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Contaminated Water Supplies at Camp Lejeune: Assessing Potential Health Effects (2009)

Chapter: Appendix E: Details of Epidemiologic Studies on Trichloroethylene and Perchloroethylene

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Suggested Citation:"Appendix E: Details of Epidemiologic Studies on Trichloroethylene and Perchloroethylene." National Research Council. 2009. Contaminated Water Supplies at Camp Lejeune: Assessing Potential Health Effects. Washington, DC: The National Academies Press. doi: 10.17226/12618.
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Suggested Citation:"Appendix E: Details of Epidemiologic Studies on Trichloroethylene and Perchloroethylene." National Research Council. 2009. Contaminated Water Supplies at Camp Lejeune: Assessing Potential Health Effects. Washington, DC: The National Academies Press. doi: 10.17226/12618.
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Suggested Citation:"Appendix E: Details of Epidemiologic Studies on Trichloroethylene and Perchloroethylene." National Research Council. 2009. Contaminated Water Supplies at Camp Lejeune: Assessing Potential Health Effects. Washington, DC: The National Academies Press. doi: 10.17226/12618.
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Suggested Citation:"Appendix E: Details of Epidemiologic Studies on Trichloroethylene and Perchloroethylene." National Research Council. 2009. Contaminated Water Supplies at Camp Lejeune: Assessing Potential Health Effects. Washington, DC: The National Academies Press. doi: 10.17226/12618.
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Suggested Citation:"Appendix E: Details of Epidemiologic Studies on Trichloroethylene and Perchloroethylene." National Research Council. 2009. Contaminated Water Supplies at Camp Lejeune: Assessing Potential Health Effects. Washington, DC: The National Academies Press. doi: 10.17226/12618.
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Suggested Citation:"Appendix E: Details of Epidemiologic Studies on Trichloroethylene and Perchloroethylene." National Research Council. 2009. Contaminated Water Supplies at Camp Lejeune: Assessing Potential Health Effects. Washington, DC: The National Academies Press. doi: 10.17226/12618.
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Suggested Citation:"Appendix E: Details of Epidemiologic Studies on Trichloroethylene and Perchloroethylene." National Research Council. 2009. Contaminated Water Supplies at Camp Lejeune: Assessing Potential Health Effects. Washington, DC: The National Academies Press. doi: 10.17226/12618.
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Suggested Citation:"Appendix E: Details of Epidemiologic Studies on Trichloroethylene and Perchloroethylene." National Research Council. 2009. Contaminated Water Supplies at Camp Lejeune: Assessing Potential Health Effects. Washington, DC: The National Academies Press. doi: 10.17226/12618.
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Suggested Citation:"Appendix E: Details of Epidemiologic Studies on Trichloroethylene and Perchloroethylene." National Research Council. 2009. Contaminated Water Supplies at Camp Lejeune: Assessing Potential Health Effects. Washington, DC: The National Academies Press. doi: 10.17226/12618.
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Suggested Citation:"Appendix E: Details of Epidemiologic Studies on Trichloroethylene and Perchloroethylene." National Research Council. 2009. Contaminated Water Supplies at Camp Lejeune: Assessing Potential Health Effects. Washington, DC: The National Academies Press. doi: 10.17226/12618.
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Suggested Citation:"Appendix E: Details of Epidemiologic Studies on Trichloroethylene and Perchloroethylene." National Research Council. 2009. Contaminated Water Supplies at Camp Lejeune: Assessing Potential Health Effects. Washington, DC: The National Academies Press. doi: 10.17226/12618.
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Suggested Citation:"Appendix E: Details of Epidemiologic Studies on Trichloroethylene and Perchloroethylene." National Research Council. 2009. Contaminated Water Supplies at Camp Lejeune: Assessing Potential Health Effects. Washington, DC: The National Academies Press. doi: 10.17226/12618.
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Suggested Citation:"Appendix E: Details of Epidemiologic Studies on Trichloroethylene and Perchloroethylene." National Research Council. 2009. Contaminated Water Supplies at Camp Lejeune: Assessing Potential Health Effects. Washington, DC: The National Academies Press. doi: 10.17226/12618.
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Suggested Citation:"Appendix E: Details of Epidemiologic Studies on Trichloroethylene and Perchloroethylene." National Research Council. 2009. Contaminated Water Supplies at Camp Lejeune: Assessing Potential Health Effects. Washington, DC: The National Academies Press. doi: 10.17226/12618.
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Suggested Citation:"Appendix E: Details of Epidemiologic Studies on Trichloroethylene and Perchloroethylene." National Research Council. 2009. Contaminated Water Supplies at Camp Lejeune: Assessing Potential Health Effects. Washington, DC: The National Academies Press. doi: 10.17226/12618.
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Suggested Citation:"Appendix E: Details of Epidemiologic Studies on Trichloroethylene and Perchloroethylene." National Research Council. 2009. Contaminated Water Supplies at Camp Lejeune: Assessing Potential Health Effects. Washington, DC: The National Academies Press. doi: 10.17226/12618.
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Suggested Citation:"Appendix E: Details of Epidemiologic Studies on Trichloroethylene and Perchloroethylene." National Research Council. 2009. Contaminated Water Supplies at Camp Lejeune: Assessing Potential Health Effects. Washington, DC: The National Academies Press. doi: 10.17226/12618.
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Suggested Citation:"Appendix E: Details of Epidemiologic Studies on Trichloroethylene and Perchloroethylene." National Research Council. 2009. Contaminated Water Supplies at Camp Lejeune: Assessing Potential Health Effects. Washington, DC: The National Academies Press. doi: 10.17226/12618.
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Suggested Citation:"Appendix E: Details of Epidemiologic Studies on Trichloroethylene and Perchloroethylene." National Research Council. 2009. Contaminated Water Supplies at Camp Lejeune: Assessing Potential Health Effects. Washington, DC: The National Academies Press. doi: 10.17226/12618.
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Suggested Citation:"Appendix E: Details of Epidemiologic Studies on Trichloroethylene and Perchloroethylene." National Research Council. 2009. Contaminated Water Supplies at Camp Lejeune: Assessing Potential Health Effects. Washington, DC: The National Academies Press. doi: 10.17226/12618.
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Suggested Citation:"Appendix E: Details of Epidemiologic Studies on Trichloroethylene and Perchloroethylene." National Research Council. 2009. Contaminated Water Supplies at Camp Lejeune: Assessing Potential Health Effects. Washington, DC: The National Academies Press. doi: 10.17226/12618.
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Suggested Citation:"Appendix E: Details of Epidemiologic Studies on Trichloroethylene and Perchloroethylene." National Research Council. 2009. Contaminated Water Supplies at Camp Lejeune: Assessing Potential Health Effects. Washington, DC: The National Academies Press. doi: 10.17226/12618.
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Suggested Citation:"Appendix E: Details of Epidemiologic Studies on Trichloroethylene and Perchloroethylene." National Research Council. 2009. Contaminated Water Supplies at Camp Lejeune: Assessing Potential Health Effects. Washington, DC: The National Academies Press. doi: 10.17226/12618.
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Suggested Citation:"Appendix E: Details of Epidemiologic Studies on Trichloroethylene and Perchloroethylene." National Research Council. 2009. Contaminated Water Supplies at Camp Lejeune: Assessing Potential Health Effects. Washington, DC: The National Academies Press. doi: 10.17226/12618.
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Suggested Citation:"Appendix E: Details of Epidemiologic Studies on Trichloroethylene and Perchloroethylene." National Research Council. 2009. Contaminated Water Supplies at Camp Lejeune: Assessing Potential Health Effects. Washington, DC: The National Academies Press. doi: 10.17226/12618.
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Suggested Citation:"Appendix E: Details of Epidemiologic Studies on Trichloroethylene and Perchloroethylene." National Research Council. 2009. Contaminated Water Supplies at Camp Lejeune: Assessing Potential Health Effects. Washington, DC: The National Academies Press. doi: 10.17226/12618.
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Suggested Citation:"Appendix E: Details of Epidemiologic Studies on Trichloroethylene and Perchloroethylene." National Research Council. 2009. Contaminated Water Supplies at Camp Lejeune: Assessing Potential Health Effects. Washington, DC: The National Academies Press. doi: 10.17226/12618.
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Suggested Citation:"Appendix E: Details of Epidemiologic Studies on Trichloroethylene and Perchloroethylene." National Research Council. 2009. Contaminated Water Supplies at Camp Lejeune: Assessing Potential Health Effects. Washington, DC: The National Academies Press. doi: 10.17226/12618.
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Suggested Citation:"Appendix E: Details of Epidemiologic Studies on Trichloroethylene and Perchloroethylene." National Research Council. 2009. Contaminated Water Supplies at Camp Lejeune: Assessing Potential Health Effects. Washington, DC: The National Academies Press. doi: 10.17226/12618.
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Suggested Citation:"Appendix E: Details of Epidemiologic Studies on Trichloroethylene and Perchloroethylene." National Research Council. 2009. Contaminated Water Supplies at Camp Lejeune: Assessing Potential Health Effects. Washington, DC: The National Academies Press. doi: 10.17226/12618.
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Suggested Citation:"Appendix E: Details of Epidemiologic Studies on Trichloroethylene and Perchloroethylene." National Research Council. 2009. Contaminated Water Supplies at Camp Lejeune: Assessing Potential Health Effects. Washington, DC: The National Academies Press. doi: 10.17226/12618.
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Suggested Citation:"Appendix E: Details of Epidemiologic Studies on Trichloroethylene and Perchloroethylene." National Research Council. 2009. Contaminated Water Supplies at Camp Lejeune: Assessing Potential Health Effects. Washington, DC: The National Academies Press. doi: 10.17226/12618.
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Suggested Citation:"Appendix E: Details of Epidemiologic Studies on Trichloroethylene and Perchloroethylene." National Research Council. 2009. Contaminated Water Supplies at Camp Lejeune: Assessing Potential Health Effects. Washington, DC: The National Academies Press. doi: 10.17226/12618.
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Suggested Citation:"Appendix E: Details of Epidemiologic Studies on Trichloroethylene and Perchloroethylene." National Research Council. 2009. Contaminated Water Supplies at Camp Lejeune: Assessing Potential Health Effects. Washington, DC: The National Academies Press. doi: 10.17226/12618.
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Suggested Citation:"Appendix E: Details of Epidemiologic Studies on Trichloroethylene and Perchloroethylene." National Research Council. 2009. Contaminated Water Supplies at Camp Lejeune: Assessing Potential Health Effects. Washington, DC: The National Academies Press. doi: 10.17226/12618.
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Suggested Citation:"Appendix E: Details of Epidemiologic Studies on Trichloroethylene and Perchloroethylene." National Research Council. 2009. Contaminated Water Supplies at Camp Lejeune: Assessing Potential Health Effects. Washington, DC: The National Academies Press. doi: 10.17226/12618.
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Suggested Citation:"Appendix E: Details of Epidemiologic Studies on Trichloroethylene and Perchloroethylene." National Research Council. 2009. Contaminated Water Supplies at Camp Lejeune: Assessing Potential Health Effects. Washington, DC: The National Academies Press. doi: 10.17226/12618.
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Suggested Citation:"Appendix E: Details of Epidemiologic Studies on Trichloroethylene and Perchloroethylene." National Research Council. 2009. Contaminated Water Supplies at Camp Lejeune: Assessing Potential Health Effects. Washington, DC: The National Academies Press. doi: 10.17226/12618.
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Suggested Citation:"Appendix E: Details of Epidemiologic Studies on Trichloroethylene and Perchloroethylene." National Research Council. 2009. Contaminated Water Supplies at Camp Lejeune: Assessing Potential Health Effects. Washington, DC: The National Academies Press. doi: 10.17226/12618.
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Suggested Citation:"Appendix E: Details of Epidemiologic Studies on Trichloroethylene and Perchloroethylene." National Research Council. 2009. Contaminated Water Supplies at Camp Lejeune: Assessing Potential Health Effects. Washington, DC: The National Academies Press. doi: 10.17226/12618.
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Suggested Citation:"Appendix E: Details of Epidemiologic Studies on Trichloroethylene and Perchloroethylene." National Research Council. 2009. Contaminated Water Supplies at Camp Lejeune: Assessing Potential Health Effects. Washington, DC: The National Academies Press. doi: 10.17226/12618.
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Suggested Citation:"Appendix E: Details of Epidemiologic Studies on Trichloroethylene and Perchloroethylene." National Research Council. 2009. Contaminated Water Supplies at Camp Lejeune: Assessing Potential Health Effects. Washington, DC: The National Academies Press. doi: 10.17226/12618.
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Suggested Citation:"Appendix E: Details of Epidemiologic Studies on Trichloroethylene and Perchloroethylene." National Research Council. 2009. Contaminated Water Supplies at Camp Lejeune: Assessing Potential Health Effects. Washington, DC: The National Academies Press. doi: 10.17226/12618.
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Suggested Citation:"Appendix E: Details of Epidemiologic Studies on Trichloroethylene and Perchloroethylene." National Research Council. 2009. Contaminated Water Supplies at Camp Lejeune: Assessing Potential Health Effects. Washington, DC: The National Academies Press. doi: 10.17226/12618.
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Suggested Citation:"Appendix E: Details of Epidemiologic Studies on Trichloroethylene and Perchloroethylene." National Research Council. 2009. Contaminated Water Supplies at Camp Lejeune: Assessing Potential Health Effects. Washington, DC: The National Academies Press. doi: 10.17226/12618.
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Suggested Citation:"Appendix E: Details of Epidemiologic Studies on Trichloroethylene and Perchloroethylene." National Research Council. 2009. Contaminated Water Supplies at Camp Lejeune: Assessing Potential Health Effects. Washington, DC: The National Academies Press. doi: 10.17226/12618.
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Suggested Citation:"Appendix E: Details of Epidemiologic Studies on Trichloroethylene and Perchloroethylene." National Research Council. 2009. Contaminated Water Supplies at Camp Lejeune: Assessing Potential Health Effects. Washington, DC: The National Academies Press. doi: 10.17226/12618.
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Appendix E Details of Epidemiologic Studies on Trichloroethylene and Perchloroethylene 272

