inadequate or insufficient information to determine whether there is an association between exposure to the compounds of interest and oral, nasal, and pharyngeal cancers. Additional information available to the committees responsible for Update 1996, Update 1998, Update 2000, Update 2002, and Update 2004 did not change that conclusion. Studies evaluated previously and in this report are summarized in Table 6-3.
OCR for page 268
Veterans and Agent Orange: Update 2006 TABLE 6-2 Average Annual Incidence (per 100,000) of Nasal, Nasopharyngeal, Oral Cavity and Pharynx, and Oropharynx Cancers in United Statesa 50–54 Years of Age 55–59 Years of Age 60–64 Years of Age All Races White Black All Races White Black All Races White Black Nose, Nasal Cavity, and Middle Ear: Men 1.2 1.1 1.2 1.6 1.5 1.8 2.0 2.0 3.0 Women 0.6 0.6 0.4 1.0 1.1 0.3 1.1 1.1 1.6 Nasopharynx: Men 1.8 1.0 1.7 2.3 1.5 1.8 3.1 1.6 4.5 Women 0.7 0.3 0.8 0.6 0.3 0.3 1.2 0.6 0.4 Oral Cavity and Pharynx: Men 28.4 27.6 42.0 37.2 36.4 53.1 47.9 47.3 66.1 Women 9.2 8.7 11.6 12.6 12.7 15.5 17.3 17.5 19.0 Oropharynx: Men 1.0 0.8 3.1 1.1 1.0 3.2 2.2 2.0 6.5 Women 0.1 0.1 0.2 0.6 0.5 1.8 0.2 0.2 0.0 a SEER (Surveillance, Epidemiology, and End Results program) nine standard registries, crude age-specific rates, 1999–2003. Update of the Epidemiologic Literature Occupational Studies McLean et al. (2006) reported on a multinational International Agency for Research on Cancer (IARC) cohort of 60,468 pulp and paper industry workers. A job–exposure matrix (JEM) was applied to 58,162 individual work histories to estimate exposure to nonvolatile organochlorine compounds (which would include TCDD). Deaths from cancers of the oral cavity and pharynx were significantly fewer among those who had been exposed to nonvolatile organochlorine compounds (n = 15; standardized mortality ratio [SMR] = 0.51, 95% confidence interval [CI] 0.29–0.85) but not among those who had never been exposed (n = 33; SMR = 0.92, 95% CI 0.63–1.29). Alavanja et al. (2005) reported that among the private pesticide applicators in the Agricultural Health Study (AHS), there were 66 cases of buccal-cavity cancer, which represented a significant deficit compared with the general population (standardized incidence ratio [SIR], 0.66, 95% CI 0.51–0.83). The corresponding results for commercial pesticide applicators were based on much smaller numbers of cases, so the confidence interval on the SIR was wide. Among the spouses of private applicators, the SIR for buccal cavity cancer was 0.73 (95% CI 0.40–1.22) on the basis of 14 cases. Nasal and pharyngeal cancers were not
OCR for page 269
Veterans and Agent Orange: Update 2006 TABLE 6-3 Selected Epidemiologic Studies—Oral, Nasal, and Pharyngeal Cancer Reference Study Population a,b Exposed Casesc Estimated Relative Risk (95% CI)c OCCUPATIONAL New Studies McLean et al., 2006 IARC cohort of pulp and paper workers Exposure to nonvolatile organochlorine compounds (oral cavity and pharynx) Never 33 0.9 (0.6–1.3) Ever 15 0.5 (0.3–0.9) Alavanja et al., 2005 US Agriculture Health Study—incidence (buccal cavity) Private applicators (men and women) 66 0.7 (0.5–0.8) Lip 25 1.4 (0.9–2.1) Spouses of private applicators (>99% women) 14 0.7 (0.4–1.2) Lip 2 1.4 (0.2–5.1) Commercial applicators (men and women) 5 0.9 (0.3–2.2) Lip 3 2.7 (0.6–8.0) Blair et al., 2005a US Agriculture Health Study (buccal cavity and pharynx) Private applicators (men and women) 5 0.3 (0.1–0.7) Spouses of private applicators (>99% women) 0 0.0 (0–25.4) ’t Mannetje et al., 2005 Phenoxy herbicide producers (men and women) (ICD-9 140–149) 2 2.8 (0.3–9.9) Lip (ICD-9 140) 0 * Mouth (ICD-9 141–145) 2 5.4 (0.7–20) Oropharynx (ICD-9 146) 0 * Nasopharynx (ICD-9 147) 0 0.0 (0.0–42) Hypopharynx and other (ICD-9 148–149) 0 * Phenoxy herbicide sprayers (>99% men) (ICD-9 140–149) 1 1.0 (0.0–5.7) Lip (ICD-9 140) 0 * Mouth (ICD-9 141–145) 0 0.0 (0.0–7.5) Oropharynx (ICD-9 146) 0 * Nasopharynx (ICD-9 147) 1 8.3 (0.2–46) Hypopharynx and other (ICD-9 148–149) 0 * Torchio et al., 1994 Italian licensed pesticide users Buccal cavity and pharynx 18 0.3 (0.2–0.5) Reif et al., 1989 New Zealand forestry workers—incidence Buccal cavity 3 0.7 (0.2–2.2) Nasopharyngeal 2 5.6 (1.6–19.5) Studies Reviewed in Update 2004 Nordby et al., 2004 Norwegian farmers born 1925–1971—incidence, lip Reported pesticide use * 0.7 (0.4–1.0) Swaen et al., 2004 Dutch licensed herbicide applicators Nose 0 — Mouth and pharynx 0 —
OCR for page 270
Veterans and Agent Orange: Update 2006 Reference Study Population a,b Exposed Casesc Estimated Relative Risk (95% CI)c Studies Reviewed in Update 2000 Caplan et al., 2000 Case–control study of US men born 1929–1953, all 70 nasal cancers (carcinomas, plus 11 lymphomas and 5 sarcomas) from CDC (1990a) study population Selected landscaping and forestry occupations 26 1.8 (1.1–3.1) Living or working on farm 23 0.5 (0.3–0.8) Herbicides or pesticides 19 0.7 (0.4–1.3) Phenoxy herbicides 5 1.2 (0.4–3.3) Studies Reviewed in Update 1998 Hooiveld et al., 1998 Workers at Dutch chemical factory (lip, oral cavity, pharynx) All working any time 1955–1985 1 2.3 (0.1–12.4) Cleaned up 1963 explosion 1 7.1 (0.2–39.6) Rix et al., 1998 Danish men and women paper mill workers Buccal cavity (ICD-7 140–144) Men 24 1.0 (0.7–1.5) Women 4 1.5 (0.4–3.8) Pharynx (ICD-7 145–149) Men 15 2.0 (1.1–3.3) Women 2 2.1 (0.2–7.6) Tonsil cancers among pharyngeal cancers 11 Kogevinas et al., 1997 IARC cohort (men and women)—Workers exposed to any phenoxy herbicide or chlorophenol Oral cavity and pharynx cancer (ICD-9 140–149) 26 1.1 (0.7–1.6) Exposed to TCDD 22 1.3 (0.8–2.0) Not exposed to TCDD 3 0.5 (0.1–1.3) Nose and nasal sinuses cancer (ICD-9 160) 3 1.6 (0.3–4.7) Exposed to TCDD 0 0.0 (0.0–3.5) Not exposed to TCDD 3 3.8 (0.8–11.1) Studies Reviewed in Update 1996 Becher et al., 1996 German phenoxy herbicide production workers (included in the IARC cohort) Buccal cavity, pharynx (ICD-9 140–149) 9 3.0 (1.4–5.6) Tongue 3 * Floor of mouth 2 * Tonsil 2 * Pharynx 2 * Asp et al., 1994 Finnish herbicide applicators Buccal and pharynx (ICD-8 140–149) Incidence 5 1.0 (0.3–2.3) Mortality 0 0.0 (0.0–3.0) “Other Respiratory” (ICD-8 160, 161, 163)—nose, larynx, pleura Incidence 4 1.1 (0.3–2.7) Mortality 1 0.5 (0.0–2.9)
