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Appendix C Epidemiologic Studies Cited in Chapter 6: Health Outcomes Table C-1 includes descriptions of epidemiologic studies cited in Chapter 6. Key and supporting studies are presented alphabetically with studies of Gulf War veterans listed in a separate section at the end of the table. Text in italics reflects the section and designation (k = key, s = supporting) of each study as it is cited in the chapter. 139

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TABLE C-1 Epidemiologic Studies Cited in Chapter 6: Health Outcomes 140 Study and Design Population Exposure Outcomes Adjustments Limitations and Comments Aronson et al. 5,414 firefighters Employed as a Cause of death. Compared with general male Modified life-table Multiple testing-findings 1994 who had worked at firefighter (yes/ population of Ontario. approach; subjects labeled as statistically any time between no); years since Total Cohort: censored at age 85 significant by chance Retrospective 1950 and 1989 at first exposure (first Brain cancer and other NS tumors (ICD9 191- years; cata stratified alone; healthy worker cohort study. six fire departments employment); years 192): SMR 201, 95% by years since first effect and survivor in Metropolitan of exposure (years CI 110-337; Other Malignant Neoplasms employment, age, effect. [Respiratory-s; Toronto. Includes of employment). (ICD9 195-199): SMR 238, 95% CI 145-367; and duration of Circulatory-k; 777 deaths. Diabetes mellitus (ICD9 250): SMR 35, 95% employment. Cancer-k; All CI 9-88; Chronic rheumatic heart disease (ICD Cause-k] 393-398, 424.0-424.3): SMR 15, 95% CI 0.4- 85; Aortic aneurysm (ICD9 441): SMR 226, 95% CI 136-354; Symptoms/Ill-defined (ICD9 780-799): SMR 17, 95% CI 0.4-95); External Causes (ICD9 E800-999): SMR 71, 95% CI 55-90) Age 60-84: Aortic aneurysm: SMR 245, 95% CI 140- 398; Chronic bronchitis, asthma, and emphysema: 155, 95% CI 101-227; Digestive system diseases: SMR 156, 95% CI 100-232; Gallbladder diseases: 420, 95% CI 136-980; all other causes NS. Aronson et al. 9,340 Fathers of Father’s occupation Cardiac congenital anomalies. Matched on birth year, 1996 all children with as a firefighter in 11 case and 9 controls had fathers who were maternal age at birth, congenital heart Toronto. firefighters (OR 1.22, 95% CI 0.46-3.33). birth order, parents’ Registry-based defects matched birth places (in or case-control to 9,340 Toronto out of Ontario), and study fathers of children mother’s marital status without an anomaly, at birth. [Reproductive-s] from the Toronto birth registry 1979- 1986. Bandaranayke et 245 firefighters Presence at a Nervous system dysfunction. Matched for age and Tests conducted 4 years al. 1993 exposed to a chemical fire in More exposed firefighters exhibited CNS years of service. after the fire event; chemical fire 1984. dysfunction than unexposed firefighters (in 3 cases of testicular Case-control in 1984, and 4 categories of symptoms, all p<0.025). cancer described. study 217 unexposed Firefighters score poorly on more firefighters matched neuropsychological tests (RR 1.32, 95% CI [Neurological-s] for age and years 1.11-1.57), particularly psychomotor tests of service in New (RR 1.51, 95% CI 1.33-1.71, compared to Zealand. unexposed firefighters.

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No differences in hospital admissions, health problems, prevalence of allergies, history of miscarriages due to abnormality or stillbirth, or birth defects, psychological histories, tobacco or alcohol use, abnormal ECGs, blood cell counts were detected between the exposed and unexposed firefighters. Baris et al. 2001 7,789 Firefighters Duration of Cause of death compared with the general US Age and calendar-year Duration of employment, in Philadelphia employment, white male population; RR between high and adjusted with a 10-year company runs and Retrospective employed between company runs, low exposure groups. lag period; stratified station house design cohort study 1 Jan. 1925, and 31 and station house Total Cohort: by position, duration as a surrogate for Dec. 1986. Females design were used All causes: SMR 0.96, 95% CI 0.92-0.99; All of employment, age individual exposure [Respiratory-s; excluded. 2,220 as a surrogate for cancers: SMR 1.10, 95% CI 1.00-1.20; Colon at risk, hire period, may be some exposure Neurological-k; deaths. individual exposure. cancer: SMR 1.51, 95% CI 1.18-1.93; Ischemic company type (ladder, misclassification. Circulatory-k; Categories of runs heart disease: SMR 1.09, 95% CI 1.02-1.16; engine or both). Healthy worker effect Cancer-k; All were categorized as Cerebrovascular Disease: SMR 0.83, 95% CI and survivor effect. Cause] low, medium, high. 0.69-0.99; Respiratory diseases: SMR 0.67, 95% CI 0.55-0.82; Genitourinary diseases: SMR 0.54, 95% CI 0.36-0.81; External causes of death: SMR 0.69, 95% CI 0.59-0.80; All accidents: SMR 0.72, 95% CI 0.59-0.86; Suicide: SMR 0.66, 95% CI 0.48-0.92; All other causes NS. ≤ 9 Years Employment: All cancers: SMR 1.26, 95% CI 1.07-1.49; Colon cancer: SMR 1.78, 95% CI 1.12-2.82; Lung cancer: SMR 1.52, 95% CI 1.16-2.01; Pancreatic cancer: SMR 2.33, 95% CI 1.36- 4.02; Prostate cancer: SMR 2.36, 95% CI 1.42- 3.91; Genitourinary disease: SMR 0.27, 95% CI 0.10-0.71; External causes of death: SMR 0.61, 95% CI 0.49-0.77; All accidents: SMR 0.56, 95% CI 0.43-0.75; All other causes NS. 10-19 Years Employment: Circulatory diseases: SMR 1.20, 95% CI 1.10- 1.31; Ischemic heart disease: SMR 1.35, 95% CI 1.21-1.49; Respiratory diseases: SMR 0.68, 95%CI 0.49-0.96; Suicide: SMR 0.37, 95% CI 0.18-0.78; All other causes NS. 141 continued