TABLE E-1 Exposure Information on Epidemiologic Studies Involving Exposure to TCE or PCE Reference Study Design, Exposure, Outcomes Exposure Assessment Exposure Metrics Comments Aschengrau et al. Population-based case-control Relative dose of PCE estimated by Ever vs never exposed (served by private Nine latency periods 2003 algorithm with variables for residential well for entire Cape Cod residence) examined (0, 5, 7, 9, 11, Cape Cod, MA history, water flow (geometry, load on 13, 15, 17, 19 years) water-distribution system), pipe Cumulative exposure for each latency PCE from inner vinyl liner in cement characteristics (such as pipe diameter, period: sum of RDDs for each residence pipes distributing tap water age); inputs determined from maps from (mass of TCE entering home in tap water local water suppliers or state DEPs over time at each address); categorized as Breast cancer never, low (up to and including median RDD), high RDD (above 50th, 75th, or 99th percentile) Blair et al. 2003 Cohort study of dry cleaners Exposure score for jobs based on published Exposure score assigned on basis of jobs Adjustment for age, sex, monitoring studies of dry-cleaning held (cleaners, high, score of 40; pressers, calendar time PCE used as solvent in dry cleaning industry; scores increased with proximity sewers, counter workers, score of 7; pickup workers, low, score of 0) Cancers, other causes of death Little or no exposure (score of 0) vs medium-high exposure (score of 7 or 40) Boice et al. 2006 Cohort of rocket-engine testing- All Rocketdyne workers employed on or Duration of employment (years) (SMR) Adjustment for year of facility workers after Jan. 1, 1948, for 6+ mo at SSFL, birth, year of hire nearby facilities (for comparison group); Potential for exposure (flush engine parts or Hydrazine, TCE identified from personnel files, work utility solvent use) (SMR) history cards; exposed were test-stand All causes of death mechanics, inspectors, test-stand Duration of employment (RR) engineers, research engineers; personnel listings used to place test-stand mechanics 4 decades of employment (RR) at specific stands in calendar years; descriptive industrial-hygiene information Years worked as test-stand mechanic (RR) to classify potential exposure to hydrazine, TCE, other chemicals; discussions with Years worked with any potential TCE workers exposure (less than 4 years vs at least 4 years) (RR) Years worked with potential TCE exposure via engine cleaning, weighted by number of engine tests (less than 4 test-years vs at least 4 test-years ) (Continued) 273

274 TABLE E-1 Continued Reference Study Design, Exposure, Outcomes Exposure Assessment Exposure Metrics Comments Brüning et al. 2003 Hospital-based case-control Telephone interview, occupational Ever employed in specific occupations questionnaire devoted to screw-cutting West Germany (site of metal, paper, industry and general for other jobs; TCE, Longest job held wood-processing industries) PCE exposure for at least one job period (1+ year), cumulative of TCE in ppm per Ever worked in tasks, occupations, or TCE, PCE job per year in job, peaks; assessment industries with TCE or PCE exposure semiquantitative for exposure to TCE, Renal-cell cancer PCE; qualitative for other occupational Cumulative exposure assessed with JEM exposures; confidence score (certain, (Pannet et al. 1985): none, low, high probable, possible) used for each exposure (dichotomized at median) assessed; assessed industry and job-title codes Self-reported exposure to TCE, PCE (separately) Occurrence of narcotic symptoms (any, nondaily, or daily) (TCE) Duration of exposure to TCE (none, less than 10 years, 10 to less than 20 years, 20+ years), PCE (none, less than 10 years, 10+ years) Chang et al. 2003 Cohort-mortality study of electronics Employment histories at different Duration of employment (SMR) categorized factory workers factories, changes in insurance status from as 1 year or less, more than 1 year but less Bureau of Labor Insurance computer than or equal to 5 yrs, more than 5 years) Taiwan database for 1978-1997; confirmed, supplemented with list of names of patients Year of death from cancer (1985-1990, TCE, PCE in labor-insurance hospitalization dataset, 1991-1997) United Labor Association; duration of Cancers employment calculated from insurance records, operation history of index electronics factory (1968-1992); EPA in Taiwan verified pollution of wells with TCE, PCE Charbotel et al. 2006 Case-control Information from occupational By industry (NACE codes) (OR) Adjustment for tobacco- questionnaires, task-exposure matrix for smoking, BMI Arve Valley (France) screw-cutting tasks; employee’s activity, By Job title (ILO 68 codes) (OR) job title encoded; assessed for exposure to TCE used as degreasing agent in solvents, oils, welding fumes, etc.; Ever vs never exposed (OR) screw-cutting industry in Arve semiquantitative assessment for exposure Valley to TCE, qualitative (low, medium, high) Cumulative exposure (ppm-years); task- for other exposures exposure matrix used to estimate cumulative

Other exposures (chlorinated dose for each job period (OR) (categorized solvents, oxygenated solvents, white- into tertiles) spirit and petroleum solvents), oils, welding fumes, lead, cadmium, Cumulative exposure with assessment for asbestos peaks (low-medium without peaks, low- medium with peaks, high without peaks, Renal-cell cancer high with peaks) (OR) Cumulative exposure with assessment for peaks (low-medium without peaks, low- medium with peaks, high without peaks, high with peaks) with only exposures scored certain or probable summed in cumulative- exposure score (OR) Costas et al. 2002 Case-control Exposure assessed based on potential for With water-distribution model, exposure residence to receive water from index developed for each hydraulic area and Woburn, MA contaminated wells G and H, not on actual month (exposure index: fraction of month contaminant concentration in wells; water- when contaminated water reached hydraulic TCE-contaminated groundwater distribution model used, validated; area multiplied by fraction of water supplied wells in Woburn, MA (site of cumulative exposure based on exposure by contaminated wells) tannery, chemical manufacturing periods, operation of wells wastes) Average, cumulative exposure scores (for seven etiologic windows) categorized as TCE (primary), PCE never vs some or never, least, most (median of some exposure used to define least, most) Childhood leukemia Etiologic windows: entire etiologic period (2 years before conception to date of case diagnosis); preconception period, duration of pregnancy; 1st, 2nd, 3nd trimester of pregnancy; period from time of birth to case diagnosis De Roos et al. 2001 Case-control (cases identified from Self-reported occupational exposures to Self-reported parental exposure to five Adjustment for child’s hospitals participating in two solvents obtained by telephone interview; categories of chemicals (halogenated age, maternal race, pediatric collaborative clinical trials) industrial-hygienist review of self-reported hydrocarbons; nonvolatile hydrocarbons; maternal age, maternal exposures volatile hydrocarbons; paints, inks, education Occupational exposure to five pigments; metals, alloys, solders (any vs categories of chemicals none) Neuroblastoma Industrial hygienist reviewed assessment of exposure on basis of questionnaire data (probable exposure assigned yes, otherwise no) (Continued) 275

276 TABLE E-1 Continued Reference Study Design, Exposure, Outcomes Exposure Assessment Exposure Metrics Comments Diot et al. 2002 Hospital-based case-control Employment periods of over 6 mo Ever vs never exposed recorded from interview, but only Central region of France employment corresponding to period High cumulative exposure score vs those before patient’s diagnosis was included; without high cumulative exposure score Occupational exposures to silica, exposure to various occupational hazards organic solvents (including TCE) asked; expert committee (occupational Cumulative exposure score: sum of exposure physicians, epidemiologists, industrial scores for each employment Systemic sclerosis hygienists) assessed exposure Exposure score: probability x intensity x frequency x duration; probability of exposure: 0 = nonexposure, 0.25 = possible exposure, 0.75 = probable exposure, 1 = certain exposure; intensity of exposure: 0 for nonexposure to 1 for highest level of exposure; length of time worked daily: <10% = 0.05, 10-50% = 0.30, >50% = 0.75; number of years worked Fabbro-Peray et al. Population-based case-control Cohort interviewed about occupational Self-reported exposure (yes vs no) Lag time of 5 years 2001 exposures, including chemicals, pesticides, before diagnosis (or Languedoc-Roussillon, France electromagnetic radiation; asked about Age at first exposure interview for controls) smoking; subjects considered exposed if Occupational exposure to benzene, exposure lasted more than 1 year Duration of exposure (never, up to 15 years, Adjustment for age, sex, rubber, coal tar, paints, waste oil, over 15 years) urban setting, education dry-cleaning solvents, petroleum products, pesticides Cumulative exposure (lifetime-days of exposure) (never-erratic, up to 810 days, Non-Hodgkin lymphoma over 810 days) Time since first exposure (never, up to 10 years, over 10 years) Further classifications for benzene, pesticides Garabrant et al. Case-control Women asked whether ever worked at Self-reported exposure to specific, all Adjustment for age, year 2003 least once a week for 3 mo or more in any solvents of birth Michigan, Ohio of 16 jobs or hobbies that commonly involve solvents; information obtained on Expert-reviewed exposure to specific, all Occupational or hobby-related job title, years, specific tasks, nine specific solvents exposure to hydrocarbons, solvents (paint thinners and removers, chlorinated solvents mineral spirits naphtha or white spirits, Self-reported jobs, hobbies gasoline, toluene, xylene, benzene, TCE, Systemic sclerosis PCE, trichloroethane), other solvents), safety precautions; reviewed by expert

Hansen et al. 2001 Cohort Historical files of individual air, urinary Period of first employment (1947-1964, Sensitivity analyses: 10- measurements of TCE exposure ( from 1965-1989) year, 20-year lag periods Denmark Labor Inspection Services of Denmark); (data not shown; no job information reconstructed from Duration of employment (less than 75 mo vs change in results) TCE national pension fund at least 75 mo) Cancer Average personal TCE exposure (less than 19 mg/m3 vs at least 19 mg/m3) Cumulative TCE exposure (less than 1,080 months-mg/m3 vs at least 1,080 months- mg/m3) Infante-Rivard et al. Population-based case-control Maternal occupational exposures to Jobs held during 2 years before, during Adjustment for age, 2005 solvents before and during pregnancy pregnancy coded as “possible,” “probable,” education Quebec, Canada estimated by coding by job for specific “definite”; level assigned (low = 1, medium contaminants (also called expert method); = 2, high = 3) Maternal occupational exposure to coded for 21 solvents; home exposure to solvents, solvent mixtures solvents evaluated on basis of activities, Any vs no exposure including hobbies, furniture stripping, Childhood ALL electronic and motor-vehicle repair, home Any vs no exposure (none and “possible” vs painting “probable” and “definite”) Level of exposure (0 = baseline, 1 = some exposure (concentration x frequency less than 4), 2 = greater exposure (concentration x frequency at least 4) Krishnadasan et al. Nested case-control Workers employed 1950-1992 at nuclear- Industry-based JEM (for all jobs held) 20-year (and zero lag) 2007 energy, rocket-engine-testing facility; exposure estimates Nuclear-energy, rocket-engine company records used to construct JEM For each job and by chemical, likelihood development, testing facility in for exposures to hydrazine, TCE, PAHs, (none, low, high), intensity (low, medium, Adjustment for Southern California benzene, mineral oil; from job-description high) for three periods (1950-1969, 1970- occupational physical manuals, walk-throughs, interviews; 1979, 1989-1999) activity, SES, other PAHs, TCE, hydrazine, mineral oil, industrial hygienist created estimate of chemical exposures benzene likelihood, intensity of exposures during Cumulative-exposure score for each worker three periods (1950s-1960s, 1970s, 1980s- for all jobs held (none, low, moderate, high); Prostatic cancer 1990s); duration of employment of cumulative-exposure score = sum of longest-held job (and others) duration of employment x estimated intensity for each job Cumulative-exposure scores categorized by quartiles: unexposed vs low-moderate vs high (Continued) 277

TABLE E-1 Continued 278 Reference Study Design, Exposure, Outcomes Exposure Assessment Exposure Metrics Comments Lee et al. 2003 Case-control; residents of two Groundwater sampling from off-site Upstream (referent) vs downstream village villages in vicinity of electronics residential wells in nearby communities (validated by groundwater well samples— factory October 1999-May 2000; exposed were detectable vinyl chloride, TCE, PCE, 1,1- downstream residents; stratified on dichloroethylene, 1,1,1,-trichloroethane, cis- Chlorinated hydrocarbons in calendar periods based on establishment of 1,2-dichloroethylene, 1,1-dichloroethane) groundwater contaminated by factory (allowing 10 years to detect health hazardous-waste site (formerly effects of exposure) Period of death: 1966-1979 (referent), 1980- electronics factory) 1989, 1990-1997 Hepatic-cancer mortality Lynge et al. 2006 Nested case-control; cohort of Occupation code “laundry and dry- Exposure categories: unexposed, dry cleaner laundry, dry-cleaning workers cleaning worker” or industry code and other exposed, other in dry cleaning, “laundry and dry cleaning”; categorized on unclassifiable Denmark, Finland, Norway, Sweden basis of fewer than 10 workers in shop, laundry workers and other workers in dry- Dry cleaner length of employment (0-1 Occupational exposure to dry- cleaning shops; length of employment in years, 2-4 years, 5-9 years, at least 10 years, cleaning solvents (predominantly shop where worked in 1970 (only the unknown) PCE) period of 1964-1979 was included); interviews with next of kin; detailed Cancer history of dry cleaning in Nordic countries Miligi et al. 2006 Population-based case-control study Job-exposure matrix of most frequent job Unexposed vs very low, low and medium, Adjustment for sex, age, titles and sectors to assign probability- and high intensity levels and duration of education, area Italy intensity-weighted scales of exposure to exposure (15 yr or less vs 15 yr) solvents, five specific categories of Occupational solvent use in chemical classes, eight individual manufacturing industries or chemicals; occupational history agriculture questionnaires Lymphoma Morgan and Cohort study of residents with Residence in census tracts near Redlands, None (SIRs—indirect standardization) Cassady 2002 contaminated drinking water CA (where concerns about contamination of groundwater, drinking water with TCE, San Bernardino County, CA (13 ammonium perchlorate; 1980 assessment census tracts) of TCE in Redlands wells ranged from 0.09 to 97 ppb; since 1991, wells either PCE, chlorate, TCE treated or removed to maintain TCE under 5 ppb Cancers