OCR for page 271
Veterans and Agent Orange: Update 2006 Reference Study Population a,b Exposed Casesc Estimated Relative Risk (95% CI)c Studies Reviewed in VAO Blair et al., 1993 White male farmers from 23 state—deaths 1984–1988 Lip 21 2.3 (1.4–3.5) Ronco et al., 1992 Italian farmers (lip, tongue, salivary glands, mouth, pharynx)—mortality Self-employed 13 0.9 (*) Employees 4 0.5 (*) Danish self-employed farmers—incidence Lip 182 1.8 (p < 0.05) Tongue 9 0.6 (*) Salivary glands 13 0.9 (*) Mouth 14 0.5 (p < 0.05) Pharynx 13 0.3 (p < 0.05) Nasal cavities and sinuses 11 0.6 (*) Danish farming employees—incidence Lip 43 2.1 (p < 0.05) Tongue 2 0.6 (*) Salivary glands 0 0.0 (*) Mouth 0 0.0 (p < 0.05) Pharynx 9 1.1 (*) Nasal cavities and sinuses 5 1.3 (*) Saracci et al., 1991 IARC cohort—exposed subcohort (men and women) Buccal cavity and pharynx (ICD-8 140–149) 11 1.2 (0.6–2.1) Nose and nasal cavities (ICD-8 160) 3 2.9 (0.6–8.5) Zober et al., 1990 BASF Aktiengesellschaft accident cohort—33 cancers among 247 workers at 34-yr follow-up Squamous-cell carcinoma of tonsil 1 * Wiklund et al., 1989a Licensed Swedish pesticide applicators—incidence Lip 14 1.8 (1.0–2.9) Coggon et al., 1986 British MCPA production workers (included in the IARC cohort) Lip (ICD-9 140) 0 * Tongue (ICD-9 141) 1 1.1 (0.0–6.2) Pharynx (ICD-9 146–149) 1 0.5 (0.0–3.0) Nose (ICD-9 160) 3 4.9 (1.0–14.4) Robinson et al., 1986 Northwestern US paper and pulp workers Buccal cavity and pharynx (ICD-7 140–148) 1 0.1 (0.0–0.7) Nasal (ICD-7 160) 0 —* Wiklund, 1983 Swedish men and women agricultural workers—incidence Lip 508 1.8 (1.6–2.1) Tongue 32 0.4 (0.2–0.6) Salivary glands 68 1.0 (0.7–1.4) Mouth 70 0.6 (0.5–0.8) Throat 84 0.5 (0.4–0.7) Nose and nasal sinuses 64 0.8 (0.6–1.2)
OCR for page 506
Veterans and Agent Orange: Update 2006 Garland FC, Gorham ED, Garland CF, Ferns JA. 1988. Non-Hodgkin’s lymphoma in US Navy personnel. Archives of Environmental Health 43(6):425–429. Giri VN, Cassidy AE, Beebe-Dimmer J, Smith DC, Bock CH, Cooney KA. 2004. Association between Agent Orange and prostate cancer: A pilot case–control study. Urology 63(4):757–760; discussion 760–761. Green LM. 1991. A cohort mortality study of forestry workers exposed to phenoxy acid herbicides. British Journal of Industrial Medicine 48(4):234–238. Greenwald P, Kovasznay B, Collins DN, Therriault G. 1984. Sarcomas of soft tissues after Vietnam service. Journal of the National Cancer Institute 73(5):1107–1109. Hallquist A, Hardell L, Degerman A, Boquist L. 1993. Occupational exposures and thyroid cancer: Results of a case–control study. European Journal of Cancer Prevention 2(4):345–349. Hansen ES, Hasle H, Lander F. 1992. A cohort study on cancer incidence among Danish gardeners. American Journal of Industrial Medicine 21(5):651–660. Hardell L. 1981. Relation of soft-tissue sarcoma, malignant lymphoma and colon cancer to phenoxy acids, chlorophenols and other agents. Scandinavian Journal of Work, Environment and Health 7(2):119–130. Hardell L, Bengtsson NO. 1983. Epidemiological study of socioeconomic factors and clinical findings in Hodgkin’s disease, and reanalysis of previous data regarding chemical exposure. British Journal of Cancer 48(2):217–225. Hardell L, Ericksson M. 1999. A case–control study of non-Hodgkin lymphoma and exposure to pesticides. Cancer 85(6):1353–1360. Hardell L, Eriksson M, Lenner P, Lundgren E. 1981. Malignant lymphoma and exposure to chemicals, especially organic solvents, chlorophenols and phenoxy acids: A case–control study. British Journal of Cancer 43:169–176. Hardell L, Johansson B, Axelson O. 1982. Epidemiological study of nasal and nasopharyngeal cancer and their relation to phenoxy acid or chlorophenol exposure. American Journal of Industrial Medicine 3(3):247–257. Hardell L, Bengtsson NO, Jonsson U, Eriksson S, Larsson LG. 1984. Aetiological aspects on primary liver cancer with special regard to alcohol, organic solvents and acute intermittent porphyria: An epidemiological investigation. British Journal of Cancer 50(3):389–397. Hardell L, Eriksson M, Degerman A. 1994. Exposure to phenoxyacetic acids, chlorophenols, or organic solvents in relation to histopathology, stage, and anatomical localization of non-Hodgkin’s lymphoma. Cancer Research 54(9):2386–2389. Hardell L, Nasman A, Ohlson CG, Fredrikson M. 1998. Case–control study on risk factors for testicular cancer. International Journal of Oncology 13(6):1299–1303. Hardell L, Lindström G, van Bavel B, Hardell K, Linde A, Carlberg M, Liljegren G. 2001. Adipose tissue concentrations of dioxins and dibenzofurans, titers of antibodies to Epstein-Barr virus early antigen and the risk for non-Hodgkin’s lymphoma. Environmental Research 87(2):99–107. Hardell L, Eriksson M, Nordstrom M. 2002. Exposure to pesticides as risk factor for non-Hodgkin’s lymphoma and hairy cell leukemia: Pooled analysis of two Swedish case–control studies. Leukemia and Lymphoma 43(5):1043–1049. Harrison CJ, Mazzullo H, Ross FM, Cheung KL, Gerrard G, Harewood L, Mehta A, Lachmann HJ, Hawkins PN, Orchard KH. 2002. Translocations of 14q32 and deletions of 13q14 are common chromosomal abnormalities in systemic amyloidosis. British Journal of Haematology 117(2):427–435. Hartge P, Colt JS, Severson RK, Cerhan JR, Cozen W, Camann D, Zahm SH, Davis S. 2005. Residential herbicide use and risk of non-Hodgkin lymphoma. Cancer Epidemiology, Biomarkers and Prevention 14(4):934–937.