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TABLE C-1 Continued 142 Study and Design Population Exposure Outcomes Adjustments Limitations and Comments ≥ 20 Years Employment: All causes: SMR 0.91, 95% CI 0.85-0.98; Colon cancer: SMR 1.68, 95% CI 1.17-2.40; Kidney cancer: SMR 2.20, 95% CI 1.18-2.49; Multiple myeloma: SMR 2.31, 95% CI 1.04- 5.16; Benign neoplasms: SMR 2.54 1.06-6.11; Circulatory diseases: SMR 0.90, 95% CI 0.82- 0.99; Respiratory diseases: SMR 0.59, 95% CI 0.42-0.82; Emphysema: SMR 0.39, 95% CI 0.16-0.93; All other causes NS. Comparing High to Low (> or ≤ 3,191 cumulative runs) Exposure: All causes: RR 0.81, 95% CI 0.72-0.92; Buccal cavity and pharynx cancer: RR 0.19, 95% CI 0.04-0.96; Circulatory diseases: RR 0.78, 95% CI 0.65-0.93; Ischemic heart diseases: RR 0.77, 95% CI 0.63-0.95; External causes of death: RR 0.61, 95%CI 0.39-0.95; All other causes NS. Bates 1987 596 men who Cardiovascular mortality ages 45 to 54 though Standardized by age, worked for 6 yrs or 1984, compared to mortality rates of Toronto. sex, and calendar year. Cohort study more in the Toronto 52 deaths from all causes, 21 from coronary Fire Department; artery diseases. [Circulatory-s] hired from 1949- Ages 45-49: SMR 1.80, 95% CI 1.01-3.19 1959. Ages 50-54: SMR 1.75, 95% CI 0.90-3.39 Ages 45-54: SMR 1.73, 95% CI 1.12-2.66. Bates 2007 3,659 firefighters Ever employed as Cancer diagnosis among firefighters compared Age, calendar period with cancer and firefighter. to cancer diagnoses among other occupations. of diagnosis, race, Registry-based 800,448 non- Esophageal: OR 1.48, 95% CI 1.14-1.91; socio-economic status case-control firefighter controls Melanoma skin: OR 1.50, 95% CI 1.33- (by census block of study with cancer, in 1.70; Prostate: OR 1.22, 95% CI 1.12-1.33; residence). from the California Testicular: OR 1.54, 95% CI 1.18-2.02; Brain: [Cancer-k] Cancer Registry, OR 1.35, 95% CI 1.06-1.72; All other sites NS. 1988-2003. Bates et al. 2001 4,305 firefighters Ever employed as a Cancer incidence and mortality, calculated as Age, sex and calendar This study follows up employed in New firefighter; duration SIR and SMR relative to New Zealand male period standardized. on a testicular cancer Retrospective Zealand between of employment as a population, follow-up 1977 through 1995 for cluster described by cohort study 1977-1995. firefighter. mortality, 1996 for cancer. Bandaranayake et al. Cancer incidence 1977-1996: All sites NS. 1993.

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[Cancer-s] Cancer incidence 1990-1996: Testicular cancer Possibly confounded by incidence: SIR 2.97, 95% CI 1.3-5.9; all other high level of awareness sites NS. of testicular cancer in Mortality 1977-1995: All causes: SMR 0.58, this population. 95% CI 0.5-0.7; Circulatory diseases: SMR Healthy worker effect. 0.54, 95% CI 0.4-0.7; Ischemic heart disease: SMR 0.58, 95% CI 0.4-0.8; External causes: SMR 0.69, 95% CI 0.3-0.8; All other causes NS. Beaumont et al. 3,066 white male Firefighter Cause of death. Compared with the general US Rate ratios standardized Reliability of death 1991 firefighters from San employment (yes/ male population. for age, year, sex, and certificates. Potential Francisco employed no). Length of All causes: RR 0.90, 95% CI 0.85-0.95; race. healthy worker effect. Retrospective 1940-1970. 1,186 employment. Tuberculosis: RR 0.26, 95% CI 0.07-0.68; cohort study. deaths. Diabetes melliutus: RR 0.36, 95% CI 0.14- 0.75; Diseases of the heart: RR 0.89, 95% CI [Respiratory-s; 0.81-0.97; Respiratory diseases: RR 0.63, 95% Neurological-s; CI 0.47-0.83; Acute respiratory infections: Circulatory-k; RR 0.63, 95% CI 0.40-0.95; Emphysema: RR Cancer-k; All 0.52; 0.24-0.99; Digestive system diseases: RR Cause] 1.57, 95% CI 1.27-1.92; Cirrhosis and other liver diseases: RR 2.27, 95% CI 1.73-2.93; Accidental falls: RR 1.9, 95% CI 1.18-2.91; Cancer of digestive organs and peritoneum: RR 1.27, 95% CI 1.04-1.55; Esophageal cancer: RR 2.04, 95% CI 1.05-3.57; Prostate cancer: RR 0.38, 95% CI 0.16-0.75. All other causes NS. 3-19 Years Since First Employment: All neoplasm sites NS. 20-29 Years Since First Employment: All cancer sites: RR 0.67, statistically significant (95% CI not reported); All other neoplasm sites NS 30-39 Years Since First Employment: Billiary passages, liver and gall bladder cancer: RR 3.87, statistically significant (95% CI not reported); All other neoplasm sites NS 40+ Years Since First Employment: Stomach cancer: RR 2.32, statistically significant (95% CI not reported); All other neoplasm sites NS. 143 continued