Perrin et al. 2007 Cohort study; offspring of dry Occupations of parents obtained from birth Mother and/or father dry cleaner(s) at time cleaners certificate of birth (yes vs no) Jerusalem, Israel Maternal or paternal occupational (dry-cleaning) exposure to TCE Schizophrenia in offspring Raaschou-Nielsen et Cohort Employment based on companies Duration of employment (less than 1 year, 1- Stratified analysis by sex al. 2003 classified by air TCE measurements in 4.9 years, at least 5 years) Denmark workplace 1947-1989 by Danish Labor Inspection Service, area and personal Year of first employment (before 1970, TCE measurements (after 1974);included 1970-1979, 1980-) companies determined by size; iron and Cancers, including non-Hodgkin metal, electronics, painting, printing, Lag time (none, 20 years) lymphoma, renal-cell carcinoma, chemical, dry cleaning, other; workers esophageal adenocarcinoma identified by Pension Fund or Central Number of employees (fewer than 50, 50-99, Population Registry (most recent job title) 100-200) Radican et al. 2006 Retrospective cohort; aircraft Subjects identified from database of Cumulative-exposure score: frequency workers former civilian employees of Hill Air (times/day), duration (min/day), calendar Force Base I, Utah; semiquantitative period of use, years of exposure; categorized TCE, 1,1,1-trichloroethane, estimate of TCE exposure obtained from into tertiles methylene chloride, carbon comprehensive exposure assessment; tetrachloride, cumulative exposure score computed for JP4 gasoline, Freon, each subject isopropyl alcohol, acetone, toluene, methyl ethyl ketone, o-dichlorobenzene, PCE, chloroform, stoddard solvent, styrene, xylene End-stage renal disease (Continued) 279

280 TABLE E-1 Continued Reference Study Design, Exposure, Outcomes Exposure Assessment Exposure Metrics Comments Ruder et al. 2001 Cohort study; dry-cleaning workers Dry-cleaning union records , people not Time since first employment (less than 20 (in IOM report) known to ever have been exposed to years, at least 20 years), duration of San Francisco, Oakland, CA; carbon tetrachloride who had worked 1+ employment in dry-cleaning shops (1-5 Chicago, IL; Detroit, MI; New York, year before 1960 in shop using PCE; shops years, 5+ years) NY visited to verify solvent use history; PCE- only subcohort, PCE-plus cohort (records PCE only solvent, PCE and other solvents Occupational exposure to PCE inadequate to confirm PCE use or another used in dry-cleaning shops solvent, mostly Stoddard solvent or other Cancer deaths petroleum solvents) Schreiber et al. 2002 Cross-sectional; residents above dry- Apartment residents above dry cleaner; air Personal monitoring of PCE with passive cleaning shops, day-care workers sampling of PCE in apartments; day-care monitors (3M organic vapor monitors) for sharing building with dry cleaner workers sharing building with dry cleaner exposed persons compared with NY State Department of Health controls, matched by age Creatinine-adjusted urinary PCE, (within 2 years), sex trichloroacetic acid, trichloroethanol for exposed persons PCE Exposed vs control groups Visual contrast sensitivity Seidler et al. 2007 Population-based case-control Complete occupational history obtained by Intensity of exposure (low, medium, high— interview: dates, job title, industry, job assigned in ppm depending on chemical); Germany tasks, job-task-specific supplementary frequency of exposure based on 40-h questions; industrial physician assessed workweek (low = 1-5%, medium = over 5 to Occupational exposure to intensity, frequency of exposure to specific 30%, high = over 30%); confidence chlorinated, organic solvents chlorinated hydrocarbons (including TCE, (possible but not probable, probable, certain) PCE), aromatic hydrocarbons Lymphoma Cumulative exposure (ppm x years): sum of intensity x frequency x duration for all jobs held; categorized among controls at 50th, 90th percentiles Sonnefeld et al. Case-control Residents of Tarawa Terrace were Duration of exposure (never exposed, 1-3 2001 considered exposed; exposure magnitude weeks, 4-10 weeks, 11-20 weeks, over 20 Camp Lejeune, NC determined by length of residence weeks and less than entire pregnancy, entire pregnancy and less than 1 year before LMP, Contaminated drinking-water TCE, entire pregnancy and at least 1 year before other compounds LMP Birthweight, small for gestational age, preterm birth

Sung et al. 2007 Retrospective cohort; female workers Female workers of former electronics Duration of employment (less than 1 mo, 1- Latency accounted for in at electronics factory factory identified through Bureau of labor 11 mo, 1-4 years, 5-9 years, at least 10 assessing person-years at Insurance 1973-1997; duration of years) risk (5 years, cancer of Taoyuan, Taiwan employment thyroid, leukemia; 15 years, breast cancer; 10 Occupational exposure to solvents years, other cancers) Stratified by calendar Cancer year (in which regulations were enacted on use of organic solvents in factories): before and after June 20, 1974 Vieira et al. 2005 Population-based case-control Used personal delivered-dose model that PDD: sum of PCE from inhalation, dermal Nine latency periods included personal data on tap-water absorption, ingestion based on RDD; examined (0, 5, 7, 9, 11, Cape Cod, MA consumption, bathing habits from subjects categorized into four groups based on 13, 15, 17, 19 years) or next of kin distribution among exposed controls: at least PCE from inner vinyl liner leaching 50th percentile, over 50th percentile, over Adjustment for age at from cement pipes distributing tap 75th percentile, over 90th percentile; ever vs diagnosis or index year, water never exposed family history of breast cancer, personal history Breast cancer Inhalation exposure: function of of breast cancer, age at temperature, frequency, duration of baths, first live birth or showers, concentration of PCE volatilized in stillbirth, occupational air from water exposure to PCE Dermal absorption: function of surface area, Fick’s law Ingestion: function of volume of tap water consumed Yauck et al. 2004 Case-control GIS used to calculate distances between Proximity measure using classification-tree Milwaukee,WI maternal residence, TCE sites; method: distance from maternal residence to classification tree analysis used to TCE-emitting facility dichotomized into TCE-emitting sites in Milwaukee, determine distance for dichotomizing exposed (residence within 1.32 miles of at surrounding areas, 1996-1999 exposure: within or outside 1.32 miles of at least one site), nonexposed (residence more least one TCE site than 1.32 miles of at least one site Congenital heart defects (Continued) 281

282 TABLE E-1 Continued Reference Study Design, Exposure, Outcomes Exposure Assessment Exposure Metrics Comments Zhao et al. 2005 Retrospective cohort; California aerospace workers 1950-1993 at JEM used to assess exposure in each job Adjustment for time Rockwell/Rocketdyne (now Boeing) several Boeing North America facilities in group: Intensity (0-3) (1950-1969, 1970- since first employment, aerospace male workers employed LA, employed before 1980 in aerospace 1979, 1980-1989) × duration SES, age at diagnosis before 1980 division of SSFL, worked 2+ years and never monitored for radiation exposure; Cumulative-exposure score: low (up to 3), Los Angeles, CA extensive industrial-hygienist review medium (over 3 up to 12), high (over 12) interested in exposure to rocket fuel Hydrazine, TCE, PAHs, mineral oil, hydrazine, TCE, PAHs, mineral oil, benzene benzene Cancer mortality, incidence Abbreviations: ALL = acute lymphocytic leukemia, BMI = body-mass index, DEP = Department of Environmental Protection, EPA = U.S. Environmental Protection Agency, GIS = geographic information system, ILO = International Labor Organization, IOM = Institute of Medicine, JEB = job-exposure matrix, LMP = last menstrual period, OR = odds ratio, PAH = polycyclic aromatic hydrocarbon, PCE = perchloroethylene, PDD = personal delivered dose, RDD = relative delivered dose, RR = relative risk, SES = socioeconomic status, SIR = standardized incidence ratio, SMR = standardized mortality ratio, SSFL = Santa Susana Field Laboratory, TCE = trichloroethylene

TABLE E-2 Studies of Cancer End Points and Exposure to TCE Reference Study Population No. Exposed Persons MOR, OR, SIR, or SMR (95% CI) BUCCAL CAVITY AND PHARYNGEAL CANCER Cohort Studies—Incidence Hansen et al. 2001a Danish workers: Men 7 2.3 (0.9-4.7) SIR Women 0 — Raaschou-Nielsen et al. 2003 Danish workers: Men employed at least 3 mo 95 1.1 (0.90-1.36) SIR Women employed at least 3 mo 10 1.8 (0.84-3.24) SIR Chang et al. 2005 Electronics-manufacturing workers in Taiwan exposed to TCE, PCE: Men 19 0.55 (0.33-0.86) SIR Women 42 0.96 (0.69-1.29) SIR Sung et al. 2007 Female electronics workers in Taoyuan, Taiwan 10b 0.74 (0.35-1.36) SIR Cohort Studies—Mortality Chang et al. 2003 Electronics-manufacturing workers in Taiwan exposed to TCE, PCE: Men 6 0.65 (0.50-0.83) SMR Women 10 0.71 (0.34-1.30) SMR Boice et al. 2006 Male workers at rocket-engine testing facility 4 1.25 (0.34-3.21) SMR ESOPHAGEAL CANCER Cohort Studies—Incidence Raaschou-Nielsen et al. 2003 Danish workers: Men: All employed at least 3 mo 23 1.8 (1.5-2.73) SIR Employed <1 year 6 1.7 (0.6-3.6) SIR Employed 1-4.9 years 9 1.9 (0.9-3.6) SIR Employed ≥5 years 8 1.9 (0.8-3.7) SIR Women: All employed at least 3 mo 0 0 (0.00-8.32) SIR Zhao et al. 2005 Aerospace workers (men) Cumulative-exposure score, lag 0: Low (0-3) 9 1.00 SIR Medium (>3-15) 8 1.66 (0.62-4.41) SIR High (>15) 2 0.82 (0.17-3.95) SIR Sung et al. 2007 Female electronics workers in Taoyuan, Taiwan 2 1.16 (0.14-4.20) SIR (Continued) 283

284 TABLE E-2 Continued Reference Study Population No. Exposed Persons MOR, OR, SIR, or SMR (95% CI) Cohort Studies—Mortality Chang et al. 2003 Electronics-manufacturing workers in Taiwan exposed to TCE, PCE: Men 0 — Women 0 — Zhao et al. 2005 Aerospace workers (men) Cumulative-exposure score, lag 0: Low (0-3) 18 1.00 SMR Medium (>3-15) 15 1.40 (0.70-2.82) SMR High (>15) 7 1.27 (0.52-3.13) SMR Boice et al. 2006 Male workers at rocket-engine testing facility 3 0.88 (0.18-2.58) SMR STOMACH CANCER Cohort Studies—Incidence Raaschou-Nielsen et al. 2003 Danish workers: Men employed at least 3 mo 77 1.0 (0.80-1.27) SIR Women employed at least 3 mo 9 1.3 (0.59-2.46) SIR Chang et al. 2005 Electronics-manufacturing workers in Taiwan exposed to TCE, PCE: Men 56c 0.73 (0.55-0.95) SIR Women 135c 0.93 (0.78-1.09) SIR Sung et al. 2007 Female electronics workers in Taoyuan, Taiwan 42 0.88 (0.64-1.19) SIR Cohort Studies—Mortality Chang et al. 2003 Electronics-manufacturing workers in Taiwan exposed to TCE, PCE: Men 7 0.93 (0.37-1.91) SMR Women 24 1.11 (0.71-1.65) SMR Boice et al. 2006 Male workers at rocket-engine testing facility 6 1.37 (0.50-2.99) SMR Case-Control Studies Lee et al. 2003 Community downstream of electronics factory in Taiwan 39 2.18 (0.97-4.89) MOR (chlorinated hydrocarbons; males) COLON CANCER Cohort Studies—Incidence Morgan and Cassady 2002 Redlands, CA, community exposed to TCE, PCE in drinking water 327d 0.86 (99%CI 0.74-0.99) SIR Raaschou-Nielsen et al. 2003 Danish workers: Men employed at least 3 mo 142 0.9 (0.77-1.08) SIR Women employed at least 3 mo 35 1.2 (0.85-1.70) SIR