OCR for page 507
Veterans and Agent Orange: Update 2006 Hayashi H, Kanisawa M, Yamanaka K, Ito T, Udaka N, Ohji H, Okudela K, Okada S, Kitamura H. 1998. Dimethylarsinic acid, a main metabolite of inorganic arsenics, has tumorigenicity and progression effects in the pulmonary tumors of A/J mice. Cancer Letters 125(1-2):83–88. Hayes RB. 1997. The carcinogenicity of metals in humans. Cancer Causes and Control 8(3): 371–385. Hebert CD, Harris MW, Elwell MR, Birnbaum LS. 1990. Relative toxicity and tumor-promoting ability of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 2,3,4,7,8-pentachlorodibenzofuran (PCDF), and 1,2,3,4,7,8-hexachlorodibenzofuran (HCDF) in hairless mice. Toxicology and Applied Pharmacology 102(2):362–377. Henneberger PK, Ferris BG Jr, Monson RR. 1989. Mortality among pulp and paper workers in Berlin, New Hampshire. British Journal of Industrial Medicine 46(9):658–664. Hertzman C, Teschke K, Ostry A, Hershler R, Dimich-Ward H, Kelly S, Spinelli JJ, Gallagher RP, McBride M, Marion SA. 1997. Mortality and cancer incidence among sawmill workers exposed to chlorophenate wood preservatives. American Journal of Public Health 87(1):71–79. Hoar SK, Blair A, Holmes FF, Boysen CD, Robel RJ, Hoover R, Fraumeni JF. 1986. Agricultural herbicide use and risk of lymphoma and soft-tissue sarcoma. Journal of the American Medical Association 256(9):1141–1147. Hobbs CG, Birchall MA. 2004. Human papillomavirus infection in the etiology of laryngeal carcinoma. Current Opinion in Otolaryngology and Head and Neck Surgery 12(2):88–92. Hoffman RE, Stehr-Green PA, Webb KB, Evans RG, Knutsen AP, Schramm WF, Staake JL, Gibson BB, Steinberg KK. 1986. Health effects of long-term exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin. Journal of the American Medical Association 255(15):2031–2038. Holcombe M, Safe S. 1994. Inhibition of 7,12-dimethylbenzanthracene-induced rat mammary tumor growth by 2,3,7,8-tetrachlorodibenzo-p-dioxin. Cancer Letters 82(1):43–47. Holford TR, Zheng T, Mayne ST, Zahm SH, Tessari JD, Boyle P. 2000. Joint effects of nine polychlorinated biphenyl (PCB) congeners on breast cancer risk. International Journal of Epidemiology 29(6):975–982. Holmes AP, Bailey C, Baron RC, Bosanac E, Brough J, Conroy C, Haddy L. 1986. West Virginia Department of Health Vietnam-Era Veterans Mortality Study: Preliminary Report. Charlestown: West Virginia Health Department. Hooiveld M, Heederik DJ, Kogevinas M, Boffetta P, Needham LL, Patterson DG Jr, Bueno de Mesquita HB. 1998. Second follow-up of a Dutch cohort occupationally exposed to phenoxy herbicides, chlorophenols, and contaminants. American Journal of Epidemiology 147(9):891–901. Høyer AP, Jørgensen T, Brock JW, Grandjean P. 2000. Organochlorine exposure and breast cancer survival. Journal of Clinical Epidemiology 53(3):323–330. IARC (International Agency for Research on Cancer). 2001. Pathology and genetics of tumours of the haemopoietic and lymphoid tissues. In: Jaffe NL, Harris H, Stein, Vardiman JW, eds. World Health Organization, IARC. IOM (Institute of Medicine). 1994. Veterans and Agent Orange Health Effects of Herbicides Used in Vietnam. Washington, DC: National Academy Press. IOM. 1996. Veterans and Agent Orange: Update 1996. Washington, DC: National Academy Press. IOM. 1999. Veterans and Agent Orange: Update 1998. Washington, DC: National Academy Press. IOM. 2001. Veterans and Agent Orange: Update 2000. Washington, DC: National Academy Press. IOM. 2003. Veterans and Agent Orange: Update 2002. Washington, DC: The National Academies Press. IOM. 2005. Veterans and Agent Orange: Update 2004. Washington, DC: The National Academies Press. IOM. 2006. Asbestos: Selected Cancers. Washington, DC: The National Academies Press. Jemal A, Siegel R, Ward E, Murray T, Xu J, Smigal C, Thun MJ. 2006. Cancer statistics—2006. CA: A Cancer Journal for Clinicians 56(2):106–130. http://www.cancer.org/downloads/STT/CAFF-2006PWSecured.pdf (Accessed March 6, 2007)].
OCR for page 508
Veterans and Agent Orange: Update 2006 Kang HK, Weatherbee L, Breslin PP, Lee Y, Shepard BM. 1986. Soft tissue sarcomas and military service in Vietnam: A case comparison group analysis of hospital patients. Journal of Occupational Medicine 28(12):1215–1218. Kang HK, Mahan CM, Lee KY, Magee CA, Selvin S. 2000. Prevalence of gynecologic cancers among female Vietnam veterans. Journal of Occupational and Environmental Medicine 42(11): 1121–1127. Kato I, Watanabe-Meserve H, Koenig KL, Baptiste MS, Lillquist PP, Frizzera G, Burke JS, Moseson M, Shore RE. 2004. Pesticide product use and risk of non-Hodgkin lymphoma in women. Environmental Health Perspectives 112(13):1275–1281. Keller-Byrne JE, Khuder SA, Schaub EA, McAfee O. 1997. A meta-analysis of non-Hodgkin’s lymphoma among farmers in the central United States. American Journal of Industrial Medicine 31(4):442–444. Kennedy C, Bajdik CD, Willemze R, Bouwes Bavinck JN. 2005. Chemical exposures other than ar-Chemical exposures other than arsenic are probably not important risk factors for squamous cell carcinoma, basal cell carcinoma and malignant melanoma of the skin. British Journal of Dermatology 152(1):194–197. Ketchum NS, Michalek JE, Burton JE. 1999. Serum dioxin and cancer in veterans of Operation Ranch Hand. American Journal of Epidemiology 149(7):630–639. Key TJ, Schatzkin A, Willett WC, Allen NE, Spencer EA, Travis RC. 2004. Diet, nutrition and the prevention of cancer. Public Health Nutrition 7(1A):187–200. Kociba RJ, Keys DG, Beyer JE, Careon RM, Wade CE, Dittenber DA, Kalnins RP, Frauson LE, Park CN, Barnar SD, Hummel RA, Humiston CG. 1978. Results of a two-year chronic toxicity and oncogenicity study of 2,3,7,8-tetrachlorodibenzo-p-dioxin in rats. Toxicology and Applied Pharmacology 46:279–303. Kogan MD, Clapp RW. 1988. Soft tissue sarcoma mortality among Vietnam veterans in Massachusetts, 1972 to 1983. International Journal of Epidemiology 17(1):39–43. Kogevinas M, Saracci R, Bertazzi PA, Bueno de Mesquita BH, Coggon D, Green LM, Kauppinen T, Littorin M, Lynge E, Mathews JD, Neuberger M, Osman J, Pearce N, Winkelmann R. 1992. Cancer mortality from soft-tissue sarcoma and malignant lymphomas in an international cohort of workers exposed to chlorophenoxy herbicides and chlorophenols. Chemosphere 25:1071–1076. Kogevinas M, Saracci R, Winkelmann R, Johnson ES, Bertazzi PA, Bueno de Mesquita BH, Kauppinen T, Littorin M, Lynge E, Neuberger M. 1993. Cancer incidence and mortality in women occupationally exposed to chlorophenoxy herbicides, chlorophenols, and dioxins. Cancer Causes and Control 4(6):547–553. Kogevinas M, Kauppinen T, Winkelmann R, Becher H, Bertazzi PA, Bas B, Coggon D, Green L, Johnson E, Littorin M, Lynge E, Marlow DA, Mathews JD, Neuberger M, Benn T, Pannett B, Pearce N, Saracci R. 1995. Soft tissue sarcoma and non-Hodgkin’s lymphoma in workers exposed to phenoxy herbicides, chlorophenols and dioxins: Two nested case–control studies. Epidemiology 6(4):396–402. Kogevinas M, Becher H, Benn T, Bertazzi PA, Boffetta P, Bueno de Mesquita HB, Coggon D, Colin D, Flesch-Janys D, Fingerhut M, Green L, Kauppinen T, Littorin M, Lynge E, Mathews JD, Neuberger M, Pearce N, Saracci R. 1997. Cancer mortality in workers exposed to phenoxy herbicides, chlorophenols, and dioxins. An expanded and updated international cohort study. American Journal of Epidemiology 145(12):1061–1075. Lampi P, Hakulinen T, Luostarinen T, Pukkala E, Teppo L. 1992. Cancer incidence following chlorophenol exposure in a community in southern Finland. Archives of Environmental Health 47(3):167–175. LaVecchia C, Negri E, D’Avanzo B, Franceschi S. 1989. Occupation and lymphoid neoplasms. British Journal of Cancer 60(3):385–388. Lawrence CE, Reilly AA, Quickenton P, Greenwald P, Page WF, Kuntz AJ. 1985. Mortality patterns of New York State Vietnam veterans. American Journal of Public Health 75(3):277–279.