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TABLE C-1 Continued 144 Study and Design Population Exposure Outcomes Adjustments Limitations and Comments 3-9, 10-19, and 20-29 Years of Employment: All neoplasm sites NS. 30+ Years of Employment: Billiary passages, liver and gall bladder cancer: RR 3.87, statistically significant (95% CI not reported); All other neoplasm sites NS. Betchley et al. Full-time and Shift or season of Spirometric measurements of lung function 1997 seasonal wildland firefighting. and self administered questionnaire data were fire management collected before and after the 1992 firefighting Cohort study workers in Region season. Cross-season data were collected on 6 of USDA Forest average 77.7 days after the last occupational [Respiratory-s] Service and smoke exposure. Bureau of Land Cross-season analysis: Mean individual Management in declines for FVC (p=0.28), FEV1 (p=0.03) Salem during the and FEF25–75 (p=0.02) of 0.033 L, 0.104 L, 1992 season. and 0.275 L/sec, respectively; no significant 76 subjects were difference in respiratory symptoms. studied for cross- Cross-shift analysis: The pre-shift to mid-shift shift and 53 for decreases were 0.089 L, 0.190 L, and 0.439 cross-season L/sec, respectively; pre-shift to post-shift analysis. declines of 0.065 L, 0.150 L, and 0.496 L/sec (all p<0.01); no significant difference in respiratory symptoms. Biggeri et al. 755 male lung Exposure model Excess relative risk of 6.7 at zero distance Adjusted for age, Lung cancer also 1996 cancer deaths and based on residential (p<0.001), with risk dropping rapidly with smoking, likelihood of significantly related to 755 controls from distance and distance (slope = –0.176). occupational carcinogen distance from the city Case-control a local autopsy direction from exposures, levels of center. study registry in Trieste, sources of pollution- PM. Italy. shipyard, iron [Cancer-s] foundry, incinerator, or city center. Bresnitz et al. 86 male incinerator High or low Spirometry, blood and urine samples, physical Stratified by smoking High and low exposure 1992 workers at a facility exposure was exams, questionnaires used to collect health, and alcohol. groups differed by in Philadelphia determined by medical, and employment information. No correction for duration of employment Cross-sectional employed in June an industrial Elevated exposure was not significantly related multiple comparisons. and alcohol intake; study 1988. hygienist based on to biomarkers of exposure, hypertension, no unexposed job description, proteinuria, or changes in pulmonary function. comparison group. [Respiratory-s] duration, and data from personal breathing zone and

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general air sample for dioxins and furans. Burnett et al. 5,744 white Ever employed as Cause of death Age, race, sex adjusted. 1994 male firefighter firefighter. Total Cohort deaths identified All cancers: PMR 110, 95% CI 106-114; Retrospective from National Rectal cancer: PMR 148, 95% CI 105-205); cohort study Occupational Skin cancer: PMR 163, 95% CI 115-223; Mortality Kidney cancer: PMR 144, 95% CI 108- [Circulatory-s; Surveillance system 189; Lymphatic and hematopoietic cancers: Cancer-s] (includes 27 states) PMR 130, 95% CI 111-151; Non-Hodgkin’s from 1984-1990. lymphoma: PMR 132, 95% CI 102-167; Multiple myeloma: PMR 148, 95% CI 102- 207; Accidental falls: PMR 149, 95% CI 109- 199; and Fire-related accidents: PMR 242, 95% CI 157-357. For deaths under age 65 All cancers: PMR 112, 95% CI 104-121; Rectal cancer: PMR 186, 95% CI 104-121); Skin cancer: PMR 167, 95% CI 107-248; Lymphatic and hematopoietic cancers: PMR 161, 95% CI 129-199; Non-Hodgkin’s lymphoma: PMR 161, 95% CI 112-224; Leukemia: PMR 171, 95% CI 118-240; Accidental falls: PMR 206, 95% CI 129-312; and Fire-related accidents: PMR 335, 95% CI 157-357. Calvert et al. Deaths among Employment as a Ischemic heart disease deaths in males 16-60 Age standardized. Differential reporting of 1999 488,539 white firefighter. for firefighting occupations. ischemic heart disease males and 104,988 434 white (PMR 104, 95% CI 94-114) and may be affected by Cohort study black males in 26 black (PMR 169, 95% CI 110-247) deaths presumption of disease the National among firefighters due to ischemic heart for certain occupational [Circulatory-s] Occupational disease. exposures (such as for Mortality firefighting); Surveillance System elevated PMRs (covers 27 states), reported for many other 1982-1992. occupations. Carozza et al. 476 cases of glioma Employment as a Glioma incidence Controlled for age, Few cases and controls 2000 in San Francisco fireman. 3 cases and 1 control among those ever gender, education, and among firemen. adults diagnosed employed as a firemen (OR 2.7, 95% CI race. Population-based 1991-1994 and 462 0.3-26.1). No significant associations when case-control controls. stratified by latency, duration of employment, study or tumor type. 145 continued [Cancer-s]