Zhao et al. 2005 Aerospace workers (men) Cumulative-exposure score, lag 0: Low (0-3) 49 1.00 SIR Medium (>3-15) 28 0.93 (0.58-1.50) SIR High (>15) 13 0.92 (0.49-1.72) SIR Sung et al. 2007 Female electronics workers in Taoyuan, Taiwan 98d 1.10 (0.89-1.34) SIR Employed before June 1974e 21d 1.02 (0.63-1.56) SIR Employed after June 1974e 77d 1.12 (0.88-1.40) SIR Cohort Studies—Mortality Chang et al. 2003 Electronics-manufacturing workers in Taiwan exposed to TCE, PCE: Men 3 0.65 (0.13-1.91) SMR Women 19 1.36 (0.82-2.13) SMR Employed <1 year (men and women) 12 1.33 SMR Employed 1-5 years (men and women) 3 0.85 SMR Employed >5 years (men and women) 4 2.94 SMR Zhao et al. 2005 Aerospace workers (men) Cumulative-exposure score, lag 0: Low (0-3) 36d 1.00 SMR Medium (>3-15) 18d 0.90 (0.51-1.60) SMR High (>15) 8d 0.76 (0.35-1.68) SMR Boice et al. 2006 Male workers at rocket-engine testing facility 13d 1.08 (0.58-1.85) SMR Case-Control Studies Lee et al. 2003 Community downstream of electronics factory in Taiwan 26d 0.83 (0.24-2.89) MOR (chlorinated hydrocarbons; males) RECTAL CANCER Cohort Studies—Incidence Raaschou-Nielsen et al. 2003 Danish workers: Men employed at least 3 mo 128 1.1 (0.95-1.35) SIR Women employed at least 3 mo 15 1.1 (0.62-1.84) SIR Cohort Studies—Mortality Chang et al. 2003 Electronics-manufacturing workers in Taiwan exposed to TCE, PCE: Men 2 0.73 (0.08-2.65) SMR Women 13 1.67 (0.89-2.85) SMR Employed <1 year (men and women) 9 1.81 SMR Employed 1-5 years (men and women) 2 1.01 SMR Employed >5 years (men and women) 2 2.50 SMR (Continued) 285

286 TABLE E-2 Continued Reference Study Population No. Exposed Persons MOR, OR, SIR, or SMR (95% CI) HEPATIC CANCER Cohort Studies—Incidence Morgan and Cassady 2002 Redlands, CA, community exposed to TCE, PCE in drinking water 28f 1.29 (99%CI 0.74-2.05) SIR Raaschou-Nielsen et al. 2003 Danish workers: Men: All employed at least 3 mo 27 1.1 (0.74-1.64) SIR Employed <1 year 9 1.3 (0.6-2.5) SIR Employed 1-4.9 years 9 1.0 (0.5-1.9) SIR Employed ≥5 years 9 1.1 (0.5-2.1) SIR Women: All employed at least 3 mo 7 2.8 (1.13-5.80) SIR Employed <1 year 2 2.8 (0.3-10.0) SIR Employed 1-4.9 years 4 4.1 (1.1-10.5) SIR Employed ≥5 years 1 1.3 (0.0-7.1) SIR Sung et al. 2007 Female electronics workers in Taoyuan, Taiwan 36f 0.79 (0.55-1.10) SIR Cohort Studies—Mortality Chang et al. 2003 Electronics-manufacturing workers in Taiwan exposed to TCE, PCE: Men 0 — Women 0 — Boice et al. 2006 Male workers at rocket-engine testing facility 4f 1.28 (0.35-3.27) SMR Case-Control Studies Lee et al. 2003 Community downstream of electronics factory in Taiwan 53 2.57 (1.21-5.46) MOR (chlorinated hydrocarbons; males) PANCREATIC CANCER Cohort Studies—Incidence Raaschou-Nielsen et al. 2003 Danish workers: Men employed at least 3 mo 66 1.1 (0.85-1.39) SIR Women employed at least 3 mo 9 1.0 (0.47-1.96) SIR Zhao et al. 2005 Aerospace workers (men) Cumulative-exposure score, lag 0: Low (0-3) 13 1.00 SIR Medium (>3-15) 7 0.85 (0.33-2.17) SIR High (>15) 1 0.28 (0.04-2.14) SIR Sung et al. 2007 Female electronics workers in Taoyuan, Taiwan 11 1.64 (0.82-2.94) SIR

Cohort Studies—Mortality Chang et al. 2003 Electronics-manufacturing workers in Taiwan exposed to TCE, PCE: Men 1 0.49 (0.01-2.73) SMR Women 5 1.39 (0.45-3.25) SMR Employed <1 year (men and women) 2 0.91 SMR Employed 1-5 years (men and women) 2 2.15 SMR Employed >5 years (men and women) 1 2.22 SMR Zhao et al. 2005 Aerospace workers (men) Cumulative-exposure score, lag 0: Low (0-3) 22 1.00 SMR Medium (>3-15) 15 1.13 (0.58-2.21) SMR High (>15) 2 0.35 (0.08-1.50) SMR Boice et al. 2006 Male workers at rocket-engine testing facility 2 0.32 (0.04-1.14) SMR LARYNGEAL CANCER Cohort Studies—Incidence Hansen et al. 2001a Danish workers: Men 2 1.1 (0.1-3.9) SIR Women 0 — Raaschou-Nielsen et al. 2003 Danish workers: Men employed at least 3 mo 53 1.2 (0.87-1.52) SIR Women employed at least 3 mo 3 1.7 (0.33-4.82) SIR Cohort Studies—Mortality Chang et al. 2003 Electronics-manufacturing workers in Taiwan exposed to TCE, PCE: Men 0 — Women 0 — Boice et al. 2006 Male workers at rocket-engine testing facility 2 1.45 (0.18-5.25) SMR LUNG CANCER Cohort Studies—Incidence Hansen et al. 2001a Danish workers: Men 16 0.8 (0.5-1.3) SIR Women 1 0.7 (0.01-3.8) SIR Morgan and Cassady 2002 Redlands, CA, community exposed to TCE, PCE in drinking water 356g 0.71 (99%CI 0.61-0.81) SIR (Continued) 287

288 TABLE E-2 Continued Reference Study Population No. Exposed Persons MOR, OR, SIR, or SMR (95% CI) Chang et al. 2005 Electronics-manufacturing workers in Taiwan exposed to TCE, PCE: Men 20 0.94 (0.57-1.45) SIR Women 34 0.95 (0.66-1.33) SIR Raaschou-Nielsen et al. 2003 Danish workers: Men: All employed at least 3 mo 559 1.4 (1.28-1.51) SIR Employed <1 year 181 1.6 (1.4-1.9) SIR Employed 1-4.9 years 193 1.3 (1.1-1.5) SIR Employed ≥5 years 185 1.4 (1.2-1.6) SIR Women: All employed at least 3 mo 73 1.9 (1.48-2.35) SIR Employed <1 year 28 2.5 (1.6-3.6) SIR Employed 1-4.9 years 25 1.6 (1.1-2.4) SIR Employed ≥5 years 20 1.6 (1.0-2.5) SIR Zhao et al. 2005 Aerospace workers (men) Cumulative-exposure score, lag 0: Low (0-3) 43 1.00 SIR Medium (>3-15) 35 1.36 (0.86-2.14) SIR High (>15) 14 1.11 (0.60-2.06) SIR Sung et al. 2007 Female electronics workers in Taoyuan, Taiwan 46h 0.92 (0.67-1.23) Cohort Studies—Mortality Chang et al. 2003 Electronics-manufacturing workers in Taiwan exposed to TCE, PCE: Men 13h 0.90 (0.48-1.53) SMR Women 25h 1.01 (0.65-1.49) SMR Zhao et al. 2005 Aerospace workers (men) Cumulative-exposure score, lag 0: Low (0-3) 99 1.00 SMR Medium (>3-15) 62 1.05 (0.76-1.44) SMR High (>15) 33 1.02 (0.68-1.53) SMR Boice et al. 2006 Male workers at rocket-engine testing facility 51h 1.24 (0.92-1.63) SMR Case-Control Studies Lee et al. 2003 Community downstream of electronics factory in Taiwan 41 1.75 (0.79-2.39) MOR (chlorinated hydrocarbons; males) BONE CANCER Cohort Studies—Incidence

Chang et al. 2005 Electronics-manufacturing workers in Taiwan exposed to TCE, PCE: Men 1 0.61 (0.01-3.39) SIR Women 6 1.28 (0.47-2.78) SIR Sung et al. 2007 Female electronics workers in Taoyuan, Taiwan 3 0.92 (0.19-2.70) SIR Cohort Studies—Mortality Chang et al. 2003 Electronics-manufacturing workers in Taiwan exposed to TCE, PCE: Men 0i — Women 4i 1.63 (0.44-4.18) SMR Employed <1 year (men and women) 2i 1.25 SMR Employed 1-5 years (men and women) 2i 3.23 SMR Employed >5 years (men and women) 0i — Boice et al. 2006 Male workers at rocket-engine testing facility 0 0 (0.00-13.8) SMR SOFT-TISSUE SARCOMA Cohort Study—Incidence Chang et al. 2005 Electronics-manufacturing workers in Taiwan exposed to TCE, PCE: Men 3 1.4 (0.3-4.2) SIR Women 8 1.0 (0.4-2.0) SIR Cohort Study—Mortality Chang et al. 2003 Electronics-manufacturing workers in Taiwan exposed to TCE, PCE: Men 0 — Women 0 — BREAST CANCER Cohort Studies—Incidence Morgan and Cassady 2002 Redlands, CA, community exposed to TCE, PCE in drinking water 536 1.09 (99%CI 0.97-1.21) SIR (women only) Raaschou-Nielsen et al. 2003 Danish workers: Men employed at least 3 mo 2 0.5 (0.06-1.90) SIR Women employed at least 3 mo 145 1.1 (0.89-1.24) SIR Chang et al. 2005 Electronics-manufacturing workers in Taiwan exposed to TCE, PCE: Men 0 0.00 (0.00-33.54) SIR Women 215 1.19 (1.03-1.36) SIR (Continued) 289

290 TABLE E-2 Continued Reference Study Population No. Exposed Persons MOR, OR, SIR, or SMR (95% CI) Sung et al. 2007 Female electronics workers in Taoyuan, Taiwan 286 1.09 (0.96-1.22) SIR Employed before June 1974e 90 1.38 (1.11-1.70) SIR Employed after June 1974e 196 0.99 (0.85-1.14) SIR Cohort Studies—Mortality Chang et al. 2003 Electronics-manufacturing workers in Taiwan exposed to TCE, PCE: Men 0 — Women 51 1.14 (0.85-1.51) SMR Employed <1 year (women) 31 1.08 SMR Employed 1-5 years (women) 14 1.25 SMR Employed >5 years (women) 6 1.32 SMR CERVICAL CANCER Cohort Studies—Incidence Morgan and Cassady 2002 Redlands, CA, community exposed to TCE, PCE in drinking water 29 0.65 (99%CI 0.38-1.02) SIR Raaschou-Nielsen et al. 2003 Danish workers (women employed for at least 3 mo) 62 1.9 (1.42-2.37) SIR Employed <1 year 30 2.5 (1.7-3.5) SIR Employed 1-4.9 years 22 1.6 (1.0-2.4) SIR Employed ≥5 years 10 1.3 (0.6-2.4) SIR Chang et al. 2005 Electronics-manufacturing workers in Taiwan exposed to TCE, PCE (women): Employed <1 year 177 1.1 (0.9-1.2) SIR Employed 1-5 years 69 1.1 (0.8-1.3) SIR Employed 5-10 years 26 1.6 (1.1-2.4) SIR Employed >10 years 1 0.1 (0.0-0.8) SIR Sung et al. 2007 Female electronics workers in Taoyuan, Taiwan 337 0.96 (0.86-1.06) SIR Employed before June 1974e 72 0.84 (0.66-1.06) SIR Employed after June 1974e 265 0.99 (0.88-1.12) SIR Cohort Studies—Mortality Chang et al. 2003 Electronics-manufacturing workers in Taiwan exposed to TCE and 21 0.80 (0.49-1.22) SMR PCE (women) Employed <1 year 14 0.84 SMR Employed 1-5 years 6 0.89 SMR Employed >5 years 1 0.34 SMR UTERINE CANCER Cohort Studies—Incidence Morgan and Cassady 2002 Redlands, CA, community exposed to TCE, PCE in drinking water 124 1.35 (99%CI 1.06-1.70) SIR

Raaschou-Nielsen et al. 2003 Danish workers (women employed at least 3 mo) 24 1.0 (0.66-1.53) SIR Chang et al. 2005 Electronics-manufacturing workers in Taiwan exposed to TCE, 337j 1.06 (0.95-1.18) SIR PCE Sung et al. 2007 Female electronics workers in Taoyuan, Taiwan 25 0.96 (0.62-1.42) SIR Cohort Studies—Mortality Chang et al. 2003 Electronics-manufacturing workers in Taiwan exposed to TCE, 5 0.91 (0.29-2.13) SMR PCE (women): Employed <1 year 3 0.88 SMR Employed 1-5 years 2 1.42 SMR Employed >5 years 0 — OVARIAN CANCER Cohort Studies—Incidence Morgan and Cassady 2002 Redlands, CA, community exposed to TCE, PCE in drinking water 81 1.16 (99%CI 0.85-1.53) SIR Raaschou-Nielsen et al. 2003 Danish workers (w omen employed at least 3 mo) 22 0.9 (0.55-1.32) SIR Sung et al. 2007 Female electronics workers in Taoyuan, Taiwan 36k 0.83 (0.58-1.15) SIR Cohort Studies—Mortality Chang et al. 2003 Electronics-manufacturing workers in Taiwan exposed to TCE, 7 0.80 (0.32-1.64) SMR PCE (women): Employed <1 year 1 0.18 SMR Employed 1-5 years 3 1.36 SMR Employed >5 years 3 3.45 SMR PROSTATIC CANCER Cohort Studies—Incidence Morgan and Cassady 2002 Redlands, CA, community exposed to TCE, PCE in drinking water 483 1.11 (99%CI 0.98-1.25) SIR Raaschou-Nielsen et al. 2003 Danish workers (men employed at least 3 mo) 163 0.9 (0.79-1.08) SIR Cohort Studies—Mortality Chang et al. 2003 Electronics-manufacturing workers in Taiwan exposed to TCE, 0 — PCE (men) Boice et al. 2006 Male workers at rocket-engine testing facility 8 0.82 (0.36-1.62) SMR Case-Control Studies Krishnadasan et al. 2007 Workers at nuclear energy and rocket-engine testing facility: Low-moderate exposure, lag 0 90 1.3 (0.81-2.1) OR High exposure, lag 0 45 2.1 (1.2-3.9) OR TESTICULAR CANCER Cohort Studies—Incidence Hansen et al. 2001a Danish workers (men) 1 0.7 (0.01-4.0) SIR (Continued) 291