OCR for page 509
Veterans and Agent Orange: Update 2006 Leavy J, Ambrosini G, Fritschi L. 2006. Vietnam military service history and prostate cancer. BMC Public Health 6:75. Lee WJ, Lijinsky W, Heineman EF, Markin RS, Weisenburger DD, Ward MH. 2004a. Agricultural pesticide use and adenocarcinomas of the stomach and oesophagus. Occupational and Environmental Medicine 61(9):743–749. Lee WJ, Cantor KP, Berzofsky JA, Zahm SH, Blair A. 2004b. Non-Hodgkin’s lymphoma among asthmatics exposed to pesticides. International Journal of Cancer 111(2):298–302. Lee WJ, Colt JS, Heineman EF, McComb R, Weisenburger DD, Lijinsky W, Ward MH. 2005. Agricultural pesticide use and risk of glioma in Nebraska, United States. Occupational and Environmental Medicine 62(11):786–792. Lee WJ, Purdue MP, Stewart P, Schenk M, De Roos AJ, Cerhan JR, Severson RK, Cozen W, Hartge P, Blair A. 2006. Asthma history, occupational exposure to pesticides and the risk of non-Hodgkin’s lymphoma. International Journal of Cancer 118(12):3174–3176. Lin TM, Rasmussen NT, Moore RW, Albrecht RM, Peterson RE. 2004. 2,3,7,8-Tetrachlorodibenzo-p-dioxin inhibits prostatic epithelial bud formation by acting directly on the urogenital sinus. Journal of Urology 172(1):365–368. Liu J, Singh B, Tallini G, Carlson DL, Katabi N, Shaha A, Tuttle RM, Ghossein RA. 2006. Follicular variant of papillary thyroidcarcinoma: A clinicopathologic study of a problematic entity. Cancer 107:1255–1264. Lynge E. 1985. A follow-up study of cancer incidence among workers in manufacture of phenoxy herbicides in Denmark. British Journal of Cancer 52(2):259–270. Lynge E. 1993. Cancer in phenoxy herbicide manufacturing workers in Denmark, 1947–87—An update. Cancer Causes and Control 4(3):261–272. Mack TM. 1995. Sarcomas and other malignancies of soft tissue, retroperitoneum, peritoneum, pleura, heart, mediastinum, and spleen. Cancer 75(1):211–244. Magnani C, Coggon D, Osmond C, Acheson ED. 1987. Occupation and five cancers: A case–control study using death certificates. British Journal of Industrial Medicine 44(11):769–776. Mahan CM, Bullman TA, Kang HK, Selvin S. 1997. A case–control study of lung cancer among Vietnam veterans. Journal of Occupational and Environmental Medicine 39(8):740–747. Manz A, Berger J, Dwyer JH, Flesch-Janys D, Nagel S, Waltsgott H. 1991. Cancer mortality among workers in chemical plant contaminated with dioxin. Lancet 338(8773):959–964. Mayo Clinic. 2007. Tonsil Diagnosis. http://www.mayoclinic.org/tonsil-cancer/diagnosis.html (Accessed February 9, 2007). McDuffie HH, Klaassen DJ, Dosman JA. 1990. Is pesticide use related to the risk of primary lung cancer in Saskatchewan? Journal of Occupational Medicine 32(10):996–1002. McDuffie HH, Pahwa P, McLaughlin JR, Spinelli JJ, Fincham S, Dosman JA, Robson D, Skinnider LF, Choi NW. 2001. Non-Hodgkin’s lymphoma and specific pesticide exposures in men: Cross-Canada study of pesticides and health. Cancer Epidemiology, Biomarkers and Prevention 10(11):1155–1163. McDuffie HH, Pahwa P, Robson D, Dosman JA, Fincham S, Spinelli JJ, McLaughlin JR. 2005. Insect repellents, phenoxyherbicide exposure, and non-Hodgkin’s lymphoma. Journal of Occupational and Environmental Medicine 47(8):806–816. McGee SF, Lanigan F, Gilligan E, Groner B. 2006. Mammary gland biology and breast cancer. Conference on Common Molecular Mechanisms of Mammary Gland Development and Breast Cancer Progression. EMBO Reports 7(11):1084–1088. McLean D, Pearce N, Langseth H, Jäppinen P, Szadkowska-Stanczyk I, Person B, Wild P, Ki- shi R, Lynge E, Henneberger P, Sala M, Teschke K, Kauppinen T, Colin D, Kogevinas M, Boffetta. 2006. Cancer mortality in workers exposed to organochlorine compounds in the pulp and paper industry: An international collaborative study. Environmental Health Perspectives 114(7):1007–1012.