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TABLE C-1 Continued 146 Study and Design Population Exposure Outcomes Adjustments Limitations and Comments Charbotel et al. 83 incinerator 2 incinerators in Spirometry measurements from 1st and 3rd Adjustment for Follow-up of Hours et 2005 workers and 76 urban areas of years. Medical history and symptoms assessed smoking, history of al. 2003. age-matched non- France. Air sampling by questionnaire. allergy or lung disease, Longitudinal exposed workers performed, presented Baseline lung function lower in exposed and examination center. study followed over 3 in an earlier workers than controls (not significant). In years. Workers publication (Maitre the third year, controls had significantly [Respiratory-s] categorized by et al. 2003). better percent predicted values for FEF50/PV exposure/task. (p=0.04), FEF25–75/PV (p=0.02), and FEF25–75/FVC (p=0.01), but not for other measures of lung function. No decrease in lung function (first to third year) was seen related to exposure. After adjustment for smoking, medical history, and examination center, FEF25–75 in the 3rd year was lower in incinerator workers than in unexposed workers (mean±SD % predicted, 94.1±27.9 vs 105.5±25.3). No relationship between exposure and lung function change during follow-up. Comba et al. 37 cases of soft Residential distance Soft tissue sarcoma incidence Matched for age and Few exposed cases. 2003 tissue sarcoma in from an industrial Less than 2 km: OR 31.4 (95% CI 5.6-176.1), sex. diagnosed 1989- waste incinerator. based on 5 cases. Case-control 1998 and residing Greater than 2 km: No significant increase in Mantua, Italy, from null. [Cancer-s] and 3 neighboring No significant decrease in risk observed communities with increasing distance from source when compared to 171 measuring continuously. randomly selected unexposed controls from the population matched for age and sex. Cordier et al. Malformed children Exposure to Obstructive uropathies; cardiac, urinary, and Adjusted for year of Few measurements of 2004 born to residents incinerator skin anomalies identified through population- birth, maternal age, total dusts, dioxins, and of 194 exposed emissions was based birth defects registry and active search department of birth, metals available; rates Ecological study communities estimated from a of medical records. population density, of cardiac anomalies, surrounding plume model. Facial cleft (RR 1.30, 95% CI 1.06-1.59) and average family income obsrtuctive uropathies, [Reproductive-s] incinerators Interested in renal dysplasia (RR 1.55, 95% CI 1.10-2.20) and, when available, and skin anomalies compared to dioxin- and metal- more frequent in exposed populations, and road traffic. likely explained by road 2678 unexposed contaminated PM. other renal anomalies was lower (RR 0.44, traffic density. communities. 95% CI 0.20-0.97). A dose–response trend

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was observed with increasing exposure for obstructive uropathies (p=0.07). Dose-response trends with increasing road traffic density were found for cardiac anomalies (p=0.02), skin anomalies (p=0.02), and obstructive uropathies (p=0.07). Cresswell et al. 1,508 cases from Based on distance Chromosomal and non-chromosomal congenital Adjusted for socio- Rate increases in later 2003 total 81,255 live from incinerator anomalies comparing the inner and outer economic deprivation years hard to interpret births, stillbirths, which went into zones. and year. without information on Ecological study induced abortions operation in 1988, No significant overall association between cumulative exposure or and fetal death after location within number of anomalies and residential proximity increases in exposure. [Reproductive-s] 14 weeks gestation inner (3 km to incinerator was found. Risks were not to mothers residing radius) or outer elevated pre- or post-1988, but when stratified within 7 km of a (3-7 km radius) by year, the risk was significantly elevated in waste incinerator, areas and pre- vs. 1995 (OR 1.73, 95% CI 1.10-2.72), 1998 (OR 1985-1999 from post-incinerator 1.56, 95% CI 1.01-2.41), and 1999 (OR 2.05, the Northern operation. 95% CI 1.20-3.52). Regional Congenital Abnormality Survey. Demers et al. 4,546 male Employment as a SMR compared with the US white male Age and calendar-year Large study size. 1992a firefighters in firefighter (yes/ population. IDR for cause of death compared standardized. Stratified Disease misclassification Seattle and Tacoma, no). Duration in fire with police officers from the same cities. by years of fire combat dependent on accuracy Retrospective WA, and Portland, combat positions. All causes: SMR 0.81, 95% CI 0.77-0.86; exposure, years since of death certificates. cohort study. OR, for at least a Kidney cancer: SMR 0.27, 95% CI 0.03-0.97; first employment, Statistical instability year, 1944-1979. Bladder and other urinary cancers: SMR and age at risk. No when comparing [Respiratory-s; 1,162 deaths 0.23, 95% CI 0.03-0.83; Brain and nervous adjustment for smoking firefighter mortality to Circulatory-k; system cancers: SMR 2.07, 95% CI 1.23-3.28; or other potential police due to relatively All Cause] Heart diseases: SMR 0.79, 95% CI 0.72-0.87; confounders. few deaths among Ischemis heart disease: SMR 0.82, 95% CI police. 0.74-0.90; All other causes NS. All causes: IDR 0.87, 95% CI 0.79-0.95; Other circulatory diseases: IDR 0.72, 95% CI 0.54- 0.96; Cerebrovascular disease: IDR 0.65, 95% CI 0.45-0.92; All other causes NS. <10 Years of Employment: All causes NS. 10-19 Years of Employment: Brain and nervous system tumors: SMR 3.53, 95% CI 1.5-7.0; All other causes NS 20-29 Years of Employment: All causes NS. 147 continued