292 TABLE E-2 Continued Reference Study Population No. Exposed Persons MOR, OR, SIR, or SMR (95% CI) Raaschou-Nielsen et al. 2003 Danish workers (men employed at least 3 months) 93 1.1 (0.92-1.40) SIR Chang et al. 2005 Electronics-manufacturing workers in Taiwan exposed to TCE, 1l 0.14 (0.00-0.76) SIR PCE Cohort Studies—Mortality Chang et al. 2003 Electronics-manufacturing workers in Taiwan exposed to TCE, 0 — PCE (men) Boice et al. 2006 Male workers at rocket-engine testing facility 0l 0 (0.00-8.53) SMR RENAL CANCER Cohort Studies—Incidence Morgan and Cassady 2002 Redlands, CA, community exposed to TCE, PCE in drinking water 54 0.80 (99%CI 0.54-1.12) SIR Raaschou-Nielsen et al. 2003 Danish workers: Men All employed at least 3 mo 93 1.2 (0.97-1.48) SIR Employed <1 year 14 0.8 (0.5-1.4) SIR Employed 1-4.9 years 25 1.2 (0.8-1.7) SIR Employed ≥5 years 29 1.6 (1.1-2.3) SIR Women: All employed at least 3 mo 10 1.2 (0.55-2.11) SIR Employed <1 year 2 1.1 (0.1-3.8) SIR Employed 1-4.9 years 3 1.2 (0.2-3.4) SIR Employed ≥5 years 3 1.5 (0.3-4.3) SIR Chang et al. 2005 Electronics-manufacturing workers in Taiwan exposed to TCE, PCE: Men 8m 1.06 (0.45-2.08) SIR Women 12m 1.09 (0.56-1.91) SIR Zhao et al. 2005 Aerospace workers (men) Cumulative-exposure score, lag 0: Low (0-3) 6 1 SIR Medium (>3-15) 6 1.87 (0.56-6.20) SIR High (>15) 4 4.90 (1.23-19.6) SIR Sung et al. 2007 Female electronics workers in Taoyuan, Taiwan 15m 1.10 (0.62-1.82) SIR Cohort Studies—Mortality Chang et al. 2003 Electronics-manufacturing workers in Taiwan exposed to TCE, PCE: Men 0m — Women 3m 1.18 (0.24-3.44) SMR Employed <1 year 1m 0.62 SMR

Employed 1-5 years 2m 3.08 SMR Employed >5 years 0m — Zhao et al. 2005 Aerospace workers (men) Cumulative-exposure score, lag 0: Low (0-3) 7 1 SMR Medium (>3-15) 7 1.43 (0.49-4.16) SMR High (>15) 3 2.03 (0.50-8.32) SMR Boice et al. 2006 Male workers at rocket-engine testing facility 7 2.22 (0.89-4.57) SMR Case-Control Studies Brüning et al. 2003 Hospital-based study in Arnsberg, Germany: Longest-held job (men and women) 117 1.80 (1.01-3.20) OR Ever employed in: Metal greasing, degreasing 15 5.57 (2.33-13.32) OR Metal processing 30 1.34 (0.81-2.23) OR Metalworking 9 2.33 (0.91-5.94) OR Pannett job-exposure matrix: Degreasing agents: Low 9 2.11 (0.86-5.18) OR High 7 1.01 (0.40-2.54) OR Solvents: Low 8 1.80 (0.70-4.59) OR High 8 1.45 (0.59-3.58)OR Self-reported exposure 25 2.47 (1.36-4.49) OR Self-reported narcotic symptoms 19 3.71 (1.80-7.54) OR Duration of self-reported exposure: None 109 1 OR <10 years 11 3.78 (1.54-9.28) OR 10-20 years 7 1.80 (0.67-4.79) OR >20 years 6 2.69 (0.84-8.66) OR Charbotel et al. 2006 Cases in Arve Valley, France: Exposed during at least one job period: Nonexposed 49 1 OR Exposed 37 1.64 (0.95-2.84) OR Cumulative dose: Low 12 1.62 (0.75-3.47) OR Medium 9 1.15 (0.47-2.77) OR High 16 2.16 (1.02-4.60) OR Cumulative dose peaks: (Continued) 293

294 TABLE E-2 Continued Reference Study Population No. Exposed Persons MOR, OR, SIR, or SMR (95% CI) Low-medium, no peaks 18 1.35 (0.69-2.63) OR Low-medium, with peaks 3 1.61 (0.36-7.30) OR High, no peaks 8 1.76 (0.65-4.73) OR High, with peaks 8 2.73 (1.06-7.07) OR BLADDER CANCER Cohort Studies—Incidence Morgan and Cassady 2002 Redlands, CA, community exposed to TCE, PCE in drinking water 82 0.98 (99%CI 0.71-1.29) SIR Raaschou-Nielsen et al. 2003 Danish workers: Men employed at least 3 mo 203 1.0 (0.89-1.18) SIR Women employed at least 3 mo 17 1.6 (0.93-2.57) SIR Zhao et al. 2005 Aerospace workers (men) Cumulative-exposure score, lag 0: Low (0-3) 20 1.00 SIR Medium (>3-15) 19 1.54 (0.81-2.92) SIR High (>15) 11 1.98 (0.93-4.22) SIR Sung et al. 2007 Female electronics workers in Taoyuan, Taiwan 3 0.34 (0.07-1.00) SIR Cohort Studies—Mortality Chang et al. 2003 Electronics-manufacturing workers in Taiwan exposed to TCE, PCE: Men 1 0.96 (0.01-5.36) SIR Women 1 0.96 (0.01-5.33) SIR Zhao et al. 2005 Aerospace workers (men) Cumulative exposure score, lag 0: Low (0-3) 8 1.00 SMR Medium (>3-15) 6 1.27 (0.43-3.73) SMR High (>15) 3 1.15 (0.29-4.51) SMR Boice et al. 2006 Male workers at rocket-engine testing facility 5n 1.66 (0.54-3.87) SMR SKIN MELANOMAS Cohort Studies—Incidence Morgan and Cassady 2002 Redlands, CA, community exposed to TCE, PCE in drinking water 137 1.42 (99%CI 1.13-1.77) SIR Raaschou-Nielsen et al. 2003 Danish workers: Men: All employed at least 3 mo 56 0.7 (0.55-0.94) SIR Employed <1 year 17 0.6 (0.4-1.0) SIR Employed 1-4.9 years 26 0.9 (0.6-1.3) SIR Employed ≥5 years 13 0.6 (0.3-1.0) SIR

Women: All employed at least 3 mo 16 0.8 (0.44-1.24) SIR Employed <1 year 9 1.2 (0.6-2.3) SIR Employed 1-4.9 years 3 0.4 (0.1-1.0) SIR E mployed ≥5 years 4 0.8 (0.2-2.1) SIR Chang et al. 2005 Electronics-manufacturing workers in Taiwan exposed to TCE, PCE: Men 2 0.48 (0.05-1.73) SIR Women 13 0.99 (0.53-1.69) SIR Zhao et al. 2005 Aerospace workers (men) Cumulative-exposure score, lag 0: Low (0-3) 17 1.00 SIR Medium (>3-15) 15 1.44 (0.71-2.92) SIR High (>15) 4 0.87 (0.29-2.64) SIR Sung et al. 2007 Female electronics workers in Taoyuan, Taiwan 22 1.03 (0.65-1.56) SIR Cohort Studies—Mortality Chang et al. 2003 Electronics-manufacturing workers in Taiwan exposed to TCE, PCE: Men 0 — Women 0 — Boice et al. 2006 Male workers at rocket-engine testing facility 0 0 (0.00-1.51) SMR CENTRAL NERVOUS SYSTEM CANCER Cohort Studie—-Incidence Hansen et al. 2001a Danish workers: Men 1 0.4 (0.01-2.1) SIR Women 0 — Morgan and Cassady 2002 Redlands, CA, community exposed to TCE, PCE in drinking water 37 1.54 (99%CI 0.96-2.31) SIR Raaschou-Nielsen et al. 2003 Danish workers: Men employed at least 3 mo 85 1.0 (0.76-1.18) SIR Women employed at least 3 mo 19 1.1 (0.67-1.74) SIR Chang et al. 2005 Electronics-manufacturing workers in Taiwan exposed to TCE, PCE: Men 2 0.40 (0.05-1.46) SIR Women 15 0.97 (0.54-1.61) SIR Zhao et al. 2005 Aerospace workers (men) Cumulative-exposure score, lag 0: Low (0-3) 7o 1.00 SIR (Continued) 295

296 TABLE E-2 Continued Reference Study Population No. Exposed Persons MOR, OR, SIR, or SMR (95% CI) Medium (>3-15) 2o 0.46 (0.09-2.25) SIR High (>15) 1o 0.47 (0.06-3.95) SIR Sung et al. 2007 Female electronics workers in Taoyuan, Taiwan: Brain 14 1.07 (0.59-1.80) SIR Other parts of nervous system 2 1.43 (0.17-5.17) SIR Cohort Studies—Mortality Chang et al. 2003 Electronics-manufacturing workers in Taiwan exposed to TCE, PCE: Men 1 0.48 (0.01-2.66) SMR Women 6 0.91 (0.33-1.99) SMR Zhao et al. 2005 Aerospace workers (men) Cumulative-exposure score, lag 0: Low (0-3) 12o 1.00 SMR Medium (>3-15) 3o 0.42 (0.12-1.50) SMR High (>15) 3o 0.83 (0.23-3.08) SMR Boice et al. 2006 Male workers at rocket-engine testing facility 3 0.81 (0.17-2.36) SMR CENTRAL NERVOUS SYSTEM CANCER IN CHILDREN Cohort Studies—Incidence Morgan and Cassady 2002 Redlands, CA, community exposed to TCE, PCE in drinking water 6 1.05 (99%CI 0.24-2.70) SIR LYMPHATIC AND HEMATOPOIETIC CANCER Cohort Studies—Incidence Chang et al. 2005 Electronics-manufacturing workers in Taiwan exposed to TCE, PCE: Men 6 0.73 (0.27-1.60) SIR Women 16 0.65 (0.37-1.05) SIR MALIGNANT LYMPHOMA Case-Control Studies Seidler et al. 2007 Cases with occupational exposure in Germany: >0 to ≤4.4 ppm-year 40 0.7 (0.4-1.1) OR >4.4 to ≤35 ppm-year 32 0.7 (0.5-1.2) OR >35 ppm-year 21 2.1 (1.0-4.8) OR NON-HODGKIN LYMPHOMA Cohort Studies—Incidence Morgan and Cassady 2002 Redlands, CA, community exposed to TCE, PCE in drinking water 111 1.09 (99%CI 0.84-1.38) SIR Raaschou-Nielsen et al. 2003 Danish workers:

Men: All employed at least 3 mo 83 1.2 (0.98-1.52) SIR Employed <1 year 23 1.1 (0.7-1.6) SIR Employed 1-4.9 years 33 1.3 (0.9-1.8) SIR Employed ≥5 years 27 1.4 (0.9-2.0) SIR Women: All employed at least 3 mo 13 1.4 (0.73-2.34) SIR Employed <1 year 2 0.7 (0.1-2.4) SIR Employed 1-4.9 years 6 1.6 (0.6-3.5) SIR Employed ≥5 years 5 1.8 (0.6-4.3) SIR Zhao et al. 2005 Aerospace workers (men) Cumulative-exposure score, lag 0: Low (0-3) 28 1.00 SIR Medium (>3-15) 16 0.88 (0.47-1.65) SIR High (>15) 1 0.20 (0.03-1.46) SIR Cohort Studies—Mortality Zhao et al. 2005 Aerospace workers (men) Cumulative-exposure score, lag 0: Low (0-3) 27 1.00 SMR Medium (>3-15) 27 1.49 (0.86-2.57) SMR High (>15) 6 1.30 (0.52-3.23) SMR Boice et al. 2006 Male workers at rocket-engine testing facility 1 0.21 (0.01-1.18) SMR Case-Control Studies Miligi et al. 2006 Cases with occupational exposure in Italy: Very low-low 35 0.8 (0.5-1.3) OR Medium-high 35 1.2 (0.7-2.0) OR ≤15 years 22 1.1 (0.6-2.1) OR >15 years 12 1.0 (0.5-2.6) OR Seidler et al. 2007 Cases with occupational exposure in Germany: B-non-Hodgkin lymphoma: >0 to ≤4.4 ppm-years 32 0.7 (0.5-1.2) OR >4.4 to ≤35 ppm-years 27 0.8 (0.5-1.3) OR >35 ppm-years 17 2.3 (1.0-5.3) OR T-non-Hodgkin lymphoma: >0 to ≤4.4 ppm-years 2 0.7 (0.2-3.3) OR >4.4 to ≤35 ppm-years 2 1.1 (0.2-5.1) OR >35 ppm-years 2 4.7 (0.8-26.1) OR (Continued) 297