OCR for page 510
Veterans and Agent Orange: Update 2006 Mellemgaard A, Engholm G, McLaughlin JK, Olsen JH. 1994. Occupational risk factors for renal-cell carcinoma in Denmark. Scandinavian Journal of Work, Environment and Health 20(3):160–165. Merletti F, Richiardi L, Bertoni F, Ahrens W, Buemi A, Costa-Santos C, Eriksson M, Guenel P, Kaerlev L, Jockel K-H, Llopis-Gonzalez A, Merler E, Miranda A, Morales-Suarez-Varela MM, Olsson H, Fletcher T, Olsen J. 2006. Occupational factors and risk of adult bone sarcomas: A multicentric case–control study in Europe. International Journal of Cancer 118(3):721–727. Michalek JE, Wolfe WH, Miner JC. 1990. Health status of Air Force veterans occupationally exposed to herbicides in Vietnam. II. Mortality. Journal of the American Medical Association 264(14):1832–1836. Miligi L, Costantini AS, Bolejack V, Veraldi A, Benvenuti A, Nanni O, Ramazzotti V, Tumino R, Stagnaro E, Rodella S, Fontana A, Vindigni C, Vineis P. 2003. Non-Hodgkin’s lymphoma, leukemia, and exposures in agriculture: Results from the Italian Multicenter Case–Control Study. American Journal of Industrial Medicine 44:627–636. Miller BA, Kolonel LN, Bernstein L, Young JL Jr, Swanson GM, West D, Key CR, Liff JM, Glover CS, Alexander GA, et al. (eds). 1996. Racial/Ethnic Patterns of Cancer in the United States 1988–1992. Bethesda, MD: National Cancer Institute. NIH Pub. No. 96-4104. Mills PK, Yang R. 2005. Breast cancer risk in Hispanic agricultural workers in California. International Journal of Occupational and Environmental Health 11(2):123–131. Mills PK, Yang R. 2006. Regression analysis of pesticide use and breast cancer incidence in California Latinas. Journal of Environmental Health 68(6):15–22 and 43–44. Mills PK, Yang R, Riordan D. 2005. Lymphohematopoietic cancers in the United Farm Workers of America (UFW), 1988–2001. Cancer Causes and Control 16(7):823–830. Moennikes O, Loeppen S, Buchmann A, Andersson P, Ittrich C, Poellinger L, Schwarz M. 2004. A constitutively active dioxin/aryl hydrocarbon receptor promotes hepatocarcinogenesis in mice. Cancer Research 64(14):4707–4710. Morris PD, Koepsell TD, Daling JR, Taylor JW, Lyon JL, Swanson GM, Child M, Weiss NS. 1986. Toxic substance exposure and multiple myeloma: A case–control study. Journal of the National Cancer Institute 76(6):987–994. Morrison H, Semenciw RM, Morison D, Magwood S, Mao Y. 1992. Brain cancer and farming in western Canada. Neuroepidemiology 11(4-6):267–276. Morrison H, Savitz D, Semenciw RM, Hulka B, Mao Y, Morison D, Wigle D. 1993. Farming and prostate cancer mortality. American Journal of Epidemiology 137(3):270–280. Morrison HI, Semenciw RM, Wilkins K, Mao Y, Wigle DT. 1994. Non-Hodgkin’s lymphoma and agricultural practices in the prairie provinces of Canada. Scandinavian Journal of Work, Environment, and Health 20(1):42–47. Mulero-Navarro S, Carvajal-Gonzalez JM, Herranz M, Ballestar E, Fraga MF, Ropero S, Esteller M, Fernandez-Salguero PM. 2006. The dioxin receptor is silenced by promoter hypermethylation in human acute lymphoblastic leukemia through inhibition of Sp1 binding. Carcinogenesis 27(5):1099–1104. Musicco M, Sant M, Molinari S, Filippini G, Gatta G, Berrino F. 1988. A case–control study of brain gliomas and occupational exposure to chemical carcinogens: The risks to farmers. American Journal of Epidemiology 128:778–785. Nanni O, Amadori D, Lugaresi C, Falcini F, Scarpi E, Saragoni A, Buiatti E. 1996. Chronic lymphocytic leukaemias and non-Hodgkin’s lymphomas by histological type in farming-animal breeding workers: A population case–control study based on a priori exposure matrices. Occupational and Environmental Medicine 53(10):652–657. Navas-Acien A, Pollan M, Gustavsson P, Plato N. 2002. Occupation, exposure to chemicals and risk of gliomas and meningiomas in Sweden. American Journal of Industrial Medicine 42(3):214–227.
OCR for page 511
Veterans and Agent Orange: Update 2006 NCI (National Cancer Institute). 2006. Surveillance, Epidemiology, and End Results (SEER) Incidence and US Mortality Statistics: SEER Incidence—Crude Rates for White/Black/Other 1973–2002. http://seer.cancer.gov/canques/ (Accessed June 15, 2006). Nordby KC, Andersen A, Kristensen P. 2004. Incidence of lip cancer in the male Norwegian agricultural population. Cancer Causes and Control 15(6):619–626. Nordstrom M, Hardell L, Magnuson A, Hagberg H, Rask-Andersen A. 1998. Occupational exposures, animal exposures and smoking as risk factors for hairy cell leukemia evaluated in a case–control study. British Journal of Cancer 77(11):2048–2052. NTP (National Toxicology Program). 1982a. Technical Report Series No. 209. Carcinogenesis Bioassay of 2,3,7,8-Tetrachlorodibenzo-p-dioxin (CAS No. 1746-01-6) in Osborne-Mendel Rats and B6c3F1 Mice (Gavage Study). NIH Publication No. 82-1765. 195 pp. National Toxicology Program, Research Triangle Park, NC, and Bethesda, MD. NTP. 1982b. Technical Report Series No. 201. Carcinogenesis Bioassay of 2,3,7,8-Ttetrachlorodibenzo-p-dioxin (CAS No. 1746-01-6) in Swiss-Webster Mice (Dermal Study). National Toxicology Program. Research Triangle Park, NC, and Bethesda, MD. NTP. 2006. NTP Technical Report on the Toxicology and Carcinogenesis Studies of 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) (CAS No. 1746-01-6) in Female Harlan Sprague-Dawley Rats (Gavage Studies). Issue 521:4–232. National Toxicology Program, Research Triangle Park, NC, and Bethesda, MD. Nyska A, Jokinen MP, Brix AE, Sells Dm, Wyde ME, Orzech D, Haseman JK, Flake G, Walker NJ. 2004. Exocrine pancreatic pathology in female Harlan Sprague-Dawley rats after chronic treatment with 2,3,7,8-tetrachlorodibenzo-p-dioxin and dioxin-like compounds. Environmental Health Perspectives 112(8):903–909. Nyska A, Yoshizawa K, Jokinen MP, Brix AE, Sells DM, Wyde ME, Orzech DP, Kissling GE, Walker NJ. 2005. Olfactory epithelial metaplasia and hyperplasia in female Harlan Sprague-Dawley rats following chronic treatment with polychlorinated biphenyls. Toxicologic Pathology 33(3):371–377. O’Brien TR, Decoufle P, Boyle CA. 1991. Non-Hodgkin’s lymphoma in a cohort of Vietnam veterans. American Journal of Public Health 81:758–760. Ojajärvi IA, Partanen TJ, Ahlbom A, Boffetta P, Hakulinen T, Jourenkova N, Kauppinen TP, Kogevinas M, Porta M, Vainio HU, Weiderpass E, Wesseling CH. 2000. Occupational exposures and pancreatic cancer: a meta-analysis. Occupational and Environmental Medicine 57:316–324. Olsson H, Brandt L. 1988. Risk of non-Hodgkin’s lymphoma among men occupationally exposed to organic solvents. Scandinavian Journal of Work, Environment and Health 14:246–251. Ott MG, Zober A. 1996. Cause specific mortality and cancer incidence among employees exposed to 2,3,7,8-TCDD after a 1953 reactor accident. Occupational and Environmental Medicine 53:606–612. Pahwa P, McDuffie HH, Dosman J, Robson D, McLaughlin JR, Spinelli JJ, Fincham S. 2003. Exposure to animals and selected risk factors among Canadian farm residents with Hodgkins’ disease, multiple myeloma, or soft tissue sarcoma. Journal of Occupational and Environmental Medicine 45(8):857–868. Pahwa P, McDuffie HH, Dosman JA, McLaughlin JR, Spinelli JJ, Robson D, Fincham S. 2006. Hodgkin lymphoma, multiple myeloma, soft tissue sarcomas, insect repellents, and phenoxyherbicides. Journal of Occupational and Environmental Medicine 48(3):264–274. Pavuk M, Michalek JE, Schecter A, Ketchum NS, Akhtar FZ, Fox KA. 2005. Did TCDD exposure or service in Southeast Asia increase the risk of cancer in Air Force Vietnam veterans who did not spray Agent Orange? Journal of Occupational and Environmental Medicine 47(4):335–342. Pavuk M, Michalek JE, Ketchum NS. 2006. Prostate cancer in US Air Force veterans of the Vietnam War. Journal of Exposure Science and Environmental Epidemiology 16(2):184–190.