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TABLE C-1 Continued 148 Study and Design Population Exposure Outcomes Adjustments Limitations and Comments ≥ 30 Years of Employment: Lymphatic and hemopatoietic cancers: SMR 2.05, 95% CI 1.1-3.6; Leukemia: SMR 2.60, 95% CI 1.0-5.4; Diseases of arteries, veins, and pulmonary circulation: SMR 1.99, 95% CI 1.3-2.9; All other causes NS. <20 and 20-29 Years Since First Employment: All causes NS. ≥30 Years Since First Employment: Prostate cancer: SMR 1.42, 95% CI 1.0-2.0; Brain and nervous system tumors: SMR 2.63, 95% CI 1.4-4.4; Lymphatic and hematopoietic cancers: SMR 1.48, 95% CI 1.0-2.2; Diseases of arteries, veins, and pulmonary circulation: SMR 1.33, 95% CI 1.0-1.8; All other causes NS. Demers et al. 4,528 male Employment as a SMR cancer deaths compared with the white Standardized by age Large study size. 1992b firefighters and firefighter or police male population of Washington State and and calendar year. No Analysis lumps police officers in officer (yes/no). SIR incident cancer cases compared with all adjustment for smoking firefighters and police Retrospective Seattle and Tacoma, males with malignancies in the same counties or other potential together, limiting cohort study WA, employed for at (follow-up 1945-1989). confounders. generalizeability. least 1 year between Cancer Incidence [Cancer-k] 1944 and 1979. 338 Prostate cancer: SIR 1.37, 95% CI 1.11-1.69; registry and 174 All others NS. death certificate Cancer Mortality identified cancer Stomach cancer: SMR 2.04, 95% CI 1.05-3.56; cases. All others NS. Demers et al. 2,447 male Employment as a SIR and IDR Cancer incidence (1974-1989). Adjusted for age Cohort previously 1994 firefighters in firefighter (yes/no); Compared with mortality rates for the Seattle and calendar-period; reported by Heyer et al. Seattle and Tacoma, Duration of active and Tacoma areas and local police officers. stratified by years 1990 and Demers et al. Retrospective WA, employed for duty firefighting/ Firefighters compared with local cancer since first employment 1992. Small numbers cohort study at least 1 between employment (years). incidence rates. and duration of of police cancer cases 1944 and 1979. 224 Prostate cancer: SIR 1.4, 95% CI 1.1-1.7; All employment; no limits the precision of [Cancer-k] cancer cases among others NS. adjustment for smoking risk estimates. firefighters. Firefighters compared with police or other potential IDR for all cancer sites NS. confounders. Deschamps et al. 830 male firefighters Time spent working Cause of death (1977-1991); compared with Age and calendar Healthy worker effect; 1995 having served at on assignments the general French male population. adjusted SMRs; no few deaths. least 5 years (as of involving active All cause mortality: SMR = 0.52 (0.35-0.75); adjustment for smoking Prospective Jan. 1, 1977) for the fire combat duty (as All causes others NS. or other potential cohort study Brigade des sapeurs- opposed to confounders.

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pompiers de Paris office-work). This [Respiratory-s; (BSPP). Includes 32 exposure was only Circulatory-s; deaths and 11,414 determined for Cancer-s; All person-years. deceased persons Cause] and was evaluated from BSPP records. Dibbs et al. 1982 171 male firefighters Firefighter (yes/no). Coronary heart disease, myocardial infarction, Data on serum Small sample of and 1,475 non- angina pectoris after 10 years of follow-up. cholesterol, blood firefighters. Lack of Longitudinal firefighters Compared with non-firefighters. pressure, BMI, age, exposure information. study participating in the Coronary heart disease: IRR 0.5, 95% CI 0.2- and cigarette smoking Normative Aging 1.4. stratified by firefighter/ [Circulatory-k] Study at the VA Myocardial infarction: IRR 0.5, 95% CI 0.1- non-firefighter to detect outpatient clinic in 1.9. differences in risk Boston, MA having factors for coronary completed three heart disease. complete medical examinations. Douglas et al. 1,006 London Years of service, Spirometry and prevalence of respiratory Controlled for age and Confidence intervals and 1985 firefighters whether fireman had symptoms. smoking. p-values not reported. interviewed and in been “punished” by Average levels of FEV1, FVC, and FEV1/FVC Longitudinal examined in 1976 smoke, and if had were similar to predicted values in both years; study and again in 1977. ever missed a week all three measures of lung function decreased or more after such with age and cigarettes; no association between [Respiratory-s] an exposure. lung function or respiratory symptoms with smoke exposure or duration of service was found. Elci et al. 2003 1,354 male lung Employed as Lung cancer: OR 6.8, 95% CI 1.3-37.4. Age and smoking status Several other cancer patients at a firefighter. adjusted. occupational also had Hospital-based hospital in Turkey, increased risk of lung case-control diagnosed and cancer (drivers, textile study 1,519 male controls workers, water treatment diagnosed with other plant workers, highway [Cancer-k] cancer diagnoses construction workers). (including some non-cancer), 1979- 1984. 149 continued