298 TABLE E-2 Continued Reference Study Population No. Exposed Persons MOR, OR, SIR, or SMR (95% CI) HODGKIN DISEASE Cohort Studies—Incidence Hansen et al. 2001a Danish workers: Men 0 — Women 0 — Morgan and Cassady 2002 Redlands, CA, community exposed to TCE, PCE in drinking water 17 0.93 (99%CI 0.44-1.67) SIR Raaschou-Nielsen et al. 2003 Danish workers: Men employed at least 3 mo 18 0.9 (0.51-1.37) SIR Women employed at least 3 mo 2 0.8 (0.09-3.00) SIR Cohort Studies—Mortality Chang et al. 2003 Electronics-manufacturing workers in Taiwan exposed to TCE, PCE: Men 0 — Women 1 2.23 (0.03-12.40) SMR Boice et al. 2006 Male workers at rocket-engine testing facility 2 2.86 (0.35-10.3) SMR Case-Control Studies Seidler et al. 2007 Cases with occupational exposure in Germany: >0 to ≤4.4 ppm-years 6 0.4 (0.2-1.1) OR >4.4 to ≤35 ppm-years 3 0.4 (0.1-1.4) OR >35 ppm-years 2 2.0 (0.4-10.5) OR MULTIPLE MYELOMA Cohort Studies—Incidence Raaschou-Nielsen et al. 2003 Danish workers: Men employed at least 3 mo 28 1.1 (0.70-1.52) SIR Women employed at least 3 mo 3 0.9 (0.18-2.56) SIR Cohort Studies—Mortality Boice et al. 2006 Male workers at rocket-engine testing facility 1 0.50 (0.01-2.77) SMR Case-Control Studies Seidler et al. 2007 Cases with occupational exposure in Germany: >0 to ≤4.4 ppm-years 3 0.5 (0.2-1.9) OR >4.4 to ≤35 ppm-years 6 1.0 (0.4-2.7) OR >35 ppm-years 1 0.7 (0.1-5.5) OR LEUKEMIA Cohort Studies—Incidence Morgan and Cassady 2002 Redlands, CA, community exposed to TCE, PCE in drinking water 77p 1.02 (99%CI 0.74-1.35) SIR

Raaschou-Nielsen et al. 2003 Danish workers: Men employed at least 3 mo 69 1.1 (0.84-1.37) SIR Women employed at least 3 mo 13 1.7 (0.89-2.86) SIR Sung et al. 2007 Female electronics workers in Taoyuan, Taiwan 23 0.78 (0.49-1.17) SIR Cohort Studies—Mortality Chang et al. 2003 Electronics-manufacturing workers in Taiwan exposed to TCE, PCE: Men 2 0.44 (0.05-1.59) SMR Women 8 0.54 (0.23-1.07) SMR Boice et al. 2006 Male workers at rocket-engine testing facility 5q 1.08 (0.35-2.53) SMR CHRONIC LYMPHOCYTIC LEUKEMIA Cohort Studies—Mortality Boice et al. 2006 Male workers at rocket-engine testing facility 1 1.19 (0.03-6.61) SMR Case-Control Studies Seidler et al. 2007 Cases with occupational exposure in Germany: >0 to ≤4.4 ppm-years 10 1.1 (0.5-2.4) OR >4.4 to ≤35 ppm-years 6 0.7 (0.3-1.7) OR >35 ppm-years 2 0.9 (0.2-4.5) OR LEUKEMIA OTHER THAN CHRONIC LYMPHOCYTIC LEUKEMIA Cohort Studies—Mortality Boice et al. 2006 Male workers at rocket-engine testing facility 4 1.05 (0.29-2.69) SMR DIFFUSE LARGE B-CELL LYMPHOMA Case-Control Studies Seidler et al. 2007 Cases with occupational exposure in Germany: >0 to ≤4.4 ppm-years 6 0.5 (0.2-1.2) OR >4.4 to ≤35 ppm-years 7 0.8 (0.3-1.8) OR >35 ppm-years 4 2.6 (0.7-3.0) OR FOLLICULAR LYMPHOMA Seidler et al. 2007 Cases with occupational exposure in Germany: >0 to ≤4.4 ppm-years 7 1.3 (0.5-3.2) OR >4.4 to ≤35 ppm-years 3 0.7 (0.2-2.6) OR >35 ppm-years 3 3.2 (0.8-12.9) OR MARGINAL ZONE LYMPHOMA Case-Control Studies Seidler et al. 2007 Cases with occupational exposure in Germany: >0 to ≤4.4 ppm-years 2 0.9 (1.2-4.3) OR (Continued) 299

300 TABLE E-2 Continued Reference Study Population No. Exposed Persons MOR, OR, SIR, or SMR (95% CI) >4.4 to ≤35 ppm-years 2 4.2 (0.8-23.9) OR >35 ppm-years 2 4.2 (0.8-23.9) CHILDHOOD LEUKEMIA Cohort Studies—Incidence Morgan and Cassady 2002 Redlands, CA, community exposed to TCE, PCE in drinking water 10 1.09 (99%CI 0.38-2.31) SIR Case-Control Studies Costas et al. 2002 Cases in Woburn, MA (drinking water contaminated with TCE, PCE, other chemicals): Ever exposed: From 2 years before conception to case diagnosis 16 2.39 (0.54-10.59) OR During 2 years before conception 8 2.61 (0.47-14.37) OR During pregnancy 10 8.33 (0.73-94.67) OR From birth to diagnosis 12 1.18 (0.28-5.05) OR Cumulative exposure: From 2 years before conception to case diagnosis Least exposed 9 5.00 (0.75-33.50) OR Most exposed 7 3.56 (0.51-24.78) OR During 2 years before conception Least exposed 4 2.48 (0.42-15.22) OR Most exposed 4 2.82 (0.30-26.42) OR During pregnancy Least exposed 3 3.53 (0.22-58.14) OR Most exposed 7 14.30 (0.92-224.52) OR From birth to diagnosis Least exposed 7 1.82 (0.31-10.84) OR Most exposed 5 0.90 (0.18-4.56) OR a Hansen et al. (2001) study not cited in IOM (2003) report analysis for this particular cancer outcome, so included here as new information. b Oral cavity. c Digestive organs and peritoneum. d Colon and rectum. e Month and date when regulations on solvent use were promulgated. f Results are for hepatic and biliary cancer combined. g Lungs and bronchi. h Trachea, bronchi, and lungs. i Bone and articular cartilage. j Female genital organs. k Ovaries, fallopian tubes, and broad ligaments.

l Testes and other male genital organs. m Kidneys and other unspecified urinary organs. n Bladder and other urinary cancers. o Brain cancer only. p All leukemias. q Leukemia and aleukemia. Abbreviations: CI = confidence interval, MOR = mortality odds ratio, OR = odds ratio, SIR = standardized incidence ratio, SMR = standardized mortality ratio. 301

302 TABLE E-3a Studies of Noncancer End Points and Exposure to TCE Reference Study Population No. Exposed Persons OR (95% CI) END-STAGE RENAL DISEASE Cohort Studies Radican et al. 2006 Aircraft workers (1973-2000) 56 1.91 (1.08-3.38) Aircraft workers (1973-2002)a 61 1.42 (0.87-2.31) SYSTEMIC SCLEROSIS Case-Control Studies Diot et al. 2002 Hospital-based study in Tours, France Men and women with occupational exposure: 13 2.39 (1.04-5.22) Men 7 4.67 (0.99-21.89) Women 6 2.10 (0.65-6.75) High final cumulative exposure (men and women) 7 7.58 (1.54-37.36) Garabrant et al. 2003 Women in Michigan and Ohio: Self-reported exposure 8 2.0 (0.8-4.8) Expert-confirmed exposure 4 1.9 (0.6-6.6) CONGENITAL HEART DEFECTS Case-Control Studies Yauck et al. 2004 Infants born in Milwaukee, WI (1997-1999): Maternal age, TCE exposure <38 years, nonexposed 1 <38 years, exposed 0.9 (0.6-1.2) ≥38 years, nonexposed 1.9 (1.1-3.5) ≥38 years, exposed 6.2 (2.6-14.5) Pre-existing diabetes 4.1 (1.5-11.2) Chronic hypertension 2.8 (1.2-6.7) Alcohol use during pregnancy 2.1 (1.1-4.2) NEUROBLASTOMA Case-Control Studies De Roos et al. 2001 Offspring with paternal occupational exposure (Unites States and Canada): Self-reported exposure to TCE 22 1.4 (0.7-2.9) Industrial-hygiene-reviewed exposure 9 0.9 (0.3-2.5) a Attenuation observed was due to greater rate of end-stage renal disease in exposed subjects in 1973-2000. Rate of disease increased in unexposed subjects in 2001 (sharp increase) and 2002 while rate in exposed subjects remained approximately constant. Abbreviations: CI = confidence interval, OR = odds ratio, TCE = trichloroethylene.

TABLE E-3b Studies of Neurologic Effects and Exposure to TCE End Point Reference Population TCE Exposure, Duration Results Neurobehavioral Reif et al. 2003 143 residents in vicinity of Four exposure groups: Adjusted mean neurobehavioral test scores (measured with Rocky Mountain Arsenal, about 10-20% lower in highest-exposure group neurobehavioral core test 1981-1986 <5 ppb, mean 20.6 years than in lowest-exposure group; some evidence battery with profile of of greater depression, confusion, tension- mood states in addition to 5-10 ppb, mean 20.5 years anxiety in highest- exposure group than in two tests of visual lowest-expopsure group, but difference not perception) 10-15 ppb, mean 18.8 years statistically significant (P = 0.08, 0.14, 0.24, respectively); study found strong interaction >15 ppb, mean 24.7 years between TCE exposure and alcohol consumption in induction of neurobehavioral deficits Parkinson disease, Gash et al. 2008 30 industrial co-workers with Exposure pathway assumed to Three workers had diagnosis of Parkinson parkinsonism Parkinson disease, be inhalation with some dermal disease before study; 14 workers self-reported parkinsonism, chronic absorption. Exposure level not parkinsonian symptoms, 13 self-reported no exposure to TCE reported. symptoms (according to Unified Parkinson’s Mean duration: 27 yr Disease Rating Scale); asymptomatic group had Median duration: 28 yr significantly slower fine motor movement than control group (P< 0.0001), slightly faster hand movement than symptomatic group (p < 0.01) 303

304 TABLE E-4 Studies of Cancer End Points and Exposure to PCE No. Exposed MOR, OR, RR, SIR, or SMR Reference Study Population Persons (95% CI) BUCCAL CAVITY, PHARYNGEAL CANCER Cohort Studies—Incidence Chang et al. 2005 Electronics-manufacturing workers in Taiwan exposed to TCE, PCE: Men 19 0.55 (0.33-0.86) SIR Women 42 0.96 (0.69-1.29) SIR Cohort Studies—Mortality Blair et al. 2003 Dry cleaners in St. Louis, MO 10 1.1 (0.5-2.0) SMR Chang et al. 2003 Electronics-manufacturing workers in Taiwan exposed to TCE, PCE: Men 6 0.65 (0.50-0.83) SMR Women 10 0.71 (0.34-1.30) SMR ESOPHAGEAL CANCER Cohort Studies—Mortality Blair et al. 2003 Dry cleaners in St. Louis, MO: 26 2.2 (1.5-3.3) SMR Little or no exposure 7 2.1 (0.9-4.4) SMR Medium-high exposure 16 2.2 (1.2-3.5) SMR Chang et al. 2003 Electronics-manufacturing workers in Taiwan exposed to TCE, PCE: Men 0 — Women 0 — Case-Control Studies Lynge et al. 2006 Nordic dry-cleaning workers 8 0.76 (0.34-1.69) RR GASTRIC CANCER Cohort Studies—Incidence Chang et al. 2005 Electronics-manufacturing workers in Taiwan exposed to TCE, PCE: Men 56a 0.73 (0.55-0.95) SIR Women 135a 0.93 (0.78-1.09) SIR Cohort Studies—Mortality Blair et al. 2003 Dry cleaners in St. Louis, MO 20 0.9 (0.6-1.4) SMR Chang et al. 2003 Electronics-manufacturing workers in Taiwan exposed to TCE, PCE: Men 7 0.93 (0.37-1.91) SMR Women 24 1.11 (0.71-1.65) SMR Case-Control Studies Lee et al. 2003 Community downstream of electronics factory in Taiwan (chlorinated 39 2.18 (0.97-4.89) MOR hydrocarbons; males)

COLON CANCER Cohort Studies—Incidence Morgan and Cassady 2002 Redlands, CA, community exposed to TCE, PCE in drinking water 327b 0.86 (99%CI 0.74-0.99) SIR Cohort Studies—Mortality Blair et al. 2003 Dry cleaners in St. Louis, MO: 60 1.2 (0.9-1.5) SMR Little or no exposure 28 1.1 (0.8-1.6) SMR Medium-high exposure 28 1.2 (0.4-1.5) SMR Chang et al. 2003 Electronics-manufacturing workers in Taiwan exposed to TCE, PCE: Men 3 0.65 (0.13-1.91) SMR Women 19 1.36 (0.82-2.13) SMR Employed <1 year (men and women) 12 1.33 SMR Employed 1-5 years (men and women) 3 0.85 SMR Employed >5 years (men and women) 4 2.94 SMR Case-Control Studies Lee et al. 2003 Community downstream of electronics factory in Taiwan (chlorinated 26b 0.83 (0.24-2.89) MOR hydrocarbons; males) RECTAL CANCER Cohort Studies—Mortality Blair et al. 2003 Dry cleaners in St. Louis, MO 15 1.3 (0.7-2.2) SMR Chang et al. 2003 Electronics-manufacturing workers in Taiwan exposed to TCE, PCE: Men 2 0.73 (0.08-2.65) SMR Women 13 1.67 (0.89-2.85) SMR Employed <1 year (men and women) 9 1.81 SMR Employed 1-5 years (men and women) 2 1.01 SMR Employed >5 years (men and women) 2 2.50 SMR HEPATIC CANCER Cohort Studies—Incidence Morgan and Cassady 2002 Redlands, CA, community exposed to TCE, PCE in drinking water 28c 1.29 (99%CI 0.74-2.05) SIR Cohort Studies—Mortality Blair et al. 2003 Dry cleaners in St. Louis, MO 10 0.8 (0.4-1.5) SMR Chang et al. 2003 Electronics-manufacturing workers in Taiwan exposed to TCE, PCE: Men 0 — Women 0 — Case-Control Studies Lee et al. 2003 Community downstream of electronics factory in Taiwan (chlorinated 53 2.57 (1.21-5.46) MOR hydrocarbons; males) Lynge et al. 2006 Nordic dry-cleaning workers 11 0.76 (0.38-1.52) RR (Continued) 305