OCR for page 512
Veterans and Agent Orange: Update 2006 Pearce NE, Smith AH, Fisher DO. 1985. Malignant lymphoma and multiple myeloma linked with agricultural occupations in a New Zealand cancer registry-based sudy. American Journal of Epidemiology 121:225–237. Pearce NE, Smith AH, Howard JK, Sheppard RA, Giles HJ, Teague CA. 1986. Non-Hodgkin’s lymphoma and exposure to phenoxyherbicides, chlorophenols, fencing work, and meat works employment: A case–control study. British Journal of Industrial Medicine 43:75–83. Pearce NE, Sheppard RA, Smith AH, Teague CA. 1987. Non-Hodgkin’s lymphoma and farming: An expanded case–control study. International Journal of Cancer 39:155–161. Percy C, Ries GL, Van Holten VD. 1990. The accuracy of liver cancer as the underlying cause of death on death certificates. Public Health Reports 105:361–368. Persson B, Dahlander AM, Fredriksson M, Brage HN, Ohlson CG, Axelson O. 1989. Malignant lymphomas and occupational exposures. British Journal of Industrial Medicine 46:516–520. Persson B, Fredriksson M, Olsen K, Boeryd B, Axelson O. 1993. Some occupational exposures as risk factors for malignant lymphomas. Cancer 72:1773–1778. Pesatori AC, Consonni D, Tironi A, Landi MT, Zocchetti C, Bertazzi PA. 1992. Cancer morbidity in the Seveso area, 1976–1986. Chemosphere 25:209–212. Petreas M, Smith D, Hurley S, Jeffrey SS, Gilliss D, Reynolds P. 2004. Distribution of persistent, lipid-soluble chemicals in breast and abdominal adipose tissues: Lessons learned from a breast cancer study. Cancer Epidemiology, Biomarkers and Prevention 13(3):416–424. Poland A, Palen D, Glover E. 1982. Tumour promotion by TCDD in skin of HRS/J hairless mice. Nature 300(5889):271–273. Raaschou-Nielsen O, Pavuk M, LeBlanc A, Dumas P, Philippe Weber J, Olsen A, Tjonneland A, Overvad K, Olsen JH. 2005. Adipose organochlorine concentrations and risk of breast cancer among postmenopausal Danish women. Cancer Epidemiology, Biomarkers and Prevention 14(1):67–74. Rajkumar SV, Gertz MA, Kyle RA. 1998. Primary systemic amyloidosis with delayed progression to multiple myeloma. Cancer 82(8):1501–1505. Rajkumar SV, Dispenzieri A, Kyle RA. 2006. Monoclonal gammopathy of undetermined significance, Waldenstrom macroglobulinemia, AL amyloidosis, and related plasma cell disorders: Diagnosis and treatment. Mayo Clinic Proceedings 81(5):693–703. Ramlow JM, Spadacene NW, Hoag SR, Stafford BA, Cartmill JB, Lerner PJ. 1996. Mortality in a cohort of pentachlorophenol manufacturing workers, 1940–1989. American Journal of Industrial Medicine 30:180–194. Rao MS, Subbarao V, Prasad JD, Scarpelli DG. 1988. Carcinogenicity of 2,3,7,8-tetrachloridibenzo-p-dioxin in the Syrian golden hamster. Carcinogenesis 9(9):1677–1679. Reif JS, Pearce N, Fraser J. 1989. Occupational risks of brain cancer: A New Zealand cancer registry-based study. Journal of Occupational Medicine 31(10):863–867. Revich B, Aksel E, Ushakova T, Ivanova I, Zhuchenko N, Klyuev N, Brodsky B, Sotskov Y. Dioxin exposure and public health in Chapaevsk, Russia. Chemosphere 43(4-7):951–966. Reynolds P, Hurley SE, Goldberg DE, Anton-Culver H, Bernstein L, Deapen D, Horn-Ross PL, Peel D, Pinder R, Ross RK, West D, Wright WE, Ziogas A. 2004. Residential proximity to agricultural pesticide use and incidence of breast cancer in the California Teachers Study cohort. Environmental Research 96(2):206–218. Reynolds P, Hurley SE, Petreas M, Goldberg DE, Smith D, Gilliss D, Mahoney ME, Jeffrey SS. 2005. Adipose levels of dioxins and risk of breast cancer. Cancer Causes and Control 16(5):525–535. Riedel D, Pottern LM, Blattner WA. 1991. Etiology and epidemiology of multiple myeloma. In: Wiernick PH, Camellos G, Kyle RA, Schiffer CA, eds. Neoplastic Disease of the Blood and Blood Forming Organs. New York: Churchill Livingstone.
OCR for page 513
Veterans and Agent Orange: Update 2006 Riihimaki V, Asp S, Hernberg S. 1982. Mortality of 2,4-dichlorophenoxyacetic acid and 2,4,5-trichlorophenoxyacetic acid herbicide applicators in Finland: First report of an ongoing prospective cohort study. Scandinavian Journal of Work, Environment and Health 8:37–42. Rix BA, Villadsen E, Engholm G, Lynge E. 1998. Hodgkin’s disease, pharyngeal cancer, and soft tissue sarcomas in Danish paper mill workers. Journal of Occupational and Environmental Medicine 40(1):55–62. Robinson CF, Waxweiler RJ, Fowler DP. 1986. Mortality among production workers in pulp and paper mills. Scandinavian Journal of Work, Environment and Health 12:552–560. Robinson CF, Schnorr TM, Cassinelli RT, Calvert GM, Steenland K, Gersic CM, Schubauer-Bergian MK. 2006. Tenth Revision U.S. Mortality Rates: For Use with the NIOSH Life Table Analysis System. Journal of Occupational and Environmental Medicine 48(7):662–667. Ronco G, Costa G, Lynge E. 1992. Cancer risk among Danish and Italian farmers. British Journal of Industrial Medicine 49:220–225. Ruder AM, Waters MA, Butler MA, Carreon T, Calvert GM, Davis-King KE, Schulte PA, Sanderson WT, Ward EM, Connally LB, Heineman EF, Mandel JS, Morton RF, Reding DJ, Rosenman KD, Talaska G. 2004. Gliomas and farm pesticide exposure in men: The Upper Midwest Health Study. Archives of Environmental Health 59(12):650–657. Saracci R, Kogevinas M, Bertazzi PA, Bueno de Mesquita BH, Coggon D, Green LM, Kauppinen T, L’Abbe KA, Littorin M, Lynge E, Mathews JD, Neuberger M, Osman J, Pearce N, Winkelmann R. 1991. Cancer mortality in workers exposed to chlorophenoxy herbicides and chlorophenols. Lancet 338:1027–1032. Schreinemachers DM. 2000. Cancer mortality in four northern wheat-producing states. Environmental Health Perspectives 108(9):873–881. Semenciw RM, Morrison HI, Morison D, Mao Y. 1994. Leukemia mortality and farming in the prairie provinces of Canada. Canadian Journal of Public Health 85:208–211. Sharma-Wagner S, Chokkalingam AP, Malker HS, Stone BJ, McLaughlin JK, Hsing AW. 2000. Occupation and prostate cancer risk in Sweden. Journal of Occupational and Environmental Medicine 42(5):517–525. Simanainen U, Adamsson A, Tuomisto JT, Miettinen HM, Toppari J, Tuomisto J, Viluksela M. 2004a. Adult 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure and effects on male reproductive organs in three differentially TCDD-susceptible rat lines. Toxicological Sciences 81(2):401–407. Simanainen U, Haavisto T, Tuomisto JT, Paranko J, Toppari J, Tuomisto J, Peterson RE, Viluksela M. 2004b. Pattern of male reproductive system effects after in utero and lactational 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure in three differentially TCDD-sensitive rat lines. Toxicological Sciences 80(1):101–108. Smith AH, Pearce NE. 1986. Update on soft tissue sarcoma and phenoxyherbicides in New Zealand. Chemosphere 15:1795–1798. Smith AH, Fisher DO, Giles HJ, Pearce NE. 1983. The New Zealand soft tissue sarcoma case–control study: Interview findings concerning phenoxyacetic acid exposure. Chemosphere 12:565–571. Smith AH, Pearce NE, Fisher DO, Giles HJ, Teague CA, Howard JK. 1984. Soft tissue sarcoma and exposure to phenoxyherbicides and chlorophenols in New Zealand. Journal of the National Cancer Institute 73:1111–1117. Smith JG, Christophers AJ. 1992. Phenoxy herbicides and chlorophenols: A case–control study on soft tissue sarcoma and malignant lymphoma. British Journal of Cancer 65:442–448. Smith-Warner SA, Spiegelman D, Yaun SS, van den Brandt PA, Folsom AR, Goldbohm RA, Graham S, Holmberg L, Howe GR, Marshall JR, Miller AB, Potter JD, Speizer FE, Willett WC, Wolk A, Hunter DJ. 1998. Alcohol and breast cancer in women: A pooled analysis of cohort studies. Journal of the American Medical Association 279(7):535–540. Solet D, Zoloth SR, Sullivan C, Jewett J, Michaels DM. 1989. Patterns of mortality in pulp and paper workers. Journal of Occupational Medicine 31:627–630.