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TABLE C-1 Continued 170 Study and Design Population Exposure Outcomes Adjustments Limitations and Comments Viel et al. 2000 Residents of Doubs, Proximity to Soft-tissue sarcoma, non-Hodgkin’s lymphoma, Age and sex France, 1980-1995. municipal solid Hodgkin’s disease. standardized. Retrospective waste incinerator. Spatial clusters of increased risk were observed cohort study for soft-tissue sarcoma (SIR 1.44, p=0.12) and non-Hodgkin’s lymphoma (SIR 1.27, p= [Cancer-s] 0.0003), but not Hodgkin’s disease (SIR 1.42, p=0.95) Viel et al. 2008a 2,147 males and Exposure to Non-Hodgkin’s lymphoma. Population density, 1,827 females with emissions from 13 Highly-exposed block groups relative to lowest urbanization, socio- Population-based non-Hodgkin’s incinerators was exposed: RR 1.12, 95% CI 1.00-1.25. economic level, case-control lymphoma in modeled from 1972- Risks were elevated among women: RR 1.178, airborne France, 1990-1999, 1985 (allowing 95% CI 1.01-1.37 in the multivariate model. traffic pollution, and [Cancer-s] in 2,270 census for a 10-year industrial pollution. block groups (cases/ latency period); controls determined the exposure by high/low dioxin model considered exposure). incinerator characteristics (capacity, functioning, dust control, fume treatment, operating years), atmospheric diffusion modeling, and distance to estimate the dioxin exposure level of each of the census block groups. Vincenti et al. All females aged Residential address Spontaneous abortions, birth defects, still None. Likely exposure 2008 16-49 living in the and work location births. misclassification. area at any time and history are used No excess risk of miscarriage (RR 1.00, No data on confounders Ecological study females working as surrogate 95% CI 0.65-1.48) or birth defects (RR such as smoking, for at least 1 week for exposure 0.64, 95% CI 0.20-1.55) in two areas closest diet, occupation, and [Reproducive-s] from 2003-2006 in 3 and estimated to incinerator; also no indication of dose– reproductive history; municipal areas near concentration response trend. small number of cases Modena, Italy; levels. Estimated No higher risk of spontaneous abortions in due to scarcity of cases are congenital concentrations are females working in factories in exposed areas exposed women and low anomalies and based on estimated (RR 1.04, 95% CI 0.38-2.30), but increased number of outcomes. stillbirths identified fall-out of dioxins prevalence of birth defects (RR 2.26, 95% CI within 28 days and furans in the 0.57-6.14).

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of birth using lower part of the a regional birth atmosphere, with 2 defects registry. areas characterized as having higher levels. Williams et al. Residents of Districts were Sex ratios (male:female) for 1975-1979 and None. Unable to account for 1992 several Scottish determined to be 1981-1983. potentially confounding districts near two of a priori interest In one “at risk” district (FK4), the m:f ratio variables (parental Ecological study incinerators that using 3-D mapping was 87, significantly reduced from 100 exposures, etc). ceased operation in techniques based (p<0.05) showing an excess of female births. [Reproducive-s] 3 “at risk” districts on the probability and 7 comparison of exposure districts were chosen incorporating for study. wind direction and strength, influence of topography, anecdotal evidence from residents, and concentrations of pollutants in soil. Young et al. 193 New South Length of service Questionnaire to determine the prevalence of Age, smoking, height. Smoking identified as 1980 Wales firefighters. (minus time in non- chronic respiratory symptoms and disease, and more significant health active fire duty) as a pulmonary function testing. risk than fire exposure Cross-sectional firefighter (years). Firefighters with chronic bronchitis had a among this population. study longer average length of exposure (p<0.05) This is a pilot study only and were more likely to be smokers and smoke using 10% of the total [Respiratory-s] more (both p<0.05) than firefighters without cohort. disease but exposure was not related to chronic bronchitis or chronic obstructive airway disease. Changes in pulmonary function were not related to exposure. Zambon et al. 172 cases of soft Modeled dioxin Soft tissue sarcoma. Matched on age and 2007 tissue sarcoma exposure based on sex. For cases/controls experiencing ≥6 fgr/m3 diagnosed from distance between average exposure compared with <4fgr/m3: OR Case-control 1990-1996 compared residence and waste 2.08, 95% CI 1.19-3.64. study with 405 controls incinerators or For cases/controls experiencing ≥6 fgr/m3 matched on age sources of industrial average exposure for ≥32 years compared with [Cancer-s] and sex randomly pollution. <4 fgr/m3: OR 3.30, 95% CI 1.24-8.73. selected from the STS risk increased with average exposure general population. among females (p trend = 0.04) but not for men. 171 continued

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TABLE C-1 Continued 172 Study and Design Population Exposure Outcomes Adjustments Limitations and Comments Studies of Gulf War veterans Barth et al. 2009 621,902 U.S. Estimated oil-well 123,478 GW Veterans were exposed to oil-well Controlling for sex, Follow-up of Kang and GW veterans fire smoke modeled. fire smoke. race, age, and unit type. Bullman 2001. Cohort study and 746,248 Increased risk of brain cancer among veterans nondeployed era exposed to oil-well fire smoke compared to veterans followed non-exposed veterans (OR 1.67, 95% CI 1.05- through 2004. 2.65) and after controlling for 2+ days of exposure to nerve agents at Khamisiyah (OR 1.81, 95% CI 1.00-3.27). Bullman et al. 100,487 U.S. Exposure to oil- Brain cancer mortality Controlling for sex, Follow-up of Kang and 2005 Army GW veterans well fires and nerve Oil-well fire smoke was not significantly race, age, and unit type. Bullman 2001. exposed to chemical agents determined related to brain cancer deaths. Cohort study warfare agents by plume model. at Khamisiyah; 224,980 unexposed Army GW veterans; exposure determined from the DoD plume model. Cowan et al. 873 cases of asthma Modeled oil-well Physician-diagnosis of asthma 3-6 years after Sex, age, race, military Pre-exposure asthma 2002 compared to 2464 fire smoke. war. rank, smoking history, status of participants controls using a Asthma associated with cumulative exposure self-reported exposure. unknown. Case-control DoD registry, among (<0.1 mg/m3/day referent) between 0.1-1.0 study GW veterans. mg/m3/day (OR 1.24, 95% CI 1.00-1.55); for exposure of 1mg/m3/day or greater (OR 1.40, 95% CI 1.11-1.75); and as a continuous variable, OR 1.08, 95% CI 1.01-1.15. Number of days at >65 µg/m3 compared to 0 days of exposure: 1-5 days of exposure (OR 1.22, 95% CI 0.99-1.51); 6-30 days of exposure (OR 1.41, 95% CI 1.12-1.77); and as a continuous variable (OR 1.03, 95% CI 1.01- 1.05). Iowa Persian 3,695 GW veterans Oil-well fire smoke Prevalence of self-reported symptoms and Stratified for age, sex, Study not designed to Gulf Study and non-GW exposure collected illnesses. rank, race, and branch investigate the effects of Group 1997 veterans living in by questionnaire. Many reported exposures were significantly of service. exposure to oil-well fire Iowa. related to multiple self-reported symptoms or smoke. Population-based illnesses; cross-sectional 85.2% of regular military and 96% of National study Guard/Reserve GW veterans reported