306 TABLE E-4 Continued No. Exposed MOR, OR, RR, SIR, or SMR Reference Study Population Persons (95% CI) PANCREATIC CANCER Cohort Studies—Mortality Blair et al. 2003 Dry cleaners in St. Louis, MO: 28 1.1 (0.7-1.5) SMR Little or no exposure 14 1.2 (0.7-2.0) SMR Medium-high exposure 11 0.8 (0.4-1.5) SMR Chang et al. 2003 Electronics-manufacturing workers in Taiwan exposed to TCE, PCE: Men 1 0.49 (0.01-2.73) SMR Women 5 1.39 (0.45-3.25) SMR Employed <1 year (men and women) 2 0.91 SMR Employed 1-5 years (men and women) 2 2.15 SMR Employed >5 years (men and women) 1 2.22 SMR Case-Control Studies Lynge et al. 2006 Nordic dry-cleaning workers 57 1.27 (0.90-1.80) RR LARYNGEAL CANCER Cohort Studies—Mortality Blair et al. 2003 Dry cleaners in St. Louis, MO: 6 1.7 (0.6-3.7) SMR Little or no exposure 0 — Medium-high exposure 6 2.7 (1.0-5.8) SMR Chang et al. 2003 Electronics-manufacturing workers in Taiwan exposed to TCE, PCE: Men 0 — Women 0 — LUNG CANCER Cohort Studies—Incidence Morgan and Cassady 2002 Redlands, CA, community exposed to TCE, PCE in drinking water 356d 0.71 (99%CI 0.61-0.81) SIR Chang et al. 2005 Electronics-manufacturing workers in Taiwan exposed to TCE, PCE: Men 20 0.94 (0.57-1.45) SIR Women 34 0.95 (0.66-1.33) SIR Cohort Studies—Mortality Blair et al. 2003 Dry cleaners in St. Louis, MO: 125 1.4 (1.1-1.6) SMR Little or no exposure 34 1.0 (0.7-1.4) SMR Medium-high exposure 78 1.5 (1.2-1.9) SMR Chang et al. 2003 Electronics-manufacturing workers in Taiwan exposed to TCE, PCE: Men 13e 0.90 (0.48-1.53) SMR Women 25e 1.01 (0.65-1.49) SMR Case-Control Studies Lee et al. 2003 Community downstream of electronics factory in Taiwan (chlorinated 41 1.75 (0.79-2.39) MOR hydrocarbons; males)

BONE CANCER Cohort Studies—Incidence Chang et al. 2005 Electronics-manufacturing workers in Taiwan exposed to TCE, PCE: Men 1 0.61 (0.01-3.39) SIR Women 6 1.28 (0.47-2.78) SIR Cohort Studies—Mortality Chang et al. 2003 Electronics-manufacturing workers in Taiwan exposed to TCE, PCE: Men 0f — Women 4f 1.63 (0.44-4.18) SMR Employed <1 year (men and women) 2f 1.25 SMR Employed 1-5 years (men and women) 2f 3.23 SMR Employed >5 years (men and women) 0f — SOFT-TISSUE SARCOMA Cohort Studies—Incidence Chang et al. 2005 Electronics-manufacturing workers in Taiwan exposed to TCE, PCE: Men 3 1.4 (0.3-4.2) SIR Women 8 1.0 (0.4-2.0) SIR Cohort Studies—Mortality Chang et al. 2003 Electronics-manufacturing workers in Taiwan exposed to TCE, PCE: Men 0 — Women 0 — BREAST CANCER Cohort Studies—Incidence Morgan and Cassady 2002 Redlands, CA, community exposed to TCE, PCE in drinking water 536 1.09 (99%CI 0.97-1.21) SIR (women only) Chang et al. 2005 Electronics-manufacturing workers in Taiwan exposed to TCE, PCE: Men 0 0.00 (0.00-33.54) SIR Women 215 1.19 (1.03-1.36) SIR Cohort Studies—Mortality Blair et al. 2003 Dry cleaners in St. Louis, MO: 68 1.0 (0.8-1.3) SMR Little or no exposure 30 0.8 (0.6-1.2) SMR Medium-high exposure 29 1.2 (0.8-1.7) SMR Chang et al. 2003 Electronics-manufacturing workers in Taiwan exposed to TCE, PCE: Men 0 — Women 51 1.14 (0.85-1.51) SMR Employed <1 year (women) 31 1.08 SMR Employed 1-5 years (women) 14 1.25 SMR Employed >5 years (women) 6 1.32 SMR (Continued) 307

308 TABLE E-4 Continued No. Exposed MOR, OR, RR, SIR, or SMR Reference Study Population Persons (95% CI) Case-Control Studies Aschengrau et al. 2003 Women with breast cancer in Cape Cod, MA, towns:g ≤ median exposure (latency 0-15 years) 377 0.9-1.5 OR > median exposure (latency 0-15 years) 402 1.1-1.4 OR > 75th percentile exposure (latency 0-15 years) 253 1.6-1.9 OR > 90th percentile exposure (latency 0-15 years) 90 1.3-1.9 OR Vieira et al. 2005 Women with breast cancer in Cape Cod, MA, towns: 0-year latency: Nonproxy subjects 101 1.1 (0.8-1.5) OR All subjects 155 1.1 (0.8-1.4) OR 5-year latency Nonproxy subjects 87 1.2 (0.9-1.8) OR All subjects 129 1.1 (0.9-1.6) OR 7-year latency Nonproxy subjects 71 1.1 (0.8-1.6) OR All subjects 111 1.1 (0.8-1.5) OR 9-year latency Nonproxy subjects 63 1.1 (0.7-1.6) OR All subjects 97 1.1 (0.8-1.5) OR 11-year latency Nonproxy subjects 49 1.1 (0.6-1.7) OR All subjects 79 1.2 (0.8-1.7) OR 13-year latency Nonproxy subjects 43 1.3 (0.7-2.1) OR All subjects 61 1.3 (0.9-2.0) OR 15-year latency Nonproxy subjects 30 1.4 (0.7-2.6) OR All subjects 44 1.4 (0.9-2.3) OR 17-year latency Nonproxy subjects 15 1.0 (0.4-2.2) OR All subjects 21 1.0 (0.6-2.0) OR 19-year latency Nonproxy subjects 6 1.1 (0.3-3.5) OR All subjects 9 1.1 (0.4-2.9) OR CERVICAL CANCER Cohort Studies—Incidence Morgan and Cassady 2002 Redlands, CA, community exposed to TCE, PCE in drinking water 29 0.65 (99%CI 0.38-1.02) SIR

Chang et al. 2005 Electronics-manufacturing workers in Taiwan exposed to TCE, PCE (women): Employed <1 year 177 1.1 (0.9-1.2) SIR Employed 1-5 years 69 1.1 (0.8-1.3) SIR Employed 5-10 years 26 1.6 (1.1-2.4) SIR Employed >10 years 1 0.1 (0.0-0.8) SIR Cohort Studies—Mortality Blair et al. 2003 Dry cleaners in St. Louis, MO: 27 1.6 (1.0-2.3) SMR Little or no exposure 12 1.5 (0.8-2.7) SMR Medium-high exposure 11 1.4 (0.7-1.7) SMR Chang et al. 2003 Electronics-manufacturing workers in Taiwan exposed to TCE, PCE 21 0.80 (0.49-1.22) SMR (women): Employed <1 year 14 0.84 SMR Employed 1-5 years 6 0.89 SMR Employed >5 years 1 0.34 SMR Case-Control Studies Lynge et al. 2006 Nordic dry-cleaning workers 36 0.98 (0.65-1.47) RR UTERINE CANCER Cohort Studies—Incidence Morgan and Cassady 2002 Redlands, CA, community exposed to TCE, PCE in drinking water 124 1.35 (99%CI 1.06-1.70) SIR Chang et al. 2005 Electronics-manufacturing workers in Taiwan exposed to TCE, PCE 337h 1.06 (0.95-1.18) SIR Cohort Studies—Mortality Blair et al. 2003 Dry cleaners in St. Louis, MO 15 1.1 (0.6-1.8) SMR Chang et al. 2003 Electronics-manufacturing workers in Taiwan exposed to TCE, PCE 5 0.91 (0.29-2.13) SMR (women): Employed <1 year 3 0.88 SMR Employed 1-5 years 2 1.42 SMR Employed >5 years 0 — OVARIAN CANCER Cohort Studies—Incidence Morgan and Cassady 2002 Redlands, CA, community exposed to TCE, PCE in drinking water 81 1.16 (99%CI 0.85-1.53) SIR PROSTATIC CANCER Cohort Studies—Incidence Morgan and Cassady 2002 Redlands, CA, community exposed to TCE, PCE in drinking water 483 1.11 (99%CI 0.98-1.25) SIR Cohort Studies—Mortality Blair et al. 2003 Dry cleaners in St. Louis, MO 17 1.0 (0.6-1.6) SMR Chang et al. 2003 Electronics-manufacturing workers in Taiwan exposed to TCE, PCE 0 — (men) (Continued) 309

310 TABLE E-4 Continued No. Exposed MOR, OR, RR, SIR, or SMR Reference Study Population Persons (95% CI) TESTICULAR CANCER Cohort Studies—Incidence Chang et al. 2005 Electronics-manufacturing workers in Taiwan exposed to TCE, PCE 1i 0.14 (0.00-0.76) SIR Cohort Studies—Mortality Chang et al. 2003 Electronics-manufacturing workers in Taiwan exposed to TCE, PCE 0 — (men) RENAL CANCER Cohort Studies—Incidence Morgan and Cassady 2002 Redlands, CA, community exposed to TCE, PCE in drinking water 54 0.80 (99%CI 0.54-1.12) SIR Chang et al. 2005 Electronics-manufacturing workers in Taiwan exposed to TCE, PCE: Men 8j 1.06 (0.45-2.08) SIR Women 12j 1.09 (0.56-1.91) SIR Cohort Studies—Mortality Blair et al. 2003 Dry cleaners in St. Louis, MO: 8 1.0 (0.4-2.0) SMR Little or no exposure 1 0.3 (<0.1-1.6) SMR Medium-high exposure 7 1.5 (0.6-3.1) SMR Chang et al. 2003 Electronics-manufacturing workers in Taiwan exposed to TCE, PCE: Men 0j — Women 3j 1.18 (0.24-3.44) SMR Employed <1 year 1j 0.62 SMR Employed 1-5 years 2j 3.08 SMR Employed >5 years 0j — Case-Control Studies Brüning et al. 2003 Hospital-based study in Arnsberg, Germany: Self-reported exposure 7 1.64 (0.61-4.40) OR Self-reported narcotic symptoms 5 1.84 (0.57-5.96) OR Duration of self-reported exposure: None 127 1 OR <10 years 4 2.46 (0.65-9.34) OR 10+ years 3 1.02 (0.24-4.27) OR Lynge et al. 2006 Nordic dry-cleaning workers 29 0.67 (0.43-1.05) RR BLADDER CANCER Cohort Studies—Incidence Morgan and Cassady 2002 Redlands, CA, community exposed to TCE, PCE in drinking water 82 0.98 (99%CI 0.71-1.29) SIR Cohort Studies—Mortality Blair et al. 2003 Dry cleaners in St. Louis, MO: 12 1.3 (0.7-2.4) SMR Little or no exposure 5 1.4 (0.4-3.2) SMR

Medium-high exposure 7 1.5 (0.6-3.1) SMR Chang et al. 2003 Electronics-manufacturing workers in Taiwan exposed to TCE, PCE: Men 1 0.96 (0.01-5.36) SIR Women 1 0.96 (0.01-5.33) SIR Case-Control Studies Lynge et al. 2006 Nordic dry-cleaning workers: 93 1.44 (1.07-1.93) RR Employed 0-1 years 6 1.50 (0.57-3.96) RR Employed 2-4 years 10 2.39 (1.09-5.22) RR Employed 5-9 years 17 0.91 (0.52-1.59) RR Employed 10 years or more 53 1.57 (1.07-2.29) RR SKIN MELANOMAS Cohort Studies—Incidence Morgan and Cassady 2002 Redlands, CA, community exposed to TCE, PCE in drinking water 137 1.42 (99%CI 1.13-1.77) SIR Chang et al. 2005 Electronics-manufacturing workers in Taiwan exposed to TCE, PCE: Men 2 0.48 (0.05-1.73) SIR Women 13 0.99 (0.53-1.69) SIR Cohort Studies—Mortality Blair et al. 2003 Dry cleaners in St. Louis, MO 4 0.8 (0.2-2.1) SMR Chang et al. 2003 Electronics-manufacturing workers in Taiwan exposed to TCE, PCE: Men 0 — Women 0 — CENTRAL NERVOUS SYSTEM CANCER Cohort Studies—Incidence Morgan and Cassady 2002 Redlands, CA, community exposed to TCE, PCE in drinking water 37 1.54 (99%CI 0.96-2.31) SIR Chang et al. 2005 Electronics-manufacturing workers in Taiwan exposed to TCE, PCE: Men 2 0.40 (0.05-1.46) SIR Women 15 0.97 (0.54-1.61) SIR Cohort Studies—Mortality Blair et al. 2003 Dry cleaners in St. Louis, MO 5 0.6 (0.2-1.4) SMR Chang et al. 2003 Electronics-manufacturing workers in Taiwan exposed to TCE, PCE: Men 1 0.48 (0.01-2.66) SMR Women 6 0.91 (0.33-1.99) SMR CENTRAL NERVOUS SYSTEM CANCER IN CHILDREN Cohort Studies—Incidence Morgan and Cassady 2002 Redlands, CA, community exposed to TCE, PCE in drinking water 6 1.05 (99%CI 0.24-2.70) SIR LYMPHATIC AND HEMATOPOIETIC CANCER Cohort Studies—Incidence (Continued) 311