OCR for page 514
Veterans and Agent Orange: Update 2006 Solomon A. 1999. What is amyloidosis? Myeloma Today 3(2). http://myeloma.org/MyelomaToday/Volume2/Number3/imf_asa.html (Accessed December 19, 2000). Steenland K, Piacitelli L, Deddens J, Fingerhut M, Chang LI. 1999. Cancer, heart disease, and diabetes in workers exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin. Journal of the National Cancer Institute 91(9):779–786. Svensson BG, Mikoczy Z, Stromberg U, Hagmar L. 1995. Mortality and cancer incidence among Swedish fishermen with a high dietary intake of persistent organochlorine compounds. Scandinavian Journal of Work, Environmental and Health 21(2):106–115. Swaen GMH, van Vliet C, Slangen JJM, Sturmans F. 1992. Cancer mortality among licensed herbicide applicators. Scandinavian Journal of Work, Environment and Health 18:201–204. Swaen GM, van Amelsvoort LG, Slangen JJ, Mohren DC. 2004. Cancer mortality in a cohort of licensed herbicide applicators. International Archives of Occupational and Environmental Health 77(4):293–295. ’t Mannetje A, McLean D, Cheng S, Boffetta P, Colin D, Pearce N. 2005. Mortality in New Zealand workers exposed to phenoxy herbicides and dioxins. Occupational and Environmental Medicine 62(1):34–40. Tarone RE, Hayes HM, Hoover RN, Rosenthal JF, Brown LM, Pottern LM, Javadpour N, O’Connell KJ, Stutzman RE. 1991. Service in Vietnam and risk of testicular cancer. Journal of the National Cancer Institute 83:1497–1499. Thiess AM, Frentzel-Beyme R, Link R. 1982. Mortality study of persons exposed to dioxin in a trichlorophenol-process accident that occurred in the BASF AG on November 17, 1953. American Journal of Industrial Medicine 3:179–189. Thomas TL. 1987. Mortality among flavour and fragrance chemical plant workers in the United States. British Journal of Industrial Medicine 44:733–737. Thomas TL, Kang HK. 1990. Mortality and morbidity among Army Chemical Corps Vietnam veterans: a preliminary report. American Journal of Industrial Medicine 18:665–673. Thomas TL, Kang H, Dalager N. 1991. Mortality among women Vietnam veterans, 1973–1987. American Journal of Epidemiology 134:973–980. Thörn Å, Gustavsson P, Sadigh J, Westerlund-Hännerstrand B, Hogstedt C. 2000. Mortality and cancer incidence among Swedish lumberjacks exposed to phenoxy herbicides. Occupational and Environmental Medicine 57:718–720. Toth K, Somfai-Relle S, Sugar J, Bence J. 1979. Carcinogenicity testing of herbicide 2,4,5-trichlorophenoxyethanol containing dioxin and of pure dioxin in Swiss mice. Nature 278(5704): 548–549. Torchio P, Lepore AR, Corrao G, Comba P, Settimi L, Belli S, Magnani C, di Orio F. 1994. Mortality study on a cohort of Italian licensed pesticide users. Science of the Total Environment 149(3):183–191. Tuomisto JT, Pekkanen J, Kiviranta H, Tukiainen E, Vartiainen T, Tuomisto J. 2004. Soft-tissue sarcoma and dioxin: A case–control study. International Journal of Cancer 108(6):893–900. US Census. 1999. Statistical Abstract of the United States: 1999, 119th Edition. Washington, DC: US Bureau of the Census. van Grevenynghe J, Bernard M, Langouet S, Le Berre C, Fest T, Fardel O. 2005. Human CD34-positive hematopoietic stem cells constitute targets for carcinogenic polycyclic aromatic hydrocarbons. Journal of Pharmacology and Experimental Therapeutics 314(2):693–702. Van Miller JP, Lalich JJ, Allen JR. 1977. Increased incidence of neoplasms in rats exposed to low levels of 2,3,7,8-tetrachlorodibenzo-p-dioxin. Chemosphere 9:537–544. Viel JF, Arveux P, Baverel J, Cahn JY. 2000. Soft-tissue sarcoma and non-Hodgkin’s lymphoma clusters around a municipal solid waste incinerator with high dioxin emission levels. American Journal of Epidemiology 152(1):13–19.