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exposure to smoke or combustion products. Exposure to smoke/combustion products was associated with depression, cognitive dysfunction, and fibromyalgia (all p<0.001). Kang et al. 2000 15,000 GW veterans Exposure to oil-well Prevalence of selected self-reported medical Stratified by sex and Study not designed to and 15,000 non-GW fires assessed by conditions. component. investigate the effects of Cross-sectional veterans, selected questionnaire. 65% of GW veterans, and 73% veterans in the exposure to oil-well fire study by stratified random VA Health Registry reported exposure to oil- smoke. sample. well fire smoke but no significant differences in prevalence of self-reported medical conditions was reported. Lange et al. 2002 1,560 GW veterans. Self-reported and Asthma and bronchitis symptoms collected by Sex, age, race, military Used symptom-based modeled exposure to structured interviews conducted 5 years after rank, smoking history, case definition of Cross-sectional oil-well fire smoke. the war. military service, level of bronchitis and asthma study No association between modeled exposure and preparedness for war. (possible disease asthma or bronchitis symptoms. misclassification). Self-reported exposure >30 days was significantly related to asthma (OR 2.83) and bronchitis (OR 4.78) symptoms. Proctor et al. Stratified random Combustion Smoke from oil well fires was not significantly Controlled for age, sex, Vehicle exhaust 1998 sample of 220 GW products. related to any system diseases but smoke from education, study site, related to cardiac and veterans from Ft. burning human waste was related to cardiac PTSD status, and war- neurological symptoms; Longitudinal Devens and 71 from symptoms (p<0.001) and pulmonary symptoms zone exposure. and smoke from tent study New Orleans, and (p<0.015). heaters related to 50 Era veterans cardiac, neurological and deployed to pulmonary outcomes. Germany, assessed 1994-1996. Smith et al. 2002 405,142 active-duty Modeled PM DoD hospitalizations 1991-1999. Adjusted for “influential Objective measure of GW veterans who exposure to Hospitalization rates among those in exposure covariates,” defined disease not subject to Cohort study were in theater represent oil-well groups 1-6 were compared to personnel as demographic or recall bias; no issues during the time of fire smoke exposure determined to be unexposed. deployment variables with self-selection; Kuwaiti oil-well used to create Only exposure level 4 was at increased risk of with p values less than however, only DoD fires. 7 categories of hospitalization (RR 1.03, 95% CI 1.00-1.05), 0.15. hospitals, only active exposure. risks for all other exposure levels NS. duty, no adjustment for 1: average daily Causes for hospitalization and levels of potential confounders exposure of 1-260 exposure: such as smoking. µg/m3 for 1-25 Infections and parasitic diseases: level 2 (RR days; Exposure level 0.87, p<0.05); 2: average daily Endocrine, nurtitional, and metabolic disorders: exposure of 1-260 level 1 (RR 0.89, p<0.05); level 4 (RR 0.87, µg/m3 for 26-50 p<0.05); level 5 (RR 0.84, p<0.05); level 6 days; Exposure level (RR 0.84, p<0.05); 173 continued 3: average daily Mental disorders: level 6 (RR 1.11, p<0.05);

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TABLE C-1 Continued 174 Study and Design Population Exposure Outcomes Adjustments Limitations and Comments exposure of 1-260 Circulatory diseases: level 2 (RR 0.88, µg/m3 for >50 days; p<0.05); level 4 (RR 0.87, p<0.05); level 5 Exposure level (RR 0.90, p<0.05); 4: average daily Respiratory diseases: level 3 (RR 0.69, exposure of >260 p<0.05); µg/m3 for 1-25 Digestive diseases: level 5 (RR 0.92, p<0.05); days; Exposure level Genitourinary diseases: level 5 (RR 0.91, 5: average daily p<0.05); exposure of >260 Pregnancy complications: level 2 (RR 0.86, µg/m3 for 26-50 p<0.05); level 3 (RR 0.48, p<0.05); level 6 days. Exposure level (0.84, p<0.05); 6: average daily Skin diseases: level 3 (RR 1.35, p<0.05); level exposure of >260 5 (RR 0.87, p<0.05); µg/m3 for >50 days. Musculoskeletal disease: level 2 (RR 0.91, p<0.05); Symptoms, signs, and ill0defined conditions: level 4 (RR 0.92, p<0.05); level 5 (RR 0.90, p<0.05); Injury and poisoning: level 4 (RR 1.11, p<0.05); All other causes and levels of exposure NS. Spencer et al. 241 veterans GW combat (heat Prevalence of unexplained illness (by PEHRC Controlled for other 2001 meeting the stress, chemical or CDC definitions) assessed by survey and simultaneous exposures. criteria for exposures, oil-well clinical study; Case-control unexplained illness fire smoke). burned latrine waste exposure was associated study in Washington or with unexplained illness (OR 2.51, 95% CI Oregon and 113 1.58-3.98); health veterans as many exposures were significantly related to controls. unexplained illness, most strongly being sun exposure, conditions of combat, and medical problems/treatment sought while deployed. Unwin et al. 8,195 GW veterans Combustion product Prevalence of self-reported symptoms and Stratified for age, rank, 1999 and Bosnia and exposure assessed illnesses. and deployment to other era veterans by questionnaire. Among all three groups of veterans, exposure Bosnia. Cross-sectional deployed elsewhere to oil-well fire smoke was not significantly study from the United associated with physical functioning. For CDC Kingdom, conducted syndrome, risks were increased among GW in 1997-1998. veterans (OR 1.8, 95% CI 1.5-2.1) and era veterans (OR 1.8, 95% CI 1.1-2.9). Risks were increased for PTSD among GW veterans (OR 2.3, 95% CI 1.7-2.9), Bosnia veterans (OR 3.2, 95% CI 1.6-6.8) and era veterans (OR 3.0, 95% CI 1.4-6.5).