312 TABLE E-4 Continued No. Exposed MOR, OR, RR, SIR, or SMR Reference Study Population Persons (95% CI) Chang et al. 2005 Electronics-manufacturing workers in Taiwan exposed to TCE, PCE: Men 6 0.73 (0.27-1.60) SIR Women 16 0.65 (0.37-1.05) SIR Cohort Studies—Mortality MALIGNANT LYMPHOMA Case-Control Studies Seidler et al. 2007 Cases with occupational exposure in Germany: >0 to ≤ 9.1 ppm-year 16 1.1 (0.5-2.3) OR >9.1 to ≤78.8 ppm-year 13 1.0 (0.5-2.2) OR >78.8 ppm-year 2 3.4 (0.7-17.3) OR NON-HODGKIN LYMPHOMA Cohort Studies—Incidence Morgan and Cassady 2002 Redlands, CA, community exposed to TCE, PCE in drinking water 111 1.09 (99%CI 0.84-1.38) SIR Cohort Studies—Mortality Blair et al. 2003 Dry cleaners in St. Louis, MO 12 0.9 (0.5-1.6) SMR Case-Control Studies Lynge et al. 2006 Nordic dry-cleaning workers 42 0.95 (0.65-1.41) RR Miligi et al. 2006 Cases with occupational exposure in Italy: Very low-low 18 0.6 (0.3-1.2) OR Medium-high 14 1.2 (0.6-2.5) OR ≤15 years 10 1.3 (0.5-3.3) OR >15 years 3 — Seidler et al. 2007 Cases with occupational exposure in Germany: B-non-Hodgkin lymphoma: >0 to ≤ 9.1 ppm-year 12 0.9 (0.4-2.0) OR >9.1 to ≤78.8 ppm-year 12 1.0 (0.5-2.3) OR >78.8 ppm-year 5 3.2 (0.6-16.7) OR T-non-Hodgkin lymphoma: >0, ≤ 9.1 ppm-year 1 1.7 (0.2-14.4) OR >9.1 to ≤78.8 ppm-year 1 1.5 (0.2-12.5) OR >78.8 ppm-year 1 — HODGKIN DIESASE Cohort Studies—Incidence Morgan and Cassady 2002 Redlands, CA, community exposed to TCE, PCE via drinking water 17 0.93 (99%CI 0.44-1.67) SIR Cohort Studies—Mortality Blair et al. 2003 Dry cleaners in St. Louis, MO 5 2.0 (0.6-4.6) SMR Chang et al. 2003 Electronics-manufacturing workers in Taiwan exposed to TCE, PCE:

Men 0 — Women 1 2.23 (0.03-12.40) SMR Case-Control Studies Seidler et al. 2007 Cases with occupational exposure in Germany: >0 to ≤ 9.1 ppm-year 3 1.7 (0.4-6.9) OR >9.1 to ≤78.8 ppm-year 1 0.7 (0.1-6.3) OR >78.8 ppm-year 0 — MULTIPLE MYELOMA Cohort Studies—Mortality Blair et al. 2003 Dry cleaners in St. Louis, MO 7 0.8 (0.3-1.6) SMR Case-Control Studies Seidler et al. 2007 Cases with occupational exposure in Germany: >0 to ≤ 9.1 ppm-year 3 1.8 (0.5-6.7) OR >9.1 to ≤78.8 ppm-year 0 — >78.8 ppm-year 0 — LEUKEMIA Cohort Studies—Incidence Morgan and Cassady 2002 Redlands, CA, community exposed to TCE, PCE in drinking water 77k 1.02 (99%CI 0.74-1.35) SIR Cohort Studies—Mortality Blair et al. 2003 Dry-cleaners in St. Louis, MO 12 0.8 (0.4-1.4) SMR Chang et al. 2003 Electronics-manufacturing workers in Taiwan exposed to TCE, PCE: Men 2 0.44 (0.05-1.59) SMR Women 8 0.54 (0.23-1.07) SMR CHRONIC LYMPHOCYTIC LEUKEMIA Case-Control Studies Seidler et al. 2007 Cases with occupational exposure in Germany: >0, ≤ 9.1 ppm-year 1 — >9.1, ≤78.8 ppm-year 2 0.6 (0.1-2.8) OR >78.8 ppm-year 0 — DIFFUSE LARGE B-CELL LYMPHOMA Case-Control Studies Seidler et al. 2007 Cases with occupational exposure in Germany: >0 to ≤ 9.1 ppm-year 3 0.9 (0.3-3.9) OR >9.1 to ≤78.8 ppm-year 6 2.1 (0.8-5.9) OR >78.8 ppm-year 1 2.3 (0.2-26.0) OR FOLLICULAR LYMPHOMA Case-Control Studies Seidler et al. 2007 Cases with occupational exposure in Germany: (Continued) 313

314 TABLE E-4 Continued Reference No. Exposed MOR, OR, RR, SIR, or SMR Study Population Persons (95% CI) >0 to ≤ 9.1 ppm-year 2 1.2 (0.3-5.5) OR >9.1 to ≤78.8 ppm-year 0 — >78.8 ppm-year 0 — MARGINAL ZONE LYMPHOMA Seidler et al. 2007 Cases with occupational exposure in Germany: >0 to ≤ 9.1 ppm-year 1 — Costas et al. 2002 Cases in Woburn, MA (drinking water contaminated with TCE, PCE, other chemicals): Ever exposed: From 2 years before conception to case diagnosis 16 2.39 (0.54-10.59) OR During 2 years before conception 8 2.61 (0.47-14.37) OR During pregnancy 10 8.33 (0.73-94.67) OR From birth to diagnosis 12 1.18 (0.28-5.05) OR Cumulative exposure: From 2 years before conception to case diagnosis: Least exposed 9 5.00 (0.75-33.50) OR Most exposed 7 3.56 (0.51-24.78) OR During 2 years before conception: Least exposed 4 2.48 (0.42-15.22) OR Most exposed 4 2.82 (0.30-26.42) OR During pregnancy: Least exposed 3 3.53 (0.22-58.14) OR Most exposed 7 14.30 (0.92-224.52) OR From birth to diagnosis: Least exposed 7 1.82 (0.31-10.84) OR Most exposed 5 0.90 (0.18-4.56) OR Infante-Rivard et al. 2005 Maternal occupational exposure: 2 years before pregnancy up to birth 0.96 (0.41-2.25) OR During pregnancy 0.84 (0.30-2.34) OR a Digestive organs and peritoneum. b Colon and rectum. c Results are for liver and biliary cancer combined. d Lungs and bronchi. e Trachea, bronchi, and lungs. f Bone and articular cartilage. g Combined data from present and previous study by Aschengrau et al. (1998). h Female genital organs. 293

i Testes and other male genital organs. j Kidney and other unspecified urinary organs. k All leukemias. Abbreviations: CI = confidence interval, MOR = mortality odds ratio, OR = odds ratio, PCE = perchloroethylene, RR = relative risk, SIR = standardized incidence ratio, SMR = standardized mortality ratio, TCE = trichloroethylene. 315

316 TABLE E-5a Studies of Noncancer End Points and Exposure to PCE Reference Study Population No. Exposed Persons OR (95% CI) SYSTEMIC SCLEROSIS Case-Control Studies Garabrant et al. 2003 Women in Michigan, Ohio: Self-reported exposure 7 1.4 (0.6-3.4) Expert-confirmed exposure 5 1.1 (0.4-2.9) PRETERM LOSS Sonnefeld et al. 2001 Infants of Camp Lejeune residents, 1968-1985: Exposure 1-3 weeks 14 1.0 (90% CI 0.6-1.6) Exposure 4-10 weeks 55 1.3 (90% CI 1.0-1.7) Exposure 11-20 weeks 86 1.3 (90% CI 1.1-1.6) Exposure >20 weeks, less than entire pregnancy 94 0.8 (90% CI 0.7-1.0) Exposure, entire pregnancy, less than 1 year before 158 1.1 (90% CI 0.9-1.3) last menstrual period Exposure entire pregnancy, at least 1 year before last 36 0.8 (90% CI 0.6-1.1) menstrual period SMALL FOR GESTATIONAL WEIGHT Sonnefeld et al. 2001 Infants of Camp Lejeune residents, 1968-1985 Exposure 1-3 weeks 15 0.9 (90% CI 0.5-1.3) Exposure 4-10 weeks 60 1.1 (90% CI 0.9-1.4) Exposure 11-20 weeks 84 1.0 (90% CI 0.8-1.2) Exposure >20 weeks, less than entire pregnancy 16 1.2 (90% CI 1.0-1.4) Exposure entire pregnancy, less than 1 year before 207 1.2 (90% CI 1.0-1.3) last menstrual period Exposure entire pregnancy, at least 1 year before last 61 1.1 (90% CI 0.9-1.4) menstrual period All births 622 1.2 (90% CI 1.0-1.3) Mother’s age <35 years 611 1.1 (90% CI 0.9-1.2) Mother’s age ≥ 35 years 11 2.1 (90% CI 0.9-4.9) Mother had no previous fetal losses 475 1.1 (90% CI 0.9-1.2) Mother had one previous fetal loss 104 1.5 (90% CI 1.1-2.0) Mother had at least two previous fetal losses 43 2.5 (90% CI 1.5-4.3) MEAN BIRTH WEIGHT Sonnenfeld et al. 2001 Infants of Camp Lejeune residents, 1968-1985 Exposure 1-3 weeks 189 Mean difference: 18 g (90% CI -40 to 76) Exposure 4-10 weeks 597 Mean difference: -17 g (90% CI -51 to 17) Exposure 11-20 weeks 915 Mean difference: -31 g (90% CI -59 to -3) Exposure >20 weeks, less than entire pregnancy 1,551 Mean difference: -28 g (90% CI -50 to -5)

Exposure entire pregnancy , less than 1 year before 1,994 Mean difference: -15 g (90% CI -35 to 5) last menstrual period Exposure entire pregnancy, at least 1 year before last 605 Mean difference: -18 g (90% CI -51 to 16) menstrual period All births 6,039 Mean difference: -26 g (90% CI -43 to -9) Mother’s age <35 years 5,968 Mean difference: -2 g (90% CI -17 to 13) Mother’s age ≥ 35 years 71 Mean difference: -130 g (90% CI -236 to -23) Mother had no previous fetal losses 4,985 Mean difference: -2 g (90% CI -17 to 13) Mother had one previous fetal loss 806 Mean difference: -16 g (90% CI -79 to 24) Mother had at least two previous fetal losses 245 Mean difference: -104 g (90% CI -174 to -34) NEUROBLASTOMA Case-Control Studies De Roos et al. 2001 Offspring with paternal occupational exposure (Unites States, Canada) Self-reported exposure to PCE 8 0.5 (0.2-1.4) OR Industrial-hygiene-reviewed exposure 4 0.5 (0.1-1.7) OR SCHIZOPHRENIA Cohort Studies—Incidence Perrin et al. 2007 Offspring of dry cleaners in Jerusalem 4 3.4 (1.3-9.2) RR NEUROBEHAVIORAL Cohort Studies Janulewicz et al. 2008 Offspring of Cape Cod, MA, residents born 1969- 1,349 (Note: end point included two 1983 diagnoses—ADD and HD— and six indicators of learning disabilities) Prenatal exposure: 1,244 Low exposure 1.0-1.5 (0.7-2.7) OR High exposure 0.8-1.1 (0.4-1.6) OR Exposure 5 years postnatally: 1,326 Low exposure 0.9-1.4 (0.7-2.5) OR High exposure 0.6-1.0 (0.3-1.7) OR Abbreviations: ADD = attention deficit disorder, CI = confidence interval, HD = hyperactivity disorder, OR = odds ratio, PCE = perchloroethylene. 317

TABLE E-5b Visual Contrast Sensitivity and Visual Acuity 318 Reference Population Exposure, Duration Effects Schreiber et al. Apartment residents above dry cleaner Mean, 778 µg/m3 Visual contrast sensitivity trend in Lanthony D15-d; no change 2002 Median, 350 µg/m3 in visual acuity Mean residence, 5.8 years Lifetime dose, 3,400 µg/m3 Day-care workers sharing building with Mean, 2,150 µg/m3 Visual contrast sensitivity; no change in visual acuity dry cleaner Median, 2,150 µg/m3 Mean work, 4.0 years Lifetime dose, 1,978 µg/m3

Contaminated Water Supplies at Camp Lejeune: Assessing Potential Health Effects Get This Book
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In the early 1980s, two water-supply systems on the Marine Corps Base Camp Lejeune in North Carolina were found to be contaminated with the industrial solvents trichloroethylene (TCE) and perchloroethylene (PCE). The water systems were supplied by the Tarawa Terrace and Hadnot Point watertreatment plants, which served enlisted-family housing, barracks for unmarried service personnel, base administrative offices, schools, and recreational areas. The Hadnot Point water system also served the base hospital and an industrial area and supplied water to housing on the Holcomb Boulevard water system (full-time until 1972 and periodically thereafter).

This book examines what is known about the contamination of the water supplies at Camp Lejeune and whether the contamination can be linked to any adverse health outcomes in former residents and workers at the base.

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