OCR for page 515
Veterans and Agent Orange: Update 2006 Vineis P, Terracini B, Ciccone G, Cignetti A, Colombo E, Donna A, Maffi L, Pisa R, Ricci P, Zanini E, Comba P. 1986. Phenoxy herbicides and soft-tissue sarcomas in female rice weeders. A population-based case-referent study. Scandinavian Journal of Work, Environment and Health 13:9–17. Vineis P, Faggiano F, Tedeschi M, Ciccone G. 1991. Incidence rates of lymphomas and soft-tissue sarcomas and environmental measurements of phenoxy herbicides. Journal of the National Cancer Institute 83:362–363. Visintainer PF, Barone M, McGee H, Peterson EL. 1995. Proportionate mortality study of Vietnam-era veterans of Michigan. Journal of Occupational and Environmental Medicine 37(4):423–428. Vorderstrasse BA, Fenton SE, Bohn AA, Cundiff JA, Lawrence BP. 2004. A novel effect of dioxin: Exposure during pregnancy severely impairs mammary gland differentiation. Toxicological Sciences 78(2):248–257. Walker NJ, Wyde ME, Fischer LJ, Nyska A, Bucher JR. 2006. Comparison of chronic toxicity and carcinogenicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in 2-year bioassays in female Sprague-Dawley rats. Molecular Nutrition and Food Research 50(10):934–944. Warner M, Eskenazi B, Mocarelli P, Gerthoux PM, Samuels S, Needham L, Patterson D, Brambilla P. 2002. Serum dioxin concentrations and breast cancer risk in the Seveso Women’s Health Study. Environmental Health Perspectives 110(7):625–628. Watanabe KK, Kang HK. 1995. Military service in Vietnam and the risk of death from trauma and selected cancers. Annals of Epidemiology 5:407–412. Watanabe KK, Kang HK. 1996. Mortality patterns among Vietnam veterans: A 24-year retrospective analysis. Journal of Occupational and Environmental Medicine 38(3):272–278. Watanabe KK, Kang HK, Thomas TL. 1991. Mortality among Vietnam veterans: With methodological considerations. Journal of Occupational Medicine 33:780–785. Waterhouse D, Carman WJ, Schottenfeld D, Gridley G, McLean S. 1996. Cancer incidence in the rural community of Tecumseh, Michigan: A pattern of increased lymphopoietic neoplasms. Cancer 77(4):763–770. Wei M, Wanibuchi H, Morimura K, Iwai S, Yoshida K, Endo G, Nakae D, Fukushima S. 2002. Carcinogenicity of dimethylarsinic acid in make F344 rats and genetic alterations in incuded urinary bladder tumors. Carcinogenesis 23(8):1387–1397. Weiderpass E, Adami HO, Baron JA, Wicklund-Glynn A, Aune M, Atuma S, Persson I. 2000. Organochlorines and endometrial cancer risk. Cancer Epidemiology, Biomarkers and Prevention 9:487–493. Wigle DT, Semenciw RB, Wilkins K, Riedel D, Ritter L, Morrison HI, Mao Y. 1990. Mortality study of Canadian male farm operators: Non-Hodgkin’s lymphoma mortality and agricultural practices in Saskatchewan. Journal of the National Cancer Institute 82:575–582. Wiklund K. 1983. Swedish agricultural workers: A group with a decreased risk of cancer. Cancer 51:566–568. Wiklund K, Lindefors BM, Holm LE. 1988. Risk of malignant lymphoma in Swedish agricultural and forestry workers. British Journal of Industrial Medicine 45:19–24. Wiklund K, Dich J, Holm LE, Eklund G. 1989a. Risk of cancer in pesticide applicators in Swedish agriculture. British Journal of Industrial Medicine 46:809–814. Wiklund K, Dich J, Holm LE. 1989b. Risk of soft tissue sarcoma, Hodgkin’s disease and non-Hodgkin’s lymphoma among Swedish licensed pesticide applicators. Chemosphere 18:395–400. Wolfe WH, Michalek JE, Miner JC, Rahe A, Silva J, Thomas WF, Grubbs WD, Lustik MB, Karrison TG, Roegner RH, Williams DE. 1990. Health status of Air Force veterans occupationally exposed to herbicides in Vietnam. I. Physical health. Journal of the American Medical Association 264:1824–1831. Woods JS, Polissar L, Severson RK, Heuser LS, Kulander BG. 1987. Soft tissue sarcoma and non-Hodgkin’s lymphoma in relation to phenoxy herbicide and chlorinated phenol exposure in western Washington. Journal of the National Cancer Institute 78:899–910.
OCR for page 516
Veterans and Agent Orange: Update 2006 Wrensch M, Minn Y, Chew T, Bondy M, Berger MS. 2002. Epidemiology of primary brain tumors: Current concepts and review of the literature. Neuro-Oncology 4(4):278–299. Wu CH, Chen HL, Su HJ, Lee CC, Shen KT, Ho WL, Ho SY, Ho YS, Wang YJ. 2004. The topical application of 2,3,7,8-tetrachlorodibenzo-p-dioxin lacks skin tumor-promoting potency but induces hepatic injury and tumor necrosis factor-alpha expression in ICR male mice. Food and Chemical Toxicology 42(8):1217–1225. Wyde ME, Braen AP, Hejtmancik M, Johnson JD, Toft JD, Blake JC, Cooper SD, Mahler J, Vallant M, Bucher JR, Walker NJ. 2004. Oral and dermal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induces cutaneous papillomas and squamous cell carcinomas in female hemizygous Tg.AC transgenic mice. Toxicological Sciences 82(1):34–45. Yamamoto S, Konishi Y, Matsuda T, Murai T, Shibata MA, Matsui-Yuasa I, Otani S, Kuroda K, Endo G, Fukushima S. 1995. Cancer incidence by an organic arsenic compound, dimethylarsinic acid (cacodylic acid), in F344/DuCrj rats after pretreatment with five carginogens. Cancer Research 55(6):1271–1276. Yamanaka K, Ohtsubo K, Hasegawa A, Hayashi H, Ohji H, Kanisawa M, Okada S. 1996. Exposure to dimethylarsinic acid, a main metabolite of inorganic arsenics, strongly promotes tumorigenesis initiated by 4-nitroquinoline 1-oxide in the lungs of mice. Carcinogenesis 17(4):767–770. Yoshizawa K, Walker NJ, Jokinen MP, Brix AE, Sells DM, Marsh T, Wyde ME, Orzech D, Haseman JK, Nyska A. 2005a. Gingival carcinogenicity in female Harlan Sprague-Dawley rats following two-year oral treatment with 2,3,7,8-tetrachlorodibenzo-p-dioxin and dioxin-like compounds. Toxicological Sciences 83(1):64–77 [erratum appears in Toxicological Sciences 2005; 83(2):405–406]. Yoshizawa K, Marsh T, Foley JF, Cai B, Peddada S, Walker NJ, Nyska A. 2005b. Mechanisms of exocrine pancreatic toxicity induced by oral treatment with 2,3,7,8-tetrachlorodibenzo-p-dioxin in female Harlan Sprague-Dawley rats. Toxicological Sciences 85(1):594–606. Zack JA, Suskind RR. 1980. The mortality experience of workers exposed to tetrachlorodibenzodioxin in a trichlorophenol process accident. Journal of Occupational Medicine 22:11–14. Zahm SH, Fraumeni JF Jr. 1997. The epidemiology of soft tissue sarcoma. Seminars in Oncology 24(5):504–514. Zahm SH, Weisenburger DD, Babbitt PA, Saal RC, Vaught JB, Cantor KP, Blair A. 1990. A case– control study of non-Hodgkin’s lymphoma and the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) in eastern Nebraska. Epidemiology 1:349–356. Zahm SH, Blair A, Weisenburger DD. 1992. Sex differences in the risk of multiple myeloma associated with agriculture (2). British Journal of Industrial Medicine 49:815–816. Zahm SH, Weisenburger DD, Saal RC, Vaught JB, Babbitt PA, Blair A. 1993. The role of agricultural pesticide use in the development of non-Hodgkin’s lymphoma in women. Archives of Environmental Health 48:353–358. Zhong Y, Rafnsson V. 1996. Cancer incidence among Icelandic pesticide users. International Journal of Epidemiology 25(6):1117–1124. Zober A, Messerer P, Huber P. 1990. Thirty-four-year mortality follow-up of BASF employees exposed to 2,3,7,8-TCDD after the 1953 accident. International Archives of Occupational and Environmental Health 62:139–157.