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Verret et al. 2008 5.666 French GW Oil-well fire. Fertility disorders, miscarriage, birth defects Adjusted for age, veterans. assessed by questionnaire in 2002-2004. service branch, rank, Cross sectional 0.9% reported infertility, 12% reported one and military status. and nested case- or more miscarriages among partners of male Controls to compare control study veterans, 2.4% fathered children with a birth the risk of birth defects defect conceived after returning from the with specific exposures Persian Gulf. were male veterans who Case-control study comparing exposures never had a child with experienced by fathers with and without a birth defect but had at children having birth defects- No exposure least one healthy child (time of mission, location of mission, oil- matched with veterans well fire smoke, sandstorm, chemical arms, who fathered a child and pesticides) was related to birth defects. with a birth defect after Incidence of birth defects among veterans was deployment on age. similar to that of the French population (except for Down syndrome, RR 0.36, 95% CI 0.13- 0.78). White et al. 2001 193 GW veterans Deployment to the Neuropsychological function. Adjusted for age, and 47 Germany GW 1990-1991 and Chemical warfare agent and pesticide education, gender, Cross-sectional deployed veterans. related self-reported exposures were related to poorer and sampling design. study exposures. neuropsychological tests performance (p<0.05), Controlled for post- oil well fire smoke, pyridostigmine bromide traumatic stress were not. Exposure to oil well fire smoke disorder, major significantly increased score on the POMS depression, and other tension scale; GW veterans performed worse known covariates. on several tests (only mood complaints Adjustment for multiple remained significant after Bonferroni comparisons. correction) than Germany-deployed veterans. Wolfe et al. 2002 1,290 GW veterans Deployment to the Prevalence of multisymptom illness (at least Stratified for GSI at Ft Devens in 1997 GW 1990-1991 and two categories of symptoms: fatigue, mood- caseness criteria. Cross-sectional (who previously related exposures. cognition, musculoskeletal). study were surveyed in 60% prevalence of multisymptom illness. 1991). Multivariate regression showed several factors to be related (female, OR 1.8, 95% CI 1.1-2.9; college education, OR 0.5, 95% CI 0.4-0.7; GSI clinical caseness, OR 9.8, 95% CI 7.3- 13.1; oil fire smoke, OR 1.6, 95% CI 1.2-2.1; chemicals, OR 2.4, 95% CI 1.6-3.6; heater in tent, OR 1.4, 95% CI 1.0-1.8; seen in clinic, OR 1.5, 95% CI 1.2-2.0; anthrax vaccine, OR 1.5, 95% CI 1.1-2.0; medium or exposure to Anti-nerve gas, OR 1.4, 95% CI 1.0-1.9 and OR 2.1, 95% CI 1.4-3.1 respectively. 175

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TABLE C-1 Continued 176 NOTE: AIDS = acquired immune deficiency syndrome; CDC = Centers for Disease Control and Prevention; CHD = coronary heart disease; CI = confidence interval; CNS = central nervous system; DoD = Department of Defense; EMS = emergency medical services; FEF25-–75 = forced expiratory flow between 25% and 75%; FEF50 = forced expiratory flow at 50%; FEV1 = forced expiratory volume in one second; FVC = forced vital capacity; GW = Gulf War; IDR = incidence density ratio; IRR = incidence rate ratio; km = kilometers; L/sec = liters per second; MN = malignant; MOR = mortality odds ratio; NS = not significant; OR = odds ratio; PEFR = peak expiratory flow rate; PM = particulate matter; PMR = proportional mortality ratio; PVC = polyvinyl chloride; RR = relative risk; RV = residual volume; SIR = standardized incidence ratio; SMR = standardized mortality ratio; SMOR = standardized mortality odds ratio; SPMR = standardized proportional mortality ratio; TEQ = toxicity equivalent; TLC = total lung capacity; V25 = maximum expiratory flow rates at 25% of FVC; V50 = maximum expiratory flow rates at 50% of FVC; VA = Department of Veterans Affairs; VC = vital capacity.

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179 APPENDIX C Liu, D., I. B. Tager, J. R. Balmes, and R. J. Harrison. 1992. The effect of smoke inhalation on lung function and airway respon - siveness in wildland fire fighters. American Review of Respiratory Disease 146(6):1469-1473. Lloyd, O. L., M. M. Lloyd, F. L. Williams, and A. Lawson. 1988. Twinning in human populations and in cattle exposed to air pollution from incinerators. British Journal of Industrial Medicine 4(8):556-560. Ma, F., L. E. Fleming, D. J. Lee, E. Trapido, and T. A. Gerace. 2006. Cancer incidence in Florida professional firefighters, 1981 to 1999. Journal of Occupational and Environmental Medicine 48(9):883-888. Ma, F., L. E. Fleming, D. J. Lee, E. Trapido, T. A. Gerace, H. Lai, and S. Lai. 2005. Mortality in Florida professional firefight - ers, 1972 to 1999. American Journal of Industrial Medicine 47(6):509-517. Ma, F., D. J. Lee, et al. 1998. Race-specific cancer mortality in US firefighters: 1984-1993. 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